A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing

Introduction: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 ( MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1- like conditions. Results: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. Discussion: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. Conclusions: We therefore suggest that routine germline MEN1 mutation testing of all cases of classical'' MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 ( Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients < 30 years old with sporadic hyperparathyroidism and multigland hyperplasia

Repressor- and activator-type ethylene response factors functioning in jasmonate signaling and disease resistance identified via a genome-wide screen of Arabidopsis transcription factor gene expression

To identify transcription factors (TFs) involved in jasmonate (JA) signaling and plant defense, we screened 1,534 Arabidopsis (Arabidopsis thaliana) TFs by real-time quantitative reverse transcription-PCR for their altered transcript at 6 h following either methyl JA treatment or inoculation with the incompatible pathogen Alternaria brassicicola. We identified 134 TFs that showed a significant change in expression, including many APETALA2/ethylene response factor (AP2/ERF), MYB, WRKY, and NACTF genes with unknown functions. Twenty TF genes were induced by both the pathogen and methyl JA and these included 10 members of the AP2/ERF TF family, primarily from the B1a and B3 subclusters. Functional analysis of the B1a TF AtERF4 revealed that AtERF4 acts as a novel negative regulator of JA-responsive defense gene expression and resistance to the necrotrophic fungal pathogen Fusarium oxysporum and antagonizes JA inhibition of root elongation. In contrast, functional analysis of the B3 TF AtERF2 showed that AtERF2 is a positive regulator of JA-responsive defense genes and resistance to F. oxysporum and enhances JA inhibition of root elongation. Our results suggest that plants coordinately express multiple repressor-and activator-type AP2/ERFs during pathogen challenge to modulate defense gene expression and disease resistance.

Isolation, solution structure, and insecticidal activity of Kalata B2, a circular protein with a twist: Do Mobius strips exist in nature?

A large number of macrocyclic miniproteins with diverse biological activities have been isolated from the Rubiaceae, Violaceae, and Cucurbitaceae plant families in recent years. Here we report the three-dimensional structure determined using H-1 NMR spectroscopy and demonstrate potent insecticidal activity for one of these peptides, kalata B2. This peptide is one of the major components of an extract from the leaves of the plant Oldenlandia affinis. The structure consists of a distorted triple-stranded beta-sheet and a cystine knot arrangement of the disulfide bonds and is similar to those described for other members of the cyclotide family. The unique cyclic and knotted nature of these molecules makes them a fascinating example of topologically complex proteins. Examination of the sequences reveals that they can be separated into two subfamilies, one of which contains a larger number of positively charged residues and has a bracelet-like circularization of the backbone. The second subfamily contains a backbone twist due to a cis-peptidyl-proline bond and may conceptually be regarded as a molecular Mobius strip. Kalata B2 is the second putative member of the Mobius cyclotide family to be structurally characterized and has a cis-peptidyl-proline bond, thus validating the suggested name for this subfamily of cyclotides. The observation that kalata B2 inhibits the growth and development of Helicoverpa armigera larvae suggests a role for the cyclotides in plant defense. A comparison of the sequences and structures of kalata B1 and B2 provides insight into the biological activity of these peptides.

Changes to porcine blastocyst vitrification methods and improved litter size after transfer

The objective was to improve the protocol that was used to obtain the first reported piglets from transferred vitrified and warmed zona-intact blastocysts. Blastocysts were collected from superovulated sows and gilts, centrifuged to polarize lipid, vitrified, warmed and cultured for 24 h or transferred immediately. Removing the zona pellucida after warming increased the number of cells in the surviving blastocysts (zona-free 60.8 +/- 4.3, zona-intact 39.1 +/- 2.8; P < 0.05). Thinning the zona pellucida produced similar results to zona removal. Changing the basal medium of the vitrification and warming solutions from modified PBS to phosphate buffered NCSU-23 increased the number of cells (44.7 +/- 2.2 versus 56.0 +/- 3.9, respectively; P < 0.05). Reducing the plunge temperature of the liquid nitrogen from - 196 degrees C to less than -204 degrees C improved the embryo survival rate (61.9% versus 82.9%, respectively; P < 0.05). These modifications were incorporated into the vitrification protocol that was used to vitrify and warm 105 blastocysts (that were subsequently transferred into four recipients). Three recipients became pregnant, farrowing three litters (average litter size, 5.3; 18.8% embryo survival in farrowing sows). Changing the warming protocol to using sucrose rather than ethylene glycol resulted in a trend towards improved embryo survival (73.5% versus 91.2%) but this was not statistically significant. Incorporating this modification, 203 blastocysts were vitrified, warmed and transferred into seven recipients. Five became pregnant and 36 fetuses were recovered (average litter size 7.2; 24.8% embryo survival in pregnant sows) at Day 40 of pregnancy. In conclusion, changes made to the vitrification protocol improved pregnancy rate and in vivo embryo survival compared to an earlier study using the original protocol. (c) 2005 Elsevier Inc. All rights reserved.

Perceptions of self and group in the context of a threatened national identity: A field study

Previous research indicates that people who are highly identified with their groups tend to remain committed to them under threat. This study examines the generalizability, of this effect to (a) a real-life context involving the perception that others view the ingroup (Australians) as intolerant of minorities and (b) various dimensions of social identification. The sample comprised 213 respondents to a random mail survey. Perceived threat was inversely related to self-stereotyping (i.e. perceptions of self-ingroup similarity), but only for individuals with weak subjective ties to other group members. Threat perceptions were also predictive of enhanced judgments of within-group variability on threat-relevant dimensions, particularly for individuals with weaker ingroup ties. Various strategies for coping with a threatened social identity are linked to different facets of social identification.

Optimal control and operation of drum granulation processes

Process optimisation and optimal control of batch and continuous drum granulation processes are studied in this paper. The main focus of the current research has been: (i) construction of optimisation and control relevant, population balance models through the incorporation of moisture content, drum rotation rate and bed depth into the coalescence kernels; (ii) investigation of optimal operational conditions using constrained optimisation techniques; (iii) development of optimal control algorithms based on discretized population balance equations; and (iv) comprehensive simulation studies on optimal control of both batch and continuous granulation processes. The objective of steady state optimisation is to minimise the recycle rate with minimum cost for continuous processes. It has been identified that the drum rotation-rate, bed depth (material charge), and moisture content of solids are practical decision (design) parameters for system optimisation. The objective for the optimal control of batch granulation processes is to maximize the mass of product-sized particles with minimum time and binder consumption. The objective for the optimal control of the continuous process is to drive the process from one steady state to another in a minimum time with minimum binder consumption, which is also known as the state-driving problem. It has been known for some time that the binder spray-rate is the most effective control (manipulative) variable. Although other possible manipulative variables, such as feed flow-rate and additional powder flow-rate have been investigated in the complete research project, only the single input problem with the binder spray rate as the manipulative variable is addressed in the paper to demonstrate the methodology. It can be shown from simulation results that the proposed models are suitable for control and optimisation studies, and the optimisation algorithms connected with either steady state or dynamic models are successful for the determination of optimal operational conditions and dynamic trajectories with good convergence properties. (c) 2005 Elsevier Ltd. All rights reserved.

Effects of physical disturbance on infaunal and epifaunal assemblages in subtropical, intertidal seagrass beds

We assessed the impact of large-scale commercial and recreational harvesting of polychaete worms Marphysa spp. on macrobenthic assemblages in a subtropical estuary in Queensland, Australia, by examining: (1) the spatial extent of harvesting activities and the rate of recovery of the seagrass habitat over an 18 to 20 mo period; (2) the recovery of infauna in and around commercial pits of known age; (3) the indirect effects of physical disturbance from trampling and deposition of sediments during harvesting on epibenthos in areas adjacent to commercial and recreational pits; (4) impacts of potential indirect effects through manipulative experimentation. Harvesting caused a loss of seagrass, changes to the topography and compaction of the sediments associated with the creation of walls around commercial pits, and the deposition of rubble dug from within the pit. The walls and rubble were still evident after 1.8 to 20 mo, but comprised only a small proportion of the total area on the intertidal banks. There was a shift from an intertidal area dominated by Zostera capricorni to one with a mixture of Z. capricorni, Halophila spp. and Halodule uninervis, but there was no overall decline in the biomass of seagrass in these areas. There were distinct impacts from harvesting on the abundance of benthic infauna, especially amphipods, polychaetes and gastropods, and these effects were still detectable after 4 mo of potential recovery. After 12 me, there were no detectable differences in the abundances of these infauna between dug areas and reference areas, which suggested that infauna had recovered from impacts of harvesting; however, an extensive bloom of toxic fireweed Lyngbya majsucula may have masked any remaining impacts. There were no detectable impacts of harvesting on epifauna living in the seagrass immediately around commercial or recreational pits.

Multiagent realization of prediction-based diagnosis and loss prevention

A multiagent diagnostic system implemented in a Protege-JADE-JESS environment interfaced with a dynamic simulator and database services is described in this paper. The proposed system architecture enables the use of a combination of diagnostic methods from heterogeneous knowledge sources. The process ontology and the process agents are designed based on the structure of the process system, while the diagnostic agents implement the applied diagnostic methods. A specific completeness coordinator agent is implemented to coordinate the diagnostic agents based on different methods. The system is demonstrated on a case study for diagnosis of faults in a granulation process based on HAZOP and FMEA analysis.

Balancing curriculum processes and content in a project centred curriculum - In pursuit of graduate attributes

Chemical engineering education is challenged around the world by demands and rapid changes encompassing a wide range of technical and social drivers. Graduates must be prepared for practice in increasingly diverse workplace environments in which generic or transferable attributes such as communication and teamwork together with technical excellence are mandated by prospective employers and society at large. If academe is to successfully deliver on these graduate attributes, effective curriculum design needs to include appropriate educational processes as well as course content. Conventional teacher centred approaches, stand-alone courses and retro-fitted remedial modules have not delivered the desired outcomes. Development of the broader spectrum of attributes is more likely when students are engaged with realistic and relevant experiences that demand the integration and practice of these attributes in contexts that the students find meaningful. This paper describes and evaluates The University of Queensland's Project Centred Curriculum in Chemical Engineering (PCC), a programme-wide approach to meeting these requirements. PCC strategically integrates project-based learning with more traditional instruction. Data collected shows improved levels of student attainment of generic skills with institutional and nationally benchmarked indicators showing significant increases in student perceptions of teaching quality, and overall satisfaction with the undergraduate experience. Endorsements from Australian academic, professional and industry bodies also support the approach as more effectively aligning engineering education with professional practice requirements.