Autocrine regulation of asthmatic airway inflammation: role of airway smooth muscle

Chronic airway inflammation is one of the main features of asthma. Release of mediators from infiltrating inflammatory cells in the airway mucosa has been proposed to contribute directly or indirectly to changes in airway structure and function. The airway smooth muscle, which has been regarded as a contractile component of the airways responding to various mediators and neurotransmitters, has recently been recognised as a rich source of pro-inflammatory cytokines, chemokines and growth factors. In this review, we discuss the role of airway smooth muscle cells in the regulation and perpetuation of airway inflammation that contribute to the pathogenesis of asthma

Declining popularity increases lack of diversity: extending the discourse of the discipline

The number of young people selecting a university Information Technology (IT) course is low and has been declining alarmingly in the last few years. While young women appear to be rejecting the discipline at a greater rate than young men, the declining popularity of IT university courses is a worrying trend that is affecting the culture of the discipline and the industry nationally and internationally. The discourse of the discipline is often focused on curriculum content and industry applications with little or no attention to the type of student who is taking our courses. This paper presents senior secondary school and university enrolment statistics that emphasise a steady decline in popularity of IT courses since 2000. Results of a quantitative survey of over 700 undergraduates are presented to provide a lens into the current student experiences in IT in secondary school, the home and at university. Factors underpinning the declining popularity of the discipline as a course and career option are explored and some thoughts on the future of the discipline are offered

Grain surface features of Apollo 17 orange and black glass

Lunar soil sample 74220 and core samples 74001/2 consist mainly of orange glass droplets, droplet fragments, and their crystallized equivalents. These samples are now generally accepted to be pyroclastic ejecta from early lunar volcanic eruptions. It has been known that they contain surface coatings and material rich in volatile condensable phases including S, Zn, F, Cl, and many volatile metals. Meyer summarizes the voluminous published chemical data and calculates the volatile enrichment ratios for most of the surface condensates. In an attempt to more completely understand this enrichment of surface volatiles, we have searched for carbon and carbon-bearing phases on droplet surfaces. We have reviewed many of our existing photomicrographs and energy dispersive analysis (EDX) of grain surfaces and have reexamined some of our older SEM mounts using an improved EDXA system capable of light element detection and analysis (oxygen, nitrogen, and carbon). In addition, we have made fresh mounts using procedures which should minimize carbon contamination or extraneous carbon x-rays and have analyzed for carbon

The Impact of Gender and Pedagogical Factors on Female Pass Rates

An assessment of student achievement according to gender in core units of study of a Faculty of Information and Communication Technology program tested four hypotheses. The first of these related to the role-model effect of female academics; the second related to the advantages of formal education qualifications of academics; the third to the application of contextualized curricula, and the fourth to the use of a variety of assessment modes. Correlation and regression analysis on the data set indicated that the presence of two of these factors can significantly improve the pass rate of female students while having a benign effect on the pass rate of male students. It is suggested that information systems faculties pay close attention to gender diversity of their teaching faculty, particularly if their female student cohort is less than one in five in a unit of study. It also gives substance to the need or preference for university lecturers having education qualifications. This study needs to be replicated in other information systems faculties and schools to verify this finding

Angiotensin II induces hypertrophy of human airway smooth muscle cells: expression of transcription factors and transforming growth factor-beta1

Increased smooth muscle mass due to hyperplasia and hypertrophy of airway smooth muscle (ASM) cells is a common feature in asthma. Angiotensin II (Ang II), a potent vasoconstrictor and mitogen for a wide variety of cells, has recently been implicated in bronchoconstriction in asthmatics. However, a possible mitogenic role as well as underlying molecular mechanisms of this octapeptide in human ASM cells are not yet known. We studied the effects of Ang II on ASM cell proliferation and growth and on the expression of three transcription factors, egr-1, c-fos, and c-jun, as well as a cytokine, transforming growth factor-beta1 (TGF-beta1). Human ASM cells were isolated by enzymatic digestion of bronchial smooth muscle obtained from lung resection tissue. Confluent cells were growth-arrested and subsequently incubated with Ang II (100 nM) for different time periods and processed for the measurement of cell growth and gene expression. Ang II significantly induced DNA and protein synthesis in human ASM cells at 8 h, resulting in a net increase in the accumulation of protein over DNA (i.e., cellular hypertrophy) at 16 h of incubation. Cell counts and MTT-reduction assay, however, showed no increase in cell number as a result of Ang II stimulation. Ang II stimulated the expression of egr-1 and c-fos as early as 15 min, reaching maximum levels at 45 min, whereas the expression of c-jun peaked at 2 h of Ang II exposure. Furthermore, steady-state mRNA levels of TGF-beta1 were upregulated by Ang II after 4 h and reached peak levels at 16 h of incubation. Secretion of biologically active TGF-beta1 from human ASM cells was significantly (P <= 0.02) enhanced by Ang II incubation after 8 h, which remained elevated until 24 h. Our results suggest that the Ang II-induced transient early expression of transcription factors may regulate autocrine genes like TGF-beta1, of which the subsequent late upregulation could contribute to cellular hypertrophy during, for example, airway remodeling in asthma

Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells

Airway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We investigated the effects of tumor necrosis factor (TNF)-alpha, a potent proinflammatory cytokine, on cultured human ASM cells by examining the expression and release of the cytokine interleukin (IL)-6, cell proliferation, and the expression pattern of c-fos and c-jun, two nuclear proto-oncogenes constituting the activator protein-1 transcription factor. Growth-arrested cell monolayers were stimulated with human recombinant TNF-alpha in a concentration- and time-dependent manner. TNF-alpha stimulated the expression of IL-6 messenger RNA (mRNA), which was detected after 15 min, reaching a maximum at 1 h. IL-6 protein was readily detected in ASM cell-conditioned medium after 2 h of TNF-alpha stimulation. Protein levels increased in a time- and concentration-dependent manner. Release of IL-6 elicited by TNF-alpha was significantly inhibited by dexamethasone, cycloheximide, and nordihydroguaiaretic acid (NDGA). TNF-alpha did not alter DNA biosynthesis up to 48 h or cell numbers up to 120 h. Northern blot analysis of proto-oncogene expression revealed that c-fos and c-jun mRNA levels were elevated after 30 min of TNF-alpha incubation with maximum levels at 1 h and 45 min, respectively. Expression of c-fos mRNA was downregulated by NDGA. Four hours of TNF-alpha treatment resulted in translocation of c-jun immunofluorescence from the cytoplasm to the nucleus in human ASM cells. Our results suggest that despite the lack of a mitogenic response to TNF-alpha, upregulation of primary response genes in human ASM cells may account for the induction of proinflammatory cytokines, such as IL-6, in human airways

Human factors assessments of the STS-57 SpaceHab-1 mission

SpaceHab-1 (STS-57) was the first of six scheduled Commercial Middeck Augmentation Module (CMAM) missions seeking to offer entrepreneurial companies an opportunity to use the resource of microgravity. The SpaceHab module, which occupies about one-fourth of the payload bay, is approximately 2-3/4 meters (9 feet) long and 4 meters (13.5 feet) in diameter. It provides a shirt-sleeve working environment and contains the storage space equivalent of 50 middeck lockers, considerably over and above the number of experiments that can be carried in the orbiter middeck alone. A modified Spacelab tunnel links the SpaceHab module to the middeck. While in orbit, the orbiter payload bay doors remain open, exposing the padded exterior of the lab and tunnel to space until preparation for reentry at the end of the flight. The crew for SpaceHab-1 was comprised of four males and two females, each of whom participated in some part of the human factors assessment (HFA) evaluation. The HFA was one of over twenty experiments manifested on this maiden flight of the SpaceHab module. HFA consisted of HFA-EPROC, HFA-LIGHT, HFA-SOUND, HFA-QUEST, and HFA-TRANS. The goal of HFA-EPROC was to assess the advantages and disadvantages of paper versus computer presentation for procedural tasks. The next two evaluations investigated the module's lighting and acoustic environment. HFA-TRANS sought to evaluate the design of the SpaceHab tunnel and to characterize translation through it. HFA-QUEST represented a consolidation of the in-flight questions generated by the HFA principal investigators involved in the acoustic, lighting, and translation studies