Mesenchymal stem cells, neural lineage potential, heparan sulfate proteoglycans and the matrix

Along with the tri-lineage of bone, cartilage and fat, human mesenchymal stem cells (hMSCs) retain neural lineage potential. Multiple factors have been described that influence lineage fate of hMSCs including the extracellular microenvironment or niche. The niche includes the extracellular matrix (ECM) providing structural composition, as well as other associated proteins and growth factors, which collectively influence hMSC stemness and lineage specification. As such, lineage specific differentiation of MSCs is mediated through interactions including cell–cell and cell–matrix, as well as through specific signalling pathways triggering downstream events. Proteoglycans (PGs) are ubiquitous within this microenvironment and can be localised to the cell surface or embedded within the ECM. In addition, the heparan sulfate (HS) and chondroitin sulfate (CS) families of PGs interact directly with a number of growth factors, signalling pathways and ECM components including FGFs, Wnts and fibronectin. With evidence supporting a role for HSPGs and CSPGs in the specification of hMSCs down the osteogenic, chondrogenic and adipogenic lineages, along with the localisation of PGs in development and regeneration, it is conceivable that these important proteins may also play a role in the differentiation of hMSCs toward the neuronal lineage. Here we summarise the current literature and highlight the potential for HSPG directed neural lineage fate specification in hMSCs, which may provide a new model for brain damage repair.

Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. Because fMRI records, through the monitoring of blood flow activity, the location of localised brain activity within the brain, the possibility of combining fMRI measurements with EEG, as a joint inversion activity, was discussed and examined in detail. (3) A major goal for the BRI is to improve understanding about ``when'' (at what time) an epileptic seizure actually commenced before it is identified on an eeg recording, ``where'' the source of this initiation is located in the brain, and ``what'' is the initiator. Because of the general agreement in the literature that, in one way or another, epileptic events and seizures represent abnormal synchronisations of localised and/or global brain activity the modelling of synchronisations was examined in some detail. References C. M. Michel, G. Thut, S. Morand, A. Khateb, A. J. Pegna, R. Grave de Peralta, S. Gonzalez, M. Seeck and T. Landis, Electric source imaging of human brain functions, Brain Res. 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Localising national identity : Albany's Anzacs

Local representations of the significance of Albany, Western Australia, in the first world war and of the city's part in the birth of Anzac register substantial points of departure from national histories. While both the Anzac mythos and official renderings of Australia's wars are vigorously contested, Albany's reformulation offers a clear example of the ways in which communities actively inflect national narratives to create expressions of differentiated local identity. This article explores the relationship between the national and the local by focusing on the local narrative of the massing and departure of'The Great Anzac Convoy' in King George Sound in 1914. Particular attention is given to the way Albany has been able to appropriate and localise this event and the origins of Anzac, consequently promoting itself as an important element of the national identity, from which it nevertheless remains distinct. This localisation of an important element of national identity confers cultural standing and a potentially empowered position in relation to this national identity.

All-environment visual place recognition with SMART

This paper presents Sequence Matching Across Route Traversals (SMART); a generally applicable sequence-based place recognition algorithm. SMART provides invariance to changes in illumination and vehicle speed while also providing moderate pose invariance and robustness to environmental aliasing. We evaluate SMART on vehicles travelling at highly variable speeds in two challenging environments; firstly, on an all-terrain vehicle in an off-road, forest track and secondly, using a passenger car traversing an urban environment across day and night. We provide comparative results to the current state-of-the-art SeqSLAM algorithm and investigate the effects of altering SMART’s image matching parameters. Additionally, we conduct an extensive study of the relationship between image sequence length and SMART’s matching performance. Our results show viable place recognition performance in both environments with short 10-metre sequences, and up to 96% recall at 100% precision across extreme day-night cycles when longer image sequences are used.

Locating people in video from semantic descriptions : a new database and approach

The location of previously unseen and unregistered individuals in complex camera networks from semantic descriptions is a time consuming and often inaccurate process carried out by human operators, or security staff on the ground. To promote the development and evaluation of automated semantic description based localisation systems, we present a new, publicly available, unconstrained 110 sequence database, collected from 6 stationary cameras. Each sequence contains detailed semantic information for a single search subject who appears in the clip (gender, age, height, build, hair and skin colour, clothing type, texture and colour), and between 21 and 290 frames for each clip are annotated with the target subject location (over 11,000 frames are annotated in total). A novel approach for localising a person given a semantic query is also proposed and demonstrated on this database. The proposed approach incorporates clothing colour and type (for clothing worn below the waist), as well as height and build to detect people. A method to assess the quality of candidate regions, as well as a symmetry driven approach to aid in modelling clothing on the lower half of the body, is proposed within this approach. An evaluation on the proposed dataset shows that a relative improvement in localisation accuracy of up to 21 is achieved over the baseline technique.

Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing

Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

Global reconfiguration of a team of networked mobile robots among obstacles

This paper presents a full system demonstration of dynamic sensorbased reconfiguration of a networked robot team. Robots sense obstacles in their environment locally and dynamically adapt their global geometric configuration to conform to an abstract goal shape. We present a novel two-layer planning and control algorithm for team reconfiguration that is decentralised and assumes local (neighbour-to-neighbour) communication only. The approach is designed to be resource-efficient and we show experiments using a team of nine mobile robots with modest computation, communication, and sensing. The robots use acoustic beacons for localisation and can sense obstacles in their local neighbourhood using IR sensors. Our results demonstrate globally-specified reconfiguration from local information in a real robot network, and highlight limitations of standard mesh networks in implementing decentralised algorithms.

Differential subcellular and extracellular localisations of proteins required for insulin-like growth factor- and extracellular matrix-induced signalling events in breast cancer progression

Background: Cancer metastasis is the main contributor to breast cancer fatalities as women with the metastatic disease have poorer survival outcomes than women with localised breast cancers. There is an urgent need to develop appropriate prognostic methods to stratify patients based on the propensities of their cancers to metastasise. The insulin-like growth factor (IGF)-I:IGF binding protein (IGFBP):vitronectin complexes have been shown to stimulate changes in gene expression favouring increased breast cancer cell survival and a migratory phenotype. We therefore investigated the prognostic potential of these IGF- and extracellular matrix (ECM) interaction-induced proteins in the early identification of breast cancers with a propensity to metastasise using patient-derived tissue microarrays. Methods: Semiquantitative immunohistochemistry analyses were performed to compare the extracellular and subcellular distribution of IGF- and ECM-induced signalling proteins among matched normal, primary cancer and metastatic cancer formalin-fixed paraffin-embedded breast tissue samples. Results: The IGF- and ECM-induced signalling proteins were differentially expressed between subcellular and extracellular localisations. Vitronectin and IGFBP-5 immunoreactivity was lower while β1 integrin immunoreactivity was higher in the stroma surrounding metastatic cancer tissues, as compared to normal breast and primary cancer stromal tissues. Similarly, immunoreactive stratifin was found to be increased in the stroma of primary as well as metastatic breast tissues. Immunoreactive fibronectin and β1 integrin was found to be highly expressed at the leading edge of tumours. Based on the immunoreactivity it was apparent that the cell signalling proteins AKT1 and ERK1/2 shuffled from the nucleus to the cytoplasm with tumour progression. Conclusion: This is the first in-depth, compartmentalised analysis of the distribution of IGF- and ECM-induced signalling proteins in metastatic breast cancers. This study has provided insights into the changing pattern of cellular localisation and expression of IGF- and ECM-induced signalling proteins in different stages of breast cancer. The differential distribution of these biomarkers could provide important prognostic and predictive indicators that may assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy.

Phosphorylation of caveolin-1 is anti-apoptotic and promotes cell attachment during oxidative stress of kidney cells

Aims: Caveolin-1 (cav1) is reported to have both cell survival and pro-apoptotic characteristics. This may be explained by its localisation or phosphorylation in injured cells. This study investigated the role of cav1 in kidney cells of different nephron origin and developmental state after oxidative stress. Methods: Renal MCDK distal tubular, HK2 proximal tubular epithelial cells and HEK293T renal embryonic cells were treated with 1mM hydrogen peroxide. Apoptosis, loss of cell adhesion, and cell survival were compared with expression of cav1 in its non-phosphorylated and phosphorylated (p-cav1) forms. Cav1 was transfected into the HEK293T cells, or caveolae were disrupted with filipin or nystatin in HK2 cells, to investigate functions of cav1 and p-cav1. Results: Oxidative stress induced more apoptosis in HK2s than MDCKs (p<0.05). HK2s had lower endogenous cav1 and p-cav1 than MDCKs (p<0.05). Both cell lines had increased p-cav1, but not cav1, with oxidative stress. This increase was greatest in MDCKs (p<0.01). Cav1 was located mainly in the plasma membrane of untreated cells and translocated to the cytoplasm with oxidative stress in both cell lines, more so in MDCKs. Disruption of caveolae caused cytoplasmic translocation of cav1 in HK2s, but did not alter high levels of oxidative stress-induced apoptosis. When HEK293Ts lacking endogenous cav1 were transfected with cav1, oxidant-induced apoptosis and loss of cell adhesion was decreased (p<0.01), and p-cav1 was induced by treatment. Conclusion: Cav1 expression and localisation in kidney cells is not anti-apoptotic, but increased expression of p-cav1 may promote cell survival after oxidative stress. © 2008 Royal College of Pathologists of Australasia.

Visual place recognition for persistent robot navigation in changing environments

This thesis demonstrates that robots can learn about how the world changes, and can use this information to recognise where they are, even when the appearance of the environment has changed a great deal. The ability to localise in highly dynamic environments using vision only is a key tool for achieving long-term, autonomous navigation in unstructured outdoor environments. The proposed learning algorithms are designed to be unsupervised, and can be generated by the robot online in response to its observations of the world, without requiring information from a human operator or other external source.

Design & performance of a networked ad-hoc acoustic communications system using inexpensive commercial CDMA modems

We present a new approach for creating and implementing an ad-hoc underwater acoustic sensor network based on connecting a small processor to the serial port of a commercial CDMA acoustic modem. The processor acts as a "node controller" providing the networking layer that the modems lack. The ad-hoc networking protocol is based on a modified dynamic source routing (DSR) approach and can be configured for maximising information throughput or minimising energy expenditure. The system was developed in simulation and then evaluated during field trials using a 10 node deployment. Experimental results show reliable multi-hop networking under a variety of network configurations, with the added ability to determine internode ranges to within 1.5 m for localisation.

Searching for semantic person queries using channel representations

It is not uncommon to hear a person of interest described by their height, build, and clothing (i.e. type and colour). These semantic descriptions are commonly used by people to describe others, as they are quick to relate and easy to understand. However such queries are not easily utilised within intelligent surveillance systems as they are difficult to transform into a representation that can be searched for automatically in large camera networks. In this paper we propose a novel approach that transforms such a semantic query into an avatar that is searchable within a video stream, and demonstrate state-of-the-art performance for locating a subject in video based on a description.

Investigation of fiducial marker and soft-tissue image guidance techniques in prostate radiation therapy

This thesis examines and compares imaging methods used during the radiotherapy treatment of prostate cancer. The studies found that radiation therapists were able to localise and target the prostate consistently with planar imaging techniques and that the use of small gold markers in the prostate reduced the variation in prostate localisation when using volumetric imaging. It was concluded that larger safety margins are required when using volumetric imaging without gold markers.

Issues in autonomous navigation of underground vehicles

This paper describes current research at the Australian Centre for Field Robotics (ACFR) in collaboration with the Commonwealth Scientific and Industrial Research Organisation (CSIRO) within the Cooperative Research Centre (CRC) for Mining Technology and Equipment (CMTE) towards achieving autonomous navigation of underground vehicles, like a Load-Haul-Dump (LHD) truck. This work is being sponsored by the mining industry through the Australian Mineral Industries Research Association Limited (AMIRA). Robust and reliable autonomous navigation can only be realised by achieving high level tasks such as path-planning and obstacle avoidance. This requires determining the pose (position and orientation) of the vehicle at all times. A minimal infrastructure localisation algorithm that has been developed for this purpose is outlined and the corresponding results are presented. Further research issues that are under investigation are also outlined briefly.

From ImageNet to mining: Adapting visual object detection with minimal supervision

This paper presents visual detection and classification of light vehicles and personnel on a mine site.We capitalise on the rapid advances of ConvNet based object recognition but highlight that a naive black box approach results in a significant number of false positives. In particular, the lack of domain specific training data and the unique landscape in a mine site causes a high rate of errors. We exploit the abundance of background-only images to train a k-means classifier to complement the ConvNet. Furthermore, localisation of objects of interest and a reduction in computation is enabled through region proposals. Our system is tested on over 10km of real mine site data and we were able to detect both light vehicles and personnel. We show that the introduction of our background model can reduce the false positive rate by an order of magnitude.