Synergistic innate immune recognition of Coxsackievirus B5 by RIG-I and MDA5

Coxsackievirus B5 (CBV5) is a positive sense, single-stranded RNA virus belonging to the Enterovirus genus of the Picornaviridae family. It can cause many serious diseases, including viral myocarditis (which can lead on to dilated cardiomyopathy), aseptic meningitis, and pancreatitis. The structure and cell cycle of CBV5 is typical of a picornavirus. Viral RNA is detected by Toll-like receptors (TLRs) and retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs). The RLR family, consisting of RIG-I, MDA5 (melanoma differentiation-associated gene 5), and LGP2, are pattern recognition receptors that detect a range of different viruses. RIG-I and MDA5 are homologous cytoplasmic proteins containing an N-terminal region with two caspase activation and recruitment domains (CARDs), a central SF2 type DExD/H-box RNA helicase domain, and a C-terminal repressor domain (RD). Once a viral ligand has been detected and bound by RIG-I and MDA5, both signal downstream through their CARDs to activate IRF3/7 and NF-κB indirectly, via the protein intermediate IPS-1 (IFN-β promoter stimulator 1), and initiate an immune response. RIG-I and MDA5 contribute to antiviral signalling in different ways depending on the virus involved. MDA5 has been shown to be critical for Picornaviridae detection, whilst RIG-I can detect a wide variety of different viruses and pathogen associated molecular patterns. Results presented here show the expression levels of both are upregulated in response to CBV5 infection in human cardiac cells, with MDA5 expression levels being slightly greater than RIG-I. However, in Huh cells, RIG-I expression levels are greater than those of MDA5, indicating that it plays a role in CBV5 sensing. The presence of both phospho-IκB (corresponding to NF-κB activation) and IRF3 is detected in both cardiac cells and Huh cells in response to CBV5, and IFN-β production is also greatly upregulated. RIG-I and MDA5 colocalise with the adaptor protein IPS-1 in response to CBV5 infection, again indicating the synergistic response by the two RLRs, and both RLRs form homodimers in the cytoplasm. Overall, this suggest that both MDA5 and RIG-I act synergistically to detect CBV5 and initiate a downstream immune response, although MDA5 appears to be the marginally stronger sensor

Atmospheric dispersion and the implications for phase calibration

The success of any ALMA phase-calibration strategy, which incorporates phase transfer, depends on a good understanding of how the atmospheric path delay changes with frequency (e.g. Holdaway & Pardo 2001). We explore how the wet dispersive path delay varies for realistic atmospheric conditions at the ALMA site using the ATM transmission code. We find the wet dispersive path delay becomes a significant fraction (>5 per cent) of the non-dispersive delay for the high-frequency ALMA bands (>160 GHz, Bands 5 to 10). Additionally, the variation in dispersive path delay across ALMA's 4-GHz contiguous bandwidth is not significant except in Bands 9 and 10. The ratio of dispersive path delay to total column of water vapour does not vary significantly for typical amounts of water vapour, water vapour scale heights and ground pressures above Chajnantor. However, the temperature profile and particularly the ground-level temperature are more important. Given the likely constraints from ALMA's ancillary calibration devices, the uncertainty on the dispersive-path scaling will be around 2 per cent in the worst case and should contribute about 1 per cent overall to the wet path fluctuations at the highest frequencies.Comment: 13 pages, 10 figures, ALMA Memo 59

Attitudes of Aboriginal Students to Schooling

In this paper the attitudes of Aboriginal students to schooling are examined. Aboriginal children from upper primary and lower secondary years responded to a questionnaire related to various aspects of their schooling experience, their intentions about remaining at school and their future education. The questionnaire contained 73 items constructed primarily with a four-point Likert scale. An analysis indicated that the questionnaire was highly reliable as a whole and in its components. The paper reports that these Aboriginal students responded highly positively on a number of significant issues in regard to their attitudes to schooling. They generally had positive attitudes to school, intended to remain at school to the end of year 12 and wished to succeed in further education

Completion of a SCUBA survey of Lynds dark clouds and implications for low-mass star formation

We have carried out a survey of optically-selected dark clouds using the bolometer array SCUBA on the James Clerk Maxwell Telescope, at 850 microns wavelength. The survey covers a total of 0.5 square degrees and is unbiased with reference to cloud size, star formation activity, or the presence of infrared emission. Several new protostars and starless cores have been discovered; the protostars are confirmed through the detection of their accompanying outflows in CO(2-1) emission. The survey is believed to be complete for Class 0 and Class I protostars, and yields two important results regarding the lifetimes of these phases. First, the ratio of Class 0 to Class protostars in the sample is roughly unity, very different from the 1:10 ratio that has previously been observed for the rho Ophiuchi star-forming region. Assuming star formation to be a homogeneous process in the dark clouds, this implies that the Class 0 lifetime is similar to the Class I phase, which from infrared surveys has been established to be approximately 200,000 yr. It also suggests there is no rapid initial accretion phase in Class 0 objects. A burst of triggered star formation some 100,000 yr ago can explain the earlier results for rho Ophiuchus. Second, the number of starless cores is approximately twice that of the total number of protostars, indicating a starless core lifetime of approximately 800,000 yr. These starless cores are therefore very short-lived, surviving only two or three free-fall times. This result suggests that, on size scales of 10,000 AU at least, the dynamical evolution of starless cores is probably not controlled by magnetic processes.Comment: 67 pages including 32 figures (highly compressed). Accepted for publication in the Astronomical Journal. Available with full resolution (legible) figures at http://www.mrao.cam.ac.uk/%7ejsr/papers/lynds2.ps.g

Teacher Perceptions of the Characteristics of Effective Teachers of Aboriginal Middle School Students

This paper reports a component of research that involved interviewing teachers identified as effective with Aboriginal students in selected primary and secondary schools in urban and regional Western Australia. The research shows that characteristics of effective teachers include understanding Aboriginal culture, history, and students’ home backgrounds; an ability to develop good relationships with Aboriginal students and their families, a sense of humour, and preparedness to invest time to interact with Aboriginal students out of the classroom in order to strengthen relationships. The research also indicates that effective teachers understand that Aboriginal students are often more independent than others, do not chastise or embarrass them in front of others, set challenging and achievable objectives, and include cultural relevance and recognition in the curriculum and classroom environment. This research provides directions for teacher pre-service training, teacher induction, and teacher in-service professional development. It is suggested that schools consider middle schooling pedagogy and curriculum principles as a means of better providing for adolescent Aboriginal students

Pheochromocytoma in a Twelve-Year-Old Girl with SDHB-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome

A twelve-year-old girl presented with a history of several weeks of worsening headaches accompanied by flushing and diaphoresis. The discovery of markedly elevated blood pressure and tachycardia led the child\u27s pediatrician to consider the diagnosis of a catecholamine-secreting tumor, and an abdominal CT scan confirmed the presence of a pheochromocytoma. The patient was found to have a mutation in the succinyl dehydrogenase B (SDHB) gene, which is causative for SDHB-related hereditary paraganglioma-pheochromocytoma syndrome. Herein, we describe her presentation and medical management and discuss the clinical implications of SDHB deficiency

The Progenitors of Dwarf Spheroidal Galaxies

Dwarf spheroidal (dSph) galaxies present an evolutionary puzzle that we explore in 40 early- and late-type dwarfs in the Local Group and nearby field. Although dSphs formed stars over extended periods, today all but one are free of detectable interstellar matter (ISM), even in the Fornax dSph, where stars still formed 100 Myr ago. Combining metallicities for red giants with HI data from the literature, we show that the well-known offset in luminosity-metallicity (L-Z) relations for dSphs and dwarf irregular (dIrr) galaxies exists also when comparing only their old stellar populations: dSphs have higher mean stellar metallicities for a fixed luminosity. Evidently younger dSphs experienced more efficient enrichment than young dIrrs. Dwarf galaxies, whose locus in the L-Z diagram is consistent with that of dSphs even for baryonic luminosities, are the ``transition-type dwarfs'' Phoenix, DDO210, LGS3, Antlia, and KKR25. They have mixed dIrr/dSph morphologies, low stellar masses, low angular momentum, and HI contents of less than a few 10^6 solar masses. Unlike dIrrs, many transition-type dwarfs would closely resemble dSphs if their gas were removed; they are likely dSph progenitors. As gas removal is key, we consider the empirical evidence for various gas removal processes. We suggest that internal gas removal mechanisms are inadequate and favor ram pressure stripping to make dSphs. A combination of initial conditions and environment seems to support the formation of dSphs, which appear to form from small galaxies with active early star formation, whose evolution halts due to externally induced gas loss. Transition-type dwarfs then are dSphs that kept their ISM, and therefore should replace dSphs in isolated locations where stripping is ineffective. (Abridged)Comment: 25 pages in AASTeX two-column preprint style, 1 table, 3 figures. Accepted for publication in the Astronomical Journal (April 2003 issue