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Selection and licensing of mammalian DNA replication origins may be regulated by epigenetic changes in chromatin structure. The Epstein–Barr virus (EBV) origin of plasmid replication ( OriP ) uses the cellular licensing machinery to regulate replication during latent infection of human cells. We found that the minimal replicator sequence of OriP , referred to as the dyad symmetry (DS), is flanked by nucleosomes. These nucleosomes were subject to cell cycle‐dependent chromatin remodeling and histone modifications. Restriction enzyme accessibility assay indicated that the DS‐bounded nucleosomes were remodeled in late G1. Remarkably, histone H3 acetylation of DS‐bounded nucleosomes decreased during late G1, coinciding with nucleosome remodeling and MCM3 loading, and preceding the onset of DNA replication. The ATP‐dependent chromatin‐remodeling factor SNF2h was also recruited to DS in late G1, and formed a stable complex with HDAC2 at DS. siRNA depletion of SNF2h reduced G1‐specific nucleosome remodeling, histone deacetylation, and MCM3 loading at DS. We conclude that an SNF2h–HDAC1/2 complex coordinates G1‐specific chromatin remodeling and histone deacetylation with the DNA replication initiation process at OriP .

In all eukaryotic cells, origins of DNA replication are characterized by the binding of the origin recognition complex (ORC). How ORC is positioned to sites where replication initiates is unknown, because metazoan ORC binds DNA without apparent sequence specificity. Thus, additional factors might be involved in ORC positioning. Our experiments indicate that a family member of the high-mobility group proteins, HMGA1a, can specifically target ORC to DNA. Coimmunoprecipitations and imaging studies demonstrate that HMGA1a interacts with different ORC subunits in vitro and in vivo. This interaction occurs mainly in AT-rich heterochromatic regions to which HMGA1a localizes. Fusion proteins of HMGA1a and the DNA-binding domain of the viral factor EBNA1 or the prokaryotic tetracycline repressor, TetR, can recruit ORC to cognate operator sites forming functional origins of DNA replication. When HMGA1a is targeted to plasmid DNA, the prereplicative complex is assembled during G₁ and the amount of ORC correlates with the local concentration of HMGA1a. Nascent-strand abundance assays demonstrate that DNA replication initiates at or near HMGA1a-rich sites. Our experiments indicate that chromatin proteins can target ORC to DNA, suggesting they might specify origins of DNA replication in metazoan cells.

Low confidence in the police and the increasing crime rates during the 1990s led to a series of government initiatives directed at changing both the structure and management of the police service. In 2006 in an attempt to define what a principled police service should resemble, the Home Office Minister, Hazel Blears, announced the development of new Code of Professional Standards for the police service, informed by the Taylor Review of 2005. While there has been a growing awareness of the role of Professional Standards within law enforcement activity, to date there has been little scholarly debate on the understanding of ethics and how that is applied to practical policing.This book provides a single text of different perspectives on how professional standards and ethics has been conceptualised and developed into practical policing processes for the purposes of policing, not only by the police but also by the partner agencies. Leading academics and practitioners consider the moral minefield of policing through examinations of undercover operatives, MI5 and deaths in police custody as well as looking forward to the future considerations and practices in professional conduct. It will be of interest to those working within the field of policing as well as students and academics focussed on policing and criminal justice.

Throughout this volume there has been agreement that unethical police policy and practice, whether exercised wittingly or unwittingly, causes considerable harm and angst to individuals, groups, communities and to the police organisation itself. Yet, as we have thus far witnessed, there is no immediate explanation for a rich understanding of what constructs ethics and how this is applied in operational practice. As the book so far as illustrated, police ethics is complex, intricate and is compounded in that what may seem ethical and integral to some parties may not be for others. Operational policing is characterised by uncertainty, responding with transforming events 'fast time' and dealing with a significant range of individuals, groups and communities - many who have conflicting and different expectations. Given the nature of policing to enforce the law fairly and justly, almost every decision made by police officers and staff has to be ethically accountably. Yet, every decision made by police officers is never the same. The discretion afforded to police officers means each of their interactions requires a different set of moral and value judgements, even in incidents that appear on the face of it very similar. This challenge is addressed in the final section of this book when looking at the future for better professional standards in policing. Neyroud and Gilmour examine how politics and policing can impact on ethical policing bringing with it the stark reality of what represents a professional service. The changing landscape of policing currently being driven by the coalition government will radically alter the structure and remit of policing. The impending introduction of Police and Crime Commissioners in particular will bring challenges in relation to what will remain operational policing and therefore independent rights of Chief Constables. Neyroud and Gilmour persuasively argue that that the conduct and standards exhibited by Chief Officers during this period of change will influence the behaviour of officers throughout the organisation. In addition these political reforms will be brought in within a radically reduced budget, a narrow focus on crime and a drastic revision of personnel costs. The authors argue that one way of approaching this policing dilemma in relation to preserving professional standards is through the prism of a 'new professionalism', which affords greater emphasis on occupational standards, personal registration and accountability, tailored education and accreditation. This would support both strategic and operational policing within an ethical framework ensuring that professional standards in the future are embedded throughout the systems, processes and culture of the police service.

Both Jackson's and Todd's chapters in Part I highlighted some of the challenges when professional standards are compromised or not maintained to the expectations demanded by the public. There is a concurrence throughout this book that police misbehaviour has a significantly disproportionate impact upon public confidence, eroding trust and loyalty. The development of independent oversight bodies has provided new forms of structures for the public to focus their complaints against police and to restore public trust, but this alone cannot redress poor professional standards; rather, that requires the police agency itself to take responsibility for ensuring high standards of professional behaviour are instilled within the organisation. Part II provides an insightful reflection of professional practice in an operational setting and identifies the challenges and complexities of ensuring the highest professional standards. An understanding of professional standard using illustrative case studies provides a mechanism whereby such learning can be translated into knowledge to ensure that the same mistakes are not repeated and to improve standards of behaviour. In particular, this chapter starts to expose that even where there are codes of conduct and codes of ethics, it does not always ensure that the behaviour of some police officers is of the highest integrity and value.

Policing in the twenty-first century, although overwhelmingly characterized (as Paul Evans informs us in the introduction to his chapter) by complexity, globalisation and new forms of terrorist threats, one of its greatest challenges today is that of uncertainty. This uncertainty has been partly generated by the coalition government's drive to reduce police numbers and make them more efficient by reducing their budget by 20 per cent over the next four years, and also by the consequences of the Hutton (2011), Winsor I and II (2012a, b) and Neyroud (2011) reports as well as the introduction of Police and Crime Commissioners. These factors collectively make it difficult to ascertain what the police service will look like, let alone be expected to deliver, in the foreseeable future. This was eloquently summed up by Sir Hugh Orde at the Leading Change in Policing conference on 4 July 2011: We are determined to preserve the service to the public. But as the service of last resort, we are going through a period of substantial change. Changes to accountability, changes to central structures and changes to pay and conditions. Change which, if mismanaged, could threaten the impartial model of policing that has existed for 180 years and is revered across the world.\"

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA–PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA–PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem–cortical interplay for consciousness.

•Time-averaged small world measures in fMRI do not yield consistent results.•Entropy of small world dynamics is a robust predictor of levels of awareness.•Network dynamics have predictive power beyond functional connectivity dynamics.•Subcortical dynamics have more predictive power than cortical dynamics.•Participation coefficient dynamics are independently predictive in the cerebellum. Small world topologies are thought to provide a valuable insight into human brain organisation and consciousness. However, functional magnetic resonance imaging studies in consciousness have not yielded consistent results. Given the importance of dynamics for both consciousness and cognition, here we investigate how the diversity of small world dynamics (quantified by sample entropy; dSW-E11dSW-E= dynamic small world entropy) scales with decreasing levels of awareness (i.e., sedation and disorders of consciousness). Paying particular attention to result reproducibility, we show that dSW-E is a consistent predictor of levels of awareness even when controlling for the underlying functional connectivity dynamics. We find that dSW-E of subcortical, and cortical areas are predictive, with the former showing higher and more robust effect sizes across analyses. We find that the network dynamics of intermodular communication in the cerebellum also have unique predictive power for levels of awareness. Consequently, we propose that the dynamic reorganisation of the functional information architecture, in particular of the subcortex, is a characteristic that emerges with awareness and has explanatory power beyond that of the complexity of dynamic functional connectivity.

When fingermarks are left on a surface, bacteria originating from the donor’s skin are also deposited. The skin microbiome is believed to be extremely diverse between individuals, allowing for potential matching between the bacterial communities and touched objects, known as “bacterial profiling”. This study stepped further and investigated how the bacterial profile could be used as an indicator of donor characteristics of potential forensic intelligence interest. Forty-five participants were asked to touch DNA-free playing cards with their dominant and non-dominant hands. Cards were swabbed and bacterial communities determined through 16S rRNA sequencing. Diversity and abundance of bacteria were compared to donor characteristics of gender, age, ethnicity, handedness, home location, sample location, occupation, diet type, use of moisturisers, use of hand sanitisers and use of public transport. Correlations between the bacterial profile with gender, ethnicity, diet type and hand sanitiser use were found. Specifically, the absence of Lactococcus indicated a primarily Chinese diet, while the absence of Alloiococcus indicated female gender, Asian ethnicity and hand sanitiser use. Testing of the prediction models demonstrated highest accuracy for gender estimation, while the prediction of other characteristics showed lower success. This study showed a correlation between the presence of certain bacterial species on donor’s hands and personal characteristics of potential forensic relevance, thus demonstrating a novel application of microbiome genotyping in forensic science.

The analysis of lipids (fats, oils and waxes) absorbed within archaeological pottery has revolutionized the study of past diets and culinary practices. However, this technique can lack taxonomic and tissue specificity and is often unable to disentangle signatures resulting from the mixing of different food products. Here, we extract ancient proteins from ceramic vessels from the West Mound of the key early farming site of Çatalhöyük in Anatolia, revealing that this community processed mixes of cereals, pulses, dairy and meat products, and that particular vessels may have been reserved for specialized foods (e.g., cow milk and milk whey). Moreover, we demonstrate that dietary proteins can persist on archaeological artefacts for at least 8000 years, and that this approach can reveal past culinary practices with more taxonomic and tissue-specific clarity than has been possible with previous biomolecular techniques. Ancient diets have been reconstructed from archaeological pottery based on lipid remains, but these can lack specificity. Here, Hendy and colleagues analyze ancient proteins from ceramic vessels up to 8000 years old to produce a more nuanced understanding of ancient food processing and diet.