Erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients

Submillimeter Array Observations of NGC 2264-C: Molecular Outflows and Driving Sources

We present 1.3 mm Submillimeter Array (SMA) observations at ∼3 arcsec resolution towards the brightest section of the intermediate/massive star-forming cluster NGC 2264-C. The millimetre continuum emission reveals ten 1.3 mm continuum peaks, of which four are new detections. The observed frequency range includes the known molecular jet/outflow tracer SiO (5−4), thus providing the first high-resolution observations of SiO towards NGC 2264-C. We also detect molecular lines of 12 additional species towards this region, including CH3CN, CH3OH, SO, H2CO, DCN, HC3N, and 12CO. The SiO (5−4) emission reveals the presence of two collimated, high-velocity (up to 30 km s−1 with respect to the systemic velocity) bipolar outflows in NGC 2264-C. In addition, the outflows are traced by emission from 12CO, SO, H2CO, and CH3OH. We find an evolutionary spread between cores residing in the same parent cloud. The two unambiguous outflows are driven by the brightest mm continuum cores, which are IR-dark, molecular line weak, and likely the youngest cores in the region. Furthermore, towards the Red MSX Source AFGL 989-IRS1, the IR-bright and most evolved source in NGC 2264-C, we observe no molecular outflow emission. A molecular line rich ridge feature, with no obvious directly associated continuum source, lies on the edge of a low-density cavity and may be formed from a wind driven by AFGL 989-IRS1. In addition, 229 GHz class I maser emission is detected towards this feature

Identification of Genes Directly Involved in Shell Formation and Their Functions in Pearl Oyster, Pinctada fucata

Mollusk shell formation is a fascinating aspect of biomineralization research. Shell matrix proteins play crucial roles in the control of calcium carbonate crystallization during shell formation in the pearl oyster, Pinctada fucata. Characterization of biomineralization-related genes during larval development could enhance our understanding of shell formation. Genes involved in shell biomineralization were isolated by constructing three suppression subtractive hybridization (SSH) libraries that represented genes expressed at key points during larval shell formation. A total of 2,923 ESTs from these libraries were sequenced and gave 990 unigenes. Unigenes coding for secreted proteins and proteins with tandem-arranged repeat units were screened in the three SSH libraries. A set of sequences coding for genes involved in shell formation was obtained. RT-PCR and in situ hybridization assays were carried out on five genes to investigate their spatial expression in several tissues, especially the mantle tissue. They all showed a different expression pattern from known biomineralization-related genes. Inhibition of the five genes by RNA interference resulted in different defects of the nacreous layer, indicating that they all were involved in aragonite crystallization. Intriguingly, one gene (UD_Cluster94.seq.Singlet1) was restricted to the ‘aragonitic line’. The current data has yielded for the first time, to our knowledge, a suite of biomineralization-related genes active during the developmental stages of P.fucata, five of which were responsible for nacreous layer formation. This provides a useful starting point for isolating new genes involved in shell formation. The effects of genes on the formation of the ‘aragonitic line’, and other areas of the nacreous layer, suggests a different control mechanism for aragonite crystallization initiation from that of mature aragonite growth

Re-creation of site-specific multi-directional waves with non-collinear current

Site-specific wave data can be used to improve the realism of tank test conditions and resulting outputs. If this data is recorded in the presence of a current, then the combined conditions must be re-created to ensure wave power, wavelength and steepness are correctly represented in a tank. In this paper we explore the impacts of currents on the wave field and demonstrate a simple, effective methodology for re-creating combined wave-current scenarios. Regular waves, a parametric unidirectional spectrum, and a complex site-specific directional sea state were re-created with current velocities representing 0.25, 0.5, and 1.0 m/s full scale. Waves were generated at a number of angles relative to the current, providing observations of both collinear and non-collinear wave-current interactions. Wave amplitudes transformed by the current were measured and corrected linearly, ensuring desired frequency and wavenumber spectra in the presence of current were obtained. This empirical method proved effective after a single iteration. Frequency spectra were within 3% of desired and wave heights normally within 1%. The generation-measurement-correction procedure presented enables effective re-creation of complex wave-current scenarios. This capability will increase the realism of tank testing, and help de-risk devices prior to deployment at sea

Development of auditing in Malaysia: Legal, political and historical influences

This work investigates the role and contribution of external auditing as practised in the Malaysian society during the forty year period from independence in 1957 to just before the onset of the Asian Financial Crisis in 1997.It applies the political economic theory introduced by Tinker (1980) and refined by Cooper & Sherer (1984), which focuses on the social relations aspects of professional activity rather than economic forces alone.In a case study format where qualitative data was gathered mainly from primary and secondary source materials, the study found that the function of auditing in the Malaysian society in most cases is devoid of any essence of mission; instead it is created, shaped and transformed by the pressures which give rise to its development over time.The largely insignificant role that it serves is intertwined within the contexts in which it operates