Genomic characterization of the human DNA excision repair gene ERCC-1.

In this report the genomic characterization of the human excision repair gene ERCC-1 is presented. The gene consists of 10 exons spread over approximately 15 kb. By means of a transfection assay the ERCC-1 promoter was confined to a region of + 170 bp upstream of the transcriptional start site. Classical promoter elements like CAAT, TATA and GC-boxes are absent from this region. Furthermore, ERCC-1 transcription is not UV-inducible. A possible explanation is provided for the previously reported alternative splicing of exon VIII. Analysis of ERCC-1 cDNA clones revealed the occurrence of differential polyadenylation which gives ERCC-1 transcripts of 3.4 and 3.8 kb in addition to the major 1.1 kb mRNA. Apparent evolutionary conservation of differential polyadenylation of ERCC-1 transcripts suggests a possible role for this mode of RNA processing in the ERCC-1 repair function

Evolution and mutagenesis of the mammalian excision repair gene ERCC-1

The human DNA excision repair protein ERCC-1 exhibits homology to the yeast RADIO repair protein and its longer C-terminus displays similarity to parts of the E.coli repair proteins uvrA and uvrC. To study the evolution of this 'mosaic' ERCC-1 gene we have isolated the mouse homologue. Mouse ERCC-1 harbors the same pattern of homology with RAD10 and has a comparable C-terminal extension as its human equivalent. Mutation studies show that the strongly conserved C-terminus is essential in contrast to the less conserved N-terminus which is even dispensible. The mouse ERCC-1 amino acid sequence is compatible with a previously postulated nuclear location signal and DNA-binding domain. The ERCC-1 promoter harbors a region which is highly conserved in mouse and man. Since the ERCC-1 promoter is devoid of all classical promoter elements this region may be responsible for the low constitutive level of expression in all mouse tissues and stages of embryogenesis examined

Listening to ironically-enjoyed music: A self-regulatory perspective

This research examines adults’ reported motivations for listening to music that they enjoy ironically. In a pilot (N = 96) and main (N = 175) studies, open-ended responses from adults were analysed using Thematic Analysis. Based on the pilot study, ironically enjoyed music was defined as “Music that is enjoyed because of being bad, despite being bad, or for different reasons than intended.” Although many relevant self-regulatory functions of listening to music in general were also relevant to ironically- enjoyed music, it also emerged that ironic enjoyment of music has characteristics that are unique to it: the additional role of mocking, ridiculing, and laughing at the music, and the social benefit that this provides. Music that was listened to “because of” its negative features had a variety of musical features, and the listening usually served functions unique to ironic enjoyment of music, such as mockery. When music was listened to “despite” negative qualities, the music itself was often described as having attractive rhythm, melody or lyrics, while the irony protected the listener from conflicting values associated with the music, helping the listener communicate to others that they did not identify with the music on a higher level. Unfamiliar music mainly played a social role, whereas familiar music related to nostalgia as well as most other functions

Sad music as a means for acceptance-based coping

Self-identified sad music (SISM) is often listened to when experiencing sad life situations. Research indicates that the most common reason people give for listening to SISM is “to be in touch with or express feelings of sadness”. But why might this be the case? We suggest that one reason people choose to listen to sad music when feeling sad is to accept aversive situations. We tested if SISM is associated with acceptance coping and consolation. We hypothesized that SISM relates to acceptance-based coping via the recognition and identification of emotional states, and that people will report more acceptance from SISM than self- identified happy music when seeking consolation. In Study 1, participants recalled how happy or sad the music sounds that they normally listen to for consolation, and if they listen to this music to gain acceptance of negative moods and situations. In Study 2, participants reported their goals when listening to sad music during a recalled time in which they experienced an adverse life situation and whether this lead to acceptance. Study 1: People reported that they were more likely to listen to sad music than happy music when seeking consolation, though they preferred happy music in general. Listening to SISM (but not self-identified happy music) when seeking consolation was associated with acceptance of both a negative situation and the associated negative emotions. Additionally, seeking to deal with emotions was associated with both SISM listening (for consolation) and acceptance. Study 2: Listening to SISM to get in touch with and express affect was the most important self-regulatory strategy (of six examined) through which acceptance was recalled to be achieved. Experiencing adverse situations or seeking consolation, people report that listening to SISM is associated with acceptance coping (through the re-experiencing of affect). Implications for music therapy and theories of emotional coping are discussed

Human plasma phospholipid transfer protein increases the antiatherogenic potential of high density lipoproteins in transgenic mice

Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoprotein particles and alters high density lipoprotein (HDL) subfraction patterns in vitro, but its physiological function is poorly understood. Transgenic mice that overexpress human PLTP were generated. Compared with wild-type mice, these mice show a 2.5- to 4.5-fold increase in PLTP activity in plasma. This results in a 30% to 40% decrease of plasma levels of HDL cholesterol. Incubation of plasma from transgenic animals at 37 degrees C reveals a 2- to 3-fold increase in the formation of pre-beta-HDL compared with plasma from wild-type mice. Although pre-beta-HDL is normally a minor subfraction of HDL, it is known to be a very efficient acceptor of peripheral cell cholesterol and a key mediator in reverse cholesterol transport. Further experiments show that plasma from transgenic animals is much more efficient in preventing the accumulation of intracellular cholesterol in macrophages than plasma from wild-type mice, despite lower total HDL concentrations. It is concluded that PLTP can act as an antiatherogenic factor preventing cellular cholesterol overload by generation of pre-beta-HDL

Global economic impacts of climate variability and change during the 20th century

Estimates of the global economic impacts of observed climate change during the 20th century obtained by applying five impact functions of different integrated assessment models (IAMs) are separated into their main natural and anthropogenic components. The estimates of the costs that can be attributed to natural variability factors and to the anthropogenic intervention with the climate system in general tend to show that: 1) during the first half of the century, the amplitude of the impacts associated with natural variability is considerably larger than that produced by anthropogenic factors and the effects of natural variability fluctuated between being negative and positive. These non-monotonic impacts are mostly determined by the low-frequency variability and the persistence of the climate system; 2) IAMs do not agree on the sign (nor on the magnitude) of the impacts of anthropogenic forcing but indicate that they steadily grew over the first part of the century, rapidly accelerated since the mid 1970's, and decelerated during the first decade of the 21st century. This deceleration is accentuated by the existence of interaction effects between natural variability and natural and anthropogenic forcing. The economic impacts of anthropogenic forcing range in the tenths of percentage of the world GDP by the end of the 20th century; 3) the impacts of natural forcing are about one order of magnitude lower than those associated with anthropogenic forcing and are dominated by the solar forcing; 4) the interaction effects between natural and anthropogenic factors can importantly modulate how impacts actually occur, at least for moderate increases in external forcing. Human activities became dominant drivers of the estimated economic impacts at the end of the 20th century, producing larger impacts than those of low-frequency natural variability. Some of the uses and limitations of IAMs are discussed

Music listening as a potential aid in reducing emotional eating: An exploratory study

Emotional Eating (EE) is understood as a maladaptive self-regulation strategy to satisfy emotional needs instead of hunger. Consequently, EE has been associated with negative health consequences. Enjoyment of food and music share similar neural activations in the brain and are both used by people for regulating affect. This suggests that music listening could potentially be a healthier alternative to EE. The present study was designed to investigate associations between EE, disordered mood, and music-related mood regulation. A total of 571 participants completed measures of EE, music listening strategies, and disordered mood. Associations between seven different music listening strategies and EE were examined, and also whether these regulation strategies were associated with depression, anxiety, and stress. Finally, we explored associations between music listening and EE in people with low and high (non-clinical) levels of disordered mood (depression, anxiety, and stress). The findings of this research indicated that music listening for discharge (releasing anger or sadness through music that expresses these same emotions) and EE were positively associated with one another. In addition, EE and the music listening strategies of entertainment, diversion or mental work were associated in people with low levels of disordered mood. When disordered mood was high, EE was higher, but was not associated with music listening strategies. These associations point towards the possibility of some music listening strategies being useful as healthier alternatives for EE

Priority for the Worse Off and the Social Cost of Carbon

The social cost of carbon (SCC) is a monetary measure of the harms from carbon emission. Specifically, it is the reduction in current consumption that produces a loss in social welfare equivalent to that caused by the emission of a ton of CO2. The standard approach is to calculate the SCC using a discounted-utilitarian social welfare function (SWF)—one that simply adds up the well-being numbers (utilities) of individuals, as discounted by a weighting factor that decreases with time. The discounted-utilitarian SWF has been criticized both for ignoring the distribution of well-being, and for including an arbitrary preference for earlier generations. Here, we use a prioritarian SWF, with no time-discount factor, to calculate the SCC in the integrated assessment model RICE. Prioritarianism is a well-developed concept in ethics and theoretical welfare economics, but has been, thus far, little used in climate scholarship. The core idea is to give greater weight to well-being changes affecting worse off individuals. We find substantial differences between the discounted-utilitarian and non-discounted prioritarian SCC