Why was urban overcrowding much more severe in Scotland than in the rest of the British Isles? Evidence from the first (1904) official household expenditure survey

This article presents an analysis of British urban working-class housing conditions in 1904, using a rediscovered survey. We investigate overcrowding and find major regional differences. Scottish households in the survey were more overcrowded despite being less poor. Investigating the causes of this overcrowding, we find little support for supply-side theories or for the idea that the Scottish households in our survey experienced particularly great variations in income, causing them to commit to overly modest accommodation. We present evidence that is consistent with idea that particularly tough Scottish tenancy and local tax laws caused excess overcrowding. We also provide evidence that Scottish workers had a relatively high preference for food, rather than housing, expenditure, which can be at least partly attributed to their inheritance of more communal patterns of urban living.

Amygdala functional connectivity with medial prefrontal cortex at rest predicts the positivity effect in older adults’ memory

As people get older, they tend to remember more positive than negative information. This age-by-valence interaction has been called “positivity effect.” The current study addressed the hypotheses that baseline functional connectivity at rest is predictive of older adults' brain activity when learning emotional information and their positivity effect in memory. Using fMRI, we examined the relationship among resting-state functional connectivity, subsequent brain activity when learning emotional faces, and individual differences in the positivity effect (the relative tendency to remember faces expressing positive vs. negative emotions). Consistent with our hypothesis, older adults with a stronger positivity effect had increased functional coupling between amygdala and medial PFC (MPFC) during rest. In contrast, younger adults did not show the association between resting connectivity and memory positivity. A similar age-by-memory positivity interaction was also found when learning emotional faces. That is, memory positivity in older adults was associated with (a) enhanced MPFC activity when learning emotional faces and (b) increased negative functional coupling between amygdala and MPFC when learning negative faces. In contrast, memory positivity in younger adults was related to neither enhanced MPFC activity to emotional faces, nor MPFC–amygdala connectivity to negative faces. Furthermore, stronger MPFC–amygdala connectivity during rest was predictive of subsequent greater MPFC activity when learning emotional faces. Thus, emotion–memory interaction in older adults depends not only on the task-related brain activity but also on the baseline functional connectivity.

Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease

Huntingtin (Htt) protein interacts with many transcriptional regulators, with widespread disruption to the transcriptome in Huntington's disease (HD) brought about by altered interactions with the mutant Htt (muHtt) protein. Repressor Element-1 Silencing Transcription Factor (REST) is a repressor whose association with Htt in the cytoplasm is disrupted in HD, leading to increased nuclear REST and concomitant repression of several neuronal-specific genes, including brain-derived neurotrophic factor (Bdnf). Here, we explored a wide set of HD dysregulated genes to identify direct REST targets whose expression is altered in a cellular model of HD but that can be rescued by knock-down of REST activity. We found many direct REST target genes encoding proteins important for nervous system development, including a cohort involved in synaptic transmission, at least two of which can be rescued at the protein level by REST knock-down. We also identified several microRNAs (miRNAs) whose aberrant repression is directly mediated by REST, including miR-137, which has not previously been shown to be a direct REST target in mouse. These data provide evidence of the contribution of inappropriate REST-mediated transcriptional repression to the widespread changes in coding and non-coding gene expression in a cellular model of HD that may affect normal neuronal function and survival.

REST: transcriptional and epigenetic regulator

Acquisition and maintenance of cell fate and potential are dependent on the complex interplay of extracellular signaling, gene regulatory networks and epigenetic states. During embryonic development, embryonic stem cells become progressively more restricted along specific lineages, ultimately giving rise to the diversity of cell types in the adult mammalian organism. Recent years have seen major advances in our understanding of the mechanisms that regulate the underlying transcriptional programmes during development. In particular, there has been a significant increase in our knowledge of how epigenetic marks on chromatin can regulate transcription by generating more or less permissive chromatin conformations. This article focuses on how a single transcription factor, repressor element-1 silencing transcription factor, can function as both a transcriptional and epigenetic regulator, controlling diverse aspects of development. We will discuss how the elucidation of repressor element-1 silencing transcription factor function in both normal and disease conditions has provided valuable insights into how the epigenome and transcriptional regulators might cooperatively orchestrate correct development.

Rescue of gene expression by modified REST decoy oligonucleotides in a cellular model of Huntington's disease

Transcriptional dysfunction is a prominent hallmark of Huntington's disease (HD). Several transcription factors have been implicated in the aetiology of HD progression and one of the most prominent is repressor element 1 (RE1) silencing transcription factor (REST). REST is a global repressor of neuronal gene expression and in the presence of mutant Huntingtin increased nuclear REST levels lead to elevated RE1 occupancy and a concomitant increase in target gene repression, including brain-derived neurotrophic factor. It is of great interest to devise strategies to reverse transcriptional dysregulation caused by increased nuclear REST and determine the consequences in HD. Thus far, such strategies have involved RNAi or mutant REST constructs. Decoys are double-stranded oligodeoxynucleotides corresponding to the DNA-binding element of a transcription factor and act to sequester it, thereby abrogating its transcriptional activity. Here, we report the use of a novel decoy strategy to rescue REST target gene expression in a cellular model of HD. We show that delivery of the decoy in cells expressing mutant Huntingtin leads to its specific interaction with REST, a reduction in REST occupancy of RE1s and rescue of target gene expression, including Bdnf. These data point to an alternative strategy for rebalancing the transcriptional dysregulation in HD.

The role of REST in transcriptional and epigenetic dysregulation in Huntington's disease

Huntington's disease (HD) is a devastating disorder that affects approximately 1 in 10,000 people and is accompanied by neuronal dysfunction and neurodegeneration. HD manifests as a progressive chorea, a decline in mental abilities accompanied by behavioural, emotional and psychiatric problems followed by, dementia, and ultimately, death. The molecular pathology of HD is complex but includes widespread transcriptional dysregulation. Although many transcriptional regulatory molecules have been implicated in the pathogenesis of HD, a growing body of evidence points to the pivotal role of RE1 Silencing Transcription Factor (REST). In HD, REST, translocates from the cytoplasm to the nucleus in neurons resulting in repression of key target genes such as BDNF. Since these original observations, several thousand direct target genes of REST have been identified, including numerous non-coding RNAs including both microRNAs and long non-coding RNAs, several of which are dysregulated in HD. More recently, evidence is emerging that hints at epigenetic abnormalities in HD brain. This in turn, promotes the notion that targeting the epigenetic machinery may be a useful strategy for treatment of some aspects of HD. REST also recruits a host of histone and chromatin modifying activities that can regulate the local epigenetic signature at REST target genes. Collectively, these observations present REST as a hub that coordinates transcriptional, posttranscriptional and epigenetic programmes, many of which are disrupted in HD. We identify several spokes emanating from this REST hub that may represent useful sites to redress REST dysfunction in HD.

Reward, rest, and antidepressant drug action

Purpose of the study: Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. We have developed a human model of reward processing to investigate the neural correlates of anhedonia. Methods: We report the data from studies that examined reward processing using functional magnetic resonance imaging (fMRI) in those vulnerable to depression. We also report the effects of antidepressant medications on our neural model of reward processing and on the resting state in healthy volunteers. Results: Our results thus far indicate that deficits in reward processing are apparent in those vulnerable to depression, and also that antidepressant medication modulates reward processing and resting state functional connectivity in parts of the brain consistent with serotonin and catecholamine transmitter pathways in healthy volunteers. Conclusions: We conclude that this type of human model of reward processing might be useful in detecting biomarkers for depression and also in illuminating why antidepressant medications may not be very effective in treating anhedonia.

Peopling of the Northern Territory part 2: the white elephant laid to rest? In the inter-war years

Over time, the Immigration Restriction Act of 1901 and its later amendments were remarkably successful in excluding 'coloured' immigrants from Australia.  It is clear, however, that although most Australians wanted to preserve the 'white' and British character of their nation, the argument that 'non-white' and non-British immigrants were more suited to the settlement of northern Australia was frequently debated in the early decades of the twentieth century.  While this idea continued to challenge the validity of a 'white Australia' in the north, public figures were divided on the issue.  This article examines in some detail the contemporary debates over the peopling of the Northern Territory in the inter-war years.

Does the concept of ″altered states of consciousness″ rest on a mistake?

Block (2002) has argued that the multiplicity of meanings ascribed to consciousness is due to the erroneous treatment of very different concepts as a single concept. Block distinguished four notions of consciousness intended to encapsulate the various meanings attributed to the term: phenomenal, access, self, and monitoring consciousness. We argue that what is common to all of these definitions is the implicit distinction between consciousness and the content of consciousness. We critically examine the term “altered state of consciousness” and argue that affixing the qualifier “altered state” to consciousness results in a theoretical confusion of consciousness and its content, that is, consciousness is mistaken for the content of consciousness. We refer to this as the consciousness/content fallacy and argue that it may be avoided if one supplants “altered states of consciousness” with “altered pattern of phenomenal properties,” an extrapolation of the term “phenomenal field.” Implications of the consciousness/content fallacy for theory and research are also considered.

Comparing Victoria's genuine progress with that of the Rest-of-Australia

While a range of exogenous and endogenous factors affect the standard of  living of most Australians in a more-or-less uniform way, the different social and economic-policies of each state government are likely to affect the levels of sustainable well-being experienced across the various states. With this in mind, a Genuine Progress Indicator (GPI) - a newly devised measure of sustainable well-being - is calculated for Victoria and the Rest- of- Australia (Australia minus Victoria) for the period 1986-2003. The GPI takes account of the various costs and benefits of economic activity in order to investigate the impact of a growing state or national economy on sustainable well-being.
By analysing the GPI results and the policies undertaken by the Victorian government, it is possible to determine what the state of Victoria is doing differently to the Rest-of-Australia that might be beneficial or detrimental to sustainable well-being. While our study reveals that Victoria is performing better than the Rest-of-Australia, it also highlights flaws in the policy-making process that have resulted in Victoria's Gross State Product (GSP) overstating its genuine progress.

The west and the rest

TOPICS
European exploration of the Orient
Oriental ism
Orientalist art
Early European views of Muslims
Universal values versus cultural relativism
The clash of civilisations
The emergence and function of rogue states
The axis of evil and the war on terror
Future predictions