bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is on-Demand HIV Pre-exposure Prophylaxis a Suitable Tool for Men Who Have Sex With Men Who Practice Chemsex? Results From a Substudy of the ANRS-IPERGAY Trial
Authors: Roux Perrine , Fressard Lisa , Suzan-Monti Marie , Chas Julie , Sagaon-Teyssier Luis , Capitant Catherine , Meyer Laurence , Tremblay Cécile , Rojas-Castro Daniela , Pialoux Gilles , Molina Jean-Michel , Spire Bruno 
Published: June 2018

Background:
Chemsex—the use of psychoactive substances during sexual encounters—among men who have sex with men is a growing concern. On-demand HIV pre-exposure prophylaxis (PrEP) may be a suitable tool to prevent HIV transmission among “chemsexers.” We used the open-label extension study of the ANRS-IPERGAY trial to describe chemsexers and their PrEP use.

Methods:
Among the 361 men who have sex with men enrolled in ANRS-IPERGAY's open-label extension study, we selected the 331 with available data on drug use. A 2-monthly web questionnaire on sociobehavioral data was used to compare sexual behaviors between questionnaires where chemsex was reported and those where it was not. Using a generalized estimating equation logistic regression, we studied whether practicing chemsex was associated with correct PrEP use.

Results:
Among the 331 participants, 30% reported chemsex practice at least once during follow-up and were considered chemsexers. Chemsex was reported in 16% of all questionnaires. Chemsexers were not significantly different from nonchemsexers regarding sociodemographic characteristics, although they reported greater use of anxiolytics and more sensation-seeking. Reporting chemsex was associated with more high-risk sexual practices and a higher perception of risk. After adjustment for other potential correlates, chemsex remained associated with correct PrEP use [odds ratio (95% confidence interval) = 2.24 (1.37 to 3.66)].

Conclusions:
Our findings show that chemsexers were more likely to report high-risk sexual practices but also had a higher perception of risk. They were also more likely to use PrEP correctly when practicing chemsex. Consequently, PrEP may be a suitable tool to reduce HIV-risk transmission among chemsexers.
Orexin-1 receptor signaling in ventral pallidum regulates demand for the opioid remifentanil
Authors: Mohammdkhani Aida , Pantazis Caroline B , Bowrey Hannah E , James Morgan H , Aston-Jones Gary 
Published: June 2018

Signaling at the orexin-1 receptor (Ox1R) is important for motivation for various drugs of abuse. Recently, our laboratory showed that systemic blockade of Ox1Rs decreased motivation for the potent and short-acting opioid remifentanil, as well as remifentanil consumption at null cost (Porter-Stransky et al., 2017). However, the central site(s) through which orexin acts to regulate opioid-seeking behaviors are not known. We investigated ventral pallidum (VP) as a potential site of orexin action, as VP is a known mediator of opioid reward and is densely innervated by orexin-immunoreactive fibers. We used a within-session behavioral economics (BE) paradigm in which remifentanil price (responses/	μg iv remifentanil) was sequentially increased throughout the session. Rats were implanted with bilateral cannulae into caudal VP (cVP), through which microinjections of SB334867 (SB), an Ox1R antagonist, were given prior to BE and reinstatement testing. Contrary to systemic SB treatment, intra-cVP SB preferentially reduced motivation (increased demand elasticity and reinstatement) for reminfentanil, without affecting remifentanil consumption at null cost. These effects were specific to cVP, as control microinjections of SB immediately dorsal to cVP did not affect remifentanil-seeking. Baseline demand for remifentanil predicted cued reinstatement of remifentanil seeking and the efficacy with which intra-cVP SB administration reduced motivation for remifentanil. These findings indicate a specific role for cVP Ox1R signaling in mediating the motivational properties of the opioid remifentanil, distinct from its consumption at null cost. Our findings also highlight the BE paradigm as an effective biomarker for predicting opioid addiction behaviors and treatment efficacy.
Induction and suppression of NF-kB signalling by a DNA virus ofDrosophila
Authors: Palmer William H. , Joosten Joep , Overheul Gijs J. , Jansen Pascal W. , Vermeulen Michiel , Obbard Darren J. , Van Rij Ronald P. 
Published: June 2018

AbstractInteractions between the insect immune system and RNA viruses have been best studied inDrosophila, where RNA interference, NF-kB and JAK-STAT pathways underlie antiviral immunity. In response to these immune mechanisms, insect viruses have convergently evolved suppressors of RNA interference that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because fewDrosophila-infectingDNA virus isolates are available. Here, we use a recently-isolated DNA virus ofDrosophila melanogaster, Kallithea virus, to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We find that fly mutants for RNA interference and Immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identify the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, strongly suggesting that Toll mediates antiviral responses during Kallithea virus infection, but that it is suppressed by the virus. Further, we find that Kallithea gp83 inhibits Toll signalling either through NF-kB transcription factor regulation, or transcriptionally. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in aDrosophilavirus, extending the known diversity of insect virus-encoded immune inhibitors.
N-terminal phosphorylation of Huntingtin: A molecular switch for regulating Htt aggregation, helical conformation, internalization and nuclear targeting
Authors: DeGuire Sean M. , Ruggeri Francesco. S. , Fares Mohamed-Bilal , Chiki Anass , Cendrowska Urszula , Dietler Giovanni , Lashuel Hilal A. 
Published: June 2018

AbstractPhosphorylation of exon1 of the Huntingtin protein (Httex1) has been shown to play important roles in regulating the structure, toxicity and cellular properties of N-terminal fragments and the full-length Huntingtin protein. Here, we investigated and compared the effect of bona fide phosphorylation at S13 and/or S16 on the structure, aggregation, membrane binding, and subcellular properties of mutant Httex1-Q18A. We show that serine phosphorylation at either S13 or S16 strongly disrupts the amphipathic α-helix of the N-terminus, inhibits the aggregation of mutant Httex1 and prompts the internalization and nuclear targeting of Httex1 preformed aggregates. In synthetic peptides phosphorylation at S13 and/or S16 strongly disrupted the amphipathic α-helix of the N-terminal 17 residues (Nt17) of Httex1 and Nt17 membrane binding. Our studies on peptides bearing a different combination of phosphorylation sites within Nt17 revealed a novel phosphorylation-dependent switch for regulating the structure of Httex1 involving crosstalk between phosphorylation at T3 and S13 or S16. Together, our results provide novel insights into the role of phosphorylation in regulating Httex1 structure and function in health and disease and underscore the critical importance of identifying enzymes responsible for regulating Htt phosphorylation and their potential as therapeutic targets for the treatment of Huntington’s disease.
Experimental determination of codon usage-dependent selective pressure on high copy-number genes inSaccharomyces cerevisiae
Authors: Jossé Lyne , Singh Tarun , von der Haar Tobias 
Published: June 2018

AbstractOne of the central hypotheses in the theory of codon usage evolution is that in highly expressed genes particular codon usage patterns arise because they facilitate efficient gene expression and are thus selected for in evolution. Here we use plasmid copy number assays and growth rate measurements to explore details of the relationship between codon usage, gene expression level, and selective pressure inSaccharomyces cerevisiae. We find that when high expression levels are required optimal codon usage is beneficial and provides a fitness advantage, consistent with evolutionary theory. However, when high expression levels are not required, optimal codon usage is surprisingly and strongly selected against. We show that this selection acts at the level of protein synthesis, and we exclude a number of molecular mechanisms as the source for this negative selective pressure including nutrient and ribosome limitations and proteotoxicity effects. These findings inform our understanding of the evolution of codon usage bias, as well as the design of recombinant protein expression systems.
Wolbachia pipientisassociated to tephritid fruit fly pests: from basic research to applications
Authors: Mateos Mariana , Martinez Humberto , Lanzavecchia Silvia B. , Conte Claudia , Guillén Karina , Morán-Aceves Brenda M. , Toledo Jorge , Liedo Pablo , Asimakis Elias D. , Doudoumis Vangelis , Kyritsis Georgios A. , Papadopoulos Nikos T. , Avgoustinos Antonios A. , Segura Diego F. , Tsiamis George , Bourtzis Kostas 
Published: June 2018

AbstractMembers of the true fruit flies (family Tephritidae) are among the most serious agricultural pests worldwide, whose control and management demands large and costly international efforts. The need for cost-effective and environmentally-friendly integrated pest management (IPM) has led to the development and implementation of autocidal control strategies. Autocidal approaches include the widely used sterile insect technique (SIT) and the incompatible insect technique (IIT). IIT relies on maternally transmitted bacteria (namelyWolbachia), to cause a conditional sterility in crosses between released mass-rearedWolbachia-infected males and wild females, which are either uninfected or infected with a differentWolbachiastrain (i.e., cytoplasmic incompatibility; CI). Herein, we review the current state of knowledge onWolbachia-tephritid interactions including infection prevalence in wild populations, phenotypic consequences, and their impact on life history traits. Numerous pest tephritid species are reported to harborWolbachiainfections, with a subset exhibiting high prevalence. The phenotypic effects ofWolbachiahave been assessed in very few tephritid species, due in part to the difficulty of manipulatingWolbachiainfection (removal or transinfection). Based on recent methodological advances (high-throughput DNA sequencing) and a breakthrough concerning the mechanistic basis of CI, we suggest research avenues that could accelerate generation of necessary knowledge for the potential use ofWolbachia-based IIT in area-wide integrated pest management (AW-IPM) strategies for the population control of tephritid pests.
Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression
Authors: Riga Danai , Schmitz Leanne JM , van Mourik Yvar , Hoogendijk Witte JG , De Vries Taco J , Smit August B , Spijker Sabine 
Published: June 2018

AbstractMajor depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.
A computational strategy for finding novel targets and therapeutic compounds for opioid dependence
Authors: Wu Xiaojun , Xie Siwei , Wang Lirong , Fan Peihao , Ge Songwei , Xie Xiang-Qun , Wu Wei 
Published: June 2018

AbstractOpioids are widely used for treating different types of pains, but overuse and abuse of prescription opioids have led to opioid epidemic in the United States. Besides analgesic effects, chronic use of opioid can also cause tolerance, dependence, and even addiction. Effective treatment of opioid addiction remains a big challenge today. Studies on addictive effects of opioids focus on striatum, a main component in the brain responsible for drug dependence and addiction. Some transcription regulators have been associated with opioid addiction, but relationship between analgesic effects of opioids and dependence behaviors mediated by them at the molecular level has not been thoroughly investigated. In this paper, we developed a new computational strategy that identifies novel targets and potential therapeutic molecular compounds for opioid dependence and addiction. We employed several statistical and machine learning techniques and identified differentially expressed genes over time which were associated with dependence-related behaviors after exposure to either morphine or heroin, as well as potential transcription regulators that regulate these genes, using time course gene expression data from mouse striatum. Moreover, our findings revealed that some of these dependence-associated genes and transcription regulators are known to play key roles in opioid-mediated analgesia and tolerance, suggesting that an intricate relationship between opioid-induce pain-related pathways and dependence may develop at an early stage during opioid exposure. Finally, we determined small compounds that can potentially target the dependence-associated genes and transcription regulators. These compounds may facilitate development of effective therapy for opioid dependence and addiction. We also built a database (http://daportals.org) for all opioid-induced dependence-associated genes and transcription regulators that we discovered, as well as the small compounds that target those genes and transcription regulators.
An activation pathway governs cell wall polymerization by a bacterial morphogenic machine
Authors: Rohs Patricia D. A. , Buss Jackson , Sim Sue , Squyres Georgia , Srisuknimit Veerasak , Smith Mandy , Cho Hongbaek , Sjodt Megan , Kruse Andrew C. , Garner Ethan , Walker Suzanne , Kahne Daniel , Bernhardt Thomas G. 
Published: June 2018

ABSTRACTCell elongation in rod-shaped bacteria is mediated by the Rod system, a conserved morphogenic complex that spatially controls cell wall (CW) assembly. InEscherichia coli, alterations in a CW synthase component of the system called PBP2 were identified that overcome other inactivating defects. Rod system activity was stimulated in the suppressors in vivo, and purified synthase complexes with these changes showed more robust CW synthesis in vitro. Polymerization of the actin-like MreB component of the Rod system was also found to be enhanced in cells with the activated synthase. The results suggest an activation pathway governing Rod system function in which PBP2 conformation plays a central role in stimulating both CW glycan polymerization by its partner RodA and the formation of cytoskeletal filaments of MreB to orient CW assembly. An analogous activation pathway involving similar enzymatic components is likely responsible for controlling CW synthesis by the division machinery.
Anomalous diffusion in inverted variable-lengthscale fluorescence correlation spectroscopy
Authors: Stolle M. , Fradin C. 
Published: June 2018

AbstractUsing fluorescence correlation spectroscopy (FCS) to distinguish between different types of diffusion processes is often a perilous undertaking, as the analysis of the resulting autocorrelation data is model-dependant. Two recently introduced strategies, however, can help move towards a model-independent interpretation of FCS experiments: 1) the obtention of correlation data at different length-scales and 2) its inversion to retrieve the mean-squared displacement associated with the process under study. We use computer simulations to examine the signature of several biologically relevant diffusion processes (simple diffusion, continuous-time random walk, caged diffusion, obstructed diffusion, two-state diffusion and diffusing diffusivity) in variable-lengthscale FCS. We show that, when used in concert, lengthscale variation and data inversion permit to identify non-Gaussian processes and, regardless of Gaussianity, to retrieve their mean-squared displacement over several orders of magnitude in time. This makes unbiased discrimination between different classes of diffusion models possible.
Neural tracking of the speech envelope in cochlear implant users
Authors: Somers Ben , Verschueren Eline , Francart Tom 
Published: June 2018

AbstractObjectiveWhen listening to speech, the brain tracks the speech envelope. It is possible to reconstruct this envelope from EEG recordings. However, in people who hear using a cochlear implant (CI), the artifacts caused by electrical stimulation of the auditory nerve contaminate the EEG. This causes the decoder to produce an artifact-dominated reconstruction, which does not reflect the neural signal processing. The objective of this study is to develop and validate a method for assessing the neural tracking of speech envelope in CI users.ApproachTo obtain EEG recordings free of stimulus artifacts, the electrical stimulation is periodically in-terrupted. During these stimulation gaps, artifact-free EEG can be sampled and used to train a linear envelope decoder. Different recording conditions were used to characterize the artifacts and their influence on the envelope reconstruction.Main resultsThe present study demonstrates for the first time that neural tracking of the speech envelope can be measured in response to ongoing electrical stimulation. The responses were validated to be truly neural and not affected by stimulus artifact.SignificanceBesides applications in audiology and neuroscience, the characterization and elimination of stimulus artifacts will enable future EEG studies involving continuous speech in CI users. Measures of neural tracking of the speech envelope reflect interesting properties of the listener’s perception of speech, such as speech intelligibility or attentional state. Successful decoding of neural envelope tracking will open new possibilities to investigate the neural mechanisms of speech perception with a CI.
Putting a New Spin of G4 Structure and Binding by Analytical Ultracentrifugation
Authors: Dean William L. , Gray Robert D. , DeLeeuw Lynn , Monsen Robert C. , Chaires Jonathan B. 
Published: June 2018

AbstractAnalytical ultracentrifugation is a powerful biophysical tool that provides information about G-quadruplex structure, stability and binding reactivity. This chapter provides a simplified explanation of the method, along with examples of how it can be used to characterize G4 formation and to monitor small-molecule binding.
A quantitative framework for motion visibility in human cortex
Authors: Birman Daniel , Gardner Justin L 
Published: June 2018

AbstractDespite the central use of motion visibility to reveal the neural basis of perception, perceptual decision making, and sensory inference there exists no comprehensive quantitative framework establishing how motion visibility parameters modulate human cortical response. Random-dot motion stimuli can be made less visible by reducing image contrast or motion coherence, or by shortening the stimulus duration. Because each of these manipulations modulates the strength of sensory neural responses they have all been extensively used to reveal cognitive and other non-sensory phenomenon such as the influence of priors, attention, and choice-history biases. However, each of these manipulations is thought to influence response in different ways across different cortical regions and a comprehensive study is required to interpret this literature. Here, human participants observed random-dot stimuli varying across a large range of contrast, coherence, and stimulus durations as we measured blood-oxygen-level dependent responses. We developed a framework for modeling these responses which quantifies their functional form and sensitivity across areas. Our framework demonstrates the sensitivity of all visual areas to each parameter, with early visual areas V1-V4 showing more parametric sensitivity to changes in contrast and V3A and MT to coherence. Our results suggest that while motion contrast, coherence, and duration share cortical representation, they are encoded with distinct functional forms and sensitivity. Thus, our quantitative framework serves as a reference for interpretation of the vast perceptual literature manipulating these parameters and shows that different manipulations of visibility will have different effects across human visual cortex and need to be interpreted accordingly.
TCR/ITK signaling via mTOR tunes CD8+ T cell homeostatic proliferation, metabolism, and anti-tumor effector function
Authors: Huang Weishan , Luo Junjie , August Avery 
Published: June 2018

AbstractT cell homeostatic proliferation (HP) is regulated by T cell receptor (TCR) signals and homeostatic cytokines, and suggested to be proportional to TCR signal strength. However, we show here that ITK, a positive regulator of TCR signaling, negatively tunes CD8+ T cell HP, metabolism, and effector function. Under lymphopenic environments, Itk−/− CD8+ T cells exhibit significant increase in T cell-intrinsic HP, which requires mTOR activity and can be driven by T cell-T cell interaction. TCR signals through ITK tune IL-7-mediated CD8+ T cell metabolism and HP in a mTOR-dependent manner. The lack of ITK also resulted in enhanced effector cell fate programming, antigen sensitivity and anti-tumor immunity by HP cells. Thus, TCR signaling via ITK, is a negative tuner of CD8+ T cell homeostasis, metabolism and effector function, and may be a target for clinical benefit in cancer therapy.One Sentence SummaryTCR signal strength had been long-thought to be proportional to T cell proliferation and effector function, here we demonstrate a counterintuitive role of the TCR signaling through ITK in negatively tuning proliferation under lymphopenic conditions via regulating mTOR activity, T cell metabolism, proliferation, and effector function.