The expression of pre- and postcopulatory sexually selected traits reflects levels of dietary stress in guppies

Environmental and ecological conditions can shape the evolution of life history traits in many animals. Among such factors, food or nutrition availability can play an important evolutionary role in moderating an animal's life history traits, particularly sexually selected traits. Here, we test whether diet quantity and/or composition in the form of omega-3 long chain polyunsaturated fatty acids (here termed 'n3LC') influence the expression of pre- and postcopulatory traits in the guppy (Poecilia reticulata), a livebearing poeciliid fish. We assigned males haphazardly to one of two experimental diets supplemented with n3LC, and each of these diet treatments was further divided into two diet 'quantity' treatments. Our experimental design therefore explored the main and interacting effects of two factors (n3LC content and diet quantity) on the expression of precopulatory (sexual behaviour and sexual ornamentation, including the size, number and spectral properties of colour spots) and postcopulatory (the velocity, viability, number and length of sperm) sexually selected traits. Our study revealed that diet quantity had significant effects on most of the pre- and postcopulatory traits, while n3LC manipulation had a significant effect on sperm traits and in particular on sperm viability. Our analyses also revealed interacting effects of diet quantity and n3LC levels on courtship displays, and the area of orange and iridescent colour spots in the males' colour patterns. We also confirmed that our dietary manipulations of n3LC resulted in the differential uptake of n3LC in body and testes tissues in the different n3LC groups. This study reveals the effects of diet quantity and n3LC on behavioural, ornamental and ejaculate traits in P. reticulata and underscores the likely role that diet plays in maintaining the high variability in these condition-dependent sexual traits.

Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.

Children of obese mothers have increased risk of metabolic syndrome as adults. Here we report the effects of a high-fat diet in the absence of maternal obesity at conception on skeletal muscle metabolic and transcriptional profiles of adult male offspring. Female Sprague Dawley rats were fed a diet rich in saturated fat and sucrose [high-fat diet (HFD): 23.5% total fat, 9.83% saturated fat, 20% sucrose wt:wt] or a normal control diet [(CD) 7% total fat, 0.5% saturated fat, 10% sucrose wt:wt] for the 3 wk prior to mating and throughout pregnancy and lactation. Maternal weights were not different at conception; however, HFD-fed dams were 22% heavier than controls during pregnancy. On a normal diet, the male offspring of HFD-fed dams were not heavier than controls but demonstrated features of insulin resistance, including elevated plasma insulin concentration [40.1 ± 2.5 (CD) vs 56.2 ± 6.1 (HFD) mU/L; P = 0.023]. Next-generation mRNA sequencing was used to identify differentially expressed genes in the offspring soleus muscle, and gene set enrichment analysis (GSEA) was used to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 upregulated pathways, including cytokine signaling (P < 0.005), starch and sucrose metabolism (P < 0.017), inflammatory response (P < 0.024), and cytokine-cytokine receptor interaction (P < 0.037). A further 8 pathways were downregulated, including oxidative phosphorylation (P < 0.004), mitochondrial matrix (P < 0.006), and electron transport/uncoupling (P < 0.022). Phosphorylation of the insulin signaling protein kinase B was reduced [2.86 ± 0.63 (CD) vs 1.02 ± 0.27 (HFD); P = 0.027] and mitochondrial complexes I, II, and V protein were downregulated by 50-68% (P < 0.005). On a normal diet, the male offspring of HFD-fed dams did not become obese adults but developed insulin resistance, with transcriptional evidence of muscle cytokine activation, inflammation, and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of prepregnancy obesity, can promote metabolic dysregulation and predispose offspring to type 2 diabetes.

Postexercise muscle cooling enhances gene expression of PGC-1α

This study aimed to investigate the influence of localized muscle cooling on postexercise vascular, metabolic, and mitochondrial-related gene expression.

Experience and expression of anger among Australian prisoners and the relationship between anger and reintegration variables

We examined the experience and expression of anger among a group of Australian prisoners prior to and following prison release, as well as the relationship between anger and several reintegration variables. Participants were 79 adult prisoners (54 male, 25 female) who completed the State-Trait Anger Expression Inventory (STAXI-2) 1 month prior to release and again at 1 to 4 weeks and 3 to 4 months post-release. A postrelease questionnaire was also administered at the two postrelease points focusing on the quality of life conditions experienced following release. Mean state and trait anger scores were significantly higher at pre-release than post-release. As well, higher levels of anger expression and anger control were reported at pre-release compared with post-release. Higher age was related to lower state anger at post-release, whereas several variables were related to trait anger at post-release. Theoretical implications for reintegration theory are discussed, together with practical applications.

Tumour but not stromal expression of β3 integrin is essential, and is required early, for spontaneous dissemination of bone-metastatic breast cancer.

Although many preclinical studies have implicated β3 integrin receptors (αvβ3 and αIIbβ3) in cancer progression, β3 inhibitors have shown only modest efficacy in patients with advanced solid tumours. The limited efficacy of β3 inhibitors in patients could arise from our incomplete understanding of the precise function of β3 integrin and, consequently, inappropriate clinical application. Data from animal studies are conflicting and indicate heterogeneity with respect to the relative contributions of β3-expressing tumour and stromal cell populations in different cancers. Here we aimed to clarify the function and relative contributions to metastasis of tumour versus stromal β3 integrin in clinically relevant models of spontaneous breast cancer metastasis, with particular emphasis on bone metastasis. We show that stable down-regulation of tumour β3 integrin dramatically impairs spontaneous (but not experimental) metastasis to bone and lung without affecting primary tumour growth in the mammary gland. Unexpectedly, and in contrast to subcutaneous tumours, orthotopic tumour vascularity, growth and spontaneous metastasis were not altered in mice null for β3 integrin. Tumour β3 integrin promoted migration, protease expression and trans-endothelial migration in vitro and increased vascular dissemination in vivo, but was not necessary for bone colonization in experimental metastasis assays. We conclude that tumour, rather than stromal, β3 expression is essential and is required early for efficient spontaneous breast cancer metastasis to bone and soft tissues. Accordingly, differential gene expression analysis in cohorts of breast cancer patients showed a strong association between high β3 expression, early metastasis and shorter disease-free survival in patients with oestrogen receptor-negative tumours. We propose that β3 inhibitors may be more efficacious if used in a neoadjuvant setting, rather than after metastases are established. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Expression of anti-viral shRNA molecules in transgenic zebrafish

 Development of transgenic zebrafish specifically resistant to Viral Hemorrhagic Septicemia Virus mediated by short-hairpin RNA interference. Introduction of shRNAs by Tol2 transgenisis in to zebrafish overwhelmed multiple facets of the endogenous microRNA pathway including Exportin-5 and Argonaute-2 and prevented normal zebrafish development.

Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk

Two cases of zinc deficiency in breastfed neonates were investigated where zinc levels in the mothers' milk were reduced by more than 75 % compared to normal. The objective of this study was to find the molecular basis of the maternal zinc deficiency condition. Significant reductions in mRNA expression and protein levels of the zinc transporters SLC30A5 and SLC30A6 were found in maternal tissue, suggesting a causal link to the zinc-deficient milk. Novel splice variants of the SLC30A6 transcript were detected. No modifications were found in coding regions, or in transcription binding sites of promoter regions or in 5' and 3' untranslated regions of both transporters in lymphoblasts and fibroblasts isolated from both mothers. Altered DNA methylation in SLC30A5 at two CpG sites was detected and may account for the reduced levels of SLC30A5 mRNA and protein in lymphoblasts. Reduced SLC30A6 mRNA and protein levels in lymphoblasts may be secondary to reduced SLC30A5 expression, as they function as a heterodimer in zinc transport. In conclusion, two cases of zinc deficiency are linked to low levels of the SLC30A5 and SLC30A6 zinc transporters. These two zinc transporters have not been previously associated with zinc deficiency in milk.

Chansu inhibits the expression of cortactin in colon cancer cell lines in vitro and in vivo

Background: Chansu is a transitional Chinese medicine that has been used for centuries as therapy for inflammation, anaesthesia and arrhythmia in China and other Asian countries. Recently, it has also been used for anti-cancer purposes. We have previously shown that Chansu has a huge pro-apoptotic potential on colon cancer cells, but to date the detailed mechanism of this action is not well understood.

Methods: One of the major components of Chansu, Cinobufagin (CBF) was used to treat cancer cells. The expressions of levels of cortactin, an important factor in tumour progression and cancer invasion, were assessed in in vitro and in vivo experiments. Additional analyses were performed in subcellular protein fractions and immune-fluorescent staining was used to define cortactin protein expression and the changes of location in CBF-treated cells.

Results: CBF strongly inhibited the expression of cortactin in HCT116 cells. There were reductions of both mRNA transcription and protein synthesis, which were more significant in the absence of oxygen in vitro. In addition, nuclear translocation of cortactin was observed in HCT116 cells post CBF exposure but not in the negative control, indicating that CBF is likely to interrupt co-localisation of cortactin to cytoskeletal proteins. Most importantly, CBF could diminish the expression of cortactin in human HCT116 xenograft tumours in nude mouse in vivo.

Conclusions: CBF inhibits cortactin expression and nuclear translocation in colon cancer cells in vitro and in mouse models bearing human colon tumour in vivo, suggesting it might disrupt actin-regulated cell movement. Thus, CBF or Chansu could be developed as an effective anti-cancer therapy to stop local invasion and metastasis.

Coassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells

The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications are the nanostructured scaffolds formed by epitope containing minimalist self-assembled peptides (SAPs), as they are bioactive on a cellular length scale, whilst presenting as an easily handled hydrogel. Here, we show that the assembly process distributes an anti-inflammatory polysaccharide, fuccoidan, localised to the nanofibers to function as an anti-inflammatory biomaterial for cancer therapy. We show that it supports healthy cells, whilst inducing apoptosis in cancerous endothelial cells, as demonstrated by the downregulation of the proinflammatory gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications as local epithelial cancer immunotherapy and drug delivery vehicles.