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Biomedical subjects

H Linn

Publications and source records attributed to H Linn.

10 recordsLinked to original sources
PubMed2001

From strategy to reality: 25 years of planning and progress in occupational injury research.

Injury as a major public health problem, although noted as early as the 1930s, was not widely accepted by the public health community until the 1980s. Over recent decades, there have been a number of strategic plans developed to prevent and control occupational injuries. These plans have been remarkably consistent in that many of the same recommendations surfaced despite different planners from different eras. The recommendations also generally align with the steps in the public health approach. Although recognition of the relevance of the public health approach to traumatic occupational injury came decades ago, significant barriers have inhibited its full implementation. Today, these barriers are being overcome, due to improved surveillance, increased collaborations among disciplines, increasing partnerships with industry, improved prevention evaluation methods, cost analysis models, and increasing funding. Of course, many of the experiences in the United States are paralleled in other countries in the Western world, and even in some developing countries. Substantial progress has been made in recent years in identifying problems and developing solutions, in addressing the recommendations of decades of planning, and of building the scientific foundation necessary to guide prevention. As a result, traumatic occupational injury research must begin to increase focus on bringing the public health process full circle, including the implementation and evaluation of preventive strategies and interventions. Now, the final steps of the process need our attention-evaluating the effectiveness of these solutions and then getting knowledge and products onto the shop floor, the construction site, and the farm, the convenience store, and the delivery truck; getting effective prevention into the workplace. Now is the time to close the loop, from science to prevention.

Humans↗
PubMed1999

The WW domain of dystrophin requires EF-hands region to interact with beta-dystroglycan.

Skeletal muscle dystrophin is a 427 kDa protein thought to act as a link between the actin cytoskeleton and the extracellular matrix. Perturbations of the dystrophin-associated complex, for example, between dystrophin and the transmembrane glycoprotein beta-dystroglycan, may lead to muscular dystrophy. Previously, the cysteine-rich region and first half of the carboxy-terminal domain of dystrophin were shown to interact with beta-dystroglycan through a stretch of fifteen amino acids at the carboxy-terminus of beta-dystroglycan. This region of dystrophin implicated in binding beta-dystroglycan contains four modular protein domains: a WW domain, two putative Ca2+-binding EF-hand motifs, and a putative zinc finger ZZ domain. The WW domain is a globular domain of 38-40 amino acids with two highly conserved tryptophan residues spaced 20-22 amino acids apart. A subset of WW domains was shown to bind ligands that contain a Pro-Pro-x-Tyr core motif (where x is any amino acid). Here we elucidate the role of the WW domain of dystrophin and surrounding sequence in binding beta-dystroglycan. We show that the WW domain of dystrophin along with the EF-hand motifs binds to the carboxy-terminus of beta-dystroglycan. Through site-specific mutagenesis and in vitro binding assays, we demonstrate that binding of dystrophin to the carboxy-terminus of beta-dystroglycan occurs via a beta-dystroglycan Pro-Pro-x-Tyr core motif. Targeted mutagenesis of conserved WW domain residues reveals that the dystrophin/beta-dystroglycan interaction occurs primarily through the WW domain of dystrophin. Precise mapping of this interaction could aid in therapeutic design.

Amino Acid Sequence↗
PubMed1998

Evaluation of a clinic-based program to promote book sharing and bedtime routines among low-income urban families with young children.

OBJECTIVE: To evaluate a program of anticipatory guidance in which pediatric residents and nurse practitioners in a continuity practice gave parents books for their young children along with developmentally appropriate educational materials describing why and how to share the books and promoting reading as part of a bedtime routine. STUDY DESIGN: Comparison of 2 cross-sectional groups using consecutive, structured, face-to-face or telephone interviews of parents. One group was a historical control or a comparison group (group 1). The other was the intervention group (group 2), which included families who had received 2 books and educational materials for the children as part of the program to promote book sharing and bedtime routines. SUBJECTS: Before the institution of the program to promote book sharing and bedtime routines, the parents in 51 families with healthy children 12 to 38 months of age who regularly attended continuity clinics conducted by the house staff were interviewed; these families constituted group 1. Group 1 included a low-income population of Hispanic, African American, and non-Hispanic white families. Group 2 included 100 families with similar sociodemographic characteristics with healthy 12- to 38-month-old children who had received 2 books and educational materials at all 6- to 36-month well-child visits as part of the program. RESULTS: The intervention was found to be effective in promoting child-centered literacy activities. When asked openended questions, 4 (8%) of the parents in group 1 and 21 (21%) of the parents in group 2 said 1 of their child's 3 favorite activities included books (P=.04); 11 (22%) of the parents in group 1 and 42 (42%) of the parents in group 2 said 1 of their 3 favorite activities with their child was book sharing (P=.01); and 10 (20%) of the parents in group 1 and 35 (35%) of the parents in group 2 said that they share books 6 or 7 times a week at bedtime (P =.05). By mentioning 1 of these 3 important child-centered book-sharing activities, 17 (33%) of the parents in group 1 and 69 (69%) of the parents in group 2 (P <.001) demonstrated positive child-centered literacy orientation . A multiple logistic regression analysis controlling for parental education, ethnicity, and reading habits, as well as for the sex and age of the children, found child-centered literacy orientation more likely to be present in group 2 than in group 1 families, with an odds ratio (OR) of 4.7 (95% confidence interval [CI], 2.1-10.5; P<.001). Book sharing as part of a bedtime routine was more frequent in group 2 (mean+/-SD, 3.9+/-2.6 nights per week) than in group 1 (mean+/-SD, 2.5+/-2.7 nights per week; P=.002); however, no significant differences in prolonged bedtime struggles, parent-child co-sleeping, frequent night waking, or how children fell asleep were found between the groups. Instead, in multivariate analysis, bedtime struggles occurred more often with younger parents (P=.03) and fewer children at home (P=.02), while parent-child co-sleeping (P<.001) and frequent night waking (P=.04) were less likely to occur when children usually fell asleep alone in their own beds. CONCLUSIONS: This simple and inexpensive intervention by pediatric house staff, consisting of the provision of children's books and educational materials at well-child visits, resulted in increased enjoyment of and participation in child-centered book-related activities in low-income families. Primary care providers (ie, physicians and nurse practitioners) serving underserved pediatric populations may have a unique opportunity to promote child-centered literacy in at-risk groups.

Beds↗
PubMed1997

The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled.

The neural protein FE65 contains two types of protein-protein interaction modules: one WW binding domain and two phosphotyrosine binding domains. The carboxyl-terminal phosphotyrosine binding domain of FE65 interacts in vivo with the beta-amyloid precursor protein, which is implicated in Alzheimer disease. To understand the function of this adapter protein, we identified binding partners for the FE65 WW domain. Proline-rich sequences sharing a proline-proline-leucine-proline core motif were recovered by screening expression libraries for ligands of the FE65 WW domain. Five proteins of molecular masses 60, 75, 80, 140, and 200 kDa could be purified from mouse brain lysates by affinity to the FE65 WW domain. We identified two of these five proteins as the 80- and 140-kDa isoforms encoded by Mena, the mammalian homolog of the Drosophila Enabled gene. Using the SPOTs technique of peptide synthesis, we identified the sequences in Mena that interact with the FE65 WW domain and found that they contain the signature proline-proline-leucine-proline motif. Finally, we demonstrated that Mena binds to FE65 in vivo by coimmunoprecipitation assay from COS cell extracts. The specificity of the Mena-FE65 WW domain association was confirmed by competition assays. Further characterization of the FE65-Mena complex may identify a physiological role for these proteins in beta-amyloid precursor protein biogenesis and may help in understanding the mechanism of molecular changes that underlie Alzheimer disease.

Amino Acid Sequence↗
PubMed1997

Characterization of the WW domain of human yes-associated protein and its polyproline-containing ligands.

We had previously identified the WW domain as a novel globular domain that is composed of 38-40 semiconserved amino acids and is involved in mediating protein-protein interaction. The WW domain is shared by proteins of diverse functions including structural, regulatory, and signaling proteins in yeast, nematode, and mammals. Functionally it is similar to the Src homology 3 domain in that it binds polyproline ligands. By screening a 16-day mouse embryo expression library, we identified two putative ligands of the WW domain of Yes kinase-associated protein which we named WW domain-binding proteins 1 and 2. These proteins interacted with the WW domain via a short proline-rich motif with the consensus sequence of four consecutive prolines followed by a tyrosine. Herein, we report the cDNA cloning and characterization of the human orthologs of WW domain-binding proteins 1 and 2. The products encoded by these cDNA clones represent novel proteins with no known function. Furthermore, these proteins show no homology to each other except for a proline-rich motif. By fluorescence in situ hybridization on human metaphase chromosomes, we mapped the human genes for WW domain-binding proteins 1 and 2 to chromosomes 2p12 and 17q25, respectively. In addition, using site-directed mutagenesis, we determined which residues in the WW domain of Yes kinase-associated protein are critical for binding. Finally, by synthesizing peptides in which the various positions of the four consecutive proline-tyrosine motif and the five surrounding residues were replaced by all possible amino acid residues, we further elucidated the binding requirements of this motif.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Using molecular repertoires to identify high-affinity peptide ligands of the WW domain of human and mouse YAP.

The WW domain is a globular protein domain that is involved in mediating protein-protein interaction and that ultimately participates in various intracellular signaling events. The domain binds to polyproline ligands containing the xPPxY consensus (where x signifies any amino acid, P is proline and Y is tyrosine). One of the first WW domain-ligand links that was characterized in vitro was the WW domain of Yes-Associated Protein (YAP) and its WBP-1 ligand. To further characterize this molecular interaction, we used two independent approaches, both of which focused on the mutational analysis of the WBP-1 ligand. We screened repertoires of synthetic decamer peptides containing the xPPxY core of WBP-1 in which all ten positions were sequentially replaced with the remaining amino acids. In addition, we screened decamer repertoires with all permutations of the amino acids which individually increased the binding to the WW domain of YAP, as compared to the wild type. In a parallel approach, we used a phage-displayed combinatorial peptide library biased for the presence of two consecutive prolines to study ligand preferences for the WW domain of YAP. Interestingly, these two lines of investigation converged and yielded the core sequence PPPPYP, which is preferred by the YAP-WW domain. This sequence was found within the p53 (tumor suppressor) binding protein-2, a probable cognate or alternative ligand interacting with YAP.

Adaptor Proteins, Signal Transducing↗