The short-lived MATα2 transcriptional regulator is ubiquitinated in vivo

The substrates of ubiquitin-dependent proteolytic pathways include both damaged or otherwise abnormal proteins and undamaged proteins that are naturally short-lived. Few specific examples of the latter class have been identified, however. Previous work has shown that the cell type-specific MAT-alpha-2 repressor of the yeast Saccharomyces cerevisiae is an extremely short-lived protein. We now demonstrate that alpha-2 is conjugated to ubiquitin in vivo. More than one lysine residue of alpha-2 can be joined to ubiquitin, and some of the ubiquitin moieties form a Lys48-linked multiubiquitin chain. Overexpression of degradation-impaired ubiquitin variants was used to show that at least a significant fraction of alpha-2 degradation is dependent on its ubiquitination

Human Communication Systems Evolve by Cultural Selection

Human communication systems, such as language, evolve culturally; their components undergo reproduction and variation. However, a role for selection in cultural evolutionary dynamics is less clear. Often neutral evolution (also known as 'drift') models, are used to explain the evolution of human communication systems, and cultural evolution more generally. Under this account, cultural change is unbiased: for instance, vocabulary, baby names and pottery designs have been found to spread through random copying. While drift is the null hypothesis for models of cultural evolution it does not always adequately explain empirical results. Alternative models include cultural selection, which assumes variant adoption is biased. Theoretical models of human communication argue that during conversation interlocutors are biased to adopt the same labels and other aspects of linguistic representation (including prosody and syntax). This basic alignment mechanism has been extended by computer simulation to account for the emergence of linguistic conventions. When agents are biased to match the linguistic behavior of their interlocutor, a single variant can propagate across an entire population of interacting computer agents. This behavior-matching account operates at the level of the individual. We call it the Conformity-biased model. Under a different selection account, called content-biased selection, functional selection or replicator selection, variant adoption depends upon the intrinsic value of the particular variant (e.g., ease of learning or use). This second alternative account operates at the level of the cultural variant. Following Boyd and Richerson we call it the Content-biased model. The present paper tests the drift model and the two biased selection models' ability to explain the spread of communicative signal variants in an experimental micro-society

Enhancing the quality of published research on ethnicity and health: is journal guidance feasible and useful?

Researching ethnicity and health presents significant ethical, conceptual and methodological challenges. While the potential contribution of research evidence to tackling ethnic inequalities in health is recognised, there are widespread concerns regarding the ethical and scientific rigour of much of this research and its potential to do more harm than good. The introduction of guidance documents at critical points in the research cycle - including within the peer-review publication process - might be one way to enhance the quality of such research. This article reports the findings from the piloting of a guidance checklist within an international journal. The checklist was positively received by authors and reviewers, the majority of whom reported it to be comprehensible, relevant and potentially useful in improving the quality of published research. However, participation in the pilot was poor, suggesting that the impact of such a checklist would be very limited unless it was perceived to be an aid to authors and reviewers, rather than an additional burden, and was strongly promoted by journal editors

The Optimal Behaviour of a Split Model of Word Recognition Resembles Observed Fixation Behaviour

We expand upon the case for believing that the initial precise splitting of the foveal projection to the visual cortex fundamentally conditions the whole process of visual word recognition. We explore the optimal behaviour of a split architecture that attempts to divide its processing load equally between its two halves. We successfully model three aspects of fixation behaviour in human readers: (a) the positioning of the optimal viewing position to the left of the midpoint of the word, (b) a displaced Gaussian curve of letter-report accuracy resembling an RVF advantage, (c) the tendency for shorter words not to be directly fixated

A review of the “metallome” within neurons and glia, as revealed by elemental mapping of brain tissue

It is now well established that transition metals, such as Iron (Fe), Copper (Cu), and Zinc (Zn) are necessary for healthy brain function. Although Fe, Cu, and Zn are essential to the brain, imbalances in the amount, distribution, or chemical form (“metallome”) of these metals is linked to the pathology of numerous brain diseases or disorders. Despite the known importance of metal ions for both brain health and disease, the metallome that exists within specific types of brain cells is yet to be fully characterised. The aim of this mini-review is to present an overview of the current knowledge of the metallome found within specific brain cells (oligodendrocytes, astrocytes, microglia, and neurons), as revealed by direct elemental mapping techniques. It is hoped this review will foster continued research using direct elemental mapping techniques to fully characterise the brain cell metallome

An Automated Text Mining Approach for Classifying Mental-Ill Health Incidents from Police Incident Logs for Data-Driven Intelligence

Data-driven intelligence can play a pivotal role in enhancing the effectiveness and efficiency of police service provision. Despite of police organizations being a rich source of qualitative data (present in less formally structured formats, such as the text logs), little work has been done in automating steps to allow this data to feed into intelligence-led policing tasks, such as demand analysis/prediction. This paper examines the use of police incident logs to better estimate the demand of officers across all incidents, with particular respect to the cases where mental-ill health played a primary part. Persons suffering from mental-ill health are significantly more likely to come into contact with the police, but statistics relating to how much actual police time is spent dealing with this type of incident are highly variable and often subjective. We present a novel deep learning based text mining approach, which allows accurate extraction of mental-ill health related incidents from police incident logs. The data gained from these automated analyses can enable both strategic and operational planning within police forces, allowing policy makers to develop long term strategies to tackle this issue, and to better plan for day-today demand on services. The proposed model has demonstrated the cross-validated classification accuracy of 89.5% on the real dataset

Categorisation as Topographic Mapping between Uncorrelated Spaces

Abstract. In this paper, I propose a neurophysiologically plausible account for the evolution of arbitrary, categorical mental relationships. Topographic, or structure-preserving, mappings are widespread within animal brains. If they can be shown to generate behaviours in simulation, it is plausible that they are responsible for them in vivo. One behaviour has puzzled philosophers, psychologists and linguists alike: the categorical nature of language and its arbitrary associations between categories of form and meaning. I show here that arbitrary categorical relationships can arise when a topographic mapping is developed between continuous, but uncorrelated activation spaces. This is shown first by simulation, then identified in humans with synaesthesia. The independence of form and meaning as sensory or conceptual spaces automatically results in a categorial structure being imposed on each, as our brains attempt to link the spaces with topographic maps. This result suggests a neurophysiologically plausible explanation of categorisation in language

Single-Base Resolution Mapping of 5-Hydroxymethylcytosine Modifications in Hippocampus of Alzheimer\u27s Disease Subjects

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our data show significant pathways for altered levels of 5-hmC in the hippocampus of AD subjects compared to age-matched normal controls involved in signaling, energy metabolism, cell function, gene expression, protein degradation, and cell structure and stabilization. Overall, our data suggest a possible role for the dysregulation of epigenetic modifications to cytosine in late stage AD

Community and Clinical Epidemiology of Borderline Personality Disorder

Several studies of the prevalence of Borderline Personality Disorder (BPD) in community and clinical settings have been carried out to date. Although results vary according to sampling method and assessment method, median point prevalence of BPD is roughly 1%, with higher or lower rates in certain community subpopulations. In clinical settings, BPD prevalence is around 10-12% in outpatient psychiatric clinics and 20-22% among inpatient clinics. Further research is needed to identify the prevalence and correlates of BPD in other clinical settings (e.g., primary care) and to investigate the impact of demographic variables on BPD prevalence

Police Risk Assessment of Domestic Abuse: The mediating role of space and time

In England and Wales, police forces deploy an evidence-based Domestic Abuse, Stalking and Harassment, and Honour-Based Violence (DASH) assessment tool when responding to reports of domestic abuse. The DASH assessment tool is primarily utilised to undertake risk prediction / estimation at the incident, though it can also be used to undertake harm and needs identification as well as demand management (Medina Ariza et al. 2016). This paper explores whether risk prediction (High, Medium and Standard) derived from 27 DASH questions differs across space and according to the time of year. Moreover, and over a period when the number of domestic abuse associated crime have seen significant growth, whilst the level of police funding has seen significant decline, the paper questions the consistency of risk prediction through time. The paper draws on a dataset of 360,000 DASH assessments, risk assessment outcomes and victim characteristics for the period 2011-2017. It deploys probabilistic and heuristic machine learning-based algorithms to evaluate the existence and degree of spatially and temporally weighted decision-making and to offer guidance as to how this might be overcome. The importance of this research rests in supporting equitable service delivery in an era of fiscal strain