5-azacytidine-induced tumorous transformation and DNA hypomethylation in Nicotiana tissue cultures

The phenomenon of habituation is considered in plant tissue cultures to be a real process of chemical tumorogenesis; the cultures acquire the capacity of autonomous growth in a hormone-free medium under the influence of a variety of chemical and physical agents. Treatments with 5-azacytidine (AzaC) of in vitro cultured cells of the Nicotiana glauca x N. langsdorffii nontumorous hybrid (NNT) during the culture cycle led to the induction of a habituated phenotype. The repetitive DNA sequences showed a significant lower level of endogenous methylation in the treated cells in comparison with the normal ones. It is worth noting that it was impossible until now to habituate this strain by conventional methods and that the treatments were effective only in the first 5 days of subculturing; various evidence (cytological and biochemical) pointed out a phenomenon of DNA amplification, occurring in the same period. Moreover, analysis of DNA from control and treated cells shows the induction of variations in the endogenous methylation pattern by AzaC in a critical period of cell culture. These results suggest that demethylation can act as a switch from hormone-dependent to autonomous proliferation by activation of genes coding for or regulating the synthesis of growth factors.     

Wherever I may roam—Human activity alters movements of red deer (Cervus elaphus) and elk (Cervus canadensis) across two continents

Human activity and associated landscape modifications alter the movements of animals with consequences for populations and ecosystems worldwide. Species performing long-distance movements are thought to be particularly sensitive to human impact. Despite the increasing anthropogenic pressure, it remains challenging to understand and predict animals' responses to human activity. Here we address this knowledge gap using 1206 Global Positioning System movement trajectories of 815 individuals from 14 red deer (Cervus elaphus) and 14 elk (Cervus canadensis) populations spanning wide environmental gradients, namely the latitudinal range from the Alps to Scandinavia in Europe, and the Greater Yellowstone Ecosystem in North America. We measured individual-level movements relative to the environmental context, or movement expression, using the standardized metric Intensity of Use, reflecting both the directionality and extent of movements. We expected movement expression to be affected by resource (Normalized Difference Vegetation Index, NDVI) predictability and topography, but those factors to be superseded by human impact. Red deer and elk movement expression varied along a continuum, from highly segmented trajectories over relatively small areas (high intensity of use), to directed transitions through restricted corridors (low intensity of use). Human activity (Human Footprint Index, HFI) was the strongest driver of movement expression, with a steep increase in Intensity of Use as HFI increased, but only until a threshold was reached. After exceeding this level of impact, the Intensity of Use remained unchanged. These results indicate the overall sensitivity of Cervus movement expression to human activity and suggest a limitation of plastic responses under high human pressure, despite the species also occurring in human-dominated landscapes. Our work represents the first comparison of metric-based movement expression across widely distributed populations of a deer genus, contributing to the understanding and prediction of animals' responses to human activity.     

Effects of Intravenous Infusion of Phosphorothioate Oligonucleotides on Coagulation,Complement Activation and Hemodynamics

Abstract

Several acute toxicities in monkeys have been associated with administration of phosphorothioate oligonucleotides including effects on coagulation and complement cascades. These effects are transient in nature and the severity is closely associated with peak plasma concentrations of the oligonucleotide. Similar properties have been observed for several oligonucleotides with different base sequences.     

Corticomotor correlates of somatosensory reaction time and variability in individuals with post concussion symptoms

Abstract

Persistent post concussion symptoms (PPCS) describe the condition when an individual experiences chronic symptoms, particularly fatigue, beyond the expected time of recovery. The aim of this study was to quantify the effect of fatigue and related ongoing symptoms on somatosensory and corticomotor pathways using reaction time (RT) testing, and single-pulse and paired-pulse transcranial magnetic stimulation (TMS). Eighty-three participants (nine female, mean age 37.9?±?11.5?years) were divided into two groups (persistent symptoms versus asymptomatic) following self-report based upon previously published clinical symptom scores. All participants completed somatosensory and visuomotor RT testing, as well as corticomotor excitability and inhibition measurements via TMS. Participants in the persistent symptom group (n?=?38) reported greater number of previous concussions (t?=?2.81, p?=?0.006) and significantly higher levels of fatigue and related symptoms in the asymptomatic group (n?=?45; t?=?11.32, p?<?0.006). Somatosensory RT showed significant slowing and increased variability in the persistent symptoms group (p?<?0.001), however no significant differences were observed between groups for visuomotor RTs. Transcranial magnetic stimulation revealed differences between groups for intracortical inhibition at all stimulus intensities and paired pulse measures. The results indicate that somatosensory and corticomotor systems reflect on-going fatigue. From a practical perspective, objective and simplistic measures such as somatosensory and corticomotor measures can be used in the assessment of PPCS and gauging the efficacy of post concussion rehabilitation programmes.     

Conscientious objection in healthcare: How much discretionary space best supports good medicine?

Daniel Sulmasy has recently argued that good medicine depends on physicians having a wide discretionary space in which they can act on their consciences. The only constraints Sulmasy believes we should place on physicians’ discretionary space are those defined by a form of tolerance he derives from Locke, whereby people can publicly act in accordance with their personal religious and moral beliefs as long as their actions are not destructive to society. Sulmasy also claims that those who would reject physicians’ right to conscientious objection eliminate discretionary space, thus undermining good medicine and unnecessarily limiting religious freedom. I argue that, although Sulmasy is correct that some discretionary space is necessary for good medicine, he is wrong in thinking that proscribing conscientious objection entails eliminating discretionary space. I illustrate this using Julian Savulescu and Udo Schuklenk’s system for restricting conscientious objections as a counter‐example. I then argue that a narrow discretionary space constrained by professional ideals will promote good medicine better than Sulmasy’s wider discretionary space constrained by his conception of tolerance. Sulmasy’s version of discretionary space would have us tolerate actions that are at odds with aspects of good medicine, including aspects that Sulmasy himself explicitly values, such as fiduciary duty. Therefore, if we want the degree of religious freedom in the public sphere that Sulmasy favours then we must decide whether it is worth the cost to the healthcare system.     

Inhibition of liver protein degradation in vivo by intensive treatment with cycloheximide.

The AA in experiments performed on male rats treated with 0,5 mCi/kg of cycloheximide have observed an inhibition of liver protein degradation and have suggested two mechanism: 1) cycloheximide prevents the acute proteolytic response induced in fibroblast culture by exposure to serum-deficient media and in rat livers after perfusion probably by inhibiting the lysosomal - autophagic system, without modifications in total activity of lysosome proteinases. 2) It may be that protein degradation rate and level of lysosomal proteinases reinterrelated; the latter probably being a factor controlling the overall cell protein turnover rate.