Krüppel-associated box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1 (HP1- ) mobilization and DNA repair in heterochromatin

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.

A note on a reaction-diffusion model describing the bone morphogen protein gradient in Drosophila embryonic patterning

In this article, we consider the Eldar model [3] from embryology in which a bone morphogenic protein, a short gastrulation protein, and their compound react and diffuse. We carry out a perturbation analysis in the limit of small diffusivity of the bone morphogenic protein. This analysis establishes conditions under which some elementary results of [3] are valid.

Effect of bone morphogenetic protein-4 (BMP-4) on the expression of Sox2, Oct-4 and c-Myc in human periodontal ligament cells during long-term culture

Recent studies demonstrated endogenous expression level of Sox2, Oct-4 and c-Myc is correlated with the pluripotency and successful induction of induced pluripotent stem cells (iPSCs). Periondontal ligament cells (PDLCs)have multi-lineage diferentiation capability and ability to maintain undifferentiated stage, which makes PDLCs a suitable cell source for tissue repair and regeneration. To elucidate the effect of in vitro culture condition on the stemness potential of PDLCs, we explored the cell growth, proliferation, cell cycle, and the expression of Sox2, Oct-4 and c-Myc in PDLCs from passage 1 to 7 with or without the addition of recombinant human BMP4(rhBMP4). Our results revealed that BMP-4 promoted cell growth and proliferation, arrested PDLCs in S phase of cell cycle and upregulated PI value. It was revealed that without the addition of rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs only maintained nucleus location until passage 3, then lost nucleus location subsequently. The mRNA expression in PDLCs further confirmed that the level of Sox2 and Oct-4 peaked at passage 3, then decreased afterwards, whereas c-Myc maintained consistently upregulation along passages. after the treatment with rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs maintained nucleus location even at passage 7 and the mRNA expression of Sox2 and Oct-4 significantly upregulated at passage 5 and 7. These results demonstrated that addition of rhBMP-4 in the culture media could improve the current culture condition for PDLCs to maintain in an undifferentiated stage.

Bilingual asynchronous online discussion groups : design and delivery of an e-Learning distance study module for nurse academics in a developing country

The advent of eLearning has seen online discussion forums widely used in both undergraduate and postgraduate nursing education. This paper reports an Australian university experience of design, delivery and redevelopment of a distance education module developed for Vietnamese nurse academics. The teaching experience of Vietnamese nurse academics is mixed and frequently limited. It was decided that the distance module should attempt to utilise the experience of senior Vietnamese nurse academics - asynchronous online discussion groups were used to facilitate this. Online discussion occurred in both Vietnamese and English and was moderated by an Australian academic working alongside a Vietnamese translator. This paper will discuss the design of an online learning environment for foreign correspondents, the resources and translation required to maximise the success of asynchronous online discussion groups, as well as the rationale of delivering complex content in a foreign language. While specifically addressing the first iteration of the first distance module designed, this paper will also address subsequent changes made for the second iteration of the module and comment on their success. While a translator is clearly a key component of success, the elements of simplicity and clarity combined with supportive online moderation must not be overlooked.

Design and delivery of a distance education programme : educating Vietnamese nurse academics from Australia

In 2008 a move away from medical staff providing nursing education in Vietnam saw the employment of many new nurse academics. To assist in the instruction of these novice academics and provide them with sound teaching and learning practice as well as curriculum design and implementation skills, Queensland University of Technology (QUT) successfully tendered an international grant. One of QUT’s initiatives in educating the Vietnamese academics was a distance learning programme. Developed specifically for Vietnamese nurse academics, the programme was designed for Australian based delivery to academics in Vietnam. This paper will present an overview of why four separate modules were utilised for the delivery of content (modules were delivered at a rate of one per semester). It will address bilingual online discussion boards which were used in each of the modules and the process of moderating these given comments were posted in both Vietnamese and English. It will describe how content was scaffolded across four modules and how the modules themselves modelled new teaching delivery strategies. Lastly, it will discuss the considerations of programme delivery given the logistics of an Australian based delivery. Feedback from the Vietnamese nurse academics across their involvement in the programme (and at the conclusion of their fourth and final module) has been overwhelmingly positive. Feedback suggests the programme has altered teaching and assessment approaches used by some Vietnamese nurse academics. Additionally, Vietnamese nurse academics are reporting that they are engaging more with the application of their content indicating a cultural shift in the approach taken in Vietnamese nurse education.

Polycaprolactone-based scaffold plus recombinant human bone morphogenic protein rhBMP-2) in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. The resulting spinal deformity consists of coronal curvature, hypokyphosis of the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral (IV) discs have been surgically cleared and the disc spaces filled with graft material. Recently a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone has been developed for bone regeneration at load bearing sites. Combined with rhBMP-2, this has been shown to be successful in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft alone. The study aimed to establish a large animal thoracic spine interbody fusion model, develop spine biodegradable scaffolds (PCL) in combination with biologics (rhBMP-2) and to establish a platform for research into spine tissue engineering constructs. Preliminary results demonstrate higher grades of radiologically evident bony fusion across all levels when comparing fusion scores between the 3 and 6 month postop groups at the PCL CaP coated scaffold level, which is observed to be a similar grade to autograft, while no fusion is seen at the scaffold only level. Results to date suggest that the combination of rhBMP-2 and scaffold engineering actively promotes bone formation, laying the basis of a viable tissue engineered constructs.

The use of hypnosis in labor and delivery : a preliminary study

Self-hypnosis was taught to 87 obstetric patients (HYP) and was not taught to 56 other patients (CNTRL), all delivered by the same family physician, in order to determine whether the use of self-hypnosis by low-risk obstetric patients leads to fewer technologic interventions during their deliveries or greater satisfaction of parturients with their delivery experience or both. The outcomes of the deliveries of these two groups were compared, and the HYP group was compared to 352 low-risk patients delivered by other family physicians at the same hospital (WCH). Questionnaires were mailed postpartum to 156 patients, all delivered by the same family physician, to determine satisfaction with delivery using the Labor and Delivery Satisfaction Index (LADSI). The hypnosis group showed a significant reduction in the number of epidurals (11.4% less than CNTRL and 17.9% less than WCH, p < 0.05) and the use of intravenous lines (18.5% less for both, p < 0.05). The number of episiotomies was significantly less in the HYP group compared to WCH (15.9%, p < 0.05) and 11.5% less when compared to CNTRL. The tear rate was not statistically different. Combined use of the intervention triad (epidural–forceps–episiotomy) was less for HYP than for CNTRL (15.8% less) and WCH (10.2% less, p < 0.05). More deliveries were done in the labor room with HYP than CNTRL (21%, p < 0.05). The second stage was shortened by 10 min (HYP vs CNTRL). Overall satisfaction of HYP and CNTRL patients was similar and generally favorable.

Spatial and temporal foraging patterns of Queensland fruit fly, Bactrocera tryoni(Froggatt) (Diptera: Tephritidae), for protein and implications for management

Fruit flies require protein for reproductive development and actively feed upon protein sources in the field. Liquid protein baits mixed with insecticide are used routinely to manage pest fruit flies, such as Bactrocera tryoni (Froggatt). However, there are still some gaps in the underpinning science required to improve the efficacy of bait spray technology. The spatial and temporal foraging behaviour of B. tryoni in response to protein was investigated in the field. A series of linked trials using either wild flies in the open field or laboratory-reared flies in field cages and a netted orchard were undertaken using nectarines and guavas. Key questions investigated were the fly's response to protein relative to: height of protein within the canopy, fruiting status of the tree, time of day, season and size of the experimental arena. Canopy height had a significant response on B. tryoni foraging, with more flies foraging on protein in the mid to upper canopy. Fruiting status also had a significant effect on foraging, with most flies responding to protein when applied to fruiting hosts. B. tryoni demonstrated a repeatable diurnal response pattern to protein, with the peak response being between 12:00–16:00 h. Season showed significant but unpredictable effects on fruit fly response to protein in the subtropical environment where the work was undertaken. Relative humidity, but not temperature or rainfall, was positively correlated with protein response. The number of B. tryoni responding to protein decreased dramatically as the spatial scale increased from field cage through to the open field. Based on these results, it is recommend that, to be most effective, protein bait sprays should be applied to the mid to upper canopies of fruiting hosts. Overall, the results show that the protein used, an industry standard, has very low attractancy to B. tryoni and that further work is urgently needed to develop more volatile protein baits.

An ensemble method for predicting subnuclear localizations from primary protein structures

Background Predicting protein subnuclear localization is a challenging problem. Some previous works based on non-sequence information including Gene Ontology annotations and kernel fusion have respective limitations. The aim of this work is twofold: one is to propose a novel individual feature extraction method; another is to develop an ensemble method to improve prediction performance using comprehensive information represented in the form of high dimensional feature vector obtained by 11 feature extraction methods. Methodology/Principal Findings A novel two-stage multiclass support vector machine is proposed to predict protein subnuclear localizations. It only considers those feature extraction methods based on amino acid classifications and physicochemical properties. In order to speed up our system, an automatic search method for the kernel parameter is used. The prediction performance of our method is evaluated on four datasets: Lei dataset, multi-localization dataset, SNL9 dataset and a new independent dataset. The overall accuracy of prediction for 6 localizations on Lei dataset is 75.2% and that for 9 localizations on SNL9 dataset is 72.1% in the leave-one-out cross validation, 71.7% for the multi-localization dataset and 69.8% for the new independent dataset, respectively. Comparisons with those existing methods show that our method performs better for both single-localization and multi-localization proteins and achieves more balanced sensitivities and specificities on large-size and small-size subcellular localizations. The overall accuracy improvements are 4.0% and 4.7% for single-localization proteins and 6.5% for multi-localization proteins. The reliability and stability of our classification model are further confirmed by permutation analysis. Conclusions It can be concluded that our method is effective and valuable for predicting protein subnuclear localizations. A web server has been designed to implement the proposed method. It is freely available at http://bioinformatics.awowshop.com/snlpr​ed_page.php.

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically

Extending services delivery with lightweight composition

The tertiary sector is an important employer and its growth is well above average. The Texo project’s aim is to support this development by making services tradable. The composition of new or value-added services is a cornerstone of the proposed architecture. It is, however, intended to cater for build-time. Yet, at run-time unforseen exceptions may occur and user’s requirements may change. Varying circumstances require immediate sensemaking of the situation’s context and call for prompt extensions of existing services. Lightweight composition technology provided by the RoofTop project enables domain experts to create simple widget-like applications, also termed enterprise mashups, without extensive methodological skills. In this way RoofTop can assist and extend the idea of service delivery through the Texo platform and is a further step towards a next generation internet of services.

A comparative study of governmental one-stop portals for public service delivery

The continuing need for governments to radically improve the delivery of public services has led to a new, holistic government reform strategy labeled “Transformational Government” that strongly emphasizes customer-centricity. Attention has turned to online portals as a cost effective front-end to deliver services and engage customers as well as to the corresponding organizational approaches for the back-end to decouple the service interface from the departmental structures. The research presented in this paper makes three contributions: Firstly, a systematic literature review of approaches to the evaluation of online portal models in the public sector is presented. Secondly, the findings of a usability study comparing the online presences of the Queensland Government, the UK Government and the South Australian Government are reported and the relative strengths and weaknesses of the different approaches are discussed. And thirdly, the limitations of the usability study in the context of a broader “Transformational Government” approach are identified and service bundling is suggested as an innovative solution to further improve online service delivery.

Advanced Bioactive Inorganic Materials for Bone Regeneration and Drug Delivery

Bioceramics play an important role in repairing and regenerating bone defects. Annually, more than 500,000 bone graft procedures are performed in the United states and approximately 2.2 million are conducted worldwide. The estimated cost of these procedures approaches $2.5billion per year. Around 60% of the bone graft substitutes available on the market involve bioceramics. It is reported that bioceramics in the world market increase by 9% per year. For this reason, the research of bioceramics has been one of the most active areas during, the past several years. Considering the significant importance of bioceramics, our goal was to compile this book to review the latest research advances in the field of bioceramics. The text also summarizes our work during the past 10 years in an effort to share innovative concepts, design of bioceramisc, and methods for material synthesis and drug delivery. We anticipate that this text will provide some useful information and guidance in the bioceramics field for biomedical engineering researchers and material scientists. Information on novel mesoporous bioactive glasses and silicate-based ceramics for bone regeneration and drug delivery are presented. Mesoporous bioactive glasses have shown multifunctional characteristics of bone regeneration and drug delivery due to their special mesopore structures,whereas silicated-based bioceramics, as typical third-generation biomaterials,possess significant osteostimulation properties. Silica nanospheres with a core-shell structure and specific properties for controllable drug delivery have been carefully reviewed-a variety of advanced synthetic strategies have been developed to construct functional mesoporous silica nanoparticles with a core-shell structure, including hollow, magnetic, or luminescent, and other multifunctional core-shell mesoporous silica nanoparticles. In addition, multifunctional drug delivery systems based on these nanoparticles have been designed and optimized to deliver the drugs into the targeted organs or cells,with a controllable release fashioned by virtue of various internal and external triggers. The novel 3D-printing technique to prepare advanced bioceramic scaffolds for bone tissue engineering applications has been highlighted, including the preparation, mechanical strength, and biological properties of 3D-printed porous scaffolds of calcium phosphate cement and silicate bioceramics. Three-dimensional printing techniques offer improved large-pore structure and mechanical strength. In addition , biomimetic preparation and controllable crystal growth as well as biomineralization of bioceramics are summarized, showing the latest research progress in this area. Finally, inorganic and organic composite materials are reviewed for bone regeneration and gene delivery. Bioactive inorganic and organic composite materials offer unique biological, electrical, and mechanical properties for designing excellent bone regeneration or gene delivery systems. It is our sincere hope that this book will updated the reader as to the research progress of bioceramics and their applications in bone repair and regeneration. It will be the best reward to all the contributors of this book if their efforts herein in some way help reader in any part of their study, research, and career development.

Modelling, collaboration and integration : a case study for the delivery of public buildings

An evolution in the use of digital modelling has occurred in the Queensland Department of Public Works Division of Project Services over the last 20 years from: the initial implementation of computer aided design and documentation (CADD); to experimentation with building information modelling (BIM); to embedding integrated practice (IP); to current steps towards integrated project delivery (IPD) including the active involvement of consultants and contractors in the design/delivery process. This case study is one of three undertaken through the Australian Sustainable Built Environment National Research Centre investigating past R&D investment. The intent of these cases is to inform the development of policy guidelines for future investment in the construction industry in Australia. This research is informing the activities of CIB Task Group 85 R&D Investment and Impact. The uptake of digital modelling by Project Services has been approached through an incremental learning approach. This has been driven by a strong and clear vision with a focus on developing more efficient delivery mechanisms through the use of new technology coupled with process change. Findings reveal an organisational focus on several areas including: (i) strategic decision making including the empowerment of innovation leaders and champions; (ii) the acquisition and exploitation of knowledge; (iii) product and process development (with a focus on efficiency and productivity); (iv) organisational learning; (v) maximising the use of technology; and (vi) supply chain integration. Key elements of this approach include pilot projects, researcher engagement, industry partnerships and leadership.