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PLoS Pathogens Jun 2023Long non-coding RNAs (lncRNAs) play critical regulatory roles in various cellular and metabolic processes in mosquitoes and all other organisms studied thus far. In...
Long non-coding RNAs (lncRNAs) play critical regulatory roles in various cellular and metabolic processes in mosquitoes and all other organisms studied thus far. In particular, their involvement in essential processes such as reproduction makes them potential targets for the development of novel pest control approaches. However, their function in mosquito biology remains largely unexplored. To elucidate the role of lncRNAs in mosquitoes' reproduction and vector competence for arboviruses, we have implemented a computational and experimental pipeline to mine, screen, and characterize lncRNAs related to these two biological processes. Through analysis of publicly available Zika virus (ZIKV) infection-regulated Aedes aegypti transcriptomes, at least six lncRNAs were identified as being significantly upregulated in response to infection in various mosquito tissues. The roles of these ZIKV-regulated lncRNAs (designated Zinc1, Zinc2, Zinc3, Zinc9, Zinc10 and Zinc22), were further investigated by dsRNA-mediated silencing studies. Our results show that silencing of Zinc1, Zinc2, and Zinc22 renders mosquitoes significantly less permissive to ZIKV infection, while silencing of Zinc22 also reduces fecundity, indicating a potential role for Zinc22 in trade-offs between vector competence and reproduction. We also found that silencing of Zinc9 significantly increases fecundity but has no effect on ZIKV infection, suggesting that Zinc9 may be a negative regulator of oviposition. Our work demonstrates that some lncRNAs play host factor roles by facilitating viral infection in mosquitoes. We also show that lncRNAs can influence both mosquito reproduction and permissiveness to virus infection, two biological systems with important roles in mosquito vectorial capacity.
Topics: Animals; Female; Zika Virus; Zika Virus Infection; Aedes; RNA, Long Noncoding; Mosquito Vectors; Reproduction
PubMed: 37319296
DOI: 10.1371/journal.ppat.1011440 -
Nature Communications Apr 2024The horizontal transfer of plasmids has been recognized as one of the key drivers for the worldwide spread of antimicrobial resistance (AMR) across bacterial pathogens....
The horizontal transfer of plasmids has been recognized as one of the key drivers for the worldwide spread of antimicrobial resistance (AMR) across bacterial pathogens. However, knowledge remain limited about the contribution made by environmental stress on the evolution of bacterial AMR by modulating horizontal acquisition of AMR plasmids and other mobile genetic elements. Here we combined experimental evolution, whole genome sequencing, reverse genetic engineering, and transcriptomics to examine if the evolution of chromosomal AMR to triclosan (TCS) disinfectant has correlated effects on modulating bacterial pathogen (Klebsiella pneumoniae) permissiveness to AMR plasmids and phage susceptibility. Herein, we show that TCS exposure increases the evolvability of K. pneumoniae to evolve TCS-resistant mutants (TRMs) by acquiring mutations and altered expression of several genes previously associated with TCS and antibiotic resistance. Notably, nsrR deletion increases conjugation permissiveness of K. pneumoniae to four AMR plasmids, and enhances susceptibility to various Klebsiella-specific phages through the downregulation of several bacterial defense systems and changes in membrane potential with altered reactive oxygen species response. Our findings suggest that unrestricted use of TCS disinfectant imposes a dual impact on bacterial antibiotic resistance by augmenting both chromosomally and horizontally acquired AMR mechanisms.
Topics: Triclosan; Plasmids; Klebsiella pneumoniae; Bacteriophages; Drug Resistance, Multiple, Bacterial; Mutation; Gene Transfer, Horizontal; Whole Genome Sequencing; Evolution, Molecular; Anti-Bacterial Agents
PubMed: 38688912
DOI: 10.1038/s41467-024-48006-9 -
Viruses Jul 2020Macrophages are the first line of defence against invading pathogens. They play a crucial role in immunity but also in regeneration and homeostasis. Their remarkable... (Review)
Review
Macrophages are the first line of defence against invading pathogens. They play a crucial role in immunity but also in regeneration and homeostasis. Their remarkable plasticity in their phenotypes and function provides them with the ability to quickly respond to environmental changes and infection. Recent work shows that macrophages undergo cell cycle transition from a G0/terminally differentiated state to a G1 state. This G0-to-G1 transition presents a window of opportunity for HIV-1 infection. Macrophages are an important target for HIV-1 but express high levels of the deoxynucleotide-triphosphate hydrolase SAMHD1, which restricts viral DNA synthesis by decreasing levels of dNTPs. While the G0 state is non-permissive to HIV-1 infection, a G1 state is very permissive to HIV-1 infection. This is because macrophages in a G1 state switch off the antiviral restriction factor SAMHD1 by phosphorylation, thereby allowing productive HIV-1 infection. Here, we explore the macrophage cell cycle and the interplay between its regulation and permissivity to HIV-1 infection.
Topics: Animals; Cell Cycle; Cell Cycle Checkpoints; Cells, Cultured; DNA Damage; G1 Phase; Gram-Negative Bacteria; HIV-1; Histone Deacetylase Inhibitors; Humans; Macrophages; Phosphorylation; Resting Phase, Cell Cycle; SAM Domain and HD Domain-Containing Protein 1; vif Gene Products, Human Immunodeficiency Virus; vpr Gene Products, Human Immunodeficiency Virus
PubMed: 32751972
DOI: 10.3390/v12080839 -
Methods in Molecular Biology (Clifton,... 2020Forced viral adaptation is a powerful technique employed to study the ways viruses may overcome various selective pressures that reduce viral replication. Here, we...
Forced viral adaptation is a powerful technique employed to study the ways viruses may overcome various selective pressures that reduce viral replication. Here, we describe methods for in vitro serial passaging of Middle East respiratory syndrome coronavirus (MERS-CoV) to select for mutations which increase replication on semi-permissive cell lines as described in Letko et al., Cell Rep 24, 1730-1737, 2018.
Topics: Adaptation, Physiological; Animals; Biological Evolution; Cell Line; Chlorocebus aethiops; Coronavirus Infections; Host Specificity; Humans; Middle East Respiratory Syndrome Coronavirus; Serial Passage; Vero Cells; Virus Replication
PubMed: 31883083
DOI: 10.1007/978-1-0716-0211-9_1 -
International Journal of Molecular... Mar 2024The association between cancer and inflammation is well established. Chronic inflammation represents a fundamental step in the development and progression of some types... (Review)
Review
The association between cancer and inflammation is well established. Chronic inflammation represents a fundamental step in the development and progression of some types of cancer. Tumors are composed of a heterogeneous population of infiltrating cells including macrophages, fibroblasts, lymphocytes, granulocytes, and mast cells, which respond to signals from the microenvironment and, in turn, produce cytokines, chemokines, transcription factors, receptors, and miRNAs. Recent data demonstrate that, in addition to classical (M1) and alternative (M2) macrophage subtypes, there are many intermediate subtypes that potentially play different roles in response to environmental stimuli. Tumors are infiltrated by macrophages called TAMs that mainly display an M2-like phenotype and tumor growth-permissive activities. There is a bidirectional interaction between tumor cells and tumor-infiltrating cells that determines macrophage polarization and ultimately tumor progression or regression. These complex interactions are still unclear but understanding them is fundamental for the development of new therapeutic strategies. Re-educating tumor-permissive macrophages into anti-tumor macrophages is a new focus of research. This review aims to analyze the most recent articles investigating the interplay between tumors, tumor-infiltrating cells, and TAMs, and the strategies for re-educating tumor-permissive macrophages.
Topics: Humans; Macrophages; Neoplasms; Cytokines; MicroRNAs; Inflammation; Tumor Microenvironment
PubMed: 38542388
DOI: 10.3390/ijms25063414 -
Public Health in Practice (Oxford,... Nov 2021Stricter firearm policies correlate with lower suicides by firearm in the US. However, much work examines policies in isolation and does not investigate firearm policies...
OBJECTIVES
Stricter firearm policies correlate with lower suicides by firearm in the US. However, much work examines policies in isolation and does not investigate firearm policies as they relate to US pro-gun culture. We examine the relation between permissiveness of state firearm laws, gun culture, and suicides by firearm.
STUDY DESIGN
Panel longitudinal study.
METHODS
The count of suicides by firearm for 50 US states from 2000 to 2016 served as the outcome. Permissiveness of multiple state firearm laws, based on ratings from the Traveler's Guide to the Firearm Laws of the Fifty States, served as the exposure. These ratings, measured at the state-year, capture not only the overall policy environment but also the extent to which the state exhibits a pro-gun culture. We applied a fixed effects negative binomial count model, which controls for the population-at-risk, to examine suicides overall and by race/ethnicity and gender.
RESULTS
A 10-unit increase in permissiveness of state firearm laws corresponds with 2% greater suicides by firearm overall (Incidence rate ratio [IRR] = 1.02; 95% CI: 1.01-1.03) and among non-Hispanic white males ([IRR] = 1.02, 95% CI: 1.01-1.02).
CONCLUSIONS
Findings, if replicated, indicate that states enacting more restrictive firearm policies, and lessening a pro-gun culture, may lead to reductions in suicide by firearm.
PubMed: 36101604
DOI: 10.1016/j.puhip.2021.100218 -
Journal of Studies on Alcohol and Drugs Mar 2023Whether college students' reports of their parents' behaviors are as reliable a predictor of student drinking as their parents' own reports remains an open question and...
OBJECTIVE
Whether college students' reports of their parents' behaviors are as reliable a predictor of student drinking as their parents' own reports remains an open question and a point of contention in the literature. To address this, the current study examined concordance between college student and mother/father reports of the same parenting behaviors relevant to parent-based college drinking interventions (relationship quality, monitoring, and permissiveness), and the extent to which student and parental reports differed in their relation to college drinking and consequences.
METHOD
The sample consisted of 1,429 students and 1,761 parents recruited from three large public universities in the United States (814 mother-daughter, 563 mother-son, 233 father-daughter, and 151 father-son dyads). Students and their parents were each invited to complete four surveys over the course of the students' first 4 years of college (one survey per year).
RESULTS
Paired samples tests revealed that parental reports of parenting constructs were typically more conservative than student reports. Intraclass correlations revealed moderate associations between parental and student reports on relationship quality, general monitoring, and permissiveness. The associations between parenting constructs and drinking and consequences were also consistent when using parental and student reports of permissiveness. Results were generally consistent for all four types of dyads, and at each of the four time points.
CONCLUSIONS
Taken together, these findings provide additional support for the use of student reports of parental behaviors as a valid proxy of parents' actual reports and as a reliable predictor of college student drinking and consequences.
Topics: Humans; Alcohol Drinking; Parent-Child Relations; Universities; Parenting; Ethanol; Students
PubMed: 36971719
DOI: 10.15288/jsad.22-00002 -
Oncolytic Virotherapy 2019Replication conditional oncolytic human adenovirus has long been considered a promising biological therapeutic to target high-grade gliomas (HGG), a group of essentially... (Review)
Review
Replication conditional oncolytic human adenovirus has long been considered a promising biological therapeutic to target high-grade gliomas (HGG), a group of essentially lethal primary brain cancer. The last decade has witnessed initiation and some completion of a number of Phase I and II clinical investigations of oncolytic adenovirus for HGG in the US and Europe. Results of these trials in patients are pivotal for not only federal approval but also filling an existing knowledge gap that primarily derives from the stark differences in permissivity to human adenovirus between humans and preclinical mouse models. DNX-2401 (Delta-24-RGD), the current mainstream oncolytic adenovirus with modifications in E1A and the fiber, has been shown to induce impressive objective response and long-term survival (>3 years) in a fraction of patients with recurrent HGG. Responders exhibited initial enlargement of the treated lesions for a few months post treatment, followed by shrinkage and near complete resolution. In accord with preclinical research, post-treatment specimens revealed virus-mediated alteration of the immune tumor microenvironment as evidenced by infiltration of CD8+ T cells and M1-polarized macrophages. These findings are encouraging and together with further information from ongoing studies have a potential to make oncolytic adenovirus a viable option for clinical management of HGG. This review deals with this timely topic; we will describe both preclinical and clinical development of oncolytic adenovirus therapy for HGG, summarize updated knowledge on clinical trials and discuss challenges that the field currently faces.
PubMed: 31750274
DOI: 10.2147/OV.S196403 -
Archives of Sexual Behavior Jan 2023Previous studies have shown that specific attitudes related to moral convictions can have an important role in the development and maintenance of problematic sexual...
Previous studies have shown that specific attitudes related to moral convictions can have an important role in the development and maintenance of problematic sexual behavior symptoms. However, although other types of attitudes, like sexual attitudes, are potentially highly relevant, they have not yet been studied in this role. We investigated how four dimensions of sexual attitudes: Permissiveness, Birth Control, Communion and Instrumentality, contribute to problematic pornography use (PPU) and hypersexual disorder (HD) symptoms, controlling for religiosity, sex, age and relationship status. The study was administered through an online questionnaire and based on a representative sample of n = 1036 (M = 43.28, SD = 14.21; 50.3% women) Polish adult citizens. When adjusting for other variables, higher sexual Permissiveness positively predicted HD and PPU among both men (HD: β = .26, p < .001; PPU: β = .22, p < .001) and women (HD: β = .44, p < .001; PPU: β = .26; p < .001). Sexual Instrumentality positively, although weakly, contributed to HD severity among men (β = .11, p < .05). Attitudes reflecting higher support for responsible sexuality (Birth Control subscale) negatively and weakly predicted HD among women (β = - .11, p < .05). Permissiveness was also the only sexual attitude dimension that consistently predicted a higher frequency of sexual activity among men and women. Based on the cutoff criteria proposed by the authors of the used screening instruments (≥ 53 points for the Hypersexual Behavior Inventory and ≥ 4 points for the Brief Pornography Screen), the prevalence of being at risk for HD was 10.0% (men: 11.4%, women: 8.7%) and for PPU was 17.8% (men: 26.8%, women: 9.1%). Our results point to a significant contribution of sexual attitudes to problematic sexual behavior symptoms, which was not encapsulated by the previously studied influence of religious beliefs, although most of the obtained relationships were relatively weak. Particularly, a consistent link between permissive attitudes and both HD and PPU among men and women may indicate that permissive attitudes can potentially contribute to the development and maintenance of problematic sexual behavior. The prevalence of being at risk for PPU (and to some degree HD) in the current representative sample was high. Such results raise questions about the appropriateness of the proposed cutoff criteria and the risk of overpathologizing normative sexual activity, if the cutoff thresholds are not tailored adequately. The results have implications for the assessment, diagnosis and theory of problematic sexual behavior.
Topics: Adult; Male; Humans; Female; Erotica; Sexual Behavior; Paraphilic Disorders; Compulsive Behavior; Surveys and Questionnaires
PubMed: 35896936
DOI: 10.1007/s10508-022-02358-9 -
Cells Nov 2023Cellular composition and the responsiveness of the immune system evolve upon aging and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit...
Cellular composition and the responsiveness of the immune system evolve upon aging and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit a decreased viral replication ex vivo compared to men's. We, thus, hypothesized that these findings could be recapitulated in vitro and infected primary CD4+ T cells with HIV-based vectors pseudotyped with VSV-G or HIV envelopes. We used cells isolated from twenty donors to interrogate the effect of sex and age on permissiveness over a six-day activation kinetics. Our data identified an increased permissiveness to HIV between 24 and 72 h post-stimulation. Sex- and age-based analyses at these time points showed an increased susceptibility to HIV of the cells isolated from males and from donors over 50 years of age, respectively. A parallel assessment of surface markers' expression revealed higher frequencies of activation marker CD69 and of immune checkpoint inhibitors (PD-1 and CTLA-4) in the cells from highly permissive donors. Furthermore, positive correlations were identified between the expression kinetics of CD69, PD-1 and CTLA-4 and HIV expression kinetics. The cell population heterogeneity was assessed using a single-cell RNA-Seq analysis and no cell subtype enrichment was identified according to sex. Finally, transcriptomic analyses further highlighted the role of activation in those differences with enriched activation and cell cycle gene sets in male and older female cells. Altogether, this study brought further evidence about the individual features affecting HIV replication at the cellular level and should be considered in latency reactivation studies for an HIV cure.
Topics: Female; Humans; Male; Middle Aged; CD4-Positive T-Lymphocytes; CTLA-4 Antigen; HIV Infections; Programmed Cell Death 1 Receptor; Virus Replication; Age Factors; Sex Factors; HIV
PubMed: 38067117
DOI: 10.3390/cells12232689