Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort
(2020)
BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.
RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.
CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
We present a data set of images of the gravitationally lensed quasar Q2237+0305, that was obtained at the Apache Point Observatory (APO) between June 1995 and January 1998. Although the images were taken under variable, often poor seeing conditions and with coarse pixel sampling, photometry is possible for the two brighter quasar images A and B with the help of exact quasar image positions from HST observations. We obtain a light curve with 73 data points for each of the images A and B. There is evidence for a long (ga 100 day) brightness peak in image A in 1996 with an amplitude of about 0.4 to 0.5 mag (relative to 1995), which indicates that microlensing has been taking place in the lensing galaxy. Image B does not vary much over the course of the observation period. The long, smooth variation of the light curve is similar to the results from the OGLE monitoring of the system (Wozniak et al. cite{Wozniak00}). Based on observations obtained with the Apache Point Observatory 3.5-meter telescope, which is owned and operated by the Astrophysical Research Consortium.
The active metabolite of vitaminA, retinoic acid (RA), plays an important role in the female reproductive system. The synthesis of RA is tightly regulated by the activity of retinaldehyde dehydrogenases (Raldh). Among these, Raldh1 and Raldh2 exhibit specific temporal and spatial expression patterns in the mouse uterus, both during the oestrous cycle and early pregnancy. In the present study, we have assessed whether oestradiol and progesterone directly influence the uterine expression of Raldh1 and Raldh2 in ovariectomised mice. We investigated the effect of gestagen (promegestone 0.3 mg kg(-1) bodyweight), oestrogen (oestradiol 3 mu g kg(-1) bodyweight) and their combination on the uterine expression of Raldh2. Expression was analysed using in situ hybridisation and quantified using real-time detection reverse transcription-polymerase chain reaction. The results show that the expression of Raldh2 is rapidly (within 1-4 h) induced in stromal cells by oestrogen, but not by gestagen, treatment, whereas combined oestrogen + gestagen treatment leads to a more prolonged (48 h) response. In contrast, oestrogen, but not progesterone, treatment downregulates (within 4 - 24 h) Raldh1 expression in the uterine glandular epithelium. We conclude that the uterine RA concentrations are regulated by oestrogens via an effect on the expression of the Raldh synthesising enzymes. Such a regulation is consistent with the natural fluctuations of Raldh expression during the oestrous cycle, early pregnancy and blastocyst implantation
Synthesis of 3D flower-like zinc-nitrilotriacetic acid (ZnNTA) mesocrystals and their conformal transformation to hierarchically porous N-doped carbon superstructures is reported. During the solvothermal reaction, 2D nanosheet primary building blocks undergo oriented attachment and mesoscale assembly forming stacked layers. The secondary nucleation and growth preferentially occurs at the edges and defects of the layers, leading to formation of 3D flower-like mesocrystals comprised of interconnected 2D micropetals. By simply varying the pyrolysis temperature (550-1000 degrees C) and the removal method of in the situ-generated Zn species, nonporous parent mesocrystals are transformed to hierarchically porous carbon flowers with controllable surface area (970-1605 m(2) g(-1)), nitrogen content (3.4-14.1 at%), pore volume (0.95-2.19 cm(3) g(-1)), as well as pore diameter and structures. The carbon flowers prepared at 550 degrees C show high CO2/N-2 selectivity due to the high nitrogen content and the large fraction of (ultra)micropores, which can greatly increase the CO2 affinity. The results show that the physicochemical properties of carbons are highly dependent on the thermal transformation and associated pore formation process, rather than directly inherited from parent precursors. The present strategy demonstrates metal-organic mesocrystals as a facile and versatile means toward 3D hierarchical carbon superstructures that are attractive for a number of potential applications.
Electron beam irradiation of poly(vinyl methyl ether) films : 1. Synthesis and film topography
(2005)
Temperature-sensitive hydrogel layers on silicon (Si) substrates were synthesized by electron beam irradiation of spin-coated poly(vinyl methyl ether) (PVME) films. The influences of the used solvent, the polymer concentration, and the spinning velocity on the homogeneity and the thickness of the PVME film were investigated. In the range of concentration c(p) = 1-15 wt% PVME in ethanol solution, homogeneous films with a thickness between d = 50 nm and 1.7 mu m were obtained. The films were cross-linked by electron beam irradiation under inert atmosphere and analyzed by sol-gel- analysis. The results were compared with bulkgels formed by electron beam irradiation of PVME in the dry state. The film topography was analyzed by high-resolution field emission scanning electron microscopy and atomic force microscopy. An islandlike structure in the dry, swollen, and shrunken state of the hydrogel films was observed
Self-assembly of block copolymers is a significant area of polymer science. The self-assembly of completely water-soluble block copolymers is of particular interest, albeit a challenging task. In the present work the self-assembly of a linear-brush architecture block copolymer, namely poly(N-vinylpyrrolidone)-b-poly(oligoethylene glycol methacrylate) (PVP-b-POEGMA), in water is studied. Moreover, the assembled structures are crosslinked via alpha-CD host/guest complexation in a supramolecular way. The crosslinking shifts the equilibrium toward aggregate formation without switching off the dynamic equilibrium of double hydrophilic block copolymer (DHBC). As a consequence, the self-assembly efficiency is improved without extinguishing the unique DHBC self-assembly behavior. In addition, decrosslinking could be induced without a change in concentration by adding a competing complexation agent for alpha-CD. The self-assembly behavior was followed by DLS measurement, while the presence of the particles could be observed via cryo-TEM before and after crosslinking.
In the present thesis, self-assembly of hydrophilic polymers, reinforced hydrogels and inorganic/polymer hybrids were examined. The thesis describes an avenue from polymer synthesis via various methods over polymer self-assembly to the formation of polymer materials that have promising properties for future applications.
Hydrophilic polymers were utilized to form multi-phase systems, water-in-water emulsions and self-assembled structures, e.g. particles/aggregates or hollow structures from completely water-soluble building blocks. The structuring of aqueous environments by hydrophilic homo and block copolymers was further utilized in the formation of supramolecular hydrogels with compartments or specific thermal behavior. Furthermore, inorganic graphitic carbon nitride (g-CN) was utilized as photoinitiator for hydrogel formation and as reinforcer for hydrogels. As such, hydrogels with remarkable mechanical properties were synthesized, e.g. high compressibility, high storage modulus or lubricity. In addition, g-CN was combined with polymers for a broad range of materials, e.g. coatings, films or latex, that could be utilized in photocatalytic applications. Another inorganic material class was combined with polymers in the present thesis as well, namely metal-organic frameworks (MOFs). It was shown that the pore structure of MOFs enables improved control over tacticity and achievement of high molar masses. Furthermore, MOF-based polymerization catalysis was introduced with improved control for coordinating monomers, catalyst recyclability and decreased metal contamination in the product. Finally, the effect of external influence on MOF morphology was studied, e.g. via solvent or polymer additives, which allowed the formation of various MOF structures.
Overall, advances in several areas of polymer science are presented in here. A major topic of the thesis was hydrophilic polymers and hydrogels that currently constitute significant materials in the polymer field due to promising future applications in biomedicine. Moreover, the combination of polymers with materials from other areas of research, i.e. g-CN and MOFs, provided various new materials with remarkable properties also of interest for applications in the future, e.g. coatings, particle structures and catalysis.
Herein, an approach via combination of confined porous textures and reversible deactivation radical polymerization techniques is proposed to advance synthetic polymer chemistry, i.e., a connection of metal-organic frameworks (MOFs) and activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). Zn-2(benzene-1,4-dicarboxylate)2(1,4-diazabicyclo[2.2.2]-octane) [Zn-2(bdc)(2)(dabco)] is utilized as a reaction environment for polymerization of various methacrylate monomers (methyl, ethyl, benzyl, and isobornyl methacrylate) in a confined nanochannel, resulting in polymers with control over dispersity, end functionalities, and tacticity with respect to distinct molecular size. To refine and reconsolidate the compartmentation effect on polymer regularity, initiator-functionalized Zn MOF was synthesized via cocrystallization with an initiator-functionalized ligand, 2-(2-bromo-2-methylpropanamido)-1,4-benzenedicarboxylate (Brbdc), in different ratios (10%, 20%, and 50%). Through the embedded initiator, surface-initiated ARGET ATRP was directly initiated from the walls of the nanochannels. The obtained polymers had a high molecular weight up to 392 000. Moreover, a significant improvement in end-group functionality and stereocontrol was observed, entailing polymers with obvious increments in isotacticity. The results highlight a combination of MOFs and ATRP that is a promising and universal methodology to prepare various polymers with high molecular weight exhibiting well-defined uniformity in chain length and microstructure as well as the preserved chain-end functionality.
This study investigated vitamin A compounds in the plasma of healthy free-ranging Central European raptors with different feeding strategies. Plasma samples of nestlings of white-tailed sea eagle [white-tailed sea eagle (WTSE), Haliaeetus albicilla) (n = 32), osprey (Pandion haliaetus) (n = 39), northern goshawk (Accipiter gentilis) (n = 25), common buzzard (Buteo buteo) (n = 31), and honey buzzard (Pernis apivorus) (n = 18) and adults of WTSE (n = 10), osprey (n = 31), and northern goshawk (n = 45) were investigated with reversed-phase-high-performance liquid chromatography (RP-HPLC). In WTSE, northern goshawks and common buzzards retinol were the main plasma component of vitamin A, whilst in ospreys and honey buzzards, 3,4-didehydroretinol predominated. The median of the retinol plasma concentration in the nestlings group ranged from 0.12 to 3.80 mu M and in the adult group from 0.15 to 6.13 mu M. Median plasma concentrations of 3,4-didehydroretinol in nestlings ranged from 0.06 to 3.55 mu M. In adults, northern goshawks had the lowest plasma concentration of 3,4-didehydroretinol followed by WTSE and ospreys. The plasma of all investigated species contained retinyl esters (palmitate, oleate, and stearate). The results show considerable species-specific differences in the vitamin A plasma concentrations that might be caused by different nutrition strategies.
To address one of the central questions of plate tectonics-How do large transform systems work and what are their typical features?-seismic investigations across the Dead Sea Transform (DST), the boundary between the African and Arabian plates in the Middle East, were conducted for the first time. A major component of these investigations was a combined reflection/ refraction survey across the territories of Palestine, Israel and Jordan. The main results of this study are: (1) The seismic basement is offset by 3-5 km under the DST, (2) The DST cuts through the entire crust, broadening in the lower crust, (3) Strong lower crustal reflectors are imaged only on one side of the DST, (4) The seismic velocity sections show a steady increase in the depth of the crust-mantle transition (Moho) from 26 km at the Mediterranean to 39 km under the Jordan highlands, with only a small but visible, asymmetric topography of the Moho under the DST. These observations can be linked to the left-lateral movement of 105 km of the two plates in the last 17 Myr, accompanied by strong deformation within a narrow zone cutting through the entire crust. Comparing the DST and the San Andreas Fault (SAF) system, a strong asymmetry in subhorizontal lower crustal reflectors and a deep reaching deformation zone both occur around the DST and the SAF. The fact that such lower crustal reflectors and deep deformation zones are observed in such different transform systems suggests that these structures are possibly fundamental features of large transform plate boundaries