PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in ...inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0-G1 transition. The crude PAO1-CDPs mixture promoted cell death in HeLa cells in a dose-dependent manner, showing efficacy similar to that of isolated PAO1-CDPs (LD
of 60-250 µM) and inducing apoptosis with EC
between 0.6 and 3.0 µM. Moreover, PAO1-CDPs showed a higher proapoptotic activity (~10³-10⁵ fold) than their synthetic analogs did. Subsequently, the PAO1-CDPs affected mitochondrial membrane potential and induced apoptosis by caspase-9-dependent pathway. The mechanism of inhibition of cells proliferation in HeLa cells involves inhibition of phosphorylation of both Akt-S473 and S6k-T389 protein kinases, showing a cyclic behavior of their expression and phosphorylation in a time and concentration-dependent fashion. Taken together our findings indicate that PI3K-Akt-mTOR-S6k signaling pathway blockage is involved in the antiproliferative effect of the PAO1-CDPs.
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•SALEN–Mn(III) and SALHD–Mn(III) were immobilized in Al-pillared bentonite.•Simultaneous pillaring/encapsulation was the best procedure.•Excellent catalytic performance in HCO3− ...assisted cyclohexene epoxidation.
Mn(3,5-dtSALEN)Cl (I) and Mn(3,5-dtSALHD)Cl (II) complexes (3,5-dtSALEN=N,N′-bis(3,5-di-tert-butylsalicylaldehyde)ethylenediamine; 3,5-dtSALHD=N′N-bis-(3,5-di-tert-butylsalicylaldehyde)-1,2-cyclohexanediamine) were successfully encapsulated within a natural bentonite by using three preparative approaches: (A) direct adsorption of every metal complex on the previously Al-pillared bentonite, Al-PILC; (B) two-step liquid phase methodology: (i) cationic adsorption of Mn2+ in Al-PILC by substituting its residual cationic exchange capacity (CEC), followed by (ii) diffusion of either 3,5-dtSALEN or 3,5-dtSALHD ligands, for in-situ generation of the corresponding interlayered metal complexes; and (C) simultaneous pillaring/encapsulation of the complexes on the raw starting clay. The materials were characterized by cationic exchange capacity, X-ray diffraction, atomic absorption, FT-Infrared and UV–vis spectroscopies, and N2 adsorption at 77K. The physical encapsulation of the complexes into final materials was proven by spectroscopic analyses. Method C yielded both highest metal incorporation and enhanced basal space on the modified clay. All materials showed to be active catalysts in cyclohexene epoxidation with hydrogen peroxide using acetonitrile as solvent (0.79atm, 293K). Addition of sodium bicarbonate as co-catalyst led to enhanced conversion (100%) and selectivity (70%) towards the epoxide in the presence of such a kind of heterogeneized metal-complex catalysts. The catalysts were stable and reusable along at least two catalytic cycles.
South America lost around 52 genera of mammals during a worldwide event known as the Late Quaternary Extinction episode. More than 80% of South American mammals weighing > 44 kg succumbed. Analysis ...of the megafaunal extinction chronology in relation to human arrival and major climate changes have revealed slightly different extinction patterns in different eco‐regions of the continent, highlighting the importance of detailed regional analysis in order to understand how the possible drivers of extinction operated. Here we present an analysis of the megafaunal extinction in the Última Esperanza (UE) area of southwestern Patagonia, Chile. We have compiled a comprehensive chronology of megafaunal extinctions and earliest human occupation between 18–7 cal ka BP, based on radiocarbon dates from published literature. We calculated confidence intervals using the GRIWM method to estimate the times of human arrival and megafaunal local extinctions, and then compared these events to the timing of major climate and vegetation changes, fire frequency increase, and the Reclús volcanic eruption. Our results suggest that a combination of human impacts and climate–vegetation change drove megafaunal extinctions in the UE area, with the balance of factors being taxon specific; the volcanic eruption does not seem to have exacerbated extinctions. Competition between humans and mega‐carnivores seems to be the most plausible cause for the extinction of the mega‐carnivores. Coexistence of humans with extinct horses, extinct camels, and mylodonts for several thousand years rules out a scenario of blitzkrieg overkill of megafauna by humans. The transition of vegetation from cold grasslands to Nothofagus forests corresponds with the disappearance of Hippidion saldiasi and Lama cf. owenii. The later full establishment of Nothofagus forests and an increasing fire frequency coincided with the disappearance of mylodonts. A climate‐driven reduction of open environments plausibly reduced herbivore's populations making them susceptible to local extinction.
One of the effects of climate change in warm areas is the asynchrony between the dates of the technological and the phenolic maturity of grapes. This is important because the quality and color ...stability of red wines are directly related to the content and distribution of phenolic compounds. A novel alternative that has been proposed to delay grape ripening and make it coincide with a seasonal period more favorable for the formation of phenolic compounds is crop forcing. This consists of severe green pruning after flowering, when the buds of the following year have already differentiated. In this way, the buds formed during the same season are forced to sprout, initiating a new delayed cycle. The aim of the present work is to study the effect on the phenolic composition and color of wines elaborated from vines fully irrigated (C), grown using conventional non-forcing (NF) and forcing (F) techniques (C-NF and C-F), and wines from vines subjected to regulated irrigation (RI), grown using NF and F techniques (RI-NF and RI-F). The trial was carried out in an experimental vineyard of the Tempranillo variety located in a semi-arid area (Badajoz, Spain) in the 2017-2019 seasons. The wines (four by treatment) were elaborated and stabilized according to the classic methodologies for red wine. All wines had the same alcohol content, and malolactic fermentation was not carried out in any of them. Anthocyanin profiles were analyzed by HPLC, and total polyphenolic content, anthocyanin content, catechin content, the contribution to color due to co-pigmented anthocyanins, and various chromatic parameters were also determined. Although a significant effect of year was found for almost all the parameters analyzed, a general increasing trend in F wines was found for most of them. The anthocyanin profile of F wines was found to differ from that of C wines, especially in delphinidin, cyanidin, petunidin, and peonidin content. These results indicate that by using the forcing technique it was possible to increase the polyphenolic content by ensuring that the synthesis and accumulation of these substances occurred at more suitable temperatures.
Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor-mediated endocytosis. The mechanism for iron release is pH-dependent and involves ...conformational changes in the protein, thus making it an attractive system for possible biomedical applications. In this contribution, two powerful X-ray techniques, namely Macromolecular X-ray Crystallography (MX) and Small Angle X-ray Scattering (SAXS), were used to study the conformational changes of iron-free (apo) and iron-loaded (holo) transferrin in crystal and solution states, respectively, at three different pH values of physiological relevance. A crystallographic model of glycosylated apo-Tf was obtained at 3.0 Å resolution, which did not resolve further despite many efforts to improve crystal quality. In the solution, apo-Tf remained mostly globular in all the pH conditions tested; however, the co-existence of closed, partially open, and open conformations was observed for holo-Tf, which showed a more elongated and flexible shape overall.
Information on familial resemblance is important for the design of effective family-based interventions. We aimed to quantify familial correlations and estimate the proportion of variation ...attributable to genetic and shared environmental effects (i.e., familiality) for dietary intake variables and determine whether they vary by generation, sex, dietary quality, or by the age of the children. The study sample consisted of 1435 families (1007 mothers, 438 fathers, 1035 daughters, and 1080 sons) from the multi-center I.Family study. Dietary intake was assessed in parents and their 2-19 years old children using repeated 24-h dietary recalls, from which the usual energy and food intakes were estimated with the U.S. National Cancer Institute Method. Food items were categorized as healthy or unhealthy based on their sugar, fat, and fiber content. Interclass and intraclass correlations were calculated for relative pairs. Familiality was estimated using variance component methods. Parent-offspring (
= 0.11-0.33), sibling (
= 0.21-0.43), and spouse (
= 0.15-0.33) correlations were modest. Parent-offspring correlations were stronger for the intake of healthy (
= 0.33) than unhealthy (
= 0.10) foods. Familiality estimates were 61% (95% CI: 54-68%) for the intake of fruit and vegetables and the sum of healthy foods and only 30% (95% CI: 23-38%) for the sum of unhealthy foods. Familial factors explained a larger proportion of the variance in healthy food intake (71%; 95% CI: 62-81%) in younger children below the age of 11 than in older children equal or above the age of 11 (48%; 95% CI: 38-58%). Factors shared by family members such as genetics and/or the shared home environment play a stronger role in shaping children's intake of healthy foods than unhealthy foods. This suggests that family-based interventions are likely to have greater effects when targeting healthy food choices and families with younger children, and that other sorts of intervention are needed to address the intake of unhealthy foods by children.
Breakfast is an important source of key nutrients in the diet. For this reason, the aim of this review was to investigate the associations between breakfast consumption and daily micronutrients ...intake in both children and adolescents (aged 2-18 years). A peer-reviewed systematic search was conducted in three datasets (PubMed, Scopus and Cochrane Library) in February 2020 in English and Spanish. Two independent reviewers evaluated 3188 studies considering the AXIS critical appraisal and PRISMA methodologies. Meta-analysis was carried out comparing results according to type of breakfast consumed (Ready to eat cereals (RTEC) breakfast or other types of breakfast) and breakfast skipping. Thirty-three articles were included in the systematic review (SR) and 7 in the meta-analysis. In the SR, we observed that those children and adolescents who usually consume RTEC at breakfast had a higher consumption of B-vitamins than those not consuming RTEC at breakfast. Breakfast consumers had a higher mineral intake (iron, calcium, magnesium, potassium, zinc, and iodine) than breakfast skippers. In the Meta-Analysis, RTEC consumers had significantly higher vitamin C intake than breakfast skippers (SMD, -4.12; 95% confidence intervals (CI): -5.09, -3.16). Furthermore, those children who usually consume breakfast had significantly higher daily intake of calcium than breakfast skippers (SMD, -7.03; 95%CI: -9.02, -5.04). Our review proposes that breakfast consumption seems to be associated with higher daily micronutrients intake than breakfast skippers.
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