Joseph Tucci

A study of regional gut endoderm potency by analysis of Cdx2 null mutant chimaeric mice

Inactivation of Cdx2 by homologous recombination results in the development of forestomach epithelium at ectopic sites in pericaecal areas of the midgut of heterozygote mice. Local factors subsequently result in the secondary induction of tissues exhibiting an orderly sequence of tissue types between the ectopic forestomach tissue and the surrounding colon. Clonal analysis of this secondarily generated tissue using Y chromosome painting in chimaeric mice indicates that once differentiated to express Cdx2, host colonic epithelium can only form small intestinal-type epithelium, while Cdx2 mutant cells give rise to a succession of gastric-type tissue but never to a small intestine morphology. Our results indicate a difference in potency between forestomach and midgut precursor endodermal cells.

The expression of the gene coding for parathyroid hormone-related protein (PTHrP) during tooth development in the rat.

By means of in situ hybridisation studies, it is shown that parathyroid hormone-related protein (PTHrP) mRNA is strongly expressed in the developing enamel organs of rat teeth. In particular, the cervical loop hybridises strongly with the PTHrP probe and expression is maintained at this site throughout life in the permanently erupting incisor teeth. In mature molar teeth, expression is downregulated to low levels and confined to the epithelial cell rests of Malassez and/or cementoblasts which may derive from these. The gene is also expressed at low levels in the tissue overlying the erupting molars and, thereafter, in the junctional epithelia and connective tissue cells of the epithelial attachment on all tooth surfaces. The premise that PTHrP may undergo post-translational processing and that the resultant products could act in different ways raises the possibility of its exerting multiple paracrine actions during tooth development. These could include the control of cell division and local vascular dilation during development.

Walnuts (Juglans regia) Chemical Composition and Research in Human Health

Walnuts are among the most widely consumed commercially grown tree nuts in the world. Many health benefits have been claimed for the consumption of these, including reduced risk of cardiovascular disease, coronary heart disease, type II diabetes treatment, and prevention and treatment of certain cancers, and the lessening of symptoms attributed to age-related and other neurological disorders. The health-promoting benefits of walnut consumption are ascribed to its fatty acid profile, which is rich in polyunsaturated fatty acids with a particularly high ω3:ω6 ratio—the highest among all the tree nuts. The content of polyphenols and other phytochemicals in walnuts, with their claimed cytotoxic properties, also make them an attractive candidate for research for the prevention of free radical-induced nucleic acid damage. Research of walnut consumption in humans and animals employing a range of data sets and statistical methods suggest that walnuts may be considered a safe potential nutraceutical or possibly pharmaceutical substance. Nevertheless, few reviews of scientific research on the proposed benefits of these nuts exist, in spite of the numerous claims attributed to them in the lay media. This brief review article attempts to disseminate much of the information surrounding walnut consumption, and human health benefits, to other scientists and the interested general reader.

Omega 3 polyunsaturated fatty acids and the treatment of depression

ABSTRACT Depression is a common, recurrent, and debilitating illness that has become more prevalent over the past 100 years. This report reviews the etiology and pathophysiology of depression, and explores the role of omega 3 polyunsaturated fatty acids (n-3 PUFA) as a possible treatment. In seeking to understand depression, genetic factors and environmental influences have been extensively investigated. Research has led to several hypotheses for the pathophysiological basis of depression but a definitive pathogenic mechanism, or group thereof, has hitherto remained equivocal. To date, treatment has been based on the monoamine hypothesis and hence, selective serotonin reuptake inhibitors have been the most widely used class of medication. In the last decade, there has been considerable interest in n-3 PUFAs and their role in depression. These fatty acids are critical for development and function of the central nervous system. Increasing evidence from epidemiological, laboratory, and randomized placebo-controlled trials suggests deficiency of dietary n-3 PUFAs may contribute to development of mood disorders, and supplementation with n-3 PUFAs may provide a new treatment option. Conclusions based on systematic reviews and meta-analyses of published trials to date vary. Research into the effects of n-3 PUFAs on depressed mood is limited. Furthermore, results from such have led to conflicting conclusions regarding the efficacy of n-3 PUFAs in affecting reduction in symptoms of depression. PUFAs are generally well tolerated by adults and children although mild gastrointestinal effects are reported. There is mounting evidence to suggest that n-3 PUFAs play a role in depression and deserve greater research efforts.

Lysis to Kill: Evaluation of the Lytic Abilities, and Genomics of Nine Bacteriophages Infective for Gordonia spp. and Their Potential Use in Activated Sludge Foam Biocontrol.

Nine bacteriophages (phages) infective for members of the genus Gordonia were isolated from wastewater and other natural water environments using standard enrichment techniques. The majority were broad host range phages targeting more than one Gordonia species. When their genomes were sequenced, they all emerged as double stranded DNA Siphoviridae phages, ranging from 17,562 to 103,424 bp in size, and containing between 27 and 127 genes, many of which were detailed for the first time. Many of these phage genomes diverged from the expected modular genome architecture of other characterized Siphoviridae phages and contained unusual lysis gene arrangements. Whole genome sequencing also revealed that infection with lytic phages does not appear to prevent spontaneous prophage induction in Gordonia malaquae lysogen strain BEN700. TEM sample preparation techniques were developed to view both attachment and replication stages of phage infection.

The Formulation of Bacteriophage in a Semi Solid Preparation for Control of Propionibacterium acnes Growth.

Aims To isolate and characterise phage which could lyse P. acnes and to formulate the phage into a delivery form for potential application in topical treatment of acne infection. Methods and Results Using standard phage isolation techniques, ten phage capable of lysing P. acnes were isolated from human skin microflora. Their genomes showed high homology to previously reported P. acnes phage. These phage were formulated into cetomacrogol cream aqueous at a concentration of 2.5x108 PFU per gram, and shown to lyse underlying P. acnes cells grown as lawn cultures. These phage formulations remained active for at least 90 days when stored at four degrees Celsius in a light protected container. Conclusions P. acnes phage formulated into cetomacrogol cream aqueous will lyse surrounding and underlying P. acnes bacteria, and are effective for at least 90 days if stored appropriately. Significance and Impact of the Study There are few reports of phage formulation into semi solid preparations for application as phage therapy. The formulation method described here could potentially be applied topically to treat human acne infections. The potential exists for this model to be extended to other phage applied to treat other bacterial skin infections.

Insertions or deletions (Indels) in the rrn 16S-23S rRNA gene internal transcribed spacer region (ITS) compromise the typing and identification of strains within the Acinetobacter calcoaceticus-baumannii (Acb) complex and closely related members.

To determine whether ITS sequences in the rrn operon are suitable for identifying individual Acinetobacter Acb complex members, we analysed length and sequence differences between multiple ITS copies within the genomes of individual strains. Length differences in ITS reported previously between A. nosocomialis BCRC15417T (615 bp) and other strains (607 bp) can be explained by presence of an insertion (indel 13i/1) in the longer ITS variant. The same Indel 13i/1 was also found in ITS sequences of ten strains of A. calcoaceticus, all 639 bp long, and the 628 bp ITS of Acinetobacter strain BENAB127. Four additional indels (13i/2–13i/5) were detected in Acinetobacter strain c/t13TU 10090 ITS length variants (608, 609, 620, 621 and 630 bp). These ITS variants appear to have resulted from horizontal gene transfer involving other Acinetobacter species or in some cases unrelated bacteria. Although some ITS copies in strain c/t13TU 10090 are of the same length (620 bp) as those in Acinetobacter strains b/n1&3, A. pittii (10 strains), A. calcoaceticus and A. oleivorans (not currently acknowledged as an Acb member), their individual ITS sequences differ. Thus ITS length by itself can not by itself be used to identify Acb complex strains. A shared indel in ITS copies in two separate Acinetobacter species compromises the specificity of ITS targeted probes, as shown with the Aun-3 probe designed to target the ITS in A. pitti. The presence of indel 13i/5 in the ITS of Acinetobacter strain c/t13TU means it too responded positively to this probe. Thus, neither ITS sequencing nor the currently available ITS targeted probes can distinguish reliably between Acb member species.

Paracetamol and Ibuprofen for Paediatric Pain and Fever

To review the literature on the pharmacology and pharmacokinetics of paracetamol and ibuprofen pertaining to their use for paediatric pain and fever.

The perceptions of pharmacists in Victoria, Australia on pharmacogenetics and its implications

Objective This study aimed to explore how well Victorian pharmacists perceived they understood pharmacogenetics, their perceived capacity to counsel a patient about such testing, how they believed pharmacogenetics would impact upon their profession, and to investigate the ways in which Victorian pharmacists would like to be educated about pharmacogenetics. Methods A cross-sectional survey was dispatched to 800 Victorian pharmacists. The participants were randomly selected and the survey was anonymous. The survey contained questions about where the pharmacists worked, the pharmacists’ perceived knowledge of pharmacogenetics, how well they believed they would be able to counsel patients about pharmacogenetic testing, how they thought pharmacists should be educated on the topic and how they believed pharmacogenetics would impact upon their profession. Results 291 surveys were returned (36% response rate). Results suggest that Victorian pharmacists generally perceived they had a poor understanding of pharmacogenetics and that those who have more recently graduated from tertiary education had a better perceived understanding than those who have been in the workforce for longer. Most pharmacists indicated that they did not believe that they could counsel a patient adequately about the results of a pharmacogenetic test. Regarding education about pharmacogenetics, participants suggested that this would be best delivered during tertiary studies, and as seminars and workshops forming part of their continuing professional development. Although some pharmacists were unsure how pharmacogenetics would affect their profession, many believed it would have a major impact upon their role as a pharmacist and lead to improved patient care. Some concerns about the implementation of pharmacogenetics were noted, including economic and ethical issues. Conclusions This study highlights the need for further research across the pharmacy profession in Australia on the issue of preparedness for the putative incorporation of pharmacogenetics into the healthcare system and everyday practice.

The activated sludge bulking filament Eikelboom morphotype 0803 embraces more than one member of the Chloroflexi

The Eikelboom filamentous morphotype 0803 is commonly found in activated sludge systems globally, where it contributes to sludge bulking events. Earlier reports have suggested that it is a member of both the Proteobacteria and Chloroflexi. This study shows that this filament contributing to a period of poor sludge settleability in an Australian activated sludge plant is a member of the Chloroflexi, but not within the Caldilinea, as reported for this morphotype in Danish plants. Instead, it is a member of the Anaerolineae. The fluorescent signals generated in these filaments using the FISH probes designed here were unevenly distributed, a situation similar to that seen earlier in the Anaerolineae morphotype 0092 to which it is more closely related phylogenetically than it is to the Caldilinea morphotype 0803. FISH-based surveys showed that this 0803 phylotype is uncommon in Australian activated sludge systems, and where seen is present usually at low abundances. The FISH probes described here will facilitate attempts to map the distribution and impact of this Australian filament morphotype 0803 in activated sludge systems of different configurations in plants around the world.