929 research outputs found
Finding the grey in the blue : transparency and disclosure in teaching
Police services have traditionally valued the ability to work without ongoing public
scrutiny of their investigations and operations. They can very reasonably cite the need
to avoid alerting criminals to police activities that might result in their arrest and
charging with offences, the need to protect police and witness safety, and the frequent
need to act swiftly and decisively without obtaining special approval from relevant
authorities or endorsement from public opinion. This necessary lack of disclosure
concerning many police operations has often extended into a general lack of
transparency regarding police activities and expenditures, to the extent that, in many
countries, the police services are regarded as unaccountable and unconcerned with
how public opinion perceives them. In such a climate, police corruption and arbitrary
exercise of police power flourishes. This paper addresses the creation of a policing
environment radically different from this through the introduction of transparency into
policing in the UK and the consequent revelation of layers of grey documentation and
data. The paper makes use of official documentation and case studies of selected
British police forces to show how the culture of policing is being changed. The
principles of open government, scrutiny, and disclosure with a view to establishing
accountability, are in the process of becoming institutionalised in the UK right across
government, local government, other ‘public authorities’ and the business and nongovernmental
organisation (NGO) sectors. The UK Human Rights Act 1998 sets the
context, and a legal framework for this transparency is provided by the Freedom of
Information Act 2000 and, to some extent, the Public Interest Disclosure Act 1998.
The press and civil society are consistently using these mechanisms to call those with
political and economic power to account. It has become apparent, even in sectors
formerly as concerned with avoiding openness as the police service, that pro-active
disclosure is the best way to meet public expectations. Police services now respond as
a matter of course to freedom of information requests, organise a range of meetings
to provide information and answer questions (from local officers’ meetings with
community groups through to major budget consultative meetings with citizens’
panels), and participate in public and semi-public enquiries into aspects of the success
or failure of police programmes and operations. The case studies in this paper will
explore the opinions of key players in this process and draw attention to the grey
information that is becoming available as a consequence
Police and media relations in an era of Freedom of Information
Changes to how police forces in England and Wales are working to manage their public image in an environment of heightened accountability and transparency are explored. The locus of control of information shaping the portrayal of the police in the news media is discussed, as is the impact of the Freedom of Information Act 2000. The findings from case studies of two police forces in the East Midlands are reported. The case studies indicate that, whilst police and media co-operation is not a new phenomenon, UK police forces are becoming increasingly proactive, strategic and professionalized in their use of the news media. For their part, the media are dependent on the news ‘fed’ to them on a regular basis by police press relations units. Nevertheless, thanks in particular to their use of the FOIA 2000, the media continue to play a role as independent watchdog and reporter of police activity
Draft genome sequences of seven isolates of Phytophthora ramorum EU2 from Northern Ireland
Here we present draft-quality genome sequence assemblies for the oomycete Phytophthora ramorum genetic lineage EU2. We sequenced genomes of seven isolates collected in Northern Ireland between 2010 and 2012. Multiple genome sequences from P. ramorum EU2 will be valuable for identifying genetic variation within the clonal lineage that can be useful for tracking its spread
Bridging the translational gap: what can synaptopathies tell us about autism?
Multiple molecular pathways and cellular processes have been implicated in the neurobiology of autism and other neurodevelopmental conditions. There is a current focus on synaptic gene conditions, or synaptopathies, which refer to clinical conditions associated with rare genetic variants disrupting genes involved in synaptic biology. Synaptopathies are commonly associated with autism and developmental delay and may be associated with a range of other neuropsychiatric outcomes. Altered synaptic biology is suggested by both preclinical and clinical studies in autism based on evidence of differences in early brain structural development and altered glutamatergic and GABAergic neurotransmission potentially perturbing excitatory and inhibitory balance. This review focusses on the NRXN-NLGN-SHANK pathway, which is implicated in the synaptic assembly, trans-synaptic signalling, and synaptic functioning. We provide an overview of the insights from preclinical molecular studies of the pathway. Concentrating on NRXN1 deletion and SHANK3 mutations, we discuss emerging understanding of cellular processes and electrophysiology from induced pluripotent stem cells (iPSC) models derived from individuals with synaptopathies, neuroimaging and behavioural findings in animal models of Nrxn1 and Shank3 synaptic gene conditions, and key findings regarding autism features, brain and behavioural phenotypes from human clinical studies of synaptopathies. The identification of molecular-based biomarkers from preclinical models aims to advance the development of targeted therapeutic treatments. However, it remains challenging to translate preclinical animal models and iPSC studies to interpret human brain development and autism features. We discuss the existing challenges in preclinical and clinical synaptopathy research, and potential solutions to align methodologies across preclinical and clinical research. Bridging the translational gap between preclinical and clinical studies will be necessary to understand biological mechanisms, to identify targeted therapies, and ultimately to progress towards personalised approaches for complex neurodevelopmental conditions such as autism
Genome Analyses of an Aggressive and Invasive Lineage of the Irish Potato Famine Pathogen
Pest and pathogen losses jeopardise global food security and ever since the 19th century Irish famine, potato late blight has exemplified this threat. The causal oomycete pathogen, Phytophthora infestans, undergoes major population shifts in agricultural systems via the successive emergence and migration of asexual lineages. The phenotypic and genotypic bases of these selective sweeps are largely unknown but management strategies need to adapt to reflect the changing pathogen population. Here, we used molecular markers to document the emergence of a lineage, termed 13_A2, in the European P. infestans population, and its rapid displacement of other lineages to exceed 75% of the pathogen population across Great Britain in less than three years. We show that isolates of the 13_A2 lineage are among the most aggressive on cultivated potatoes, outcompete other aggressive lineages in the field, and overcome previously effective forms of plant host resistance. Genome analyses of a 13_A2 isolate revealed extensive genetic and expression polymorphisms particularly in effector genes. Copy number variations, gene gains and losses, amino-acid replacements and changes in expression patterns of disease effector genes within the 13_A2 isolate likely contribute to enhanced virulence and aggressiveness to drive this population displacement. Importantly, 13_A2 isolates carry intact and in planta induced Avrblb1, Avrblb2 and Avrvnt1 effector genes that trigger resistance in potato lines carrying the corresponding R immune receptor genes Rpi-blb1, Rpi-blb2, and Rpi-vnt1.1. These findings point towards a strategy for deploying genetic resistance to mitigate the impact of the 13_A2 lineage and illustrate how pathogen population monitoring, combined with genome analysis, informs the management of devastating disease epidemic
The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes
Venom systems have evolved on multiple occasions
across the animal kingdom, and they can act as key
adaptations to protect animals from predators.
Consequently, venomous animals serve as models
for a rich source of mimicry types, as non-venomous
species benefit from reductions in predation risk by
mimicking the coloration, body shape, and/or movement
of toxic counterparts. The frequent evolution
of such deceitful imitations provides notable
examples of phenotypic convergence and are often
invoked as classic exemplars of evolution by natural
selection. Here, we investigate the evolution of fangs,
venom, and mimetic relationships in reef fishes from
the tribe Nemophini (fangblennies). Comparative
morphological analyses reveal that enlarged canine
teeth (fangs) originated at the base of the Nemophini
radiation and have enabled a micropredatory feeding
strategy in non-venomous Plagiotremus spp. Subsequently,
the evolution of deep anterior grooves and
their coupling to venom secretory tissue provide
Meiacanthus spp. with toxic venom that they effectively
employ for defense. We find that fangblenny
venom contains a number of toxic components that
have been independently recruited into other animal
venoms, some of which cause toxicity via interactions
with opioid receptors, and result in a multifunctional
biochemical phenotype that exerts potent hypotensive
effects. The evolution of fangblenny venom has
seemingly led to phenotypic convergence via the formation
of a diverse array of mimetic relationships that
provide protective (Batesian mimicry) and predatory
(aggressive mimicry) benefits to other fishes.
Our results further our understanding of how novel
morphological and biochemical adaptations stimulate
ecological interactions in the natural world
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Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.
Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies
Surface Co-Expression of Two Different PfEMP1 Antigens on Single Plasmodium falciparum-Infected Erythrocytes Facilitates Binding to ICAM1 and PECAM1
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens play a major role in cytoadhesion of infected erythrocytes (IE), antigenic variation, and immunity to malaria. The current consensus on control of variant surface antigen expression is that only one PfEMP1 encoded by one var gene is expressed per cell at a time. We measured var mRNA transcript levels by real-time Q-PCR, analysed var gene transcripts by single-cell FISH and directly compared these with PfEMP1 antigen surface expression and cytoadhesion in three different antibody-selected P. falciparum 3D7 sub-lines using live confocal microscopy, flow cytometry and in vitro adhesion assays. We found that one selected parasite sub-line simultaneously expressed two different var genes as surface antigens, on single IE. Importantly, and of physiological relevance to adhesion and malaria pathogenesis, this parasite sub-line was found to bind both CD31/PECAM1 and CD54/ICAM1 and to adhere twice as efficiently to human endothelial cells, compared to infected cells having only one PfEMP1 variant on the surface. These new results on PfEMP1 antigen expression indicate that a re-evaluation of the molecular mechanisms involved in P. falciparum adhesion and of the accepted paradigm of absolutely mutually exclusive var gene transcription is required
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