A disease of more than 39.6 million people worldwide, HIV-1 infection has no curative therapy. To date, one man has achieved a sterile cure, with millions more hoping to avoid the potential pitfalls ...of lifelong antiretroviral therapy and other HIV-related disorders, including neurocognitive decline. Recent developments in immunotherapies and gene therapies provide renewed hope in advancing efforts toward a sterilizing or functional cure. On the horizon is research concentrated in multiple separate but potentially complementary domains: vaccine research, viral transcript editing, T-cell effector response targeting including checkpoint inhibitors, and gene editing. Here, we review the concept of targeting the HIV-1 tissue reservoirs, with an emphasis on the central nervous system, and describe relevant new work in functional cure research and strategies for HIV-1 eradication.
Love and Money Henderson, Lisa
01/2013, Letnik:
18
eBook
Love and Money argues that we can't understand contemporary queer cultures without looking through the lens of social class. Resisting old divisions between culture and economy, identity and ...privilege, left and queer, recognition and redistribution, Love and Money offers supple approaches to capturing class experience and class form in and around queerness.Contrary to familiar dismissals, not every queer television or movie character is like Will Truman on Will and Grace - rich, white, healthy, professional, detached from politics, community, and sex. Through ethnographic encounters with readers and cultural producers and such texts as Boys Don't Cry, Brokeback Mountain, By Hook or By Crook, and wedding announcements in the New York Times, Love and Money sees both queerness and class across a range of idioms and practices in everyday life. How, it asks, do readers of Dorothy Allison's novels use her work to find a queer class voice? How do gender and race broker queer class fantasy? How do independent filmmakers cross back and forth between industry and queer sectors, changing both places as they go and challenging queer ideas about bad commerce and bad taste?With an eye to the nuances and harms of class difference in queerness and a wish to use culture to forge queer and class affinities, Love and Money returns class and its politics to the study of queer life.
Chronic stress is a major risk factor for a number of mental health disorders, including depression and pathological anxiety. Adaptive cognitive emotion regulation (CER) strategies (i.e. ...positively-focused thought processes) can help to prevent psychiatric disturbance when enduring unpleasant and stressful experiences, but little is known about the inter-individual factors that govern their success. Sleep plays an important role in mental health, and may moderate the effectiveness of adaptive CER strategies by maintaining the executive functions on which they rely. In this study, we carried out a secondary analysis of self-reported mental health and sleep data acquired during a protracted and naturally-occurring stressor – the COVID-19 pandemic – to firstly test the hypothesis that adaptive CER strategy use is associated with positive mental health outcomes and secondly, that the benefits of adaptive CER strategy use for mental health are contingent on high-quality sleep. Using established self-report tools, participants estimated their depression (N = 551) and anxiety (N = 590)22Due to a minor coding error that resulted in an incorrectly computed predictor measure, we have more missing data than was originally reported in our Stage 1 Registered Report. Our total sample size therefore differs from that reported in our Stage 1 Registered Report for both the pilot study (from n = 118 to n = 117 for the depression sample and from n = 123 to n = 122 for the anxiety sample) and the main study (from n = 562 to n = 551 for the depression sample and from n = 604 to n = 590 for the anxiety sample). These corrections received editorial approval on 30th November 2022. levels, sleep quality and tendency to engage in adaptive and maladaptive CER strategies during the Spring and Autumn of 2020. Using a linear mixed modelling approach, we found that greater use of adaptive CER strategies and higher sleep quality were independently associated with lower self-reported depression and anxiety. However, adaptive CER strategy use was not a significant predictor of self-reported anxiety when accounting for sleep quality in our final model. The positive influence of adaptive CER strategy use on depression was observed at different levels of sleep quality. These findings highlight the importance of adaptive CER strategy use and good sleep quality in promoting resilience to depression and anxiety when experiencing chronic stress.
Background
Vocabulary is crucial for an array of life outcomes and is frequently impaired in developmental disorders. Notably, ‘poor comprehenders’ (children with reading comprehension deficits but ...intact word reading) often have vocabulary deficits, but underlying mechanisms remain unclear. Prior research suggests intact encoding but difficulties consolidating new word knowledge. We test the hypothesis that poor comprehenders’ sleep‐associated vocabulary consolidation is compromised by their impoverished lexical‐semantic knowledge.
Methods
Memory for new words was tracked across wake and sleep to assess encoding and consolidation in 8‐to‐12‐year‐old good and poor comprehenders. Each child participated in two sets of sessions, one beginning in the morning (AM‐encoding) and the other in the evening (PM‐encoding). In each case, they were taught 12 words and were trained on a spatial memory task. Memory was assessed immediately, 12‐ and 24‐hr later via stem‐completion, picture‐naming, and definition tasks to probe different aspects of word knowledge. Long‐term retention was assessed 1–2 months later.
Results
Recall of word‐forms improved over sleep and postsleep wake, as measured in both stem‐completion and picture‐naming tasks. Counter to hypotheses, deficits for poor comprehenders were not observed in consolidation but instead were seen across measures and throughout testing, suggesting a deficit from encoding. Variability in vocabulary knowledge across the whole sample predicted sleep‐associated consolidation, but only when words were learned early in the day and not when sleep followed soon after learning.
Conclusions
Poor comprehenders showed weaker memory for new words than good comprehenders, but sleep‐associated consolidation benefits were comparable between groups. Sleeping soon after learning had long‐lasting benefits for memory and may be especially beneficial for children with weaker vocabulary. These results provide new insights into the breadth of poor comprehenders’ vocabulary weaknesses, and ways in which learning might be better timed to remediate vocabulary difficulties.
Prior linguistic knowledge is proposed to support the acquisition and consolidation of new words. Adults typically have larger vocabularies to support word learning than children, but the developing ...brain shows enhanced neural processes that are associated with offline memory consolidation. This study investigated contributions of prior knowledge to initial word acquisition and consolidation at different points in development, by teaching children and adults novel words (e.g., ballow) that varied in the number of English word‐form “neighbours” (e.g., wallow, bellow). Memory for the novel word‐forms was tested immediately after training, the next day and 1 week later, to assess the time‐course of prior knowledge contributions. Children aged 7–9 years (Experiments 1, 3) and adults (Experiment 2) recalled words with neighbours better than words without neighbours when tested immediately after training. However, a period of offline consolidation improved overall recall and reduced the influence of word‐form neighbours on longer term memory. These offline consolidation benefits were larger in children than adults, supporting theories that children have a greater propensity for consolidating phonologically distinctive language information. Local knowledge of just a single word‐form neighbour was enough to enhance learning, and this led to the individual differences in word recall that were related to adults’ global vocabulary ability. The results support the proposal that the relative contributions of different learning mechanisms change across the lifespan, and highlight the importance of testing theoretical models of word learning in the context of development.
We taught children and adults pseudowords with and without word‐form neighbours to test whether local prior knowledge connections facilitate new word learning. Pseudowords with word‐form neighbours were remembered better than pseudowords without word‐form neighbours. However, offline consolidation strengthened memory for the pseudowords without neighbours, reducing the influence of prior knowledge on word memory a week later. This consolidation benefit was stronger for children than for adults.
Language acquisition is argued to be dependent upon an individuals’ sensitivity to serial-order regularities in the environment (sequential learning), and impairments in reading and spelling in ...dyslexia have recently been attributed to a deficit in sequential learning. The present study examined the learning and consolidation of sequential knowledge in 30 adults with dyslexia and 29 typical adults matched on age and nonverbal ability using two tasks previously reported to be sensitive to a sequence learning deficit. Both groups showed evidence of sequential learning and consolidation on a serial response time (SRT) task (i.e., faster and more accurate responses to sequenced spatial locations than randomly ordered spatial locations during training that persisted one week later). Whilst typical adults showed evidence of sequential learning on a Hebb repetition task (i.e., more accurate serial recall of repetitive sequences of nonwords versus randomly ordered sequences), adults with dyslexia showed initial advantages for repetitive versus randomly ordered sequences in the first half of training trials, but this effect disappeared in the second half of trials. This Hebb repetition effect was positively correlated with spelling in the dyslexic group; however, there was no correlation between sequential learning on the two tasks, placing doubt over whether sequential learning in different modalities represents a single capacity. These data suggest that sequential learning difficulties in adults with dyslexia are not ubiquitous, and when present may be a consequence of task demands rather than sequence learning per se.
The presence of phonological neighbours facilitates word-form learning, suggesting that prior phonological knowledge supports vocabulary acquisition. We tested whether prior semantic knowledge ...similarly benefits word learning by teaching 7-to-10-year-old children (Experiment 1) and adults (Experiment 2) pseudowords assigned to novel concepts with low or high semantic neighbourhood density according to feature norms. Form recall, definition recall, and semantic categorisation tasks were administered immediately after training, the next day, and one week later. Across sessions, pseudowords assigned to low-density (versus high-density) semantic neighbourhood concepts elicited better word-form recall (for adults) and better meaning recall (for children). Exploratory cross-experiment analyses demonstrated that the neighbourhood influence was most robust for recalling meanings. Children showed greater gains in form recall than adults across the week, regardless of links to semantic knowledge. While the results suggest that close semantic neighbours interfere with word learning, we consider alternative semantic dimensions that may be beneficial.
The aim of this study was to measure the protein concentration and biological activity of HIV-1 Tat in cerebrospinal fluid (CSF) of individuals on suppressive antiretroviral therapy (ART).
CSF was ...collected from 68 HIV-positive individuals on ART with plasma viral load less than 40 copies/ml, and from 25 HIV-negative healthy controls. Duration of HIV infection ranged from 4 to more than 30 years.
Tat levels in CSF were evaluated by an ELISA. Tat protein and viral RNA were quantified from exosomes isolated from CSF, followed by western blot or quantitative reverse transcription PCR, respectively. Functional activity of Tat was assessed using an LTR transactivation assay.
Tat protein was detected in 36.8% of CSF samples from HIV-positive patients. CSF Tat concentration increased in four out of five individuals after initiation of therapy, indicating that Tat was not inhibited by ART. Similarly, exosomes from 34.4% of CSF samples were strongly positive for Tat protein and/or TAR RNA. Exosomal Tat retained transactivation activity in a CEM-LTR reporter assay in 66.7% of samples assayed, which indicates that over half of the Tat present in CSF is functional. Presence of Tat in CSF was highly associated with previous abuse of psychostimulants (cocaine or amphetamines; P = 0.01) and worse performance in the psychomotor speed (P = 0.04) and information processing (P = 0.02) cognitive domains.
Tat and TAR are produced in the central nervous system despite adequate ART and are packaged into CSF exosomes. Tat remains biologically active within this compartment. These studies suggest that Tat may be a quantifiable marker of the viral reservoir and highlight a need for new therapies that directly inhibit Tat.
The ability to extract patterns from sensory input across time and space is thought to underlie the development and acquisition of language and literacy skills, particularly the subdomains marked by ...the learning of probabilistic knowledge. Thus, impairments in procedural learning are hypothesized to underlie neurodevelopmental disorders, such as dyslexia and developmental language disorder. In the present meta‐analysis, comprising 2396 participants from 39 independent studies, the continuous relationship between language, literacy, and procedural learning on the Serial Reaction Time task (SRTT) was assessed across children and adults with typical development (TD), dyslexia, and Developmental Language Disorder (DLD). Despite a significant, but very small, relationship between procedural learning and overall language and literacy measures, this pattern was not observed at the group‐level when examining TD, dyslexic, and DLD groups separately. Based on the procedural/declarative model, a positive relationship was expected between procedural learning and language and literacy measures for the typically developing group; however, no such relationship was observed. This was also the case for the disordered groups (ps > .05). Also counter to expectations, the magnitude of the relationship between procedural learning and grammar and phonology did not differ between TD and DLD (ps > .05), nor between the TD and dyslexic group on reading, spelling, and phonology (ps > .05). While lending little support to the procedural/declarative model, we consider that these results may be the consequence of poor psychometric properties of the SRTT as a measure of procedural learning.
•Animacy induces difficulty in phrase production and comprehension across ages.•The animacy effects vary with age and backward digit span (BDS) only in production.•BDS development interacts with ...phrase planning from late childhood to adolescence.•Language development varies with task difficulty calling for more general theories.
Some animacy configurations elicit parallel semantic interference in adult production and comprehension; for example, phrases with similar animate nouns like the man that the girl is hugging are more difficult than phrases like the doll that the girl is hugging. Yet little is known about how this interference manifests in development, particularly, beyond early childhood. Because frontal brain maturation and cognitive control improvements are known to occur across late childhood and adolescence, we investigated (a) how animacy-induced difficulty in production and comprehension vary with age throughout this period and (b) whether control processes reflected in the backward digit span (BDS) test uniquely explained these differences besides other language measures. In separate tasks, participants (8- to 15-year-old children; N = 91) heard auditory descriptions of depicted characters, produced characters’ descriptions, and completed BDS, vocabulary, and reading experience tests. Results indicated that, as in adults, animacy modulated performance in production and comprehension across all ages. The animacy modulation interacted with age in production but not in comprehension, suggesting age-related animacy differences in production but relatively stable differences in comprehension despite processing speed improvements. Importantly, these age-related production differences were also modulated by the BDS scores; only participants with higher BDS scores displayed age-related animacy differences. Together, these results indicate that comprehension and production develop at different rates and that the development of BDS performance interacts with age-dependent changes in sentence planning from late childhood to adolescence. More generally, the study highlights tasks’ disparities to be explained by cognitive and developmental models of language.
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