Retroviral integration site targeting is not random and plays a critical role in expression and long-term survival of the integrated provirus. To better understand the genomic environment surrounding retroviral integration sites, we performed a meta-analysis of previously published integration site data from evolutionarily diverse retroviruses, including new experimental data from HIV-1 subtypes A, B, C and D. We show here that evolutionarily divergent retroviruses exhibit distinct integration site profiles with strong preferences for integration near non-canonical B-form DNA (non-B DNA). We also show that in vivo-derived HIV-1 integration sites are significantly more enriched in transcriptionally silent regions and transcription-silencing non-B DNA features of the genome compared to in vitro-derived HIV-1 integration sites. Integration sites from individuals infected with HIV-1 subtype A, B, C or D viruses exhibited different preferences for common genomic and non-B DNA features. In addition, we identified several integration site hotspots shared between different HIV-1 subtypes, all of which were located in the non-B DNA feature slipped DNA. Together, these data show that although evolutionarily divergent retroviruses exhibit distinct integration site profiles, they all target non-B DNA for integration. These findings provide new insight into how retroviruses integrate into genomes for long-term survival.

Specialized DNA Structures Act as Genomic Beacons for Integration by Evolutionarily Diverse Retroviruses.

Central sensitization (CS) is defined as an increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state associated with noxious inputs (eg, polyarthritis). The concept of CS has recently been adopted in clinical assessments of chronic pain, but its diagnosis in humans may now include a wide range of hypervigilant responses. The purpose of this review is to ascertain whether self-report questionnaires linked with CS are associated with enhanced nociceptive responses or whether they measure sensitivity in a broader sense (ie, emotional responses). According to our published, PROSPERO-registered review protocol (CRD42021208731), a predefined search of studies that involve the Central Sensitization Inventory (CSI) or Pain Sensitivity Questionnaire (PSQ), correlated with either nociceptive sensory tests or emotional hypervigilance was conducted on MEDLINE, PsycINFO, and Web of Science. Correlations between the CSI or PSQ with our primary outcomes were extracted and meta-analysed. A review of 66 studies totalling 13,284 participants found that the CSI (but not the PSQ) strongly correlated with psychological constructs: depression, anxiety, stress, pain catastrophising, sleep, and kinesiophobia. The CSI and PSQ showed weak or no correlations with experimental measures of nociceptive sensitivity: pain thresholds, temporal summation, or conditioned pain modulation. The PSQ did, however, correlate strongly with phasic heat and tonic cold pain tests. The studies reviewed did not provide sufficient evidence that self-report measures reflect a canonical understanding of CS. The CSI more closely reflects psychological hypervigilance than increased responsiveness of nociceptive neurons.

Do "central sensitization" questionnaires reflect measures of nociceptive sensitization or psychological constructs? A systematic review and meta-analyses.

Two often-studied forms of uncertain decision-making (DM) are risky-DM (outcome probabilities known) and ambiguous-DM (outcome probabilities unknown). While DM in general is associated with activation of several brain regions, previous neuroimaging efforts suggest a dissociation between activity linked with risky and ambiguous choices. However, the common and distinct neurobiological correlates associated with risky- and ambiguous-DM, as well as their specificity when compared to perceptual-DM (as a 'control condition'), remains to be clarified. We conducted multiple meta-analyses on neuroimaging results from 151 studies to characterize common and domain-specific brain activity during risky-, ambiguous-, and perceptual-DM. When considering all DM tasks, convergent activity was observed in brain regions considered to be consituents of the canonical salience, valuation, and executive control networks. When considering subgroups of studies, risky-DM (vs. perceptual-DM) was linked with convergent activity in the striatum and anterior cingulate cortex (ACC), regions associated with reward-related processes (determined by objective functional decoding). When considering ambiguous-DM (vs. perceptual-DM), activity convergence was observed in the lateral prefrontal cortex and insula, regions implicated in affectively-neutral mental processes (e.g., cognitive control and behavioral responding; determined by functional decoding). An exploratory meta-analysis comparing brain activity between substance users and non-users during risky-DM identified reduced convergent activity among users in the striatum, cingulate, and thalamus. Taken together, these findings suggest a dissociation of brain regions linked with risky- and ambiguous-DM reflecting possible differential functionality and highlight brain alterations potentially contributing to poor decision-making in the context of substance use disorders.

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