Membraneless compartments, such as complex coacervates, have been hypothesized as plausible prebiotic micro-compartments due to their ability to sequester RNA; however, their compatibility with ...essential RNA World chemistries is unclear. We show that such compartments can enhance key prebiotically-relevant RNA chemistries. We demonstrate that template-directed RNA polymerization is sensitive to polycation identity, with polydiallyldimethylammonium chloride (PDAC) outperforming poly(allylamine), poly(lysine), and poly(arginine) in polycation/RNA coacervates. Differences in RNA diffusion rates between PDAC/RNA and oligoarginine/RNA coacervates imply distinct biophysical environments. Template-directed RNA polymerization is relatively insensitive to Mg
concentration when performed in PDAC/RNA coacervates as compared to buffer, even enabling partial rescue of the reaction in the absence of magnesium. Finally, we show enhanced activities of multiple nucleic acid enzymes including two ribozymes and a deoxyribozyme, underscoring the generality of this approach, in which functional nucleic acids like aptamers and ribozymes, and in some cases key cosolutes localize within the coacervate microenvironments.
The mycotoxin alternariol (AOH) is found in food and beverages infected by
Alternaria alternata. Because consumption of foodstuffs contaminated with
A. alternata has been implicated in an elevated ...incidence of esophageal carcinogenesis, we have investigated the estrogenic potential, the effect on cell proliferation, and the genotoxic effect of AOH in cultured mammalian cells.
AOH replaced E2 from isolated human estrogen receptors α and β and increased the level of alkaline phosphatase (ALP) mRNA and the enzymatic activity of ALP in a human endometrial adenocarcinoma cell line (Ishikawa cells). The estrogenicity of AOH was about 0.01% of that of E2. The effects in Ishikawa cells were reversed by the ER antagonist ICI 182,780.
Analysis of cell proliferation by flow cytometry and microscopy of Ishikawa and Chinese hamster V79 cells revealed that AOH inhibited cell proliferation by interference with the cell cycle.
The genotoxic potential was assessed by the micronucleus (MN) assay and immunochemical differentiation between MN containing whole chromosomes (kinetochore-positive) and DNA fragments (kinetochore-negative) in Ishikawa and V79 cells. AOH induced kinetochore-negative MN in both cell lines.
This is the first report on the estrogenic potential, inhibition of cell proliferation and clastogenicity of AOH in Ishikawa and V79 cells in vitro.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We derive the upper limit for power extraction from an open-channel flow with lateral bypass representing tidal power or run-of-river plants for the complete range of blockage
$\unicodeSTIX{x1D70E}$
..., Froude number
$Fr_{2}$
and turbine head
$H_{T}$
. For this, a generic turbine model is used: a momentum and energy sink distributed over the geometric blocking
$\unicodeSTIX{x1D70E}$
of the channel allowing lateral bypass. It is indicated that existing models neglect important aspects of the free-surface deformation due to the energy extraction, yielding unphysical behaviour at high blockage, high Froude number or high turbine head. The asymptotic validity of existing theories for
$\unicodeSTIX{x1D70E}\rightarrow 0$
,
$Fr_{2}\rightarrow 0$
,
$H_{T}\rightarrow 0$
becomes evident: firstly, by comparing existing theories with the presented general theory; and secondly, by the experimental validation of the existing and presented theories. The accompanying systematic experimental study comprises a wide range of blockage ratios,
$0.25\leqslant \unicodeSTIX{x1D70E}\leqslant 1.0$
, of downstream Froude numbers,
$0.2\leqslant Fr_{2}\leqslant 0.5$
, and of different turbine heads,
$H_{T}$
, measured in multiples of the specific energy
$E_{0}$
of the undisturbed flow. The subsequent model-based optimisation allows an indication of the optimal turbine head
$H_{T,opt}/E_{0}$
as well as the maximal obtainable coefficient of performance
$C_{P,opt}$
as a function of
$\unicodeSTIX{x1D70E}$
and
$Fr_{2}$
or downstream water depth
$h_{2}/E_{0}$
, respectively. The theory reveals points of operation in which there is a surge wave in the tailwater. The new physical insight and optimisation results may serve for plant design and operation, as well as for investment decisions.
Zearalenone (ZEA) is a macrocyclic β-resorcylic acid lactone produced by numerous species of Fusarium. It frequently contaminates corn and cereal products in many regions of the world. The biological ...activity of ZEA is dominated by its pronounced oestrogenicity, which is even enhanced in certain reductive metabolites. This review updates the metabolism in fungi, plants and mammalian systems, as well as the pharmacokinetics of ZEA. The present evidence for the hormonal effects of the parent mycoestrogen and some of its metabolites in vitro and in farm and experimental animals in vivo is reviewed, together with its association with endocrine-disruptive effects in humans. Possible mechanisms of the oestrogenic and carcinogenic activity of ZEA are discussed and future areas of research proposed.
To evaluate the influence of ocular shell biomechanical characteristics on corneal deformation response to an air puff.
The Ohio State University, Columbus, Ohio, USA.
Experimental study.
Twenty-four ...eyes of 12 human donors were obtained in matched pairs. One eye was secured in a purpose-designed whole globe mount (whole-globe group). The cornea from the fellow eye was placed in a Barron artificial anterior chamber (artificial-chamber group). The corneas were mounted sequentially and connected to a pressure-control system. Deformation data were acquired using the Corvis ST, a dynamic Scheimpflug analyzer. Internal pressure was set to 10, 20, 30, 40, and 50 mm Hg; at least 4 examinations were performed at each pressure.
Statistically significantly higher maximum deformation amplitude was observed in the whole-globe group than in the artificial-chamber group at all pressures. The mean amplitude differences were 1.006 mm ± 0.238 SD, 0.614 ± 0.137 mm, 0.384 ± 0.099 mm, 0.229 ± 0.087 mm, and 0.133 ± 0.068 mm at 10, 20, 30, 40, and 50 mm Hg, respectively (P<.0001, P<.0001, P<.0001, P<.0001, and P<.0002, respectively). Nonlinear regression of the deformation amplitude differences between pairs showed a significant decrease with increasing pressure (P<.0001, R(2) = 0.8385).
The deformation response to an air puff was affected by the type of mount used, with a stiffer shell producing a stiffer corneal response and decreasing differences at higher internal pressures. In vivo air-puff examinations may be affected by scleral stiffness in addition to the cornea.
Dr. Roberts is a consultant to Oculus Optikgeräte GmbH and Ziemer Ophthalmic Systems AG and has received research funding from Carl Zeiss Meditec AG and travel funds from Sooft Italia. No other author has a financial or proprietary interest in any material or method mentioned.
Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for ...therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population.
The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018.
CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors.
Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes
Endele et al. (2010)
Nature Genetics 42(11):1021–1026
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The relationship between placental and fetal brain growth is poorly understood and difficult to assess. The objective of this study was to interrogate placental and fetal brain growth in healthy ...pregnancies and those complicated by fetal growth restriction (FGR).
In a prospective, observational study, pregnant women with normal pregnancies or pregnancies complicated by FGR underwent fetal magnetic resonance imaging (MRI). Placental, global and regional brain volumes were calculated.
A total of 114 women (79 controls and 35 FGR) underwent MRI (median gestational age (GA) 30 weeks, range 18 to 39). All measured volumes increased exponentially with advancing GA. Placental, total brain, cerebral and cerebellar volumes were smaller in FGR compared with controls (P<0.05). Increasing placental volume was associated with increasing cerebral and cerebellar volumes (P<0.05).
Quantitative fetal MRI can accurately detect decreased placental and brain volumes in pregnancies with FGR and may provide insight into the timing and mechanisms of brain injury in FGR.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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