King's College London

About: King's College London is a education organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Mental health. The organization has 43107 authors who have published 113125 publications receiving 4498103 citations. The organization is also known as: King's & KCL.

Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer.

Abstract: It is increasingly proposed that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a key role in human cancer development [1–6], especially as evidence is growing that antioxidants may prevent or delay the onset of some types of cancer (reviewed in [7,8]). ROS is a collective term often used by biologists to include oxygen radicals [superoxide (O # J−), hydroxyl (OHJ), peroxyl (RO # J) and alkoxyl (ROJ)] and certain nonradicals that are either oxidizing agents and}or are easily converted into radicals, such as HOCl, ozone (O $ ), peroxynitrite (ONOO−), singlet oxygen ("O # ) and H # O # . RNS is a similar collective term that includes nitric oxide radical (NOJ), ONOO−, nitrogen dioxide radical (NO # J), other oxides of nitrogen and products arising when NOJ reacts with O # J−, ROJ and RO # J. ‘Reactive ’ is not always an appropriate term; H # O # , NOJ and O # J− react quickly with very few molecules, whereas OHJ reacts quickly with almost anything. RO # J, ROJ, HOCl, NO # J, ONOO− and O $ have intermediate reactivities. ROS and RNS have been shown to possess many characteristics of carcinogens [4] (Figure 1). Mutagenesis by ROS}RNS could contribute to the initiation of cancer, in addition to being important in the promotion and progression phases. For example, ROS}RNS can have the following effects. (1) Cause structural alterations in DNA, e.g. base pair mutations, rearrangements, deletions, insertions and sequence amplification. OHJ is especially damaging, but "O # , RO # J, ROJ, HNO # , O $ , ONOO− and the decomposition products of ONOO− are also effective [9–13]. ROS can produce gross chromosomal alterations in addition to point mutations and thus could be involved in the inactivation or loss of the second wild-type allele of a mutated proto-oncogene or tumour-suppressor gene that can occur during tumour promotion and progression, allowing expression of the mutated phenotype [4]. (2) Affect cytoplasmic and nuclear signal transduction pathways [14,15]. For example, H # O # (which crosses cell and organelle membranes easily) can lead to displacement of the inhibitory subunit from the cytoplasmic transcription factor nuclear factor κB, allowing the activated factor to migrate to the nucleus [14]. Nitration of tyrosine residues by ONOO− may block phosphorylation. (3) Modulate the activity of the proteins and genes that respond to stress and which act to regulate the genes that are related to cell proliferation, differentiation and apoptosis [4,14–17]. For example, H # O # can stimulate transcription of c-jun

Synaptic, transcriptional and chromatin genes disrupted in autism

Abstract: The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

Personality development: stability and change.

Abstract: In this review, we evaluate four topics in the study of personality development where discernible progress has been made since 1995 (the last time the area of personality development was reviewed in this series). We (a) evaluate research about the structure of personality in childhood and in adulthood, with special attention to possible developmental changes in the lower-order components of broad traits; (b) summarize new directions in behavioral genetic studies of personality; (c) synthesize evidence from longitudinal studies to pinpoint where and when in the life course personality change is most likely to occur; and (d) document which personality traits influence social relationships, status attainment, and health, and the mechanisms by which these personality effects come about. In each of these four areas, we note gaps and identify priorities for further research.