Elterliches Züchtigungsrecht und Strafrecht in rechtsvergleichender Sicht

Diese Arbeit befasst sich mit dem elterlichen Züchtigungsrecht. Durch die Neufassung des § 1631 Abs. 2 BGB wurde ein solches spätestens abgeschafft. Diese Abschaffung und die sich daraus ergebenden Konsequenzen werden näher untersucht. Hierbei wird ein Rechtsvergleich zu dem schwedischen und dem österreichischem Recht gezogen. Mit Hilfe dieses rechtsvergleichenden Ansatzes soll untersucht werden, ob sich ein solches Verbot in der Praxis bewähren kann. Die Neufassung des § 1631 Abs. 2 BGB wird dann unter zivilrechtlichen und verfassungsrechtlichen Aspekten untersucht. Der Hauptteil dieser Arbeit befasst sich mit den strafrechtlichen Konsequenzen, die durch die Reform des § 1631 II BGB ausgelöst worden sind. Hierbei geht es um das zentrale Problem, wie eine Kriminalisierung der Familie verhindert werden kann. In diesem Rahmen werden die strafrechtlichen Konsequenzen in Bezug auf den Tatbestand der Nötigung (§ 240 StGB), der Freiheitsberaubung (§ 239 StGB) und der Beleidigung (185 StGB) betrachtet. Im Mittelpunkt der strafrechtlichen Untersuchung steht der Tatbestand der Körperverletzung. Es werden verschiedene Ansätze dargestellt und durchdiskutiert, wie eine unverhältnissmäßige Kriminalisierung von Eltern verhindert werden kann

A Bivalent Activatable Fluorescent Probe for Screening and Intravital Imaging of Chemotherapy‐Induced Cancer Cell Death

The detection and quantification of apoptotic cells is a key process in cancer research, particularly during the screening of anticancer therapeutics and in mechanistic studies using preclinical models. Intravital optical imaging enables high-resolution visualisation of cellular events in live organisms; however, there are few fluorescent probes that can reliably provide functional readouts in situ without interference from tissue autofluorescence. Here we report the design and optimisation of the fluorogenic probe Apotracker Red for real-time detection of cancer cell death. The strong fluorogenic behaviour, high selectivity, and excellent stability of Apotracker Red make it a reliable optical reporter for the characterisation of the effects of anticancer drugs in cells in vitro and for direct imaging of chemotherapy-induced apoptosis in vivo in mouse models of breast cancer

Insight into the mechanism of ferroptosis inhibition by ferrostatin-1

Ferroptosis is a form of cell death primed by iron and lipid hydroperoxides and prevented by GPx4. Ferrostatin-1 (fer-1) inhibits ferroptosis much more efficiently than phenolic antioxidants. Previous studies on the antioxidant efficiency of fer-1 adopted kinetic tests where a diazo compound generates the hydroperoxyl radical scavenged by the antioxidant. However, this reaction, accounting for a chain breaking effect, is only minimally useful for the description of the inhibition of ferrous iron and lipid hydroperoxide dependent peroxidation. Scavenging lipid hydroperoxyl radicals, indeed, generates lipid hydroperoxides from which ferrous iron initiates a new peroxidative chain reaction. We show that when fer-1 inhibits peroxidation, initiated by iron and traces of lipid hydroperoxides in liposomes, the pattern of oxidized species produced from traces of pre-existing hydroperoxides is practically identical to that observed following exhaustive peroxidation in the absence of the antioxidant. This supported the notion that the anti-ferroptotic activity of fer-1 is actually due to the scavenging of initiating alkoxyl radicals produced, together with other rearrangement products, by ferrous iron from lipid hydroperoxides. Notably, fer-1 is not consumed while inhibiting iron dependent lipid peroxidation. The emerging concept is that it is ferrous iron itself that reduces fer-1 radical. This was supported by electroanalytical evidence that fer-1 forms a complex with iron and further confirmed in cells by fluorescence of calcein, indicating a decrease of labile iron in the presence of fer-1. The notion of such as pseudo-catalytic cycle of the ferrostatin-iron complex was also investigated by means of quantum mechanics calculations, which confirmed the reduction of an alkoxyl radical model by fer-1 and the reduction of fer-1 radical by ferrous iron. In summary, GPx4 and fer-1 in the presence of ferrous iron, produces, by distinct mechanism, the most relevant anti-ferroptotic effect, i.e the disappearance of initiating lipid hydroperoxides

The Oxygen Paradox, the French Paradox, and age-related diseases

open46openDavies, Joanna M. S.; Cillard, Josiane; Friguet, Bertrand; Cadenas, Enrique; Cadet, Jean; Cayce, Rachael; Fishmann, Andrew; Liao, David; Bulteau, Anne-Laure; Derbré, Frédéric; Rébillard, Amélie; Burstein, Steven; Hirsch, Etienne; Kloner, Robert A.; Jakowec, Michael; Petzinger, Giselle; Sauce, Delphine; Sennlaub, Florian; Limon, Isabelle; Ursini, Fulvio; Maiorino, Matilde; Economides, Christina; Pike, Christian J.; Cohen, Pinchas; Salvayre, Anne Negre; Halliday, Matthew R.; Lundquist, Adam J.; Jakowec, Nicolaus A.; Mechta-Grigoriou, Fatima; Mericskay, Mathias; Mariani, Jean; Li, Zhenlin; Huang, David; Grant, Ellsworth; Forman, Henry J.; Finch, Caleb E.; Sun, Patrick Y.; Pomatto, Laura C. D.; Agbulut, Onnik; Warburton, David; Neri, Christian; Rouis, Mustapha; Cillard, Pierre; Capeau, Jacqueline; Rosenbaum, Jean; Davies, Kelvin J. A.Davies, Joanna M. S.; Cillard, Josiane; Friguet, Bertrand; Cadenas, Enrique; Cadet, Jean; Cayce, Rachael; Fishmann, Andrew; Liao, David; Bulteau, Anne-Laure; Derbré, Frédéric; Rébillard, Amélie; Burstein, Steven; Hirsch, Etienne; Kloner, Robert A.; Jakowec, Michael; Petzinger, Giselle; Sauce, Delphine; Sennlaub, Florian; Limon, Isabelle; Ursini, Fulvio; Maiorino, Matilde; Economides, Christina; Pike, Christian J.; Cohen, Pinchas; Salvayre, Anne Negre; Halliday, Matthew R.; Lundquist, Adam J.; Jakowec, Nicolaus A.; Mechta-Grigoriou, Fatima; Mericskay, Mathias; Mariani, Jean; Li, Zhenlin; Huang, David; Grant, Ellsworth; Forman, HENRY J.; Finch, Caleb E.; Sun, Patrick Y.; Pomatto, Laura C. D.; Agbulut, Onnik; Warburton, David; Neri, Christian; Rouis, Mustapha; Cillard, Pierre; Capeau, Jacqueline; Rosenbaum, Jean; Davies, Kelvin J. A

O simbolismo das condutas motoras

Não informado.Not informed

Innate Immunity and Cancer Pathophysiology

Chronic inflammation increases the risk of several cancers, including gastric, colon, and hepatic cancers. Conversely, tumors, similar to tissue injury, trigger an inflammatory response coordinated by the innate immune system. Cellular and molecular mediators of inflammation modulate tumor growth directly and by influencing the adaptive immune response. Depending on the balance of immune cell types and signals within the tumor microenvironment, inflammation can support or restrain the tumor. Adding to the complexity, research from the past two decades has revealed that innate immune cells are highly heterogeneous and plastic, with variable phenotypes depending on tumor type, stage, and treatment. The field is now on the cusp of being able to harness this wealth of data to (a) classify tumors on the basis of their immune makeup, with implications for prognosis, treatment choice, and clinical outcome, and (b) design therapeutic strategies that activate antitumor immune responses by targeting innate immune cells. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates

Novel insights on the mechanistic aspects of GPx-catalyzed H2O2 reduction: a DFT computational study

A state-of-the-art accurate quantum chemistry computational approach is proposed to investigate the mechanism of H2O2 reduction at the active site of GPx. In the model we consider explicitly six amino acids surrounding the catalytic SEC or CYS residue. The geometries of the plausible intermediate species and transition states as well as the energetics are carefully predicted. The computational protocol, rooted in advanced Density Functional Theory methodologies, is employed to explore possible mechanistic paths involving different initial active species (Se-; SeH; S- ; SH) and stability of protonated surrounding amino acids, in particular Gln (O), Gly (N) and Trp (N). The data so far acquired have demonstrated the following: i) the chosen amino acids forming the catalytic \u201ccage\u201d are fully optimized and their minimum energy conformation is perfectly superimposed to the initial crystal structure (see Fig. 1) and no difference has been observed when the active site contains either Se or S; ii) the proton of selenol or thiol has been dislocated in all of the available surrounding amino acids and it has been optimized in most of the tested locations leading to the conclusion that it is displaced in the positively charged catalytic pocket rather than exclusively bound to selenium or sulphur, iii) hydrogen peroxide is extremely instable in the active site and selenenic/sulphenic acid and water are formed instantaneously. This transition is the minimum energy path of the system and account for the non saturation kinetics of GPx where there is no evidence for the formation of a stable enzyme substrate complex. This set of data strongly suggests that for the catalysis of H2O2 reduction the active site of GPx is crucial, while the redox residue can be either SEC or CYS

Possible mechanistic paths of the enzymatic activity of GPx

Glutathione peroxidases (GPx, Fig. 1) belong to a widespread family of proteins that, over the years, have been discovered in almost all kingdoms of life.[1] They catalyze the reduction of H2O2 or organic hydroperoxides to water or corresponding alcohols, thus mitigating their toxicity.[2] The global reaction is ROOH+2GSH \uf0e0 GSSG+ROH+H2O, where GSH indicates glutathione. In the GPx family the active site SeCys or Cys is surrounded by highly conserved residues (Asn, Gln and Trp) forming the catalytic tetrad. One of the main open questions is about the specific role of either SeCys or Cys in the catalysis: it is not yet clear why selenium rather than sulphur has been chosen by nature selection given that a complex and energetically very expensive co-traslational insertion machinery for SeCys is needed. Fig. 1 GPx Fig. 2 Model catalytic site The basic catalytic scheme involves three main steps, i.e. (i) O-O bond cleavage and formation of selenenic/sulphenic acid Se/S-OH and ROH; (ii) formation of a seleno-sulfide (disulfide) intermediate and elimination of H2O; (iii) formation of the disulfide product and regeneration of the catalyst. We present a detailed investigation of different possible paths of the reduction of H2O2 catalyzed by Se-based as well as S-based GPxs with the aim of validating at quantum chemistry (DFT) level the experimental findings obtained by recent mass spectrometry and biochemistry methods (enzymatic kinetics); a core of seven aminoacids has been identified, which suitably represents the GPx core (Fig. 2). From our results a complex energy landscape emerges, where novel mechanistic paths are possible and novel perspectives on the intriguing behaviour of GPx can be outlined