Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4

The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1.

Human single-stranded DNA binding proteins are essential for maintaining genomic stability

The double-stranded conformation of cellular DNA is a central aspect of DNA stabilisation and protection. The helix preserves the genetic code against chemical and enzymatic degradation, metabolic activation, and formation of secondary structures. However, there are various instances where single-stranded DNA is exposed, such as during replication or transcription, in the synthesis of chromosome ends, and following DNA damage. In these instances, single-stranded DNA binding proteins are essential for the sequestration and processing of single-stranded DNA. In order to bind single-stranded DNA, these proteins utilise a characteristic and evolutionary conserved single-stranded DNA-binding domain, the oligonucleotide/oligosaccharide-binding (OB)-fold. In the current review we discuss a subset of these proteins involved in the direct maintenance of genomic stability, an important cellular process in the conservation of cellular viability and prevention of malignant transformation. We discuss the central roles of single-stranded DNA binding proteins from the OB-fold domain family in DNA replication, the restart of stalled replication forks, DNA damage repair, cell cycle-checkpoint activation, and telomere maintenance.

The association of early life supplemental nutrition with lean body mass and grip strength in adulthood : evidence from APCAPS

In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants’ LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)2; mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (β = −0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a “programming” effect of early nutrition supplementation on adult LBM and muscle strength.

The structural basis of DNA binding by the single-stranded DNA-binding protein from Sulfolobus solfataricus

Canonical single-stranded DNA-binding proteins (SSBs) from the oligosaccharide/oligonucleotide-binding (OB) domain family are present in all known organisms and are critical for DNA replication, recombination and repair. The SSB from the hyperthermophilic crenarchaeote Sulfolobus solfataricus (SsoSSB) has a ‘simple’ domain organization consisting of a single DNA-binding OB fold coupled to a flexible C-terminal tail, in contrast with other SSBs in this family that incorporate up to four OB domains. Despite the large differences in the domain organization within the SSB family, the structure of the OB domain is remarkably similar all cellular life forms. However, there are significant differences in the molecular mechanism of ssDNA binding. We have determined the structure of the SsoSSB OB domain bound to ssDNA by NMR spectroscopy. We reveal that ssDNA recognition is modulated by base-stacking of three key aromatic residues, in contrast with the OB domains of human RPA and the recently discovered human homologue of SsoSSB, hSSB1. We also demonstrate that SsoSSB binds ssDNA with a footprint of five bases and with a defined binding polarity. These data elucidate the structural basis of DNA binding and shed light on the molecular mechanism by which these ‘simple’ SSBs interact with ssDNA.

Making connections within the Asia-Pacific region: Case study around the Mentoring for Effective Teaching (MET) program

University strategic plans emphasise the essential nature of partnerships at national and international levels. Along with establishing collaborative research partnerships, providing professional development to key stakeholders is considered a crucial activity for making and sustaining partnerships. Utilising knowledge from professional development in Australian contexts can be managed creatively for making connections internationally. Indeed, knowledge transfer is a cornerstone for the globalisation of education and needs to occur as a multiplex dialogue between participating countries. This paper presents a qualitative study around the Mentoring for Effective Teaching (MET) program, its growth and development nationally (e.g., scope and impact) along with insights into making connections within the Asia-Pacific region. At a national level, we outline how to facilitate a program though relationship building and face-to-face implementation of professional learning. Internationally, we highlight how to mould and shape Australian professional learning for the Asia-Pacific region, particularly with regard to facilitating fluid interactions within environments outside of Australia. The contexts for the study include a university in Hong Kong and another university in the Philippines. In this presentation, examples will be provided from the MET program to demonstrate contextual differences and similarities for implementation in Australian and Asian contexts. For instance, determining strategies for mentoring pedagogical knowledge can elicit viewpoints that align between cultures (e.g., use of specific teaching and questioning strategies) and also present alternative ideas as a result of cultural differences. We have learnt about having a structured program that draws on the research yet has sufficient flexibility to cater for cultures and contexts. With openmindedness, facilitating professional learning can become a two-way knowledge transfer, where learnings from other cultures and contexts can be refined for advancing programs in Australia.

Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification

The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80+Mac-2+) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80+Mac-2neg), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window...

Life-course determinants of bone mass in young adults from a transitional rural community in India: The Andhra Pradesh Children and Parents Study (APCAPS)

Background: Undernutrition and physical inactivity are both associated with lower bone mass. Objective: This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development. Design: This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987–1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009–2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18–23 y). Results: Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm2; lumbar spine: 0.86 (women), 0.93 (men) g/cm2]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories. Conclusions: Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage.

hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway

The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is the most frequent modification. Previous studies have established that human single-stranded DNA-binding protein 1 (hSSB1) is essential for the repair of double-stranded DNA breaks by the process of homologous recombination. Here we show that hSSB1 is also required following oxidative damage. Cells lacking hSSB1 are sensitive to oxidizing agents, have deficient ATM and p53 activation and cannot effectively repair 8-oxoGs. Furthermore, we demonstrate that hSSB1 forms a complex with the human oxo-guanine glycosylase 1 (hOGG1) and is important for hOGG1 localization to the damaged chromatin. In vitro, hSSB1 binds directly to DNA containing 8-oxoguanines and enhances hOGG1 activity. These results underpin the crucial role hSSB1 plays as a guardian of the genome.

Nutrition in remote Aboriginal communities: Lessons from Mai Wiru and the Anangu Pitjantjatjara Yankunytjatjara Lands

Objective To examine the impact of efforts to improve nutrition on the Anangu Pitjantjatjara Yankunytjatjara (APY) Lands from 1986, especially in Mai Wiru stores. Methods Literature was searched in a systematic manner. In 2012, the store-turnover method was used to quantify dietary intake of the five APY communities that have a Mai Wiru (good food) store. Results were compared with those available from 1986. Prices of a standard market basket of basic foods, implementation of nutrition policy requirements and healthy food checklists were also assessed in all seven APY community stores from 2008 and compared with available data from 1986. Results Despite concerted efforts and achievements decreasing intake of sugar and increasing the availability and affordability of healthy foods, particularly fruit and vegetables, and consequent improvements in some nutrient indicators, the overall effect has been a decrease in diet quality as indicated primarily by the increased supply and proportion of energy intake from discretionary foods, particularly sugar-sweetened beverages, convenience meals and take-away foods. Conclusions The study findings reinforce the notion that, in the absence of supportive regulation and market intervention, adequate and sustained resources are required to improve nutrition and prevent diet-related chronic disease on the APY Lands. Implications This study also provides insights into food supply/security issues affecting other remote Aboriginal communities and wider Australia.

Australia’s first Allied Health Prescribing Program - exploring participants' perspectives on the study program's learning objectives

BACKGROUND The Queensland University of Technology in collaboration with Queensland Health pioneered development of the Allied Health Prescribing Training Program to assist allied health professionals (AHPs) to competently prescribe medicines within their scope of practice. The study program consisted of two modules: Introduction to Clinical Therapeutics for Prescribers and Prescribing and Quality Use of Medicines. METHODS Pre- and post- surveys were developed for both modules. Key themes explored were understanding and confidence in selecting therapeutic choices for patients. For module 2 the learning objectives for safe and effective prescribing were investigated. Data were collected from participants in weeks one and thirteen of the modules via online surveys. RESULTS In the pre-module survey for the first module, participants had a limited degree of understanding and confidence regarding safe and effective use of medicines and appropriate therapeutic choices for managing patients, particularly for complex patients. This improved significantly in the post-module survey. In the pre-module survey for module 2, participants had a moderate degree of understanding and confidence regarding various prescribing learning objectives (including safe and effective prescribing, professional, legal and ethical aspects, communicating medication orders, prescribing safely in their select areas of practice, prescribing safely for complex patients in their area of practice). This increased significantly in the post-module survey. DISCUSSION This training program was implemented to develop a framework of knowledge and skills for AHPs to undertake a prescribing role. The program delivered an increase in participants’ knowledge in the key prescribing areas; and increased participants’ confidence in prescribing safely for patients and for complex patients in their select practice areas. An important aspect of this program was inclusion of prescribing–related activities under supervision of a designated medical practitioner. In conclusion, this educational program for Queensland Health AHP prescribers was successfully developed and is in the final stages of delivery.

The polycomb group gene EMF2B is essential for maintenance of floral meristem determinacy in rice

Polycomb Repressive Complex 2 (PRC2) represses the transcriptional activity of target genes through trimethylation of lysine 27 of histone H3. The functions of plant PRC2 have been chiefly described in Arabidopsis, but specific functions in other plant species, especially cereals, are still largely unknown. Here we characterize mutants in the rice EMF2B gene, an ortholog of the Arabidopsis EMBRYONIC FLOWER2 (EMF2) gene. Loss of EMF2B in rice results in complete sterility, and mutant flowers have severe floral organ defects and indeterminacy that resemble loss-of-function mutants in E-function floral organ specification genes. Transcriptome analysis identified the E-function genes OsMADS1, OsMADS6 and OsMADS34 as differentially expressed in the emf2b mutant compared with wild type. OsMADS1 and OsMADS6, known to be required for meristem determinacy in rice, have reduced expression in the emf2b mutant, whereas OsMADS34 which interacts genetically with OsMADS1 was ectopically expressed. Chromatin immunoprecipitation for H3K27me3 followed by quantitative (q)RT-PCR showed that all three genes are presumptive targets of PRC2 in the meristem. Therefore, in rice, and possibly other cereals, PRC2 appears to play a major role in floral meristem determinacy through modulation of the expression of E-function genes.

Recruitment pattern and fish production within the Andoni River system in the Niger Delta of Nigeria

Biweekly samples of fish species obtained from five randomly selected Andoni artisanal fisheries within the Andoni River system, Niger Delta of Nigeria were collected between January and December 1999 and their length frequencies analyzed using FISAT (FAO-ICLARM STOCK ASSESSMENT TOOL). The peak recruitment period for Chrysichthys nigrodigitatus, Ethmalosa fimbriata, Eucinostomus melanopterus, Galeodes decadactylus, Pomadasys jubelini and Sarotherodon melanotheron constituting 54.55% was between June and October while Liza grandisquamis and Lutjanus goreensis, Ilisha Africana. Tilapia guinensis and Pseudotolithus elongate constituting 27.27% had two peak recruitment periods including March-May and May- October. In view of this result it is advisable for fishers to intensify fishing effort between May and October for most commercially important fish species for bountiful harvest

Arctic charr from Ennerdale Water: a pilot study

There are three fish species in the north west of England, Arctic charr (Salvelinus alpinus, L.), schelly (Coreqonus lavaretus. L.), and vendace (C. albula, L.), which have been reported as rare and vulnerable and have been identified as requiring the preparation and implementation of a conservation management plan. The presence of Arctic charr in Ennerdale Water has resulted in it being designated as a Site of Special Scientific Interest. These fish and one race of the species in Lake Windermere are the only English populations of charr known to spawn in running water. Associated with Ennerdale charr is the copepod parasite Salmincola edwardsii which has not been recorded from any other charr inhabited waters of the Lake District. However, it has been recorded on charr from four Scottish Lochs (Stack, Lee, Tay and Doon). The unique nature of Ennerdale is further highlighted by the presence of two crustaceans, Mysis relicta and Limnocalanus macrurus. The former has been recorded in Ireland while the latter is not known to exist anywhere else in the British Isles. The aim of this pilot study was to obtain baseline data on charr that spawn in Smithy Beck and the River Liza. This would indicate the current status of the population and help identify areas requiring further investigation. A total of 161 fish (95 males and 66 females) was caught and tagged over the 3 day period, 141 from Smithy Beck and 20 from the Liza. The raw data of the findings is presented in two appendices.

Arctic charr from Ennerdale water - relicts of the ice age

The work discussed in this report deals with aspects of the ecology of Arctic charr (Salvelinus alpinus, L.). The main aims of the study were: (1) To assess the relative abundance of migrants entering the River Liza and Smithy Beck in the English Lake District). (2) To assess the degree of stream specificity. (3) To determine the period of residency in the streams. (4) To obtain a better understanding of migratory behaviour. (5) To determine the growth rate of mature fish. (6) To determine the morphometric and meristic attributes. In conjunction with this work a study was carried out to investigate the feasibility of using a video recording system to monitor the migration of charr in Smithy Beck.

Collection of juvenile mullet species from a brackishwater tidal farm in Nigeria

The major constraint to the development of aquaculture in Nigeria has been the non-availability of fingerlings in required numbers of cultivable species. A specifically designed trap to collect mullet (Liza falcipinnis; Liza grandisquamis) juveniles during high tides was successful in collecting juveniles year-round. The collectors was more successful during night spring tides than during neap tides or daytime collections. Thus, the use of traps, especially in the tidal zones, could provide a cost-effective method of stocking fish farms by collecting juveniles and seed from the natural environment.