Abstract:
:Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (CNS) is unknown. Here we show that CNS-derived HIV-1 strains possess polymorphisms within and surrounding the Sp transcription factor motifs in the long terminal repeat (LTR). These polymorphisms result in decreased ability of the transcription factor specificity protein 1 to bind CNS-derived LTRs, reducing the transcriptional activity of CNS-derived viruses. These mutations result in CNS-derived viruses being less responsive to activation by the HDACi panobinostat and romidepsin compared with lymphoid-derived viruses from the same subjects. Our findings suggest that HIV-1 strains residing in the CNS have unique transcriptional regulatory mechanisms, which impact the regulation of latency, the consideration of which is essential for the development of HIV-1 eradication strategies.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Gray LR,Cowley D,Welsh C,Lu HK,Brew BJ,Lewin SR,Wesselingh SL,Gorry PR,Churchill MJdoi
10.1038/mp.2015.111subject
Has Abstractpub_date
2016-04-01 00:00:00pages
574-84issue
4eissn
1359-4184issn
1476-5578pii
mp2015111journal_volume
21pub_type
杂志文章abstract::To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheime...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/mp.2013.86
更新日期:2014-06-01 00:00:00
abstract::Converging advances in the fields of molecular biology, molecular genetics, cellular biology and embryology have given researchers the tools for the targeted delivery and stable germline transmission of foreign genes (transgenes) in the mouse. In the realm of neuropsychiatry, this so-named transgenic technology has be...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1996-05-01 00:00:00
abstract::Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-inv...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0356-x
更新日期:2020-04-01 00:00:00
abstract::Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.153
更新日期:2016-08-01 00:00:00
abstract::Cigarette smoking is more prevalent in subjects with schizophrenia compared to those with other psychiatric disorders or the general population and could therefore affect molecular pathways that impact the pathophysiology of this disorder. As smoking is also known to suppress immune responses, we investigated the effe...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.120
更新日期:2010-04-01 00:00:00
abstract::While localizing sensory and motor deficits is one of the cornerstones of clinical neurology, behavioral and cognitive deficits in psychiatry remain impervious to this approach. In psychiatry, major challenges include the relative subtlety by which neural circuits are perturbed, and the limited understanding of how ba...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2016.183
更新日期:2017-02-01 00:00:00
abstract::Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology te...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2008.31
更新日期:2008-06-01 00:00:00
abstract::Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.39
更新日期:2009-11-01 00:00:00
abstract::Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with th...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4001909
更新日期:2007-01-01 00:00:00
abstract::Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started wi...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.6
更新日期:2010-11-01 00:00:00
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journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0422-4
更新日期:2019-04-16 00:00:00
abstract::The network theory conceptualizes mental disorders as complex networks of symptoms influencing each other by creating feedback loops, leading to a self-sustained syndromic constellation. Symptoms central to the network have the greatest impact in sustaining the rest of symptoms. This analysis focused on the network st...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0232-0
更新日期:2020-07-01 00:00:00
abstract::Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulatio...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.104
更新日期:2015-11-01 00:00:00
abstract::The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic var...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000744
更新日期:2000-07-01 00:00:00
abstract::A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients with schizophrenia. Genotypes of 407 patients were analyzed for 334,563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy w...
journal_title:Molecular psychiatry
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/mp.2008.56
更新日期:2009-08-01 00:00:00
abstract::The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associa...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4001809
更新日期:2006-04-01 00:00:00
abstract::Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophr...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0553-7
更新日期:2020-04-01 00:00:00
abstract::Perturbation of Disrupted-In-Schizophrenia-1 (DISC1) and D-serine/NMDA receptor hypofunction have both been implicated in the pathophysiology of schizophrenia and other psychiatric disorders. In the present study, we demonstrate that these two pathways intersect with behavioral consequences. DISC1 binds to and stabili...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.97
更新日期:2013-05-01 00:00:00
abstract::The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite con...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析,评审
doi:10.1038/sj.mp.4001336
更新日期:2003-07-01 00:00:00
abstract::Recent in vivo studies have shown low dopamine D2 receptor and dopamine transporter densities among late onset (type 1) alcoholics. We have now studied 6-[18F]-FDOPA (FDOPA) uptake in 10 type 1 alcoholics and eight matched controls to test the hypothesis that striatal presynaptic dopamine function is lower among alcoh...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000365
更新日期:1998-03-01 00:00:00
abstract::Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions a...
journal_title:Molecular psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1038/mp.2013.42
更新日期:2014-03-01 00:00:00
abstract::A genetic predisposition to the development of neuroleptic malignant syndrome (NMS) has been suggested by clinical studies. Although the molecular basis of NMS is unclear, a dopaminergic blockade mechanism has been considered the main cause. We therefore investigated the association between NMS and three functional po...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001422
更新日期:2004-03-01 00:00:00
abstract::High-affinity transporters for norepinephrine (NE) and serotonin (5-HT), which ensure neurotransmitter clearance at the synapse, are the principal targets of widely used antidepressant drugs. Antidepressants targeting these high-affinity transporters, however, do not provide positive treatment outcomes for all patient...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.87
更新日期:2012-09-01 00:00:00
abstract::The glutamate hypothesis of schizophrenia derived from evidence that phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is defici...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001404
更新日期:2004-01-01 00:00:00
abstract::Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0271-6
更新日期:2020-09-01 00:00:00
abstract::Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizop...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001925
更新日期:2007-03-01 00:00:00
abstract::The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in par...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.155
更新日期:2018-07-01 00:00:00
abstract::Anxiety disorders constitute a major disease and social burden worldwide; however, many questions concerning the underlying molecular mechanisms still remain open. Besides the involvement of the major excitatory (glutamate) and inhibitory (gamma aminobutyric acid (GABA)) neurotransmitter circuits in anxiety disorders,...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.87
更新日期:2017-03-01 00:00:00
abstract::Attention deficit hyperactivity disorder, combined type (ADHD-CT) is associated with spatial working memory deficits. These deficits are known to be subserved by dysfunction of neural circuits involving right prefrontal, striatal and parietal brain regions. This study determines whether decreased right prefrontal, str...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001999
更新日期:2007-09-01 00:00:00
abstract::The Raf kinases Raf-1 and B-Raf are upstream activators of the extracellular signal-regulated kinase (ERK)-signaling pathway and therefore participates in many physiological functions in brain, including neuronal survival and synaptic plasticity. Previously, we observed that activation of ERK-1/2, the downstream compo...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001744
更新日期:2006-01-01 00:00:00