Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes.

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases

Optimal attentional focus during exposure therapy in specific phobia: a meta-analysis

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Focus–specific clinical profiles in human African trypanosomiasis caused by <i>Trypanosoma brucei rhodesiense</i>

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Diverse clinical features have been reported in human African trypanosomiasis (HAT) foci caused by &lt;i&gt;Trypanosoma brucei rhodesiense&lt;/i&gt; (&lt;i&gt;T.b.rhodesiense&lt;/i&gt;) giving rise to the hypothesis that HAT manifests as a chronic disease in South-East African countries and increased in virulence towards the North. Such variation in disease severity suggests there are differences in host susceptibility to trypanosome infection and/or genetic variation in trypanosome virulence. Our molecular tools allow us to study the role of host and parasite genotypes, but obtaining matched extensive clinical data from a large cohort of HAT patients has previously proved problematic.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods/Principal Findings:&lt;/b&gt; We present a retrospective cohort study providing detailed clinical profiles of 275 HAT patients recruited in two northern foci (Uganda) and one southern focus (Malawi) in East Africa. Characteristic clinical signs and symptoms of &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection were recorded and the degree of neurological dysfunction determined on admission. Clinical observations were mapped by patient estimated post-infection time. We have identified common presenting symptoms in &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection; however, marked differences in disease progression and severity were identified between foci. HAT was characterised as a chronic haemo-lymphatic stage infection in Malawi, and as an acute disease with marked neurological impairment in Uganda. Within Uganda, a more rapid progression to meningo-encephaltic stage of infection was observed in one focus (Soroti) where HAT was characterised by early onset neurodysfunction; however, severe neuropathology was more frequently observed in patients in a second focus (Tororo).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; We have established focus-specific HAT clinical phenotypes showing dramatic variations in disease severity and rate of stage progression both between northern and southern East African foci and between Ugandan foci. Understanding the contribution of host and parasite factors in causing such clinical diversity in &lt;i&gt;T.b.rhodesiense&lt;/i&gt; HAT has much relevance for both improvement of disease management and the identification of new drug therapy.&lt;/p&gt

The accrual anomaly – focus on changes in specific unexpected accruals results in new evidence.

This paper deals with the accrual anomaly first documented by Sloan (1996), i.e. the finding that the stock market prices appear to overweigh the role of accruals persistence and under-weigh the role of operating cash flow persistence. In an analysis based on Danish financial statement data it is demonstrated that different specific components of earnings have significantly different earnings persistence characteristics and that these differences are not fully reflected in share prices. In the analysis presented here the earnings persistence effect of two particular unexpected accrual components are specifically analyzed, namely the unexpected inventory accrual component and the unexpected accounts receivable accrual component, i.e. changes in accruals not motivated by corresponding changes in company activity-level. Additionally and for comparison, the accounting accruals are split into expected and unexpected accruals, estimated by the extended Jones model like in both some US-analyses and some international studies of the accrual anomaly phenomenon. It is found that the persistence of earnings is decreasing in the magnitude of the unexpected accrual components of earnings and that the persistence of current earnings performance is particularly decreasing in the magnitude of unexpected changes in inventory. The special accrual parts are related to the perceptions of earnings persistence implicit in the market prices, and it is found that the differences in earnings persistence are not rationally reflected by share price differencesDiscretionary accruals; Earnings management; Earnings Persistence; Accrual anomaly;

Positive emotion broadens attention focus through decreased position-specific spatial encoding in early visual cortex: evidence from ERPs

Recent evidence has suggested that not only stimulus-specific attributes or top-down expectations can modulate attention selection processes, but also the actual mood state of the participant. In this study, we tested the prediction that the induction of positive mood can dynamically influence attention allocation and, in turn, modulate early stimulus sensory processing in primary visual cortex (V1). High-density visual event-related potentials (ERPs) were recorded while participants performed a demanding task at fixation and were presented with peripheral irrelevant visual textures, whose position was systematically varied in the upper visual field (close, medium, or far relative to fixation). Either a neutral or a positive mood was reliably induced and maintained throughout the experimental session. The ERP results showed that the earliest retinotopic component following stimulus onset (C1) strongly varied in topography as a function of the position of the peripheral distractor, in agreement with a near-far spatial gradient. However, this effect was altered for participants in a positive relative to a neutral mood. On the contrary, positive mood did not modulate attention allocation for the central (task-relevant) stimuli, as reflected by the P300 component. We ran a control behavioral experiment confirming that positive emotion selectively impaired attention allocation to the peripheral distractors. These results suggest a mood-dependent tuning of position-specific encoding in V1 rapidly following stimulus onset. We discuss these results against the dominant broaden-and-build theory

Prosodic focus in Vietnamese

This paper reports on pilot work on the expression of Information Structure in Vietnamese and argues that Focus in Vietnamese is exclusively expressed prosodically: there are no specific focus markers, and the language uses phonology to express intonational emphasis in similar ways to languages like English or German. The exploratory data indicates that (i) focus is prosodically expressed while word order remains constant, (ii) listeners show good recoverability of the intended focus structure, and (iii) that there is a trading relationship between several phonetic parameters (duration, f0, amplitude) involved to signal prosodic (acoustic) emphasis

The Making of a Eurasian: Writing, Miscegenation, and Redemption in Sui Sin Far

This paper examines the literary itinerary of Sui Sin Far/Edith Eaton with a specific focus on the shaping of her Eurasian authorship

2005 Report – International Secretariat Clean Clothes Campaign

The report summarizes the activities of the Clean Clothes Campaign’s International Secretariat for the year of 2005, with a specific focus on the right to organize

New Roles for Collective Bargaining

[Excerpt] In this article I will focus on some behaviors that are role-specific. In particular, I will examine the unique contributions of agents, subject matter experts, leaders, and facilitators