The survival and growth of embryonic and postnatal sympathetic neurons is dependent on both NGF and NT3. While it has been established that adult sensory neurons survive independently of neurotrophins, the case is less clear for adult sympathetic neurons, where the studies of survival responses to neurotrophins have relied upon using long-term cultures of embryonic neurons. We have previously established a method to culture purified young (7 day) and adult (12 week) sympathetic neurons isolated from adult rat superior cervical ganglia (SCG) in order to examine their survival and growth responses to neurotrophins. We now show that by 12 weeks after birth virtually all neurons (90%) survive for 24 h in the absence of neurotrophins. Neuron survival is unaffected by treatment with anti-NGF antibodies (anti-NGF) or with the tyrosine kinase inhibitor, K252a, confirming the lack of dependence on extrinsic neurotrophins. Duration of neuron survival in culture increases significantly between E19 and day 7 and week 12 posnatally, and is similarly unaffected by the presence of anti-NGF or K252a. Saturating concentrations of NGF and NT3 are equipotent in promoting neurite extension and branching. However, we find that NGF is more potent than NT3 in promoting neurite growth, irrespective of postnatal age. The growth-promoting effects of NGF and NT3 are almost entirely blocked by K252a, demonstrating that these effects are mediated via activation of Trk receptors, which therefore appear to remain crucial to plasticity of adult neurons. Our results indicate that maturing neurons acquire protection against cell death, induced in the absence of neurotrophin, while retaining their growth responsiveness to these factors.
Mitochondrial replacement techniques (MRTs
The concept of vulnerability has been subject to numerous different interpretations but accounts are still beset with significant problems as to their adequacy, such as their contentious application or the lack of genuine explanatory role for the concept. The constant failure to provide a compelling conceptual analysis and satisfactory definition leaves the concept open to an eliminativist move whereby we can question whether we need the concept at all. I highlight problems with various kinds of approach and explain why a satisfactory account of vulnerability is unlikely ever to be offered if we wish the concept to play a genuinely explanatory role in bioethical contexts. I outline why an eliminativist position should be taken with regard to this concept in light of these concerns but mitigate some of the severity of this position by arguing that we can still make sense of retaining our widespread use of the term by viewing it as nothing more than a useful pragmatic linguistic device that acts as a marker to draw attention to certain kinds of issue. These issues will be entirely governed by other, better understood ethical concepts and theories.
The Mental Capacity Act 2005 has provided unified scope in the British medical system for proxy consent with regard to medical decisions, in the form of a lasting power of attorney. While the intentions are to increase the autonomous decision making powers of those unable to consent, the author of this paper argues that the whole notion of proxy consent collapses into a paternalistic judgement regarding the other person's best interests and that the new legislation introduces only an advisor, not a proxy with the moral authority to make treatment decisions on behalf of another. The criticism is threefold. First, there is good empirical evidence that people are poor proxy decision makers as regards accurately representing other people's desires and wishes, and this is therefore a pragmatically inadequate method of gaining consent. Second, philosophical theory explaining how we represent other people's thought processes indicates that we are unlikely ever to achieve accurate simulations of others' wishes in making a proxy decision. Third, even if we could accurately simulate other people's beliefs and wishes, the current construction of proxy consent in the Mental Capacity Act means that it has no significant ethical authority to match that of autonomous decision making. Instead, it is governed by a professional, paternalistic, best-interests judgement that undermines the intended role of a proxy decision maker. The author argues in favour of clearly adopting the paternalistic best-interests option and viewing the proxy as solely an advisor to the professional medical team in helping make best-interests judgements.
The US National Academies of Science, Engineering and Medicine recently provided conditional endorsement for mitochondrial transfer. While its approach is more conservative in some respects than that of the United Kingdom (which passed its own regulations in 2015), it marks a significant policy development for a potentially large implementer of this emerging intervention. In this perspective, we consider some of the ethical and legal aspects of these policy responses.
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