Breast Tumors with Elevated Expression of 1q Candidate Genes Confer Poor Clinical Outcome and Sensitivity to Ras/PI3K Inhibition

Genomic aberrations are common in cancers and the long arm of chromosome 1 is known for its frequent amplifications in breast cancer. However, the key candidate genes of 1q, and their contribution in breast cancer pathogenesis remain unexplored. We have analyzed the gene expression profiles of 1635 breast tumor samples using meta-analysis based approach and identified clinically significant candidates from chromosome 1q. Seven candidate genes including exonuclease 1 (EXO1) are consistently over expressed in breast tumors, specifically in high grade and aggressive breast tumors with poor clinical outcome. We derived a EXO1 co-expression module from the mRNA profiles of breast tumors which comprises 1q candidate genes and their co-expressed genes. By integrative functional genomics investigation, we identified the involvement of EGFR, RAS, PI3K / AKT, MYC, E2F signaling in the regulation of these selected 1q genes in breast tumors and breast cancer cell lines. Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA–drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors. Thus, we identified seven 1q candidate genes strongly associated with the poor survival of breast cancer patients and identified the possibility of targeting them with EGFR/RAS/PI3K inhibitors.     

X-ray fluorescence elemental mapping of roots,stems and leaves of the nickel hyperaccumulators Rinorea cf. bengalensis and Rinorea cf. javanica (Violaceae) from Sabah (Malaysia), Borneo

Plant and Soil - The following article is part of the Special Issue “Agroforestry: a belowground perspective” Guest Edited by Rémi Cardinael, Zhun Mao, Claire Chenu, Philippe...     

Neuregulins are essential for spermatogonial proliferation and meiotic initiation in neonatal mouse testis

The transition from mitosis to meiosis is unique to germ cells. In murine embryonic ovaries and juvenile testes, retinoic acid (RA) induces meiosis via the stimulated by retinoic acid gene 8 (Stra8), but its molecular pathway requires elucidation. We present genetic evidence in vivo and in vitro that neuregulins (NRGs) are essential for the proliferation of spermatogonia and the initiation of meiosis. Tamoxifen (TAM) was injected into 14-day post-partum (dpp) Sertoli cell-specific conditional Nrg1(Ser-/-) mutant mice. TAM induced testis degeneration, suppressed BrdU incorporation into spermatogonia and pre-leptotene primary spermatocytes, and decreased and increased the number of STRA8-positive and TUNEL-positive cells, respectively. In testicular organ cultures from 5-6 dpp wild-type mice and cultures of their re-aggregated spermatogonia and Sertoli cells, FSH, RA [all-trans-retinoic acid (ATRA), AM580, 9-cis-RA] and NRG1 promoted spermatogonial proliferation and meiotic initiation. However, TAM treatment of testicular organ cultures from the Nrg1(Ser-/-) mutants suppressed spermatogonial proliferation and meiotic initiation that was promoted by FSH or AM580. In re-aggregated cultures of purified spermatogonia, NRG1, NRG3, ATRA and 9-cis-RA promoted their proliferation and meiotic initiation, but neither AM580 nor FSH did. In addition, FSH, RAs and NRG1 promoted Nrg1 and Nrg3 mRNA expression in Sertoli cells. These results indicate that in juvenile testes RA and FSH induced meiosis indirectly through Sertoli cells when NRG1 and NRG3 were upregulated, as NRG1 amplified itself and NRG3. The amplified NRG1 and NRG3 directly induced meiosis in spermatogonia. In addition, ATRA and 9-cis-RA activated spermatogonia directly and promoted their proliferation and eventually meiotic initiation.     

Engineering tubular bone constructs

Cell-sheet techniques have been proven effective in various soft tissue engineering applications. In this experiment, we investigated the feasibility of bone tissue engineering using a hybrid of mesenchymal stem cell (MSC) sheets and PLGA meshes. Porcine MSCs were cultured to a thin layer of cell sheets via osteogenic induction. Tube-like long bones were constructed by wrapping the cell sheet on to PLGA meshes resulting in constructs which could be cultured in spinner flasks, prior to implantation in nude rats. Our results showed that the sheets were composed of viable cells and dense matrix with a thickness of about 80-120 microm, mineral deposition was also observed in the sheet. In vitro cultures demonstrated calcified cartilage-like tissue formation and most PLGA meshes were absorbed during the 8-week culture period. In vivo experiments revealed that dense mineralized tissue was formed in subcutaneous sites and the 8-week plants shared similar micro-CT characteristics with native bone. The neo tissue demonstrated histological markers for both bone and cartilage, indicating that the bone formation pathway in constructs was akin to endochondral ossification, with the residues of PLGA having an effect on the neo tissue organization and formation. These results indicate that cell-sheet approaches in combination with custom-shaped scaffolds have potential in producing bone tissue.     

Effects of photophase and altitude on oviposition rhythm of the himalayan strains of Drosophila ananassae

The effects of varying photophase and altitude of origin on the phase angle difference (Ψ) of the circadian rhythm of oviposition during entrainment to light-dark (LD) cycles and the aftereffects of such photophases on the period of the free-running rhythm (τ) in constant darkness (DD) were evaluated in two Himalayan strains of Drosophila ananassae, the high-altitude (HA) strain from Badrinath (5,123 m above sea level=ASL) and the low-altitude (LA) strain from Firozpur (179 m ASL). The Ψ (i.e., the hours from lights-on of the LD cycle to oviposition median) of both strains was determined in LD cycles in which the photophase at 100 lux varied from 6 to 18 h/24 h. The HA strain was entrained by all LD cycles except the one with 6 h photophase in which it was weakly rhythmic, but the LA strain was entrained by only three LD cycles with photophases of 10, 12, and 14 h, but photophases of 6, 8, 16, and 18 h rendered it arrhythmic. Lights-off transition of LD cycles was the phase-determining signal for both strains as oviposition medians of the HA strain occurred∼6 h prior to lights-off, while those of the LA strain occurred∼1 h after lights-off. The Ψ of the HA strain increased from∼2 h in 8 h photophase to∼11 h in 18 h photophase, while that of the LA strain increased from∼11 h in 10 h photophase to∼15 h in 14 h photophase. The aftereffects of photophase of the prior entraining LD cycles on τ in DD were determined by transferring flies from LD cycles to DD. The τ of the HA strain increased from∼19 to∼25 h when transferred to DD from LD 8:16 and LD 18:6 cycles, respectively, whereas the τ of the LA strain increased from∼26 to∼28 h when transferred to DD from LD 10:14 and LD 14:10 cycles, respectively. Thus, these results demonstrate that the photophases of entraining LD cycles and the altitude of origin affected several parameters of entrainment and the period of the free-running rhythm of these strains.     

Altitudinal variation in phase response curves for the Himalayan strains of Drosophila helvetica

In previous research, it was determined that the altitude of origin altered the parameters of photic entrainment and free-running rhythmicity of adult locomotor activity of the high-altitude Himalayan (haH) strain (Hemkund-Sahib, 4121 m above sea level) of Drosophila helvetica compared to the low-altitude Himalayan (laH) strain (Birahi, 1132 m above sea level) of the same species. The present study investigated whether the altitude of origin also affects the parameters of the light pulse phase response curve (PRC) of the adult locomotor activity rhythm of the haH strain. Light pulse PRCs were determined for both strains against the background of constant darkness. Although both were "weak" or type 1 PRCs, the PRC for the haH strain differed from that of the laH strain in three basic parameters. The PRC for the haH strain was of low amplitude, had a protracted dead zone, and showed a ratio of the advance to delay region (A/D>1), while the PRC of the laH strain was characterized by high amplitude, absence of dead zone, and a A/D ratio<1. The asymmetric PRCs of these strains might explain the process of photic entrainment to 24 h light-dark cycles, as the long period of the free-running rhythm (tau) of the haH strain is complemented with a larger advance portion of its PRC (A/D>1), whereas the short tau of the laH strain is matched with a larger delay portion of its PRC (A/D<1). Prolonged dead zone and low amplitude in the PRC of the haH strain imply that the photic sensitivity of this strain has been drastically diminished as an adaptation to environmental conditions at the altitude of its origin. While adults of this strain begin activity in very bright light in the forenoon due to non-permissible low temperature in the morning, the converse is true for the laH strain.     

Temporal variation in condition index and meat quality of Lunella undulata (Turbinidae), in relation to the reproductive cycle

ABSTRACT

Lunella undulata is a subtropical-temperate marine gastropod which is harvested commercially from temperate reefs in Australia. This paper aimed to evaluate monthly variation in the condition index (CI) and biochemical composition of the foot tissue of L. undulata in relation to the spawning cycle. The gonadosomatic index (GSI) varied significantly between males and females and across months (P?=?0.0001), ranging from 43% to 70% in males and 41% to 71% for females. The highest GSI, as well as the highest CI for both sexes was recorded in December and April, whilst meat yield peaked in January, September and October. Protein, lipid, fatty acid and heavy metals in the foot tissue also significantly varied between months (P?<?0.05). Throughout all 14 months of sampling, the foot tissue of L. undulata showed good nutritional quality, with high levels of protein and the polyunsaturated fatty acids, docosapentaenoic acid, eicosapentaenoic acid and arachidonic acid. Overall, despite some temporal variability in the biochemical composition, L. undulata could be harvested at any time of the year for human consumption, although it may be best to avoid peak spawning times, which occur around January in northern NSW.     

Differences in evolutionary history translate into differences in invasion success of alien mammals in South Africa

Attempts to investigate the drivers of invasion success are generally limited to the biological and evolutionary traits distinguishing native from introduced species. Although alien species introduced to the same recipient environment differ in their invasion intensity – for example, some are “strong invaders”; others are “weak invaders” – the factors underlying the variation in invasion success within alien communities are little explored. In this study, we ask what drives the variation in invasion success of alien mammals in South Africa. First, we tested for taxonomic and phylogenetic signal in invasion intensity. Second, we reconstructed predictive models of the variation in invasion intensity among alien mammals using the generalized linear mixed‐effects models. We found that the family Bovidae and the order Artiodactyla contained more “strong invaders” than expected by chance, and that such taxonomic signal did not translate into phylogenetic selectivity. In addition, our study indicates that latitude, gestation length, social group size, and human population density are only marginal determinant of the variation in invasion success. However, we found that evolutionary distinctiveness – a parameter characterising the uniqueness of each alien species – is the most important predictive variable. Our results indicate that the invasive behavior of alien mammals may have been “fingerprinted” in their evolutionary past, and that evolutionary history might capture beyond ecological, biological and life‐history traits usually prioritized in predictive modeling of invasion success. These findings have applicability to the management of alien mammals in South Africa.     

Modeling of crude oil biodegradation using two phase partitioning bioreactor

In this work, crude oil biodegradation has been optimized in a solid‐liquid two phase partitioning bioreactor (TPPB) by applying a response surface methodology based d ‐optimal design. Three key factors including phase ratio, substrate concentration in solid organic phase, and sodium chloride concentration in aqueous phase were taken as independent variables, while the efficiency of the biodegradation of absorbed crude oil on polymer beads was considered to be the dependent variable. Commercial thermoplastic polyurethane (Desmopan®) was used as the solid phase in the TPPB. The designed experiments were carried out batch wise using a mixed acclimatized bacterial consortium. Optimum combinations of key factors with a statistically significant cubic model were used to maximize biodegradation in the TPPB. The validity of the model was successfully verified by the good agreement between the model‐predicted and experimental results. When applying the optimum parameters, gas chromatography‐mass spectrometry showed a significant reduction in n‐alkanes and low molecular weight polycyclic aromatic hydrocarbons. This consequently highlights the practical applicability of TPPB in crude oil biodegradation. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:797–805, 2014