Unravelling the Diversity of Microorganisms in Ticks from Australian Wildlife.

Ticks and tick-borne pathogens pose a significant threat to the health and welfare of humans and animals. Our knowledge about pathogens carried by ticks of Australian wildlife is limited. This study aimed to characterise ticks and tick-borne microorganisms from a range of wildlife species across six sites in Victoria, Australia.

Maternal transmission of an Igf2r domain 11: IGF2 binding mutant allele (Igf2r) results in partial lethality, overgrowth and intestinal adenoma progression.

The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. Specific IGF2 and M6P high-affinity binding occurs via domain-11 and domains-3-5-9, respectively. Mammalian maternal Igf2r allele expression exceeds the paternal allele due to imprinting (silencing).

Regeneration of Dopaminergic Neurons in Adult Zebrafish Depends on Immune System Activation and Differs for Distinct Populations.

Adult zebrafish, in contrast to mammals, regenerate neurons in their brain, but the extent and variability of this capacity is unclear. Here we ask whether the loss of various dopaminergic neuron populations is sufficient to trigger their functional regeneration. Both sexes of zebrafish were analyzed.

A synthetic cell permeable antioxidant protects neurons against acute oxidative stress.

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson's disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches.

Cleaving the Halqeh-ye-nur diamonds: a dynamic fracture analysis.

The degree of surface roughness and clarity with which a surface in a brittle material can be formed via fracture is known to be related to the speed of the propagating crack. Cracks traversing a brittle material at low speed produce very smooth surfaces, while those propagating faster create less reflective and rough surfaces (Buehler MJ, Gao H. 2006 Nature 439, 307-310 (doi:10.

Reporting for duty: the paternal function and clinical formulations.

The author highlights some developments in the theory of the preoedipal paternal function and paternal functionary and incorporates these ideas in developing clinical formulations for four clinical cases that privilege the preoedipal paternal function. In particular, four aspects of the preoedipal paternal function are identified, and for each a clinical case is discussed. Emphasis is placed on the necessity of widening clinical formulations to ensure clinicians have the widest possible set of clinical ideas and hence interventions and techniques at their fingertips.

ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation.

Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb muscular weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the British and German LGMD2L patients so far reported.

Comparative outcome of oesophagogastric cancer in younger patients.

Introduction: The incidence of oesophageal and gastric cardia adenocarcinoma has increased rapidly over the previous two decades. There has been a rise in the number of younger patients affected, and the disease may be more aggressive and have a worse prognosis in these individuals. Current UK guidelines for urgent cancer referral focus on patients who are over 55 years.

Interstitial in vivo ALA-PpIX mediated metronomic photodynamic therapy (mPDT) using the CNS-1 astrocytoma with bioluminescence monitoring.

Background: We report the first truly metronomic delivery of photodynamic therapy using the rat-derived CNS-1 astrocytoma, a model with close histopathology with human brain tumours.

Methods: Metronomic PDT (mPDT) was delivered to CNS-1 bearing female Lewis rats. 5-Aminoluvelinic acid was delivered continuously through drinking water, while light was delivered via tetherless, light-weight, LED-based fiber coupled optical sources.

Tetherless fiber-coupled optical sources for extended metronomic photodynamic therapy.

Background: Metronomic photodynamic therapy (mPDT) involves the delivery of a low fluence rate of light and photosensitizing drug, continuously and over an extended period. However, in mPDT trials, there has been a perceived need for light sources that can deliver light reliably for extended periods, while being small enough to be tolerated by small animals.

Methods: We report on the development of tetherless, lightweight, fiber-coupled optical sources for in vivo delivery of interstitial mPDT.

Gastrointestinal stromal tumors (GIST) and laparoscopic resection.

Aim: To review management, outcome and the lessons learnt from a laparoscopic approach to GISTs.

Method: All cases of GIST presenting to the upper GI MDT between 2000 and 2006 were reviewed. Presentation, preoperative investigations, management and follow-up were recorded.

An unusual presentation of a Gastrointestinal stromal tumour (GIST).

Background: Gastrointestinal stromal tumours (GIST) are rare tumours, now more frequently identified with the new imaging modalities like computerised tomography (CT) and magnetic resonance imaging (MRI). We report a rare presentation of a GIST with an unusual diagnostic workup in a multidisciplinary setting leading to a definitive diagnosis and treatment.

Case Presentation: A 55-year-old lady was admitted under the general surgeons, with 3-day history of abdominal pain, three-week history of loss of appetite and weight.

No immediate pain relief for the pharmaceutical industry.

Over many years, the pharmaceutical industry has developed a highly successful model for making new medicines. Currently, there are an estimated 13,000 prescription drugs on the market. However, the model that has served the sector so well for so long is now breaking down.

Bayesian variable selection in multinomial probit models to identify molecular signatures of disease stage.

Here we focus on discrimination problems where the number of predictors substantially exceeds the sample size and we propose a Bayesian variable selection approach to multinomial probit models. Our method makes use of mixture priors and Markov chain Monte Carlo techniques to select sets of variables that differ among the classes. We apply our methodology to a problem in functional genomics using gene expression profiling data.

Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms.

Inhibition of the ATPase activity of the chaperone protein HSP90 is a potential strategy for treatment of cancers. We have determined structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays. The compounds induce upregulation of HSP70 and downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent on HSP90 inhibition.