Human neural cell interactions with orientated electrospun nanofibers in vitro

Aim: Electrospun nanofibers represent potent guidance substrates for nervous tissue repair. Development of nanofiber-based scaffolds for CNS repair requires, as a first step, an understanding of appropriate neural cell type-substrate interactions. Materials & methods: Astrocyte–nanofiber interactions (e.g., adhesion, proliferation, process extension and migration) were studied by comparing human neural progenitor-derived astrocytes (hNP-ACs) and a human astrocytoma cell line (U373) with aligned polycaprolactone (PCL) nanofibers or blended (25% type I collagen/75% PCL) nanofibers. Neuron–nanofiber interactions were assessed using a differentiated human neuroblastoma cell line (SH-SY5Y). Results & discussion: U373 cells and hNP-AC showed similar process alignment and length when associated with PCL or Type I collagen/PCL nanofibers. Cell adhesion and migration by hNP-AC were clearly improved by functionalization of nanofiber surfaces with type I collagen. Functionalized nanofibers had no such effect on U373 cells. Another clear difference between the U373 cells and hNP-AC interactions with the nanofiber substrate was proliferation; the cell line demonstrating strong proliferation, whereas the hNP-AC line showed no proliferation on either type of nanofiber. Long axonal growth (up to 600 µm in length) of SH-SY5Y neurons followed the orientation of both types of nanofibers even though adhesion of the processes to the fibers was poor. Conclusion: The use of cell lines is of only limited predictive value when studying cell–substrate interactions but both morphology and alignment of human astrocytes were affected profoundly by nanofibers. Nanofiber surface functionalization with collagen significantly improved hNP-AC adhesion and migration. Alternative forms of functionalization may be required for optimal axon–nanofiber interactions.

Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes

OBJECTIVE: Childhood-onset type 1 diabetes is associated with neurocognitive deficits, but there is limited evidence to date regarding associated neuroanatomical brain changes and their relationship to illness variables such as age at disease onset. This report examines age-related changes in volume and T2 relaxation time (a fundamental parameter of magnetic resonance imaging that reflects tissue health) across the whole brain. RESEARCH DESIGN AND METHODS: Type 1 diabetes, N = 79 (mean age 20.32 ± 4.24 years), and healthy control participants, N = 50 (mean age 20.53 ± 3.60 years). There were no substantial group differences on socioeconomic status, sex ratio, or intelligence quotient. RESULTS: Regression analyses revealed a negative correlation between age and brain changes, with decreasing gray matter volume and T2 relaxation time with age in multiple brain regions in the type 1 diabetes group. In comparison, the age-related decline in the control group was small. Examination of the interaction of group and age confirmed a group difference (type 1 diabetes vs. control) in the relationship between age and brain volume/T2 relaxation time. CONCLUSIONS: We demonstrated an interaction between age and group in predicting brain volumes and T2 relaxation time such that there was a decline in these outcomes in type 1 diabetic participants that was much less evident in control subjects. Findings suggest the neurodevelopmental pathways of youth with type 1 diabetes have diverged from those of their healthy peers by late adolescence and early adulthood but the explanation for this phenomenon remains to be clarified.

A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival. Results In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319). In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR) 1.42, 95% CI 1.02-1.96). This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34). This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site. Conclusions We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival.

Regional integration 2.0 : facilitating regional integration and development with collaborative technologies

The current global economic instability and the vulnerability of small nations provide the impetus for greater integration between the countries of the South Pacific region. This exercise is critical for their survival. Past efforts of regional integration in the South Pacific have mostly failed. However, today’s IT collaborative capabilities provide the opportunity to develop a shared IT infrastructure to facilitate integration in the South Pacific. In developing an IT-backed model of regional integration, this study identifies and reports on the antecedents of the current stage for integration in the Pacific. We conducted interviews with twenty five individuals from various sectors and find that while most respondents were optimistic about the potential of IT-backed regional integration, significant challenges exists. The study identifies and discusses these challenges providing policy implications to stakeholders in the regional integration process. The findings will assist in suggesting a model of regional integration 2.0 for the Pacific region.

Positive emotional experiences with portable interactive products

Positive emotions are central to human life and have implications to the overall quality of people's life (Fredrickson, 1998). This paper reports on positive experiences with two types of portable interactive devices (PIDs), specifically media/entertainment and medical/health devices. The study is based on a six-month longitudinal study exploring people's emotional experience and how PIDs mediate these experiences in everyday contexts. Previous findings by the authors (Gomez, Popovic & Blackler, 2011) presented four categories of activities including Feature, Functional, Mediation and Auxiliary activities and their relationship to emotional experience. The paper presents emotional experiences with specific activities reported with a focus on positive emotions. It concludes with a discussion of the findings on positive experiences and the implications for the future design of PIDs.

“Yarning” as a method for community-based health research with indigenous women : the indigenous women's wellness research program

This project explores yarning as a methodology for understanding health and wellness from an indigenous woman's perspective. Previous research exploring indigenous Australian women's perspectives have used traditional Western methodologies and have often been felt by the women themselves to be inappropriate and ineffective in gathering information and promoting discussion. This research arose from the indigenous women themselves, and resulted in the exploration of using yarning as a methodology. Yarning is a conversational process that involves the sharing of stories and the development of knowledge. It prioritizes indigenous ways of communicating, in that it is culturally prescribed, cooperative, and respectful. The authors identify different types of yarning that are relevant throughout their research, and explain two types of yarning—family yarning and cross-cultural yarning—which have not been previously identified in research literature. This project found that yarning as a research method is appropriate for community-based health research with indigenous Australian women. This may be an important finding for health professionals and researchers to consider when working and researching with indigenous women from other countries.

Molecular cocrystals of 5-(4-bromophenyl)-1,3,4-thiadiazol-2-amine: hydrogen bonding in the structures of the 1:1 adduct with 2-(naphthalen-2-yloxy)acetic acid and the salt with 3,5-dinitrobenzoic acid

The structures of the anhydrous products from the interaction of 2-amino-5-(4-bromophenyl)-1,3,4-thiadiazole with (2-naphthoxy)acetic acid, the 1:1 adduct C8H6BrN3S . C12H10O3 (I) and 3,5-dinitrobenzoic acid, the salt C8H7BrN3S+ C7H3N2O6- (II) have been determined. In the adduct (I), a heterodimer is formed through a cyclic hydrogen-bonding motif [graph set R2/2(8)], involving carboxylic acid O-H...N(hetero)and amine N-H...O(carboxyl) interactions. The heterodimers are essentially planar with a thiadiazole to naphthyl ring dihedral angle of 15.9(2)deg. and the intramolecular thiadiazole to phenyl ring angle of 4.7(2)deg. An amine N-H...N(hetero) hydrogen bond between the heterodimers generates a one-dimensional chain structure extending down [001]. Also present are weak benzene-benzene and naphthalene-naphthalene pi-pi stacking interactions down the b axis [minimum ring centroid separation, 3.936(3) Ang.]. With the salt (II), the cation-anion association is also through a cyclic R2/2(8) motif but involving duplex N-H...O(carboxyl) hydrogen bonds, giving a heterodimer which is close to planar [dihedral angles between the thiadiazole ring and the two benzene rings, 5.00(16)deg. (intra) and 7.23(15)deg. (inter)]. A secondary centrosymmetric cyclic N-H...O(carboxyl) hydrogen-bonding association involving the second amino H-atom generates a heterotetramer. Also present in the crystal are weak pi-pi i-\p interactions between thiadiazolium rings [minimum ring centroid separation, 3.936(3)Ang.], as well as a short Br...O(nitro) interaction [3.314(4)Ang.]. The two structures reported here now provide a total of three crystallographically characterized examples of co-crystalline products from the interaction of 2-amino-5-(4-bromophenyl)-1,3,4-thiadiazole with carboxylic acids, of which only one involves proton-transfer.

Lattice-free descriptions of collective motion with crowding and adhesion

Cell-to-cell adhesion is an important aspect of malignant spreading that is often observed in images from the experimental cell biology literature. Since cell-to-cell adhesion plays an important role in controlling the movement of individual malignant cells, it is likely that cell-to-cell adhesion also influences the spatial spreading of populations of such cells. Therefore, it is important for us to develop biologically realistic simulation tools that can mimic the key features of such collective spreading processes to improve our understanding of how cell-to-cell adhesion influences the spreading of cell populations. Previous models of collective cell spreading with adhesion have used lattice-based random walk frameworks which may lead to unrealistic results, since the agents in the random walk simulations always move across an artificial underlying lattice structure. This is particularly problematic in high-density regions where it is clear that agents in the random walk align along the underlying lattice, whereas no such regular alignment is ever observed experimentally. To address these limitations, we present a lattice-free model of collective cell migration that explicitly incorporates crowding and adhesion. We derive a partial differential equation description of the discrete process and show that averaged simulation results compare very well with numerical solutions of the partial differential equation.

On the importance of an acid additive in the synthesis of pyrido[1,2-a]benzimidazoles by direct copper-catalyzed amination

Pyrido[1,2-a]benzimidazoles1, 2a are interesting compounds both from the viewpoint of medicinal chemistry2–7 (solubility,7 DNA intercalation3) and materials chemistry8 (fluorescence). Of note among the former is the antibiotic drug Rifaximin,5 which contains this heteroaromatic core. The classical synthetic approach for the assembly of pyrido[1,2-a]benzimidazoles is by [3+3] cyclocondensation of benzimidazoles containing a methylene group at C2 with appropriate bielectrophiles.2a However, these procedures are often low-yielding, involve indirect/lengthy sequences, and/or provide access to a limited range of products, primarily providing derivatives with substituents located on the pyridine ring (A ring, Scheme 1).2–4 Theoretically, a good alternative synthetic method for the synthesis of pyrido[1,2-a]benzimidazoles with substituents in the benzene ring (C ring) should be accessible by intramolecular transition-metal-catalyzed CN bond formation in N-(2-chloroaryl)pyridin-2-amines, based on chemistry recently developed in our research group.9 These substrates themselves are easily available through SNAr or selective Pd-catalyzed amination10 of 2-chloropyridine with 2-chloroanilines.11 If a synthetic procedure that eliminated the need for preactivation of the 2-position of the 2-chloroarylamino entity could be developed, this would be even more powerful, as anilines are more readily commercially available than 2-chloroanilines. Therefore the synthesis of pyrido[1,2-a]benzimidazoles (4) by a transition-metal-catalyzed intramolecular CH amination approach from N-arylpyridin-2-amines (3) was explored (Scheme 1).

Designing mixed species tree plantations for the tropics : balancing ecological attributes of species with landholder preferences in the Philippines

A mixed species reforestation program known as the Rainforestation Farming system was undertaken in the Philippines to develop forms of farm forestry more suitable for smallholders than the simple monocultural plantations commonly used then. In this study, we describe the subsequent changes in stand structure and floristic composition of these plantations in order to learn from the experience and develop improved prescriptions for reforestation systems likely to be attractive to smallholders. We investigated stands aged from 6 to 11 years old on three successive occasions over a 6 year period. We found the number of species originally present in the plots as trees >5 cm dbh decreased from an initial total of 76 species to 65 species at the end of study period. But, at the same time, some new species reached the size class threshold and were recruited into the canopy layer. There was a substantial decline in tree density from an estimated stocking of about 5000 trees per ha at the time of planting to 1380 trees per ha at the time of the first measurement; the density declined by a further 4.9% per year. Changes in composition and stand structure were indicated by a marked shift in the Importance Value Index of species. Over six years, shade-intolerant species became less important and the native shade-tolerant species (often Dipterocarps) increased in importance. Based on how the Rainforestation Farming plantations developed in these early years, we suggest that mixed-species plantations elsewhere in the humid tropics should be around 1000 trees per ha or less, that the proportion of fast growing (and hence early maturing) trees should be about 30–40% of this initial density and that any fruit tree component should only be planted on the plantation margin where more light and space are available for crowns to develop.

Fun with Fibonacci

We introduce a function which measures the number of distinct ways in which a number can be expressed as the sum of Fibonacci numbers. Using a binary table and other devices, we explore the values that can take and reveal some interesting patterns. The article shows how standard spreadsheet functionalities make it possible to reveal quite striking patterns in data, and is intended to be used in the classroom.

The quik fix study : a randomised controlled trial of brief interventions for young people with alcohol-related injuries and illnesses accessing emergency department and crisis support care

Background: Alcohol is a major preventable cause of injury, disability and death in young people. Large numbers of young people with alcohol-related injuries and medical conditions present to hospital emergency departments (EDs). Access to brief, efficacious, accessible and cost effective treatment is an international health priority within this age group. While there is growing evidence for the efficacy of brief motivational interviewing (MI) for reducing alcohol use in young people, there is significant scope to increase its impact, and determine if it is the most efficacious and cost effective type of brief intervention available. The efficacy of personality-targeted interventions (PIs) for alcohol misuse delivered individually to young people is yet to be determined or compared to MI, despite growing evidence for school-based PIs. This study protocol describes a randomized controlled trial comparing the efficacy and cost-effectiveness of telephone-delivered MI, PI and an Assessment Feedback/Information (AF/I) only control for reducing alcohol use and related harm in young people. Methods/design: Participants will be 390 young people aged 16 to 25 years presenting to a crisis support service or ED with alcohol-related injuries and illnesses (including severe alcohol intoxication). This single blinded superiority trial randomized young people to (i) 2 sessions of MI; (ii) 2 sessions of a new PI or (iii) a 1 session AF/I only control. Participants are reassessed at 1, 3, 6 and 12 months on the primary outcomes of alcohol use and related problems and secondary outcomes of mental health symptoms, functioning, severity of problematic alcohol use, alcohol injuries, alcohol-related knowledge, coping self-efficacy to resist using alcohol, and cost effectiveness. Discussion: This study will identify the most efficacious and cost-effective telephone-delivered brief intervention for reducing alcohol misuse and related problems in young people presenting to crisis support services or EDs. We expect efficacy will be greatest for PI, followed by MI, and then AF/I at 1, 3, 6 and 12 months on the primary and secondary outcome variables. Telephone-delivered brief interventions could provide a youth-friendly, accessible, efficacious, cost-effective and easily disseminated treatment for addressing the significant public health issue of alcohol misuse and related harm in young people. Trial registration: This trial is registered with the Australian and New Zealand Clinical Trials Registry ACTRN12613000108718.

Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure. Results Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope. Conclusions Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.

Rheumatoid arthritis sera react with a phage-displayed peptide selected by a monoclonal antibody to type II collagen that has homology to EBNA-1

Antibodies to type II collagen, and to Epstein Barr virus nuclear antigen-1 (EBNA-1) have been associated with rheumatoid arthritis (RA). In studies involving probing of phage-displayed random peptide libraries with an antibody to type II collagen, CII-C1, we observed that among 17 phagotopes selected 5 expressed peptides with homology with the sequence of EBNA-1. The residues in common were RLPFG. Hence we tested sera from 50 patients with RA, of whom 26 had antibodies to native type II collagen, and 43 healthy controls, for reactivity by ELISA with a phagotope selected 4 times, which expressed the peptide RRLPFGSQM. Eight RA sera (16%) but no normal sera reacted with the phagotope (p = 0.025). This reactivity could not be correlated with reactivity of RA sera with EBNA-1 by semi-quantitative western blot, with which reactivity occurred in 78% of RA patients and 81% of controls. Evidence for molecular mimicry was not found insofar as the phagotope did not inhibit reactivity of RA sera with EBNA-1 and CII-C1 was not reactive with EBNA-1. We conclude that the reactivity of the RA sera with the phagotope is most likely due to the phagotope being a mimic of an epitope of type II collagen for a proportion of RA sera.

The return to work experiences of middle-aged Australian workers diagnosed with colorectal cancer: a matched cohort study

Background Few studies have been undertaken to understand the employment impact in patients with colorectal cancer and none in middle-aged individuals with cancer. This study described transitions in, and key factors influencing, work participation during the 12 months following a diagnosis of colorectal cancer. Methods We enrolled 239 adults during 2010 and 2011who were employed at the time of their colorectal cancer diagnosis and were prospectively followed over 12 months. They were compared to an age- and gender-matched general population group of 717 adults from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data were collected using telephone and postal surveys. Primary outcomes included work participation at 12 months, changes in hours worked and time to work re-entry. Multivariable logistic and Cox proportional hazards models were undertaken. Results A significantly higher proportion of participants with colorectal cancer (27%) had stopped working at 12 months than participants from the comparison group (8%) (p < 0.001). Participants with cancer who returned to work took a median of 91 days off work (25–75 percentiles: 14–183 days). For participants with cancer, predictors of not working at 12 months included: being older, lower BMI and lower physical well-being. Factors related to delayed work re-entry included not being university-educated, working for an employer with more than 20 employees in a non-professional or managerial role, longer hospital stay, poorer perceived financial status and having or had chemotherapy. Conclusions In middle-adulthood, those working and diagnosed with colorectal cancer can expect to take around three months off work. Individuals treated with chemotherapy, without a university degree and from large employers could be targeted for specific assistance for a more timely work entry.