Aligning Academic Activities: Implications for Teaching and Research in a New Zealand Institute of Technology

A problem situation that is at the heart of a New Zealand higher education institute applying for university status is meeting the requirement for sufficient academic staff with postgraduate qualifications. For this particular New Zealand higher education institute that was originally a teaching institution offering only sub-degree qualifications, the move to firstly offering degrees and secondly seeking university status has meant that employment conditions have shifted for many academics. In order to explore the multiple world views on the impact to the whole system of a significant number of staff upgrading qualifications whilst engaged in full-time teaching at the same time, views were sought from senior executives, heads of schools, human resource personnel and staff engaged in their own postgraduate study. Multiple conceptual models have been utilised to gain an understanding of this problem situation: Soft Systems Methodology (Checkland and Scholes, 1990, 1999) in both its original and its current form; complexity theory (McKenna, 1999; Merry, 1995; Stacey, 1996) and context-dependent cluster model (CDCM) (Fielden and London, 2001). These multiple conceptual models have all contributed to providing a basis upon which to compare multiple-perceived worlds with appropriate conceptual models upon which to base a future action plan.Outcomes discussed are both positive and negative factors including: recognition, time, stress, employment contracts, senior staff expectations, family, collegial and institutional support and the integration of own study with teaching practice and content. Implications for alignment across institutional organisational levels and also for higher education outside of the university sector are also discussed.     

Multiple regions within 8q24 independently affect risk for prostate cancer

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.     

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.     

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer.     

Hugo de Vries and the rediscovery of Mendel's laws

Hugo de Vries claimed that he had discovered Mendel's laws before he found Mendel's paper. De Vries's first ratios, published in 1897, for the second generation of hybrids (F₂) were 2/3:1/3 and 80%:20%. By 1900, both of these ratios had become 3:1. These changing ratios suggest that as late as 1897 de Vries had not discovered the laws, although he asserted, from 1900 on, that he had found the laws in 1896. An Appendix details de Vries's Mendelian experiments as described in the original edition (1903) of volume two of Die Mutationstheorie, but omitted entirely from the English translation (1910).     

The EM immunocytochemical demonstration of lysozyme in macrophage giant cells in sarcoidosis

Summary The giant cells (multinucleate macrophages) of human sarcoidosis have been shown by the unlabelled antibody immunoperoxidase technique at electron microscope level to contain lysozyme within cytoplasmic granules.Acknowledgment. We are grateful to M. R. C. Canada for financial support, to Dr S. Erlandsen for instruction in technique, and to Dr L. Black for help in obtaining fresh material.     

Mechanism of force generation by myosin heads in skeletal muscle

Muscles generate force and shortening in a cyclical interaction between the myosin head domains projecting from the myosin filaments and the adjacent actin filaments. Although many features of the dynamic performance of muscle are determined by the rates of attachment and detachment of myosin and actin, the primary event in force generation is thought to be a conformational change or 'working stroke' in the actin-bound myosin head. According to this hypothesis, the working stroke is much faster than attachment or detachment, but can be observed directly in the rapid force transients that follow step displacement of the filaments. Although many studies of the mechanism of muscle contraction have been based on this hypothesis, the alternative view-that the fast force transients are caused by fast components of attachment and detachment--has not been excluded definitively. Here we show that measurements of the axial motions of the myosin heads at ?ngstr?m resolution by a new X-ray interference technique rule out the rapid attachment/detachment hypothesis, and provide compelling support for the working stroke model of force generation.     

Two-headed binding of a processive myosin to F-actin

Myosins are motor proteins in cells. They move along actin by changing shape after making stereospecific interactions with the actin subunits. As these are arranged helically, a succession of steps will follow a helical path. However, if the myosin heads are long enough to span the actin helical repeat (approximately 36 nm), linear motion is possible. Muscle myosin (myosin II) heads are about 16 nm long, which is insufficient to span the repeat. Myosin V, however, has heads of about 31 nm that could span 36 nm and thus allow single two-headed molecules to transport cargo by walking straight. Here we use electron microscopy to show that while working, myosin V spans the helical repeat. The heads are mostly 13 actin subunits apart, with values of 11 or 15 also found. Typically the structure is polar and one head is curved, the other straighter. Single particle processing reveals the polarity of the underlying actin filament, showing that the curved head is the leading one. The shape of the leading head may correspond to the beginning of the working stroke of the motor. We also observe molecules attached by one head in this conformation.