Role of LMP1 in immune control of EBV infection

The Epstein-Barr virus (EBV) encoded latent membrane protein (LMP1) plays a crucial role in the long-term persistence of this virus within the cells of the immune system. Not only is this protein critical for the transformation of resting B cells by EBV, it also displays pleiotropic effects on various cellular proteins expressed in the host cell. These include up-regulation of expression of B cell activation antigens, adhesion molecules and various components of the antigen processing pathway. Here we discuss how LMP1 acts like an expression 'switch' which, depending on the stage of EBV infection, manoeuvres various pathways that either modulate the immune system towards or against its survival.

Use of the web to provide learning support for a large metabolism and nutrition class

To support student learning in a large Metabolism and Nutrition class, we have introduced a web-based package, using a commercially available program, WebCT. The package was developed at a minimal cost and with limited resources. In addition to downloadable (PDF) versions of lecture Powerpoint presentations, tutorial outlines and a practical class exercise, web-based self-directed learning exercises were included to reinforce and extend lecture material in an active learning environment. The web-site also contained a variety of formative and summative assessment tasks that examined both factual recall and higher order thinking Detailed course information, timetables and a bulletin board were also readily accessible. Student usage of the site was generally high, but varied widely between individual students. Students who achieved a high overall score for the course completed on average three times as many formative assessment items and achieved a higher score for all tests than students who did poorly. Student feedback about the site was very positive with the majority of students reporting that the course material and assessment items that were available were useful to their learning. Administration of the course was also facilitated. (C) 2001 IUBMB. Published by Elsevier Science Ltd. All rights reserved.

Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis

We describe a functional and biochemical link between the myogenic activator MyoD, the deacetylase HDAC1, and the tumor suppressor pRb. Interaction of MyoD with HDAC1 in undifferentiated myoblasts mediates repression of muscle-specific gene expression. Prodifferentiation cues, mimicked by serum removal, induce both downregulation of HDAC1 protein and pRb hypophosphorylation. Dephosphorylation of pRb promotes the formation of pRb-HDAC1 complex in differentiated myotubes. pRb-HDAC1 association coincides with disassembling of MyoD-HDAC1 complex, transcriptional activation of muscle-restricted genes, and cellular differentiation of skeletal myoblasts. A single point mutation introduced in the HDAC1 binding domain of pRb compromises its ability to disrupt MyoD-HDAC1 interaction and to promote muscle gene expression. These results suggest that reduced expression of HDAC1 accompanied by its redistribution in alternative nuclear protein complexes is critical for terminal differentiation of skeletal muscle cells.

Sexual recombination in Phytophthora cinnamomi in vitro and aggressiveness of single-oospore progeny to Eucalyptus

Fifty single oospore progeny were established from an in vitro mating of A1 and A2 mating type isolates of Phytophthora cinnamomi from South Africa. Forty-nine progeny were identified as F-1 hybrids using seven random amplified polymorphic DNA (RAPD) primers, and one was a selfed isolate of the A1 mating type parent. Among the hybrid progeny, 24 and 25 were A1 and A2 mating type, respectively. Aggressiveness of progeny and parental isolates was assessed on 1-year-old seedlings of Eucalyptus smithii. The mean aggressiveness of hybrid oosporic isolates, expressed as lesion length, was significantly (P = 0.0001) lower than that of the parental isolates. No significant difference in aggressiveness of A1 and A2 mating type F-1 hybrid isolates was observed. This is the first report demonstrating sexual recombination in vitro in P. cinnamomi.

Design of a polyepitope construct for the induction of HLA-A0201-restricted HIV 1-specific CTL responses using HLA-A*0201 transgenic, H-2 class IKO mice

HLA-A*0201 transgenic, H-2D(b)/mouse beta2-microglobulin double-knockout mice were used to compare and optimize the immunogenic potential of 17HIV 1-derived, HLA-A0201-restricted epitopic peptides. A tyrosine substitution in position 1 of the epitopic peptides, which increases both their affinity for and their HLA-A0201 molecule stabilizing capacity, was introduced in a significant proportion, having verified that such modifications enhance their immunogenicity in respect of their natural antigenicity. Based on these results, a 13-polyepitope construct was inserted in the pre-S2 segment of the hepatitis B middle glycoprotein and used for DNA immunization. Long-lasting CTL responses against most of the inserted epitopes could be elicited simultaneously in a single animal with cross-recognition in several cases of their most common natural variants.

Child-Pugh class, nutritional indicators and early liver transplant outcomes

Background/Aims: Patients with chronic liver disease undergoing liver transplantation have reduced body fat and muscle mass. The extent to which nutritional indicators and Child-Pugh class are predictive of postoperative outcome in adults is unclear. The aims of this study were to determine in adult patients undergoing transplant 1) the influence of preoperative Child-Pugh class and nutritional indicators on early transplant outcomes and one-year survival, 2) the relationship between nutritional indicators and Child-Pugh class and disease type. This study included 80 patients (1990-1994). Methodology: The nutritional indicators utilized were grip strength, triceps skinfold thickness and uncorrected mid-arm muscle area. Measured outcomes were ventilator time, intensive care stay, postoperative hospital stay and one-year survival. Results: Early morbidity was determined in survivors. Child-Pugh class C patients required longer ventilation and spent more time in the intensive care unit than Child-Pugh classes A and B. No significant relationships were found length of hospital stay. Relationships between the nutritional indicators (when controlled for Child-Pugh class) and early morbidity could not be determined due;to insufficient data. No relationship was established between one-year survival and Child-Pugh class or the nutritional indicators. Grip strength and mid-arm muscle area were lower in the patients in Child-Pugh:classes B and C. Parenchymal liver disease was associated with lower grip strength and mid-arm muscle area when compared to cholestatic disease. Conclusions: Child-Pugh class C is associated with greater early postoperative morbidity. Advanced Child-Pugh class is also associated with diminished muscle status and parenchymal disease.

Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Developmental expression of a class IV POU gene in the gastropod Haliotis asinina supports a conserved role in sensory cell development in bilaterians

POU-IV genes regulate neuronal development in a number of deuterostomes (chordates) and ecdysozoans (arthropods and nematodes). Currently their function and expression in the third bilaterian clade, the Lophotrochozoa, comprising molluscs, annelids and. their affiliates, is unclear. Herein we characterise the developmental expression of HasPOU-IV in the gastropod mollusc, Haliotis asinina. The POU-IV gene is transiently expressed in I I distinct larval territories during the first 3 days of development. HasPOU-IV is first expressed in sets of ventral epidermal cells in the newly hatched trochophore larvae. As larval morphogenesis proceeds, we observe HasPOU-IV transcripts in cells that putatively form a range of sensory systems including chemo- and mechanosensory cells in the foot, cephalic tentacles, the ctenidia. the geosensory statocyst and the eyes. By comparing HasPOU-IV expression with POU-IV genes in other bilaterians we infer that this class of POU-domain genes had an ancestral role in regulating sensory cell development.

The number of rational points of a class of Artin-Schreier curves

We determine the number of F-q-rational points of a class of Artin-Schreier curves by using recent results concerning evaluations of some exponential sums. In particular, we determine infinitely many new examples of maximal and minimal plane curves in the context of the Hasse-Weil bound. (C) 2002 Elsevier Science (USA).

The compositional inverse of a class of permutation polynomials over a finite field

A new class of bilinear permutation polynomials was recently identified. In this note we determine the class of permutation polynomials which represents the functional inverse of the bilinear class.

Germline BRCA1 promoter deletions in UK and Australian familial breast cancer patients: Identification of a novel deletion consistent with BRCA1 :psi VBRCA1 recombination

Inherited susceptibility to breast cancer results from germline mutations in one of a number of genes including BRCA1. A significant number of BRCA1-linked familial breast cancer patients, however, have no detectable BRCA1 mutation. This could be due in part to the inability of commonly used mutation-detection techniques to identify mutations outside the BRCA1 coding region. This paper addresses the hypothesis that non coding region mutations, specifically in the BRCA1 promoter, account for some of these cases. We describe a new and detailed restriction map of the 5' region of the BRCA1 gene including the nearby NBR2, psiBRCA1, and NBR1 genes and the isolation of a number of new informative hybridization probes suitable for Southern analysis. Using this information we screened DNA from lymphoblastoid cell-lines made from 114 UK familial breast cancer patients and detected one large deletion in the 5' region of BRCA1. We show that the breakpoints for this deletion are in BRCA1 intron 2 and between NBR2 and exon 2 of psiBRCA1, raising the possibility that this deletion arose via a novel mechanism involving BRCA1:psiBRCA1 recombination. We have also screened 60 familial breast cancer patients from the Australian population, using an amplification refractory mutation system (ARMS) technique described previously by our group, and found one patient with a genotype consistent with a BRCA1 promoter deletion. These findings indicate that germline BRCA1 promoter deletions are a rare and yet significant mutation event and that they could arise via a novel genetic mechanism. Hum Mutat 19:435-442, 2002. (C) 2002 Wiley-Liss, Inc.

A curious experiment: the paradigm switch from observation and speculation to experimentation, in the understanding of neuromuscular function and disease

The four-link chain of the motor unit represents the contemporary end-point of some two millennia of evolving knowledge in neuroscience. The paradigm shift in neuromuscular epistemology occurred in the mid-17th century. In 1666, the newly graduated Dutch doctor, Jan Swammerdam (1637-1680) published his former investigations of dissected nerve-muscle preparations. These experiments comprised the quantum leap from observation and speculation, to that of experimentation in the field of neuroanatomy and neurophysiology. In what he termed 'A Curious Experiment' he also described the phenomenon of intrinsic muscle excitability - I cannot observe that the muscle in the living animal ever absolutely ceases from all motion. Eighty years later (1752), von Haller demonstrated experimentally that irritability (contractility) was an intrinsic property of all muscular tissue; and distinguished between the sensibility of nerve impulses and the irritability of muscular contraction. This experimental progression from Swammerdam to von Haller culminated in 1850, when Claude Bernard's studies in experimental pharmacology confirmed that muscle was a functional unit, independent of any electrical innervation via its supplying nerve. This account comprises an audit of Swammerdam's work in the perspective of neuromuscular knowledge. (C) 2002 Elsevier Science B.V. All rights reserved.