Longitudinal Intergenerational Birth Cohort Designs: A Systematic Review of Australian and New Zealand Studies

Background

The longitudinal birth cohort design has yielded a substantial contribution to knowledge of child health and development. The last full review in New Zealand and Australia in 2004 identified 13 studies. Since then, birth cohort designs continue to be an important tool in understanding how intrauterine, infant and childhood development affect long-term health and well-being. This updated review in a defined geographical area was conducted to better understand the factors associated with successful quality and productivity, and greater scientific and policy contribution and scope.

Methods

We adopted the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach, searching PubMed, Scopus, Cinahl, Medline, Science Direct and ProQuest between 1963 and 2013. Experts were consulted regarding further studies. Five inclusion criteria were used: (1) have longitudinally tracked a birth cohort, (2) have collected data on the child and at least one parent or caregiver (3) be based in Australia or New Zealand, (4) be empirical in design, and (5) have been published in English.

Results

10665 records were initially retrieved from which 23 birth cohort studies met the selection criteria. Together these studies recruited 91,196 participants, with 38,600 mothers, 14,206 fathers and 38,390 live births. Seventeen studies were located in Australia and six in New Zealand. Research questions initially focused on the perinatal period, but as studies matured, longer-term effects and outcomes were examined.

Conclusions

This review demonstrates the significant yield from this effort both in terms of scientific discovery and social policy impact. Further opportunities have been recognised with cross-study collaboration and pooling of data between established and newer studies and international studies to investigate global health determinants.     

Investigation on Toxicity and Teratogenicity in Rats of a Retinoid‐Polyamine Conjugate with Potent Anti‐Inflammatory Properties

Previous studies have shown that N¹,N¹²‐bis(all‐trans‐retinoyl)spermine (RASP), a retinoid analog, inhibits RNase P activity and angiogenesis in the chicken embryo chorioallantoic membrane, demonstrates anti‐tumor activity on prostate cancer cells, and acts as anti‐inflammatory agent, being more effective and less toxic than all‐trans retinoic acid. In an attempt to further characterize the biological profile of RASP, we tested its effects on organ toxicity and teratogenicity by daily oral gavage of RASP at a level of 50 mg/Kg of body weight in two generations of rats. We found that this compound does not induce changes to the body growth, the appearance of physical features, and the animal's reflexes. Additionally, no substantial histopathological lesions were found in brain, heart, lung, thymus, liver, thyroid gland, adrenal gland, pituitary gland, kidneys, spleen, skin, femora, prostate, testis, epididymis, vagina, uterus, and ovaries of RASP‐treated animals. These results suggest RASP, as a promising lead compound for the treatment of several dermatological disorders and certain cancer types, has apparently minimal toxic side‐effects as revealed in this two‐generation reproduction study in rats.     

Baselines for Lifetime of Organic Solar Cells

The process of accurately gauging lifetime improvements in organic photovoltaics (OPVs) or other similar emerging technologies, such as perovskites solar cells is still a major challenge. The presented work is part of a larger effort of developing a worldwide database of lifetimes that can help establishing reference baselines of stability performance for OPVs and other emerging PV technologies, which can then be utilized for pass‐fail testing standards and predicting tools. The study constitutes scanning of literature articles related to stability data of OPVs, reported until mid‐2015 and collecting the reported data into a database. A generic lifetime marker is utilized for rating the stability of various reported devices. The collected data is combined with an earlier developed and reported database, which was based on articles reported until mid‐2013. The extended database is utilized for establishing the baselines of lifetime for OPVs tested under different conditions. The work also provides the recent progress in stability of unencapsulated OPVs with different architectures, as well as presents the updated diagram of the reported record lifetimes of OPVs. The presented work is another step forward towards the development of pass‐fail testing standards and lifetime prediction tools for emerging PV technologies.     

Altered expression pattern of integrin alphavbeta3 correlates with actin cytoskeleton in primary cultures of human breast cancer

Background

Integrins are transmembrane adhesion receptors that provide the physical link between the actin cytoskeleton and the extracellular matrix. It has been well established that integrins play a major role in various cancer stages, such as tumor growth, progression, invasion and metastasis. In breast cancer, integrin alphavbeta3 has been associated with high malignant potential in cancer cells, signaling the onset of widespread metastasis. Many preclinical breast cancer studies are based on established cell lines, which may not represent the cell behavior and phenotype of the primary tumor of origin, due to undergone genotypic and phenotypic changes. In the present study, short-term primary breast cancer cell cultures were developed. Integrin alphavbeta3 localization was studied in correlation with F-actin cytoskeleton by means of immunofluorescence and immunogold ultrastructural localization. Integrin fluorescence intensities were semi-quantitatively assessed by means of computerized image analysis, while integrin and actin expression was evaluated by Western immunoblotting.

Results

In the primary breast cancer epithelial cells integrin alphavbeta3 immunofluorescence was observed in the marginal cytoplasmic area, whereas in the primary normal breast epithelial cells it was observed in the main cell body, i.e. in the ventrally located perinuclear area. In the former, F-actin cytoskeleton appeared well-formed, consisting of numerous and thicker stress fibers, compared to normal epithelial cells. Furthermore, electron microscopy showed increased integrin alphavbeta3 immunogold localization in epithelial breast cancer cells over the area of stress fibers at the basal cell surface. These findings were verified with Western immunoblotting by the higher expression of integrin beta3 subunit and actin in primary breast cancer cells, revealing their reciprocal relation, in response to the higher motility requirements, determined by the malignant potential of the breast cancer cells.

Conclusion

A model system of primary breast cancer cell cultures was developed, in an effort to maintain the closest resembling environment to the tumor of origin. Using the above system model as an experimental tool the study of breast tumor cell behavior is possible concerning the adhesion capacity and the migrating potential of these cells, as defined by the integrin alphavbeta3 distribution in correlation with F-actin cytoskeleton.     

Effect of Processing and Storage Parameters on the Oxidative Deterioration of Oil-in-Water Emulsions

The effect of storage temperature, pH, and homogenization pressure on the oxidative deterioration of Tween 20 and sodium caseinate sunflower oil-in-water emulsions was studied by monitoring conjugated dienes (CD), lipid hydroperoxides (LH), and thiobarbituric acid reactive substances (TBARs). CD increased linearly with storage time, and the rate constant was temperature dependent according to the Arrhenius equation with an activation energy equal to 37.5 kJ mol⁻¹. The increase in LH and TBARs with temperature (5–60°C) was in good agreement with CD variation. Tween-stabilized emulsions oxidized faster as pH increased from 3 to 7, whereas a different behavior was observed in emulsions stabilized with sodium caseinate or a mixture of both emulsifiers. A change of homogenization pressure (30–900 bars), reflecting variation of emulsion average droplet size, had no effect on the oxidative stability of the emulsions.     

Export pathway selectivity of Escherichia coli twin arginine translocation signal peptides

The Escherichia coli genome encodes at least 29 putative signal peptides containing a twin arginine motif characteristic of proteins exported via the twin arginine translocation (Tat) pathway. Fusions of the putative Tat signal peptides plus six to eight amino acids of the mature proteins to three reporter proteins (short-lived green fluorescent protein, maltose-binding protein (MBP), and alkaline phosphatase) and also data from the cell localization of epitope-tagged full-length proteins were employed to determine the ability of the 29 signal peptides to direct export through the Tat pathway, through the general secretory pathway (Sec), or through both. 27/29 putative signal peptides could export one or more reporter proteins through Tat. Of these, 11 signal peptides displayed Tat specificity in that they could not direct the export of Sec-only reporter proteins. The rest (16/27) were promiscuous and were capable of directing export of the appropriate reporter either via Tat (green fluorescent protein, MBP) or via Sec (PhoA, MBP). Mutations that conferred a >or=+1 charge to the N terminus of the mature protein abolished or drastically reduced routing through the Sec pathway without affecting the ability to export via the Tat pathway. These experiments demonstrate that the charge of the mature protein N terminus affects export promiscuity, independent of the effect of the folding state of the mature protein.     

Diversity of saproxylic basidiomycetes in Quercus ilex woodlands of central and insular Greece

The sclerophyllous forests of Quercus ilex (holm oak) possess a unique position in earth’s biosphere, existing only in countries of the Mediterranean basin. However, very little information exists about mushrooms associated with holm oak in east Mediterranean, including Greece, where Q. ilex appears mostly in relict forests and fragmented stands. A pertinent long-term investigation was undertaken in selected Q. ilex dominated habitats of Crete, Andros, Naxos and Ikaria islands (Aegean Archipelago) as well as in mountains of Attica. Specimens of xylotrophic basidiomycetes were collected and identified. As a result, 74 species were recorded; among them Hemimycena cephalotricha, Hyphoderma cremeoalbum, Hyphodontia radula, Irpex litschaueri, Mycena algeriensis, Phanerochaete martelliana, Phloeomana alba and Phlebia unica constitute new records for the Greek mycobiota, while 68 species are reported for the first time on Q. ilex in Greece. Moreover, the presence of Fomitiporia mediterranea on this host was evidenced through ITS sequencing, and comments are made about its relationship to F. punctata and F. pseudopunctata. The importance of findings is discussed in conjunction with their environmental value; five species could be assigned in the “Species of Special Interest” categories, and other five polypores are proposed as suitable indicators for Q. ilex habitat assessment and conservation.     

In-vitro bacteriocin-mediated antagonism by oral streptococci against human carrier strains of staphylococci

All strains of oral streptococci tested and specially those of Streptococcus mutans, Strep. sanguis and Strep. minor produced more than one distinct bacteriocin-like substance with variable inhibitory activity on 20 indicator staphylococci. Inhibitory activity was comparatively higher on nasal strains of Staph. aureus and Staph. epidermidis than on strains of both species isolated from the mouth. Nineteen of 20 staphylococcal indicators were inhibited by 1–12 of the 12 effector streptococci. Sensitivity of nasal staphylococci to bacteriocins (frequency of positive inhibitory tests and total inhibition zone diameters) was significantly higher ( P < 0·001, χ² test and P < 0·05, t test respectively) than that of oral ones. The sensitivity of nasal over oral Staph. aureus ( P < 0·001 and P < 0·01) and of oral Staph. epidermidis over oral Staph. aureus ( P < 0·01 and P < 0·05) was also significantly higher. The evaluation of variability of inhibitory patterns of bacteriocins produced by streptococci (p-typing), of sensitivity patterns of staphylococci to bacteriocins (s-typing) and of the significantly higher sensitivity of nasal over oral staphylococci to bacteriocins from the epidemiological and ecological veiwpoints are discussed.     

Genetic analysis of G protein-coupled receptor expression in Escherichia coli: inhibitory role of DnaJ on the membrane integration of the human central cannabinoid receptor

The overexpression of G protein-coupled receptors (GPCRs) and of many other heterologous membrane proteins in simple microbial hosts, such as the bacterium Escherichia coli, often results in protein mistargeting, aggregation into inclusion bodies or cytoplasmic degradation. Furthermore, membrane protein production is very frequently accompanied by severe cell toxicity. In this work, we have employed a genetic strategy to isolate E. coli mutants that produce markedly increased amounts of the human central cannabinoid receptor (CB1), a pharmacologically significant GPCR that expresses very poorly in wild-type E. coli. By utilizing a CB1 fusion with the green fluorescent protein (GFP) and fluorescence-activated cell sorting (FACS), we screened an E. coli transposon library and identified an insertion in dnaJ that resulted in a large increase in CB1-GFP fluorescence and a dramatic enhancement in bacterial production of membrane-integrated CB1. Furthermore, the dnaJ::Tn5 inactivation suppressed the severe cytotoxicity associated with CB1 production. This revealed an unexpected inhibitory role of the chaperone/ co-chaperone DnaJ in the protein folding or membrane insertion of bacterially produced CB1. Our strategy can be easily adapted to identify expression bottlenecks for different GPCRs or any other integral membrane protein, provide useful and unanticipated mechanistic insights, and assist in the construction of genetically engineered E. coli strains for efficient heterologous membrane protein production.