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Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.
We study the thermal Markovian diffusion of tracer particles in a 2D medium with spatially varying diffusivity D(r), mimicking recently measured, heterogeneous maps of the apparent diffusion coefficient in biological cells. For this heterogeneous diffusion process (HDP) we analyse the mean squared displacement (MSD) of the tracer particles, the time averaged MSD, the spatial probability density function, and the first passage time dynamics from the cell boundary to the nucleus. Moreover we examine the non-ergodic properties of this process which are important for the correct physical interpretation of time averages of observables obtained from single particle tracking experiments. From extensive computer simulations of the 2D stochastic Langevin equation we present an in-depth study of this HDP. In particular, we find that the MSDs along the radial and azimuthal directions in a circular domain obey anomalous and Brownian scaling, respectively. We demonstrate that the time averaged MSD stays linear as a function of the lag time and the system thus reveals a weak ergodicity breaking. Our results will enable one to rationalise the diffusive motion of larger tracer particles such as viruses or submicron beads in biological cells.
Time-Travel-Treasures
(2014)
Vielheit statt Einheit
(2014)
Wir alle sind Nachbarn?
(2014)
Heimatgefühl als Schlüssel?
(2013)
Chillen gestern
(2013)
Von wegen Kinderspiel
(2013)
Herzog macht Stadt
(2012)
Bilder machen Geschichte
(2012)
The term “bilateral deficit” (BLD) has been used to describe a reduction in performance during bilateral contractions when compared to the sum of identical unilateral contractions. In old age, maximal isometric force production (MIF) decreases and BLD increases indicating the need for training interventions to mitigate this impact in seniors. In a cross-sectional approach, we examined age-related differences in MIF and BLD in young (age: 20–30 years) and old adults (age: >65 years). In addition, a randomized-controlled trial was conducted to investigate training-specific effects of resistance vs. balance training on MIF and BLD of the leg extensors in old adults. Subjects were randomly assigned to resistance training (n = 19), balance training (n = 14), or a control group (n = 20). Bilateral heavy-resistance training for the lower extremities was performed for 13 weeks (3 × / week) at 80% of the one repetition maximum. Balance training was conducted using predominately unilateral exercises on wobble boards, soft mats, and uneven surfaces for the same duration. Pre- and post-tests included uni- and bilateral measurements of maximal isometric leg extension force. At baseline, young subjects outperformed older adults in uni- and bilateral MIF (all p < .001; d = 2.61–3.37) and in measures of BLD (p < .001; d = 2.04). We also found significant increases in uni- and bilateral MIF after resistance training (all p < .001, d = 1.8-5.7) and balance training (all p < .05, d = 1.3-3.2). In addition, BLD decreased following resistance (p < .001, d = 3.4) and balance training (p < .001, d = 2.6). It can be concluded that both training regimens resulted in increased MIF and decreased BLD of the leg extensors (HRT-group more than BAL-group), almost reaching the levels of young adults.
On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy
(2014)
Gemcitabine (2′,2′-difluorocytidine) is a well-known radiosensitizer routinely applied in concomitant chemoradiotherapy. During irradiation of biological media with high-energy radiation secondary low-energy (<10 eV) electrons are produced that can directly induce chemical bond breakage in DNA by dissociative electron attachment (DEA). Here, we investigate and compare DEA to the three molecules 2′-deoxycytidine, 2′-deoxy-5-fluorocytidine, and gemcitabine. Fluorination at specific molecular sites, i.e., nucleobase or sugar moiety, is found to control electron attachment and subsequent dissociation pathways. The presence of two fluorine atoms at the sugar ring results in more efficient electron attachment to the sugar moiety and subsequent bond cleavage. For the formation of the dehydrogenated nucleobase anion, we obtain an enhancement factor of 2.8 upon fluorination of the sugar, whereas the enhancement factor is 5.5 when the nucleobase is fluorinated. The observed fragmentation reactions suggest enhanced DNA strand breakage induced by secondary electrons when gemcitabine is incorporated into DNA.
Das Bundesland
(2010)
Das Land und die Bezirke
(2010)
Die Provinz
(2010)
Die Mark
(2010)
Jede Software ist "Social"
(2010)
KMDL® v2.2
(2014)