Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry.

We used on-line electron capture dissociation (ECD) for the large scale identification and localization of sites of phosphorylation. Each FT-ICR ECD event was paired with a linear ion trap collision-induced dissociation (CID) event, allowing a direct comparison of the relative merits of ECD and CID for phosphopeptide identification and site localization. Linear ion trap CID was shown to be most efficient for phosphopeptide identification, whereas FT-ICR ECD was superior for localization of sites of phosphorylation. The combination of confident CID and ECD identification and confident CID and ECD localization is particularly valuable in cases where a phosphopeptide is identified just once within a phosphoproteomics experiment

The impact on staff of working with personality disordered offenders: A systematic review

© 2015 Freestone et al. Background: Personality disordered offenders (PDOs) are generally considered difficult to manage and to have a negative impact on staff working with them. Aims: This study aimed to provide an overview of studies examining the impact on staff of working with PDOs, identify impact areas associated with working with PDOs, identify gaps in existing research,and direct future research efforts. Methods: The authors conducted a systematic review of the English-language literature from 1964-2014 across 20 databases in the medical and social sciences. Results: 27 papers were included in the review. Studies identified negative impacts upon staff including: negative attitudes, burnout, stress, negative counter-transferential experiences; two studies found positive impacts of job excitement and satisfaction, and the evidence related to perceived risk of violence from PDOs was equivocal. Studies demonstrated considerable heterogeneity and meta-analysis was not possible. The overall level of identified evidence was low: 23 studies (85%) were descriptive only, and only one adequately powered cohort study was found. Conclusions: The review identified a significant amount of descriptive literature, but only one cohort study and no trials or previous systematic reviews of literatures. Clinicians and managers working with PDOs should be aware of the potential impacts identified, but there is an urgent need for further research focusing on the robust evaluation of interventions to minimise harm to staff working with offenders who suffer from personality disorder Copyright

Theorizing Institutional Scandal and the Regulatory State

One by one, UK public institutions are being scandalised for corruption, immorality or incompetence and subjected to trial by media and criminal prosecution. The state?s historic response to public sector scandal ? denial and neutralisation ? has been replaced with acknowledgement and regulation in the form of the re-vamped public inquiry. Public institutions are being cut adrift and left to account in isolation for their scandalous failures. Yet the state?s attempts to distance itself from its scandalised institutions, while extending its regulatory control over them, are risky. Both the regulatory state and its public inquiries risk being consumed by the scandal they are trying to manage

Envelope 2 protein phosphorylation sites S75 & 277 of hepatitis C virus genotype 1a and interferon resistance: A sequence alignment approach

<p>Abstract</p> <p>Background</p> <p>Hepatitis C is a major health problem affecting more than 200 million individuals in world including Pakistan. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed to eliminate virus completely from the patient's body.</p> <p>Results</p> <p>Interferon induced antiviral protein kinase R (PKR) has a role in the hepatitis C virus (HCV) treatment as dsRNA activated PKR has the capacity to phosphorylate the serine and threonine of E2 protein and dimerization viral RNA. E2 gene of hepatitis C virus (HCV) genotype 1 has an active role in IFN resistance. E2 protein inhibits and terminates the kinase activity of PKR by blocking it in protein synthesis and cell growth. This brings forward a possible relation of E2 and PKR through a mechanism via which HCV evades the antiviral effect of IFN.</p> <p>Conclusion</p> <p>A hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural anlysis has pointed out serine 75 and 277 of the HCV E2 gene as a promising candidate for the serine phosphorylation. It is proposed that serine phosphorylation of HCV E2 gene has a significant role in interferon resistance.</p

The SLUGGS Survey: kinematics for over 2500 globular clusters in twelve early-type galaxies

We present a spectrophotometric survey of 2522 extragalactic globular clusters (GCs) around 12 early-type galaxies, nine of which have not been published previously. Combining space-based and multicolour wide-field ground-based imaging, with spectra from the Keck/DEep Imaging Multi-Object Spectrograph (DEIMOS) instrument, we obtain an average of 160 GC radial velocities per galaxy, with a high-velocity precision of ∼15 km s−1 per GC. After studying the photometric properties of the GC systems, such as their spatial and colour distributions, we focus on the kinematics of metal-poor (blue) and metal-rich (red) GC subpopulations to an average distance of ∼8 effective radii from the galaxy centre. Our results show that for some systems the bimodality in GC colour is also present in GC kinematics. The kinematics of the red GC subpopulations are strongly coupled with the host galaxy stellar kinematics. The blue GC subpopulations are more dominated by random motions, especially in the outer regions, and decoupled from the red GCs. Peculiar GC kinematic profiles are seen in some galaxies: the blue GCs in NGC 821 rotate along the galaxy minor axis, whereas the GC system of the lenticular galaxy NGC 7457 appears to be strongly rotation supported in the outer region. We supplement our galaxy sample with data from the literature and carry out a number of tests to study the kinematic differences between the two GC subpopulations. We confirm that the GC kinematics are coupled with the host galaxy properties and find that the velocity kurtosis and the slope of their velocity dispersion profiles are different between the two GC subpopulations in more massive galaxies

Life History of Female Preferences for Male Faces: A Comparison of Pubescent Girls, Nonpregnant and Pregnant Young Women, and Middle-aged Women

Although scientific interest in facial attractiveness has developed substantially in recent years, few studies have contributed to our understanding of the ontogeny of facial preferences. In this study, attractiveness of 30 male faces was evaluated by four female groups: girls at puberty, nonpregnant and pregnant young women, and middle-aged women. The main findings are as follows: (1) Preference for sexy-looking faces was strongest in young, nonpregnant women. (2) Biologically more mature girls displayed more adultlike preferences. (3) The intragroup consistency for postmenopausal women was relatively low. (4) In terms of the preference pattern, pregnant women were more similar to perimenopausal women than they were to their nonpregnant peers. (5) Preference for youthful appearance decreased with the age of the women. I argue that the life history of female preferences for male faces is, to a large extent, hormone-driven and underpinned by a set of evolutionary adaptations

Serious case reviews: The lived experience of Black children

Despite the many high‐profile Black child deaths in England, race as a factor remains a largely underexplored factor of serious case reviews (SCRs). Evidence from analysis of SCRs indicates that race receives limited attention, or is virtually absent. Given that the main function of SCRs is to provide opportunities for learning lessons to improve practice, the way in which issues of race and culture may influence child protection processes for Black children is therefore of critical importance. In this article, we employ content analysis to examine the extent that race and cultural factors are considered in SCRs involving Black children. It is argued that race is often an important factor influencing Black children's experiences of abuse and neglect, as well as their encounters in the child protection system. This article therefore poses two key questions: (a) What questions are asked about race, ethnicity, and culture in SCRs concerning Black children? (b) How did the SCRs extract lessons to be learnt for improving practice to safeguard Black children? By extending the analysis of race and ethnicity in SCRs, this article furthers our understandings of the needs of Black children in the child protection system

The potential utility of B cell-directed biologic therapy in autoimmune diseases

Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs—rituximab, a chimeric monoclonal antibody against the B cell-specific surface marker CD20—was recently approved for treating rheumatoid arthritis in patients with an inadequate response to other biologic therapies. The aim of this review is to discuss the potential use of rituximab in the management of other autoimmune disorders. Results from early phase clinical trials indicate that rituximab may provide clinical benefit in systemic lupus erythematosus, Sjögren’s syndrome, vasculitis, and thrombocytopenic purpura. Numerous case reports and several small pilot studies have also been published reporting the use of rituximab in conditions such as myositis, antiphospholipid syndrome, Still’s disease, and multiple sclerosis. In general, the results from these preliminary studies encourage further testing of rituximab therapy in formalized clinical trials. Based on results published to date, it is concluded that rituximab, together with other B cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these difficult-to-treat autoimmune disorders

Parental diet, pregnancy outcomes and offspring health:metabolic determinants in developing oocytes and embryos

The periconceptional period, embracing the terminal stages of oocyte growth and post-fertilisation development up to implantation, is sensitive to parental nutrition. Deficiencies or excesses in a range of macro- and micronutrients during this period can lead to impairments in fertility, fetal development and long-term offspring health. Obesity and genotype-related differences in regional adiposity are associated with impaired liver function and insulin resistance, and contribute to fatty acid-mediated impairments in sperm viability and oocyte and embryo quality, all of which are associated with endoplasmic reticulum stress and compromised fertility. Disturbances to maternal protein metabolism can elevate ammonium concentrations in reproductive tissues and disturb embryo and fetal development. Associated with this are disturbances to one-carbon metabolism, which can lead to epigenetic modifications to DNA and associated proteins in offspring that are both insulin resistant and hypertensive. Many enzymes involved in epigenetic gene regulation use metabolic cosubstrates (e.g. acetyl CoA and S-adenosyl methionine) to modify DNA and associated proteins, and so act as 'metabolic sensors' providing a link between parental nutritional status and gene regulation. Separate to their genomic contribution, spermatozoa can also influence embryo development via direct interactions with the egg and by seminal plasma components that act on oviductal and uterine tissues

True Religion and Hume's Practical Atheism

The argument and discussion in this paper begins from the premise that Hume was an atheist who denied the religious or theist hypothesis. However, even if it is agreed that that Hume was an atheist this does not tell us where he stood on the question concerning the value of religion. Some atheists, such as Spinoza, have argued that society needs to maintain and preserve a form of “true religion”, which is required for the support of our ethical life. Others, such as D’Holbach have argued that religion is not only false it is pernicious and it should be eradicated. This paper argues that Hume rejected both theseproposals, on the ground that they rest, in different ways, on excessively optimistic assumptions. The sensible, practical form of atheism that Hume defends has a more modest and realistic aim, which is simply to restrict and limit the most pernicious forms of religion. Understood this way, Hume’s practical atheism is very different from the forms of “old” atheism associated with Spinoza and D’Holbach, as well as from the “new atheism” of thinkers such as Dawkins and Dennett. Reprinted in Paul Russell, "Recasting Hume and Early Modern Philosophy: Selected Essays" (New York: Oxford University Press, 2021): 340-383