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Viruses Jan 2016Hepatitis B virus (HBV) is a small DNA virus that infects the liver. Current anti-HBV drugs efficiently suppress viral replication but do not eradicate the virus due to... (Review)
Review
Hepatitis B virus (HBV) is a small DNA virus that infects the liver. Current anti-HBV drugs efficiently suppress viral replication but do not eradicate the virus due to the persistence of its episomal DNA. Efforts to develop reliable in vitro systems to model HBV infection, an imperative tool for studying HBV biology and its interactions with the host, have been hampered by major limitations at the level of the virus, the host and infection readouts. This review summarizes major milestones in the development of in vitro systems to study HBV. Recent advances in our understanding of HBV biology, such as the discovery of the bile-acid pump sodium-taurocholate cotransporting polypeptide (NTCP) as a receptor for HBV, enabled the establishment of NTCP expressing hepatoma cell lines permissive for HBV infection. Furthermore, advanced tissue engineering techniques facilitate now the establishment of HBV infection systems based on primary human hepatocytes that maintain their phenotype and permissiveness for infection over time. The ability to differentiate inducible pluripotent stem cells into hepatocyte-like cells opens the door for studying HBV in a more isogenic background, as well. Thus, the recent advances in in vitro models for HBV infection holds promise for a better understanding of virus-host interactions and for future development of more definitive anti-viral drugs.
Topics: Animals; Antiviral Agents; Disease Models, Animal; Hepatitis B; Hepatitis B virus; Hepatocytes; Humans
PubMed: 26784218
DOI: 10.3390/v8010021 -
BioEssays : News and Reviews in... Jan 2021The quest for molecular mechanisms that guide axons or specify synaptic contacts has largely focused on molecules that intuitively relate to the idea of an...
The quest for molecular mechanisms that guide axons or specify synaptic contacts has largely focused on molecules that intuitively relate to the idea of an "instruction." By contrast, "permissive" factors are traditionally considered background machinery without contribution to the information content of a molecularly executed instruction. In this essay, I recast this dichotomy as a continuum from permissive to instructive actions of single factors that provide relative contributions to a necessarily collaborative effort. Individual molecules or other factors do not constitute absolute instructions by themselves; they provide necessary context for each other, thereby creating a composite that defines the overall instruction. The idea of composite instructions leads to two main conclusions: first, a composite of many seemingly permissive factors can define a specific instruction even in the absence of a single dominant contributor; second, individual factors are not necessarily related intuitively to the overall instruction or phenotypic outcome.
Topics: Axons; Brain; Humans
PubMed: 33145823
DOI: 10.1002/bies.202000166 -
BioRxiv : the Preprint Server For... Nov 2023SARS-CoV-2 emerged, and is evolving to efficiently infect humans worldwide. SARS-CoV-2 evades early innate recognition, interferon signaling activated only in bystander...
SARS-CoV-2 emerged, and is evolving to efficiently infect humans worldwide. SARS-CoV-2 evades early innate recognition, interferon signaling activated only in bystander cells. This balance of innate activation and viral evasion has important consequences, but the pathways involved are incompletely understood. Here we find that autophagy genes regulate innate immune signaling, impacting the basal set point of interferons, and thus permissivity to infection. Mechanistically, autophagy genes negatively regulate MAVS, and this low basal level of MAVS is efficiently antagonized by SARS-CoV-2 ORF9b, blocking interferon activation in infected cells. However, upon loss of autophagy increased MAVS overcomes ORF9b-mediated antagonism suppressing infection. This has led to the evolution of SARS-CoV-2 variants to express higher levels of ORF9b, allowing SARS-CoV-2 to replicate under conditions of increased MAVS signaling. Altogether, we find a critical role of autophagy in the regulation of innate immunity and uncover an evolutionary trajectory of SARS-CoV-2 ORF9b to overcome host defenses.
PubMed: 38014114
DOI: 10.1101/2023.11.13.566859 -
Health Psychology Review Jun 2020Sexual health reflects physical, emotional, mental, and social elements of sexual well-being. Researchers often position self-esteem (i.e., global or domain-specific... (Meta-Analysis)
Meta-Analysis
Sexual health reflects physical, emotional, mental, and social elements of sexual well-being. Researchers often position self-esteem (i.e., global or domain-specific evaluations of self) as a key correlate of sexual health. We present the first comprehensive meta-analysis of correlations between self-esteem and sexual health. Our synthesis includes 305 samples from 255 articles, containing 870 correlations from 191,161 unique participants. The overall correlation between self-esteem and sexual health was positive and small ( = .12, 95% CI: .09, .15), characterised by considerable heterogeneity and robust to different corrections. Sexual functioning (27, 95% CI: .21, .34) was more strongly associated with self-esteem than were safe sex (= .10, 95% CI: .07, .13) and sexual consent (= .19, 95% CI: .13, .24), and sexual permissiveness was unassociated with self-esteem (= -.02, 95% CI: -.05, .008). Most moderators were nonsignificant, although moderator data were inconsistently available, and samples were North American-centric. Evidence of publication bias was inconsistent, and study quality, theory usage, and background research were not reliably associated with study outcomes. Our synthesis suggests a need for more specific theories of self-esteem corresponding to unique domains of sexual, highlighting a need for future theorising and research.
Topics: Emotions; Humans; Self Concept; Sexual Health
PubMed: 31163109
DOI: 10.1080/17437199.2019.1625281 -
Advances in Experimental Medicine and... 2018Tumour Budding (TB) is recognized as an adverse prognostic factor in colorectal cancer (CRC). TB is the detachment of isolated cancer cells or small clusters of such... (Review)
Review
Tumour Budding (TB) is recognized as an adverse prognostic factor in colorectal cancer (CRC). TB is the detachment of isolated cancer cells or small clusters of such cells mainly at the invasion front. One question that arises is of the role of the tumour stroma regarding the permissiveness of the formation and progression of TB. In this review, we will examine potential factors affecting TB, in particular we will analyse the potential effect of inflammation, hypoxia, extracellular matrix and Cancer-Associated Fibroblasts (CAFs).
Topics: Colorectal Neoplasms; Extracellular Matrix; Fibroblasts; Humans; Hypoxia; Inflammation; Tumor Microenvironment
PubMed: 30623368
DOI: 10.1007/978-3-030-02771-1_7 -
Medical Humanities Jun 2023The later decades of the 20th century saw dramatic changes in sexual attitudes and behaviour in Britain: rates of divorce and remarriage increased; premarital sex and...
The later decades of the 20th century saw dramatic changes in sexual attitudes and behaviour in Britain: rates of divorce and remarriage increased; premarital sex and illegitimacy became more common, even as the pill and legal abortion opened up new reproductive choices; and following on from the decriminalisation of homosex, liberation movements began to celebrate gay lives. These shifts generated new possibilities, but often entailed much inner turmoil. The same period witnessed an unprecedented flourishing of professional and popular psychological expertise. Influential social and cultural theorists have argued that the intertwined rise of "permissiveness" and therapeutic culture caused an important shift in the ethical dimensions of modern life, in which citizens and subjects came to idolise self-realisation over the public good.This article uses women's magazine problem pages, exploring the role of advice columnists on and off the page, to examine the intersections of "permissiveness" and the psychologisation of everyday life. Millions looked to agony aunts in mass-market women's magazines to help them negotiate new emotional and sexual worlds. As purveyors of counsel, but not (usually) formally trained counsellors, magazine advisors worked with the new languages and concepts of psychological expertise and disseminated them to avid readers.Across this period, problem pages demonstrated greater openness towards sex and displacement of morality from external standards to the individual. However, advisors also continued to emphasise self-control and responsibility, and to provide practical guidance that took at best a superficially psychological veneer. These trends were underpinned by a model of sex as an essential part of loving, stable relationships, and the (largely unexpressed) notion that such relationships were essential to social functioning. In the woman's world of the magazine, before and beyond the 1980s, the problem page does not show the rise of individualism or the pursuit of pleasure above all else.
Topics: Pregnancy; Female; Humans; Sexual Behavior; Morals
PubMed: 36549861
DOI: 10.1136/medhum-2022-012497 -
European Neuropsychopharmacology : the... Feb 2021We are currently facing the challenge of improving treatments for psychiatric disorders such as major depression. Notably, antidepressants have an incomplete efficacy,... (Review)
Review
We are currently facing the challenge of improving treatments for psychiatric disorders such as major depression. Notably, antidepressants have an incomplete efficacy, mostly due to our limited knowledge of their action. Here we present a theoretical framework that considers the distinction between instructive and permissive causality, which allows formalizing and disentangling the effects exerted by different therapeutic strategies commonly used in psychiatry. Instructive causality implies that an action determines a specific effect while permissive causality allows an action to take effect or not. We posit that therapeutic strategies able to improve the quality of the living environment or the ability to face it, including changes in lifestyle and psychotherapeutic interventions, rely mainly on instructive causality and thus shape the individual's ability to face the psychopathology and build resilience. By contrast, pharmacological treatments, such as selective serotonin reuptake inhibitors, act primarily through a permissive causality: they boost neural plasticity, i.e. the ability of the brain to change itself, and therefore allow for instructive interventions to produce beneficial effects or not. The combination of an instructive and a permissive action represents the most promising approach since the quality of the living environment can shape the path leading to mental health while drug treatment can increase the likelihood of achieving such a goal.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Mental Health; Psychotropic Drugs; Selective Serotonin Reuptake Inhibitors
PubMed: 33384216
DOI: 10.1016/j.euroneuro.2020.12.001 -
Biophysical Journal Feb 2021Multistability and natural biological variability can result in significant heterogeneity within a cell population, leading to challenges in understanding and modulating...
Multistability and natural biological variability can result in significant heterogeneity within a cell population, leading to challenges in understanding and modulating cell behavior. Energy landscapes can offer qualitatively intuitive visualizations of cell phenotype and facilitate a more quantitative understanding of cellular dynamics, but current methods for landscape generation are mathematically involved and often require specific system properties (e.g., ergodicity or independent gene/protein probability distributions) that do not always hold. Here, we present a simple kinetic Monte Carlo-based method for landscape generation from a system of ordinary differential equations using only simulation trajectories initialized throughout the phase space of interest. The resulting landscape produces three quantitative features relevant to understanding cell behavior: stability (reflected by the depth or potential of landscape valleys), velocity (representing average directional movement on the landscape), and variance in velocity (indicative of landscape positions with heterogeneous movements). We applied this method to a genetic toggle switch, a core decision-making network in binary cellular responses, to elucidate effects of biologically relevant intrinsic and extrinsic cues. Intrinsic noise, such as stochasticity in transcription-translation and differences in cell cycle position, manifests through changes in valley width and position, reflecting increased population heterogeneity and more probabilistic cell fate transitions. The landscapes also capture the effect of an external inducer, revealing a quantitative correlation between the rate of cell fate transition and the energy barrier above a threshold inducer concentration determined by the permissivity of the valley. Further, in tracking dynamically changing landscapes under time-varying external cues, we unexpectedly found that an oscillatory inducer input can modulate cell fate heterogeneity and lead to periodic cell fate transitions entrained to the input frequency, depending on the intrinsic degradation rate of the switch. The landscape generation approach outlined herein is generalizable to other network topologies and may provide new quantitative insights into their dynamics.
Topics: Cell Cycle; Cell Differentiation; Computer Simulation; Gene Regulatory Networks; Kinetics
PubMed: 33453275
DOI: 10.1016/j.bpj.2020.11.2279 -
Frontiers in Psychology 2021Religiosity and sexuality present numerous interconnections. Little is known regarding the specific causal pathways between each religiosity dimension and sexual...
Religiosity and sexuality present numerous interconnections. Little is known regarding the specific causal pathways between each religiosity dimension and sexual behavior. The objectives of this study were (1) to explore the relationship between religiosity (measured through attendance at religious services, salience, and prayer) and sexual initiation in adolescents and (2) to establish the role of sexual permissiveness as mediator of the impact produced by religiosity in sexual initiation. This study analyzes data from an ongoing school-based international study examining what young people feel and think about relationships, love, and sexuality. An anonymous, self-administered online questionnaire was developed in Spanish. A total of 4,366 students, aged 14-18, completed the questionnaire. A final sample of 2,919 questionnaires was analyzed. Two unconditional logistic regression models were fit with religiosity variables and possible confounders as independent variables (with and without permissiveness, respectively). The dependent variable was sexual initiation. A final path analysis was performed to further understand the results. Our study highlights that, in predominantly Catholic and Spanish-speaking countries, the fact of attending church and praying may greatly contribute to postponing sexual relations during adolescence, even independently of their attitudes on sexual permissiveness. Conversely, the effect of salience on sexual initiation seems to be fostered only through the mediation of sexual permissiveness. Our findings point to an indirect effect of the three religiosity dimensions (and in particular, religious salience) through permissive attitudes. Religiosity could be a relevant factor to explain sexual initiation during adolescence.
PubMed: 34858256
DOI: 10.3389/fpsyg.2021.715032 -
One Health (Amsterdam, Netherlands) Dec 2023The interplay between agent-host-environment characteristics is responsible for the emergence and zoonotic potential of infectious disease pathogens. Many studies have...
The interplay between agent-host-environment characteristics is responsible for the emergence and zoonotic potential of infectious disease pathogens. Many studies have investigated key agent characteristics and environmental factors responsible for these phenomena. However, little is known about the role played by host characteristics in zoonoses, disease emergence and the ability of pathogens to infect multiple hosts. We compiled a dataset of 8114 vertebrate host-agent interactions from published literature. Multiple host characteristics and the pathogen's zoonotic, emergence and multi-host potential were then linked to the dataset. The associations between zoonotic, emerging human pathogen and multi-host pathogenicity and several host characteristics were explored using logistic regression models. The numbers of publications and sequences from the agent-host combinations were used to control for the research effort. Hosts in the class Aves (odds ratio [OR] 20.87, 95% CI 2.66-163.97) and Mammalia (OR 26.09, 95% CI 3.34-203.87) were more likely to host a zoonotic pathogen compared to the class Amphibia. Similarly, hosts having Bursa fabricii (i.e., birds) (OR 1.8, 95% CI 1.4-2.3) were more likely to host an emerging human pathogen. The odds of being a zoonotic pathogen were highest when the host female required a greater number of days for maturity, and the pathogen was able to affect a greater number of host species. In contrast, the hosts from which a higher number of pathogens were reported were less likely (OR 0.39, 95% CI 0.31-0.49) to be associated with an emerging human pathogen. The odds of an emerging human pathogen were highest when the host had a higher adult body mass, and the specific pathogen could affect more host species. The odds of a pathogen infecting multiple hosts were highest when a host had shorter female maturity days (>670-2830 days) and lower birth/hatching weight (>42.2-995 g) compared to longer female maturity days (>2830-6940 days) and greater birth/hatching weight (>3.31-1160 kg). We conclude that several host characteristics - such as mass, maturity, immune system and pathogen permissiveness- are linked with zoonoses, disease emergence or multi-host pathogenicity. These findings can contribute to preparedness for emerging infections and zoonotic diseases.
PubMed: 37404948
DOI: 10.1016/j.onehlt.2023.100596