Showing papers by "University of Alberta published in 1999"

Critical Inquiry in a Text-Based Environment: Computer Conferencing in Higher Education

Abstract: The purpose of this study is to provide conceptual order and a tool for the use of computer-mediated communication (CMC) and computer conferencing in supporting an educational experience. Central to the study introduced here is a model of community inquiry that constitutes three elements essential to an educational transaction—cognitive presence, social presence, and teaching presence. Indicators (key words/phrases) for each of the three elements emerged from the analysis of computer-conferencing transcripts. The indicators described represent a template or tool for researchers to analyze written transcripts, as well as a guide to educators for the optimal use of computer conferencing as a medium to facilitate an educational transaction. This research would suggest that computer conferencing has considerable potential to create a community of inquiry for educational purposes.

Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori

Abstract: Helicobacter pylori, one of the most common bacterial pathogens of humans, colonizes the gastric mucosa, where it appears to persist throughout the host's life unless the patient is treated. Colonization induces chronic gastric inflammation which can progress to a variety of diseases, ranging in severity from superficial gastritis and peptic ulcer to gastric cancer and mucosal-associated lymphoma. Strain-specific genetic diversity has been proposed to be involved in the organism's ability to cause different diseases or even be beneficial to the infected host and to participate in the lifelong chronicity of infection. Here we compare the complete genomic sequences of two unrelated H. pylori isolates. This is, to our knowledge, the first such genomic comparison. H. pylori was believed to exhibit a large degree of genomic and allelic diversity, but we find that the overall genomic organization, gene order and predicted proteomes (sets of proteins encoded by the genomes) of the two strains are quite similar. Between 6 to 7% of the genes are specific to each strain, with almost half of these genes being clustered in a single hypervariable region.

Assessing Social Presence In Asynchronous Text-based Computer Conferencing

Abstract: Instructional media such as computer conferencing engender high levels of student-student and student-teacher interaction; therefore, they can support models of teaching and learning that are highly interactive and consonant with the communicative ideals of university education. This potential and the ubiquity of computer conferencing in higher education prompted three of the authors of the this article to develop a community of inquiry model that synthesizes pedagogical principles with the inherent instructional and access benefits of computer conferencing (Garrison, Anderson, & Archer, 2000). This article explicates one element of the model, social presence. Social presence is defined as the ability of learners to project themselves socially and affectively into a community of inquiry. A template for assessing social presence in computer conferencing is presented through content analysis of conferencing transcripts. To facilitate explication of the scheme and subsequent replication of this study, selections of coded transcripts are included, along with interrater reliability figures. The article concludes with a discussion of the implications and benefits of assessing social presence for instructors, conference moderators, and researchers. Les medias educatifs, tel le forum electronique, sont susceptibles d'engendrer un niveau eleve d'interaction entre les etudiants et entre le tuteur et chaque etudiant; par consequent, ils peuvent soutenir des modeles d'enseignement et d'apprentissage qui mettent en valeur l'interaction et qui sont compatibles avec les ideaux communicationnels d'une education universitaire. Ce potentiel, ainsi que l'ubiquite du forum asynchrone dans l'education superieure, ont mene trois des auteurs de cet article a developper un modele de communaute de recherche qui resume les principes pedagogiques applicables au forum electronique en incluant les benefices que l'enseignement peut en retirer et les avantages relatifs a l'accessibilite (Garrison, Anderson, & Archer, 2000). Cet article explique un element du modele : la presence sociale. On y definit la presence sociale comme la capacite des apprenants de se projeter sur le plan social et emotionnel dans une communaute de recherche. On y decrit un gabarit utilise pour evaluer la presence sociale lors d'une analyse de contenu de transcriptions de forums electroniques. Afin d'aider la comprehension des modalites d'evaluation et de faciliter la reproduction subsequente de cette etude, un echantillonnage de transcriptions codees ainsi que les baremes de fiabilite inter-evaluateurs sont fournis. L'article se termine par une discussion des consequences et des avantages de l'evaluation de la presence sociale du point de vue des formateurs, des animateurs de conference et des chercheurs.

Genetics of mouse behavior: interactions with laboratory environment.

Abstract: Strains of mice that show characteristic patterns of behavior are critical for research in neurobehavioral genetics. Possible confounding influences of the laboratory environment were studied in several inbred strains and one null mutant by simultaneous testing in three laboratories on a battery of six behaviors. Apparatus, test protocols, and many environmental variables were rigorously equated. Strains differed markedly in all behaviors, and despite standardization, there were systematic differences in behavior across labs. For some tests, the magnitude of genetic differences depended upon the specific testing lab. Thus, experiments characterizing mutants may yield results that are idiosyncratic to a particular laboratory.

The glucagon-like peptides.

Abstract: I. Introduction II. History of the Incretin Concept: Discovery of Gastric Inhibitory Polypeptide III. Discovery of GLP-1 IV. Structures of GLPs and Family of Glucagon-Related Peptides V. Tissue Distribution of the Expression of GLPs A. Pancreatic α-cells B. Intestinal L cells C. Central nervous system VI. Proglucagon Biosynthesis A. Organization/structure of the proglucagon gene B. Regulation of glucagon gene expression C. Posttranslational processing of proglucagon VII. Regulation of GLP Secretion A. Overview B. Intracellular signals C. Carbohydrates D. Fats E. Proteins F. Endocrine G. Neural H. GLP-2 VIII. Metabolism of GLPs A. GLP-1 B. GLP-2 IX. Physiological Actions of GLPs A. Overview B. Pancreatic islets C. Counterregulatory actions of GLP-1 and leptin on β-cells D. Stomach E. Lung F. Brain G. Liver, skeletal muscle, and fat H. Pituitary, hypothalamus, and thyroid I. Cardiovascular system J. GLP-2 X. GLP Receptors A. Structure B. Signaling C. Distribution D. Regulation E. GLP-2 XI. Pathophysiology o...

Culture specific and cross-culturally generalizable implicit leadership theories: Are attributes of charismatic/transformational leadership universally endorsed?

Abstract: This study focuses on culturally endorsed implicit theories of leadership (CLTs). Although cross-cultural research emphasizes that different cultural groups likely have different conceptions of what leadership should entail, a controversial position is argued here: namely that attributes associated with charismatic/transformational leadership will be universally endorsed as contributing to outstanding leadership. This hypothesis was tested in 62 cultures as part of the Global Leadership and Organizational Behavior Effectiveness (GLOBE) Research Program. Universally endorsed leader attributes, as well as attributes that are universally seen as impediments to outstanding leadership and culturally contingent attributes are presented here. The results support the hypothesis that specific aspects of charismatic/transformational leadership are strongly and universally endorsed across cultures.

Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke.

Abstract: ContextRecombinant tissue-type plasminogen activator (rt-PA) improves outcomes for patients with acute ischemic stroke, but current approved use is limited to within 3 hours of symptom onset. This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset.ObjectiveTo test the efficacy and safety of rt-PA in patients with acute ischemic stroke when administered between 3 and 5 hours after symptom onset.DesignThe Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study is a phase 3, placebo-controlled, double-blind randomized study conducted between December 1993 and July 1998, with up to 90 days of follow-up.SettingOne hundred forty university and community hospitals in North America.PatientsAn intent-to-treat population of 613 acute ischemic stroke patients was enrolled, with 547 of these treated as assigned within 3 to 5 hours of symptom onset. A total of 39 others were treated within 3 hours of symptom onset, 24 were treated more than 5 hours after symptom onset, and 3 never received any study drug.InterventionAdministration of 0.9 mg/kg of rt-PA (n = 272) or placebo (n = 275) intravenously over 1 hour.Main Outcome MeasuresPrimary efficacy was an excellent neurologic recovery at day 90 (National Institutes of Health Stroke Scale [NIHSS] score of ≤1); secondary end points included excellent recovery on functional outcome measures (Barthel index, modified Rankin scale, and Glasgow Outcome Scale) at days 30 and 90. Serious adverse events were also assessed.ResultsIn the target population, 32% of the placebo and 34% of rt-PA patients had an excellent recovery at 90 days (P = .65). There were no differences on any of the secondary functional outcome measures. In the first 10 days treatment with rt-PA significantly increased the rate of symptomatic intracerebral hemorrhage (ICH) (1.1% vs 7.0% [P<.001]), a symptomatic ICH (4.7% vs 11.4% [P = .004]), and fatal ICH (0.3% vs 3.0% [P<.001]). Mortality at 90 days was 6.9% with placebo and 11.0% with rt-PA (P = .09). Results in the intent-to-treat population were similar.ConclusionsThis study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours.

Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure

Abstract: Background—Angiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits. Methods and Results—We randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction #30% to double-blind treatment with either low doses (2.5 to 5.0 mg daily, n51596) or high doses (32.5 to 35 mg daily, n51568) of the ACE inhibitor, lisinopril, for 39 to 58 months, while background therapy for heart failure was continued. When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death (P50.128) but a significant 12% lower risk of death or hospitalization for any reason (P50.002) and 24% fewer hospitalizations for heart failure (P50.002). Dizziness and renal insufficiency was observed more frequently in the high-dose group, but the 2 groups were similar in the number of patients requiring discontinuation of the study medication. Conclusions—These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small. (Circulation. 1999;100:2312-2318.)

The DNA sequence of human chromosome 22

Abstract: Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.

Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators.

Abstract: Background—We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL)...

Responses of tundra plants to experimental warming:meta‐analysis of the international tundra experiment

Abstract: The International Tundra Experiment (ITEX) is a collaborative, multisite experiment using a common temperature manipulation to examine variability in species response across climatic and geographic gradients of tundra ecosystems. ITEX was designed specifically to examine variability in arctic and alpine species response to increased temperature. We compiled from one to four years of experimental data from 13 different ITEX sites and used meta-analysis to analyze responses of plant phenology, growth, and reproduction to experimental warming. Results indicate that key phenological events such as leaf bud burst and flowering occurred earlier in warmed plots throughout the study period; however, there was little impact on growth cessation at the end of the season. Quantitative measures of vegetative growth were greatest in warmed plots in the early years of the experiment, whereas reproductive effort and success increased in later years. A shift away from vegetative growth and toward reproductive effort and success in the fourth treatment year suggests a shift from the initial response to a secondary response. The change in vegetative response may be due to depletion of stored plant reserves, whereas the lag in reproductive response may be due to the formation of flower buds one to several seasons prior to flowering. Both vegetative and reproductive responses varied among life-forms; herbaceous forms had stronger and more consistent vegetative growth responses than did woody forms. The greater responsiveness of the herbaceous forms may be attributed to their more flexible morphology and to their relatively greater proportion of stored plant reserves. Finally, warmer, low arctic sites produced the strongest growth responses, but colder sites produced a greater reproductive response. Greater resource investment in vegetative growth may be a conservative strategy in the Low Arctic, where there is more competition for light, nutrients, or water, and there may be little opportunity for successful germination or seedling development. In contrast, in the High Arctic, heavy investment in producing seed under a higher temperature scenario may provide an opportunity for species to colonize patches of unvegetated ground. The observed differential response to warming suggests that the primary forces driving the response vary across climatic zones, functional groups, and through time.

A meta-analysis of the relationship between anxiety toward mathematics and achievement in mathematics

Abstract: In this meta-analysis I examined 26 studies on the relationship between anxiety toward mathematics and achievement in mathematics among elementary and secondary students. The common population correlation for the relationship is significant (-.27). A series of general linear models indicated that the relationship is consistent across gender groups, grade-level groups, ethnic groups, instruments measuring anxiety, and years of publication. The relationship, however, differs significantly among instruments measuring achievement as well as among types of publication. Researchers using standardized achievement tests tend to report a relationship of significantly smaller magnitude than researchers using mathematics teachers' grades and researcher-made achievement tests. Published studies tend to indicate a significantly smaller magnitude of the relationship than unpublished studies. There are no significant interaction effects among key variables such as gender, grade, and ethnicity.

Relating populations to habitats using resource selection functions.

Abstract: Habitat use can be characterized by resource selection functions (RSFs) that are proportional to the probability of an area being used by an animal. We highlight two procedures that have recently been used to relate RSFs to population density, dependent upon which field procedures are practical for a species. These new developments allow RSF models to be interfaced with geographical information systems (GIS) to map the probability of use, and ultimately populations, across landscapes.

Calreticulin: one protein, one gene, many functions.

Abstract: The endoplasmic reticulum (ER) plays a critical role in the synthesis and chaperoning of membrane-associated and secreted proteins. The membrane is also an important site of Ca(2+) storage and release. Calreticulin is a unique ER luminal resident protein. The protein affects many cellular functions, both in the ER lumen and outside of the ER environment. In the ER lumen, calreticulin performs two major functions: chaperoning and regulation of Ca(2+) homoeostasis. Calreticulin is a highly versatile lectin-like chaperone, and it participates during the synthesis of a variety of molecules, including ion channels, surface receptors, integrins and transporters. The protein also affects intracellular Ca(2+) homoeostasis by modulation of ER Ca(2+) storage and transport. Studies on the cell biology of calreticulin revealed that the ER membrane is a very dynamic intracellular compartment affecting many aspects of cell physiology.

GIS for district-level administration in India: problems and opportunities

Abstract: This paper describes a research study, carried out over the period 1993-95, of the efforts made in India to develop and use geographical information systems (GIS) to aid district-level administration. We give a detailed description of our research approach, drawing from contextualism as a broad research methodology and using actor-network theory for analytical purposes. The main section of the paper provides an in-depth analysis of a major GIS initiative from a particular Indian government ministry. We conclude that the creation and maintenance of a relatively stable set of key actors with aligned interests related to the GIS technology had not been achieved in any of the districts studied by the end of the research period. Our analysis leads to implications for future action that go beyond traditional prescriptions, such as improved participation or better training, toward the need for higher level-interventions in such areas as educational processes and administrative structures. We then turn to criteria for judging the merits of an intensive research study and illustrate to what extent this study satisfies the criteria. Finally, we draw conclusions on the contribution of this paper to the promotion of intensive research and to the opening up of new fields of IS research.

Banks and Corporate Control in Japan

Abstract: Using a large sample of Japanese firm level data, we find that Japanese banks act primarily in the short term interests of creditors when dealing with firms outside bank groups. Corporate control mechanisms other than bank oversight appear necessary in these firms. When dealing with firms in bank groups, banks may act in the broader interests of a range of stakeholders, including shareholders. However, our findings are also consistent with banks “propping up” troubled bank group firms. We conclude that bank oversight need not lead to value maximizing corporate governance. POOR LIQUIDITY AND CASH F LOW PREDICT banker appointments to the boards of bank group firms; poor share price performance does not. When dealing with firms in bank groups, banks act in the broader interests of a range of stakeholders, including shareholders. Poor stock market performance, job creation, liquidity, and cash f low all predict banker appointments to bank group firms. We argue that Japanese banks’ dual role as creditors and shareholders ~Prowse ~1992!! constrains their incentives to advance shareholders’ interests, especially in firms outside bank groups. Corporate governance mechanisms other than oversight by banks would seem necessary in these firms. Firms outside bank groups undergo sharp downsizing following banker appointments but bank group firms do not, consistent with banks “propping up” weak bank group firms ~Hoshi, Kashyap, and Scharfstein ~1990!!. Entertainment spending falls as cash f low falls in firms outside bank groups, but does not in bank group firms. ~A similar, but statistically insignificant pattern exists in entertainment spending per dollar of sales.! If entertainment expenses represent “perks” consumption, rather than investment in networking, closer bank monitoring may lead to “tighter ships” outside bank

Spatial Pattern Analysis in Plant Ecology

Abstract: Preface 1. Concepts of spatial pattern 2. Sampling 3. Basic methods for one dimension and one species 4. Spatial pattern of two species 5. Multispecies pattern 6. Two-dimensional analysis of spatial pattern 7. Point patterns 8. Pattern on an environmental gradient 9. Conclusions and future directions Bibliography Glossary of abbreviations List of plant species Index.

Modulation of Polyketide Synthase Activity by Accessory Proteins During Lovastatin Biosynthesis

Abstract: Polyketides, the ubiquitous products of secondary metabolism in microorganisms, are made by a process resembling fatty acid biosynthesis that allows the suppression of reduction or dehydration reactions at specific biosynthetic steps, giving rise to a wide range of often medically useful products. The lovastatin biosynthesis cluster contains two type I polyketide synthase genes. Synthesis of the main nonaketide-derived skeleton was found to require the previously known iterative lovastatin nonaketide synthase (LNKS), plus at least one additional protein (LovC) that interacts with LNKS and is necessary for the correct processing of the growing polyketide chain and production of dihydromonacolin L. The noniterative lovastatin diketide synthase (LDKS) enzyme specifies formation of 2-methylbutyrate and interacts closely with an additional transesterase (LovD) responsible for assembling lovastatin from this polyketide and monacolin J.

Control of acid resistance in Escherichia coli.

Abstract: Acid resistance (AR) in Escherichia coli is defined as the ability to withstand an acid challenge of pH 2.5 or less and is a trait generally restricted to stationary-phase cells. Earlier reports described three AR systems in E. coli. In the present study, the genetics and control of these three systems have been more clearly defined. Expression of the first AR system (designated the oxidative or glucose-repressed AR system) was previously shown to require the alternative sigma factor RpoS. Consistent with glucose repression, this system also proved to be dependent in many situations on the cyclic AMP receptor protein. The second AR system required the addition of arginine during pH 2.5 acid challenge, the structural gene for arginine decarboxylase (adiA), and the regulator cysB, confirming earlier reports. The third AR system required glutamate for protection at pH 2.5, one of two genes encoding glutamate decarboxylase (gadA or gadB), and the gene encoding the putative glutamate:γ-aminobutyric acid antiporter (gadC). Only one of the two glutamate decarboxylases was needed for protection at pH 2.5. However, survival at pH 2 required both glutamate decarboxylase isozymes. Stationary phase and acid pH regulation of the gad genes proved separable. Stationary-phase induction of gadA and gadB required the alternative sigma factor ςS encoded by rpoS. However, acid induction of these enzymes, which was demonstrated to occur in exponential- and stationary-phase cells, proved to be ςS independent. Neither gad gene required the presence of volatile fatty acids for induction. The data also indicate that AR via the amino acid decarboxylase systems requires more than an inducible decarboxylase and antiporter. Another surprising finding was that the ςS-dependent oxidative system, originally thought to be acid induced, actually proved to be induced following entry into stationary phase regardless of the pH. However, an inhibitor produced at pH 8 somehow interferes with the activity of this system, giving the illusion of acid induction. The results also revealed that the AR system affording the most effective protection at pH 2 in complex medium (either Luria-Bertani broth or brain heart infusion broth plus 0.4% glucose) is the glutamate-dependent GAD system. Thus, E. coli possesses three overlapping acid survival systems whose various levels of control and differing requirements for activity ensure that at least one system will be available to protect the stationary-phase cell under naturally occurring acidic environments.

Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene

Abstract: Mammalian cytochrome c oxidase (COX) catalyses the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Mitochondrial DNA (mtDNA) encodes three COX subunits (I-III) and nuclear DNA (nDNA) encodes ten. In addition, ancillary proteins are required for the correct assembly and function of COX (refs 2, 3, 4, 5, 6). Although pathogenic mutations in mtDNA-encoded COX subunits have been described, no mutations in the nDNA-encoded subunits have been uncovered in any mendelian-inherited COX deficiency disorder. In yeast, two related COX assembly genes, SCO1 and SCO2 (for synthesis of cytochrome c oxidase), enable subunits I and II to be incorporated into the holoprotein. Here we have identified mutations in the human homologue, SCO2, in three unrelated infants with a newly recognized fatal cardioencephalomyopathy and COX deficiency. Immunohistochemical studies implied that the enzymatic deficiency, which was most severe in cardiac and skeletal muscle, was due to the loss of mtDNA-encoded COX subunits. The clinical phenotype caused by mutations in human SCO2 differs from that caused by mutations in SURF1, the only other known COX assembly gene associated with a human disease, Leigh syndrome.

Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features

Abstract: Syphilis is a chronic disease with a waxing and waning course, the manifestations of which have been described for centuries. It occurs worldwide, and the incidence varies significantly with geographic location. Transmission is mainly by sexual contact. The causative organism, Treponema pallidum, was first described in 1905, but because of the inability to culture the organism and the limitations of direct microscopy, serologic testing is the mainstay of laboratory diagnosis. The disease has been arbitrarily divided into several stages. The primary stage is defined by a chancre at the site of inoculation. The secondary stage is characterized by a polymorphic rash, lymphadenopathy, and other systemic manifestations. A variable asymptomatic latent period follows, which for epidemiologic purposes is divided into early ( 1 year) stages. The early stages (primary, secondary, and early latent) are potentially infectious. The tertiary stage is the most destructive and is marked by cardiovascular and neurologic sequelae and gummatous involvement of any organ system. Congenital infection may result in protean early or late manifestations. Unlike many other bacteria causing infectious diseases, the organism remains sensitive to penicillin, and this remains the mainstay of therapy.

Synthesis of β-Tubulin, Actin, and Other Proteins in Axons of Sympathetic Neurons in Compartmented Cultures

Abstract: The proteins needed for growth and maintenance of the axon are generally believed to be synthesized in the cell bodies and delivered to the axons by anterograde transport. However, recent reports suggest that some proteins can also be synthesized within axons. We used [35S]methionine metabolic labeling to investigate axonal protein synthesis in compartmented cultures of sympathetic neurons from newborn rats. Incubation of distal axons for 4 hr with [35S]methionine resulted in a highly specific pattern of labeled axonal proteins on SDS-PAGE, with 4 prominent bands in the 43–55 kDa range. The labeled proteins in axons were not synthesized in the cell bodies, because they were also produced by axons after the cell bodies had been removed. Two of the proteins were identified by immunoprecipitation as actin and β-tubulin. Axons synthesized <1% of the actin and tubulin synthesized in the cell bodies and transported into the axons, and 75–85% inhibition of axonal protein synthesis by cycloheximide and puromycin failed to inhibit axonal elongation. Nonetheless, the specific production by axons of the major proteins of the axonal cytoskeleton suggests that axonal protein synthesis arises from specific mechanisms and likely has biological significance. One hypothetical scenario involves neurons with long axons in vivo in which losses from turnover during axonal transport may limit the availability of cell body synthesized proteins to the distal axons. In this case, a significant fraction of axonal proteins might be supplied by axonal synthesis, which could, therefore, play important roles in axonal maintenance, regeneration, and sprouting.

Calreticulin Is Essential for Cardiac Development

Abstract: Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt −/− cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.