Different pilot-scale outdoor photobioreactors using medium recycling were operated in a greenhouse under different environmental conditions and the growth rates (0.1 to 0.5 day⁻¹) obtained evaluated ...in order to compare them with traditional systems used in aquaculture. The annualized volumetric growth rate for Nannochloropsis gaditana was 0.26 g l⁻¹ day⁻¹ (peak 0.4 g l⁻¹ day⁻¹) at 0.4 day⁻¹ in a 5-cm wide flat-panel bioreactor (FP-PBR). The biomass productivity achieved in this reactor was 10-fold higher than in traditional reactors, reaching values of 28 % and 45 % dry weight (d.w.) of lipids and proteins, respectively, with a 4.3 % (d.w.) content of eicosapentaenoic acid (EPA). A model for predicting EPA productivity from N. gaditana cultures that takes into account the existence of photolimitation and photoinhibition of growth under outdoor conditions is presented. The effect of temperature and average irradiance on EPA content is also studied. The maximum EPA productivity attained is 30 mg l⁻¹ day⁻¹.
Caveolins are a family of membrane proteins required for the formation of small plasma membrane invaginations called caveolae that are implicated in cellular trafficking processes. In addition to ...this structural role, these scaffolding proteins modulate numerous intracellular signaling pathways; often via direct interaction with specific binding partners. Caveolin-1 is particularly well-studied in this respect and has been attributed a large variety of functions. Thus, Caveolin-1 also represents the best-characterized isoform of this family with respect to its participation in cancer. Rather strikingly, available evidence indicates that Caveolin-1 belongs to a select group of proteins that function, depending on the cellular settings, both as tumor suppressor and promoter of cellular traits commonly associated with enhanced malignant behavior, such as metastasis and multi-drug resistance. The mechanisms underlying such ambiguity in Caveolin-1 function constitute an area of great interest. Here, we will focus on discussing how Caveolin-1 modulates cell death and survival pathways and how this may contribute to a better understanding of the ambiguous role this protein plays in cancer.
A well-defined season of sexual rest controlled by photoperiod is observed in female sheep and goats during spring and summer, delineating their “anestrous season”; bucks also decrease sexual ...activity at about the same time. Nutrition and/or socio-sexual stimuli play only secondary roles. However, the presence of sexually active males can reduce the length of seasonal anestrus. Whether it can also completely suppress anestrus has not been investigated. Here we tested this in goats in 3 experiments, using bucks rendered sexually active out of season by exposure to long days. The continuous presence of these males prevented goats to display seasonal anestrus: 12/14 females cycled the year round, vs. 0/13 and 0/11 for females with un-treated bucks or without bucks (experiment 1). When active bucks were removed, females immediately entered anestrus (7/7 stopped ovulating vs. 1/7 if maintained with active bucks; experiment 2). Finally, 7/7 anestrous does with bucks in sexual rest since 1.5months commenced cycling rapidly during mid-anestrous, when these bucks became sexually active following a treatment with artificial long days, vs. 0/7 with un-treated bucks or no bucks (experiment 3). The presence/withdrawal of active bucks had a highly significant effect in the three experiments (P≤0.002). Therefore, the presence of a mating opportunity can completely override the photoperiodic inhibition of reproduction of females throughout the anestrous season. Results suggest that we must re-evaluate the relative contributions of photoperiod vs. other external cues in controlling seasonal reproduction, thus offering new non-pharmaceutical ways for controlling out-of-season reproduction in small ruminants.
•Female and male goats display seasonal variations of their sexual activity.•Sexual activity of males was induced in the sexual rest by photoperiodic treatments.•Presence of photo-stimulated males prevented the anestrous season in does.•When sexually active bucks were removed, does entered in anestrus.
ObjectiveFibroblast growth factor 15/19 (FGF15/19), an enterokine that regulates synthesis of hepatic bile acids (BA), has been proposed to influence fat metabolism. Without FGF15/19, mouse liver ...regeneration after partial hepatectomy (PH) is severely impaired. We studied the role of FGF15/19 in response to a high fat diet (HFD) and its regulation by saturated fatty acids. We developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration.Design Fgf15−/− mice were fed a HFD. Liver fat and the expression of fat metabolism and endoplasmic reticulum (ER) stress-related genes were measured. Influence of palmitic acid (PA) on FGF15/19 expression was determined in mice and in human liver cell lines. In vivo half-life and biological activity of Fibapo and FGF19 were compared. Hepatoprotective and proregenerative activities of Fibapo were evaluated in obese db/db mice undergoing PH.ResultsHepatosteatosis and ER stress were exacerbated in HFD-fed Fgf15−/− mice. Hepatic expression of Pparγ2 was elevated in Fgf15−/− mice, being reversed by FGF19 treatment. PA induced FGF15/19 expression in mouse ileum and human liver cells, and FGF19 protected from PA-mediated ER stress and cytotoxicity. Fibapo reduced liver BA and lipid accumulation, inhibited ER stress and showed enhanced half-life. Fibapo provided increased db/db mice survival and improved regeneration upon PH.ConclusionsFGF15/19 is essential for hepatic metabolic adaptation to dietary fat being a physiological regulator of Pparγ2 expression. Perioperative administration of Fibapo improves fatty liver regeneration.
Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides ...nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and β-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-β-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased β-catenin protein levels, β-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced β-catenin protein levels and β-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These findings provide evidence for the existance of a posititve feedback loop connecting survivin expression in tumor cells to PI3K/Akt enhanced β-catenin-Tcf/Lef-dependent transcription followed by secretion of VEGF and angiogenesis.
It is well known that there exist real-valued, non-measurable functions on the plane, whose restrictions to the graph of all measurable functions on the real line are measurable. In this paper, it is ...shown that there is, in fact, a continuum-dimensional vector space all of whose members, except for zero, are functions on the plane satisfying the mentioned property. Versions of this fact are proved in the Baire category setting and in the case where the graphs are generated by softer functions.
There is a growing interest in applying natural products in agriculture to stimulate growth and/or resistance of plants, and ultimately to increase productivity without causing further environmental ...degradation. Microalgae synthesize a wide variety of high-value products, including phytostimulants. Even if applied to plants in small proportions, these substances can increase crop yield and protect the plants from biotic and abiotic stress. The microalga
Scenedesmus
sp
.
was grown in simulated treated wastewater to demonstrate its ability to bioremediate and to be a source of phytostimulants. Optimization of the cell disruption method is required to improve the extraction of biomolecules. Therefore, in this work, cell disruption methods, namely high-pressure homogenization (HPH), ultrasonication (US), and hydrolysis, were compared. To evaluate the biostimulant potential, extracts were evaluated using the germination index of watercress seeds, rooting bioassay in mung bean and cucumber, and cotyledon expansion in cucumber. There was a 44% increase in the germination index when watercress were treated with a combination of HPH and enzymatic hydrolysis disrupted extracts. In the mung bean bioassay, the best results were obtained with extracts prepared by HPH and enzymatic hydrolysis, achieving 160% rooting compared to 100% rooting in the control treated with distilled water. For rooting activity in cucumber, the best results were obtained after biomass pre-treatment by HPH, both with or without the enzymatic hydrolysis treatment, achieving maximum root development values of 275%. Differences in cotyledon expansion were not significant. This work demonstrated the biostimulant effect of
Scenedesmus
sp. biomass on three plant species. HPH and enzymatic hydrolysis increased the overall effect although their inclusion might not be economical.
•Active ageing is multidimensional: health-participation-lifelong learning-security.•There is no consensus on how to measure the construct and its different components.•Little care is paid to the ...role of active ageing in reducing mortality as people age.•We identified the factor structure of each active ageing domain using principal component analysis.•Promoting the physical health component of active ageing is key to enhance survival.
The World Health Organization’s active ageing model is based on the optimisation of four key “pillars”: health, lifelong learning, participation and security. It provides older people with a policy framework to develop their potential for well-being, which in turn, may facilitate longevity. We sought to assess the effect of active ageing on longer life expectancy by: i) operationalising the WHO active ageing framework, ii) testing the validity of the factors obtained by analysing the relationships between the pillars, and iii) exploring the impact of active ageing on survival through the health pillar.
Based on data from a sample of 801 community-dwelling older adults, we operationalised the active ageing model by taking each pillar as an individual construct using principal component analysis. The interrelationship between components and their association with survival was analysed using multiple regression models.
A three-factor structure was obtained for each pillar, except for lifelong learning with a single component. After adjustment for age, gender and marital status, survival was only significantly associated with the physical component of health (HR = 0.66; 95% CI = 0.47−0.93; p = 0.018). In turn, this component was loaded with representative variables of comorbidity and functionality, cognitive status and lifestyles, and correlated with components of lifelong learning, social activities and institutional support.
According to how the variables clustered into the components and how the components intertwined, results suggest that the variables loading on the biomedical component of the health pillar (e.g. cognitive function, health conditions or pain), may play a part on survival chances.
Oaxaca cheese is a Mexican pasta filata-type cheese, and can be considered as a potential vehicle for delivering probiotic cells. Their processing conditions are harsher than for most other cheeses. ...Thus, the challenge is to provide an adequate protection to the probiotic cells in order that they reach in sufficient numbers the sites for exerting their functionality. Lactobacillus plantarum cells were entrapped in double emulsions (DE) (aguamiel, Ag, or sweet whey, SW, as inner aqueous phase) and incorporated during cheese manufacture to obtain cheese treatments CTAg and CTSW. A control cheese (CTControl) was made with non-encapsulated free cells. Log CFU g−1 was of 6.81 ± 0.08, 8.15 ± 0.17 and 8.22 ± 0.09 for CTControl, CTSW and CTAg, respectively, immediately after CT's manufacture. After melting, Log CFU g−1 dropped down by 2.18 ± 0.17, 1.42 ± 0.15 and 1.94 ± 0.12 for CTControl, CTSW and CTAg, respectively. The exposure of CTAg and CTSW to simulated gastrointestinal conditions (pH of 2.3 and bile salts) did not affect significantly cells viability (6.32 ± 0.13 and 6.02 ± 0.1 Log CFU g−1, respectively), but CTControl exhibited a significant decrease (p<0.05) to 3.36 ± 0.01 Log CFU g−1. The inclusion of cells in DE is an effective method for protecting their viability against harsh processing and usage conditions.
•Lactobacillus plantarum was encapsulated in the inner aqueous phase of double emulsions.•Oaxaca cheese treatments were produced incorporating the double emulsions.•Aguamiel and sweet whey were used as inner aqueous phase in double emulsions.•Cells viability was evaluated after cheese manufacture, melting and GI conditions.•Encapsulated cells counts after GI exposure complied food functional requirements.
Epigenetic modifications such as DNA and histone methylation functionally cooperate in fostering tumor growth, including that of hepatocellular carcinoma (HCC). Pharmacological targeting of these ...mechanisms may open new therapeutic avenues. We aimed to determine the therapeutic efficacy and potential mechanism of action of our dual G9a histone‐methyltransferase and DNA‐methyltransferase 1 (DNMT1) inhibitor in human HCC cells and their crosstalk with fibrogenic cells. The expression of G9a and DNMT1, along with that of their molecular adaptor ubiquitin‐like with PHD and RING finger domains‐1 (UHRF1), was measured in human HCCs (n = 268), peritumoral tissues (n = 154), and HCC cell lines (n = 32). We evaluated the effect of individual and combined inhibition of G9a and DNMT1 on HCC cell growth by pharmacological and genetic approaches. The activity of our lead compound, CM‐272, was examined in HCC cells under normoxia and hypoxia, human hepatic stellate cells and LX2 cells, and xenograft tumors formed by HCC or combined HCC+LX2 cells. We found a significant and correlative overexpression of G9a, DNMT1, and UHRF1 in HCCs in association with poor prognosis. Independent G9a and DNMT1 pharmacological targeting synergistically inhibited HCC cell growth. CM‐272 potently reduced HCC and LX2 cells proliferation and quelled tumor growth, particularly in HCC+LX2 xenografts. Mechanistically, CM‐272 inhibited the metabolic adaptation of HCC cells to hypoxia and induced a differentiated phenotype in HCC and fibrogenic cells. The expression of the metabolic tumor suppressor gene fructose‐1,6‐bisphosphatase (FBP1), epigenetically repressed in HCC, was restored by CM‐272. Conclusion: Combined targeting of G9a/DNMT1 with compounds such as CM‐272 is a promising strategy for HCC treatment. Our findings also underscore the potential of differentiation therapy in HCC.