P27KIP1 is a Mediator of Cell Migration in Metastatic Breast Cancer Stem Cells

Despite advances in treatment, breast cancer remains one of the leading causes of cancer deaths among women. Although early detection through mammograms and advances in treatments have shown great promise, tumor relapse still poses a major challenge. Breast cancer stem cells (CSCs) have been recently identified as a small subpopulation of breast cancer cells thought to promote breast cancer progression and drug resistance. Similar to normal stem cells, CSCs have the capacity for self-renewal, proliferation, and pluripotency. Breast CSCs also display increased cell migration and invasion. Therefore, targeting the growth of breast CSCs will provide novel strategies to combat breast cancer. p27Kip1 (p27), a member of the cyclin-dependent kinase inhibitor (CIP/KIP) family, mediates nuclear G1 cell cycle arrest with subsequent quiescence. p27 performs cell cycle-dependent and cell cycle-independent functions based on subcellular localization. Interestingly, cytoplasmic p27 displays CDK-independent functions, including enhanced cell migration and metastasis in a variety of solid tumors. Yet, the role for p27 in migration in breast CSCs has yet to be tested. We hypothesize that p27 increases the metastatic potential of breast cancer stem cells through increasing cell migration. This hypothesis is based on preliminary observations that revealed that p27 protein levels were markedly enhanced in CSCs isolated from metastatic breast cancer cell lines compared to those that were non-metastatic in nature. Using in vitro mammosphere assays, transwell cell migration assays and gene silencing, we found that p27 increased migratory populations from breast CSCs, suggesting that it could be an attractive target to combat breast cancer

A Common Data Model for Meta-Data in Interoperable Environments

A Common Data Model is a unifying structure used to allow heterogeneous environments to interoperate. An Object Oriented common model is presented in this paper, which provides this unifying structure for a Meta-Data Repository Visualisation Tool. The creation of this common model from the Meta-Data held in component databases is described. The role this common model has in interoperable environments is discussed, and the physical architecture created from the examination of the Meta-Data in the Repository common model is described

Detection of flying-foxes using automated audio recorders

Flying-foxes are little understood in Australia largely due to their extreme mobility. This mobility is particularly evident in the two species (spectacled and little red) found across the north of Australia, where huge numbers of animals will suddenly converge on a region and then leave a few weeks later. To improve management of these species we need to understand the movement and ecology of the animals and this is not straightforward as the camps are often remote and inaccessible. In this project we aimed to test the viability of using automated acoustic recorders for determining the presence of spectacled flying-foxes at camp locations. A Song Meter SM4 recorder was used to record flying-foxes in a number camps around South East QLD/Northern Rivers (black and grey-headed flying-foxes) and Cairns (spectacled flying-fox). A total of 35 hour of flying-foxes calls were recorded over a period of 8 weeks from August to October 2017. The recordings were processed using a Binary Winnow classifier and Hidden Markov Model in Kaleidoscope Software (Wildlife Acoustics). Tagged one-minute recordings were used to train the Hidden Markov Model in Kaleidoscope which was subsequently used in classifying the remaining recordings. Using this approach, we were able to quickly and easily detect the presence of flying-foxes in the acoustic recordings. In this way, ecologists can easily implement projects for long-term monitoring of flying-fox populations using remotely deployed acoustic recorders. It may also assist management agencies for urban planning in northern Australia. For future work, we will be investigate advanced machine learning algorithms coupled with flying-fox behavioural call patterns to attempt to distinguish the species of flying-fox from acoustic recordings

Scorpion toxin peptide action at the ion channel subunit level

This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling

Carotenoporphyrins as selective photodiagnostic agents for tumours.

The covalent binding of a carotene moiety to one phenyl ring and meso-tetraphenyl-substituted porphyrins (see Figure 1) efficiently quenches the photosensitising activity of the porphyrin while a relatively large yield of fluorescence emission around 650 nm is retained. Pharmacokinetic studies performed with two carotenoporphyrins (CPs) and the corresponding porphyrins (Ps) in Balb/c mice bearing an MS-2 fibrosarcoma show that the two Ps give a high selectivity of tumour localisation (tumour/peritumoral tissue ratios of dye concentration ranging between c. 30 and 90 at 24 h after injection of 4.2-8.4 mumol kg-1 in a Cremophor emulsion) and photosensitive tumour necrosis upon red light irradiation. For the same injected doses, the two CPs show no tumour-photosensitising activity even though they localise in the tumour in concentrations of the order of 10-40 micrograms g-1 at 24 h with tumour/peritumoral ratios larger than 10. Thus, the fluorescence emitted by these CPs in the tumour can be used for photodiagnostic purposes with no risk of skin photosensitisation. However, this approach is presently limited by the large accumulation and prolonged retention of the CPs in the liver and spleen

Emotional Reactivity, Emotion Regulation Capacity, and Posttraumatic Stress Disorder in Traumatized Refugees: An Experimental Investigation

Refugees who suffer from posttraumatic stress disorder (PTSD) often react with strong emotions when confronted with trauma reminders. In this study, we aimed to investigate the associations between low emotion regulation capacity (as indexed by low heart rate variability [HRV]), probable PTSD diagnosis, and fear and anger reaction and recovery to trauma-related stimuli. Participants were 81 trauma-exposed refugees (probable PTSD, n = 23; trauma-exposed controls, n = 58). The experiment comprised three 5-min phases: a resting phase (baseline); an exposition phase, during which participants were exposed to trauma-related images (stimulus); and another resting phase (recovery). We assessed HRV at baseline, and fear and anger were rated at the end of each phase. Linear mixed model analyses were used to investigate the associations between baseline HRV and probable DSM-5 PTSD diagnosis in influencing anger and fear responses both immediately after viewing trauma-related stimuli and at the end of the recovery phase. Compared to controls, participants with probable PTSD showed a greater increase in fear from baseline to stimulus presentation, d = 0.606. Compared to participants with low emotion regulation capacity, participants with high emotion regulation capacity showed a smaller reduction in anger from stimulus presentation to recovery, d = 0.548. Our findings indicated that following exposure to trauma-related stimuli, probable PTSD diagnosis predicted increased fear reactivity, and low emotion regulation capacity predicted decreased anger recovery. Impaired anger recovery following trauma reminders in the context of low emotion regulation capacity might contribute to the increased levels of anger found in postconflict samples

Predominance of Ehrlichia ewingii in Missouri dogs

To investigate the species distribution of Ehrlichia present in Missouri dogs, we tested 78 dogs suspected of having acute ehrlichiosis and 10 healthy dogs. Blood from each dog was screened with a broad-range 16S rRNA gene PCR assay that detects known pathogenic species of Ehrlichia and Anaplasma. The species was determined by using species-specific PCR assays and nucleotide sequencing. Ehrlichia antibody testing was performed by using an indirect immunofluorescence assay with Ehrlichia chaffeensis as the antigenic substrate. The broad-range assay detected Ehrlichia or Anaplasma DNA in 20 (26%) of the symptomatic dogs and 2 (20%) of the asymptomatic dogs. E. ewingii accounted for 20 (91%), and E. chaffeensis accounted for 1 (5%) of the positives. Anaplasma phagocytophilum DNA was detected in one dog, and the sequences of regions of the 16S rRNA gene and the groESL operon amplified from the blood of this dog matched the published sequences of this organism. Antibodies reactive with E. chaffeensis were detected in 14 (67%) of the 21 PCR-positive dogs and in 12 (19%) of the 64 PCR-negative dogs. Combining the results of PCR and serology indicated that 33 (39%) of 85 evaluable dogs had evidence of past or current Ehrlichia infection. We conclude that E. ewingii is the predominant etiologic agent of canine ehrlichiosis in the areas of Missouri included in this survey. E. canis, a widely recognized agent of canine ehrlichiosis, was not detected in any animal. The finding of E. ewingii in asymptomatic dogs suggests that dogs could be a reservoir for this Ehrlichia species