Functional expression of the polymeric immunoglobulin receptor from cloned cDNA in fibroblasts.

The polymeric immunoglobulin receptor, a transmembrane protein, is made by a variety of polarized epithelial cells. After synthesis, the receptor is sent to the basolateral surface where it binds polymeric IgA and IgM. The receptor-ligand complex is endocytosed, transported across the cell in vesicles, and re-exocytosed at the apical surface. At some point the receptor is proteolytically cleaved so that its extracellular ligand binding portion (known as secretory component) is severed from the membrane and released together with the polymeric immunoglobulin at the apical surface. We have used a cDNA clone coding for the rabbit receptor and a retroviral expression system to express the receptor in a nonpolarized mouse fibroblast cell line, psi 2, that normally does not synthesize the receptor. The receptor is glycosylated and sent to the cell surface. The cell cleaves the receptor to a group of polypeptides that are released into the medium and co-migrate with authentic rabbit secretory component. Cleavage and release of secretory component do not depend on the presence of ligand. The cells express on their surface 9,600 binding sites for the ligand, dimeric IgA. The ligand can be rapidly endocytosed and then re-exocytosed, all within approximately 10 min. Very little ligand is degraded. At least some of the ligand that is released from the cells is bound to secretory component. The results presented indicate that we have established a powerful new system for analyzing the complex steps in the transport of poly-Ig and the general problem of membrane protein sorting

Financial Administration and Management in the Electronics Industry under National Defense Contracts

Thesis (M.B.A.)--Boston Universit

The essential role of bursicon during Drosophila development

<p>Abstract</p> <p>Background</p> <p>The protective external cuticle of insects does not accommodate growth during development. To compensate for this, the insect life cycle is punctuated by a series of molts. During the molt, a new and larger cuticle is produced underneath the old cuticle. Replacement of the smaller, old cuticle culminates with ecdysis, a stereotyped sequence of shedding behaviors. Following each ecdysis, the new cuticle must expand and harden. Studies from a variety of insect species indicate that this cuticle hardening is regulated by the neuropeptide bursicon. However, genetic evidence from <it>Drosophila melanogaster </it>only supports such a role for bursicon after the final ecdysis, when the adult fly emerges. The research presented here investigates the role that bursicon has at stages of <it>Drosophila </it>development which precede adult ecdysis.</p> <p>Results</p> <p>We addressed the mechanism and timing of hormonal release from bursicon-positive motor neurons at the larval neuromuscular junction. Our findings indicate that vesicle membrane proteins which are required for classical neurotransmitter release are also expressed at these peptidergic motor neuron terminals; and that these terminals secrete hormones including bursicon at the neuromuscular junction, coinciding with larval ecdysis. This release surprisingly occurs in two waves, indicating bursicon secretion preceding and following the ecdysis sequence. Next, we addressed the functional significance of bursicon signaling during development, by disrupting the expression of its receptor, rickets, in different target tissues. We determined that rickets is developmentally required in the epidermis and imaginal discs for proper formation of the prepupa. It is also required to harden the pharate adult cuticle before eclosion. Significantly, we have also found that the available rickets mutants are not genetic nulls as previously believed, which necessitated the use of targeted RNA interference to disrupt rickets expression.</p> <p>Conclusions</p> <p>Our results are consistent with the view that bursicon is the insect tanning hormone. However, this is the first study to rigorously demonstrate both its release and function during development. Importantly, we provide new evidence that bursicon release can precede the initiation of larval ecdysis, and that bursicon tans the puparium. Our results firmly establish bursicon signaling as essential to insect growth and development.</p

Understanding Parents’ Attitudes Towards Complexity in Children\u27s Books

Experts in children\u27s literature and child development value complexity in the language, socio-emotional content, and structure of books, yet little is known regarding parents’ attitudes towards these aspects. The study thus examined how parents’ gender, education, and profession, children\u27s age and gender, and frequency of parent-child reading interactions predict parents’ support for complexity in children’s books. Participants were 104 parents to children aged 4-7. Parents completed questionnaires measuring frequency of shared book reading and levels of support for complexity of children’s narrative books in three areas: language, socio-emotional content, and structure. Results showed that parents supported complexity of socio-emotional content, followed by language, and least supported structural complexity. Only parents\u27 profession and frequency of shared book reading interactions predicted support for complexity in books. Parents who read more to their children and parents in social professions showed greater support for complexity. The study stresses the importance of guiding parents to consider a variety of aspects when selecting books to read with their children

Analysis of the DFS-2 in the workplace

51 leaves ; 29 cm.Includes abstract.Includes bibliographical references (leaves 44-48).The current research investigated the relationship of eight Canadian Forces Occupational Stress Questionnaire (CFOSQ) job characteristics, and transformational leadership as measured by the Global Transformational Leadership (GTL) with flow and its nine dimensions as defined by Csikszentmihalyi (1990), measured by the Dispositional Flow Scale-2 (DFS-2). The sample was comprised of SMU students and non-SMU participants, who were working at the time of the study. The results showed that none of the job characteristics or transformational leadership had a significant relationship with flow and all nine dimensions. One important outcome of the present research is that a nine dimension flow model may be overly complex in a work context. Contrary to expectations transformational leadership did not have a significant relationship with flow or any of the nine dimensions. Routinization and skill use had the highest number of significant relationships with flow and the nine dimensions

A Comparison of Vocabulary Learning From Joint Reading of Narrative and Informational Books With Dual Language Learner Children

A Comparison of Vocabulary Learning From Joint Reading of Narrative and Informational Books With Dual Language Learner Children By: Deborah Bergman Deitcher Advisor: Professor Helen L. Johnson This study examined joint reading of narrative and informational texts in the home setting, between parents and their English-Hebrew dual language learning preschool children. Parent-child dyads were video-recorded while reading two sets of books; each set contained one narrative and one informational text on the same theme. Children\u27s target word learning of 48 target words (12 words per book) of varying difficulty levels was measured from pretest to posttest. Results showed that children learned target words at both the receptive and expressive levels, with scores nearly tripling from pretest to posttest at the expressive level. Child\u27s age, prior vocabulary knowledge, and target word difficulty level were significantly predictive of children\u27s receptive word learning. Age, number of years the child was in Israel, prior vocabulary knowledge, and target word difficulty level were significantly predictive of children\u27s expressive word learning. Contrary to expectation, book genre was not significantly predictive of word learning. However, parent book reading style differed by genre, with more overall talk, and nearly twice the number of the following elements occurring during readings of informational texts: references to vocabulary words, questions, text-to-text and text-to-reader references, restatements, and elaborations. Educational implications are discussed

Fibrolase: Trials and Tribulations

Fibrolase is the fibrinolytic enzyme isolated from Agkistrodon contortrix contortrix (southern copperhead snake) venom. The enzyme was purified by a three-step HPLC procedure and was shown to be homogeneous by standard criteria including reverse phase HPLC, molecular sieve chromatography and SDS-PAGE. The purified enzyme is a zinc metalloproteinase containing one mole of zinc. It is composed of 203 amino acids with a blocked amino-terminus due to cyclization of the terminal Gln residue. Fibrolase shares a significant degree of homology with enzymes of the reprolysin sub-family of metalloproteinases including an active site homology of close to 100%; it is rapidly inhibited by chelating agents such as EDTA, and by alpha2-macroglobulin (α2Μ). The enzyme is a direct-acting thrombolytic agent and does not rely on plasminogen for clot dissolution. Fibrolase rapidly cleaves the A(α)-chain of fibrinogen and the B(β)-chain at a slower rate; it has no activity on the γ-chain. The enzyme exhibits the same specificity with fibrin, cleaving the α-chain more rapidly than the β-chain. Fibrolase was shown to have very effective thrombolytic activity in a reoccluding carotid arterial thrombosis model in the canine. A recombinant version of the enzyme was made in yeast by Amgen, Inc. (Thousand Oaks, CA, USA) and called alfimeprase. Alfimeprase is identical to fibrolase except for a two amino acid truncation at the amino-terminus and the insertion of a new amino-terminal amino acid in the truncated protein; these changes lead to a more stable enzyme for prolonged storage. Alfimeprase was taken into clinical trials by Nuvelo, Inc. (San Carlos, CA), which licensed the enzyme from Amgen. Alfimeprase was successful in Phase I and II clinical trials for peripheral arterial occlusion (PAO) and central venous access device (CVAD) occlusion. However, in Phase III trials alfimeprase did not meet the expected end points in either PAO or CVAD occlusion and in a Phaase II stroke trial, and Nuvelo dropped further development in 2008

Effectiveness of a large-scale distribution programme of free nicotine patches: a prospective evaluation

Abstract BACKGROUND: After an increase in cigarette taxes and implementation of smoke-free workplace legislation, the New York City Department of Health and Mental Hygiene, the New York State Department of Health, and the Roswell Park Cancer Institute undertook large-scale distribution of free nicotine replacement therapy (NRT). We did a 6 month follow-up survey to assess the success of this programme in improving smoking cessation on a population basis. METHODS: 34,090 eligible smokers who phoned a toll-free quitline were sent a 6-week course of nicotine patches (2 weeks each of 21 mg, 14 mg, and 7 mg per day). Brief follow-up counselling calls were attempted. At 6 months after treatment, we assessed smoking status of 1305 randomly sampled NRT recipients and a non-randomly selected comparison group of eligible smokers who, because of mailing errors, did not receive the treatment. NRT recipients were compared with local survey-derived data for heavy smokers in New York City. FINDINGS: An estimated 5% of all adults in New York City who smoked ten cigarettes or more daily received NRT; most (64%) recipients were non-white, foreign-born, or resided in a low-income neighbourhood. Of individuals contacted at 6 months, more NRT recipients than comparison group members successfully quit smoking (33%vs 6%, p\u3c0.0001), and this difference remained significant after adjustment for demographic factors and amount smoked (odds ratio 8.8, 95% CI 4.4-17.8). Highest quit rates were associated with those who were foreign born (87 [39%]), older than 65 years (40 [47%]), and smoked less than 20 cigarettes per day (116 [35%]). Those who received a counselling call were more likely to stop smoking than those who did not (246 [38%] vs 189 [27%], p=0.001). With the conservative assumption that every 6-month follow-up survey non-respondent continued to smoke, the stop rate among NRT recipients was 20%. At least 6038 successful quits were attributable to NRT receipt, and cost was 464 US dollars per quit. INTERPRETATION: Easy access to cessation medication for diverse populations could help many more smokers to stop