bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing Retinoid X Receptor Alpha Expression Enhances Early-Stage Hepatitis B Virus Infection In Cell Cultures
Authors: Song Mei , Sun Yinyan , Tian Ji , He Wenhui , Xu Guangwei , Jing Zhiyi , Li Wenhui 
Published: February 2018

ABSTRACT

Multiple steps of the life cycle of hepatitis B virus (HBV) are known to be coupled to hepatic metabolism. However, the details of involvement of the hepatic metabolic milieu in HBV infection remain incompletely understood. Hepatic lipid metabolism is controlled by a complicated transcription factor network centered on retinoid X receptor alpha (RXRα). Here, we report that RXRα negatively regulates HBV infection at an early stage in cell cultures. The RXR-specific agonist bexarotene inhibits HBV in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) (HepG2-NTCP), HepaRG cells, and primary
Tupaia
hepatocytes (PTHs); reducing RXRα expression significantly enhanced HBV infection in the cells. Transcriptome sequencing (RNA-seq) analysis of HepG2-NTCP cells with a disrupted
RXR
α gene revealed that reduced gene expression in arachidonic acid (AA)/eicosanoid biosynthesis pathways, including the AA synthases phospholipase A2 group IIA (PLA2G2A), is associated with increased HBV infection. Moreover, exogenous treatment of AA inhibits HBV infection in HepG2-NTCP cells. These data demonstrate that RXRα is an important cellular factor in modulating HBV infection and implicate the participation of AA/eicosanoid biosynthesis pathways in the regulation of HBV infection.

IMPORTANCE
Understanding how HBV infection is connected with hepatic lipid metabolism may provide new insights into virus infection and its pathogenesis. By a series of genetic studies in combination with transcriptome analysis and pharmacological assays, we here investigated the role of cellular retinoid X receptor alpha (RXRα), a crucial transcription factor for controlling hepatic lipid metabolism, in
de novo
HBV infection in cell cultures. We found that silencing of RXRα resulted in elevated HBV covalently closed circular DNA (cccDNA) formation and viral antigen production, while activation of RXRα reduced HBV infection efficiency. Our results also showed that silencing phospholipase A2 group IIA (PLA2G2A), a key enzyme of arachidonic acid (AA) synthases, enhanced HBV infection efficiency in HepG2-NTCP cells and that exogenous AA treatment reduced
de novo
HBV infection in the cells. These findings unveil RXRα as an important cellular factor in modulating HBV infection and may point to a new strategy for host-targeted therapies against HBV.
Physiological Heterogeneity Triggers Sibling Conflict Mediated by the Type VI Secretion System in an Aggregative Multicellular Bacterium
Authors: Troselj Vera , Treuner-Lange Anke , Søgaard-Andersen Lotte , Wall Daniel 
Published: February 2018

ABSTRACT

A hallmark of social microorganisms is their ability to engage in complex and coordinated behaviors that depend on cooperative and synchronized actions among many cells. For instance, myxobacteria use an aggregation strategy to form multicellular, spore-filled fruiting bodies in response to starvation. One barrier to the synchronization process is physiological heterogeneity within clonal populations. How myxobacteria cope with these physiological differences is poorly understood. Here, we investigated the interactions between closely related but physiologically distinct
Myxococcus xanthus
populations. We used a genetic approach to create amino acid auxotrophs and tested how they interact with a parental prototroph strain. Importantly, we found that auxotrophs were killed by their prototroph siblings when the former were starved for amino acids but not when grown on rich medium or when both strains were starved. This antagonism depended on the type VI secretion system (T6SS) as well as gliding motility; in particular, we identified the effector-immunity pair (TsxEI) as the mediator of this killing. This sibling antagonism resulted from lower levels of the TsxI immunity protein in the starved population. Thus, when starving auxotrophs were mixed with nonstarving prototrophs, the auxotrophs were susceptible to intoxication by the TsxE effector delivered by the T6SS from the prototrophs. Furthermore, our results suggested that homogeneously starving populations have reduced T6SS activity and, therefore, do not antagonize each other. We conclude that heterogeneous populations of
M. xanthus
use T6SS-dependent killing to eliminate starving or less-fit cells, thus facilitating the attainment of homeostasis within a population and the synchronization of behaviors.

IMPORTANCE
Social bacteria employ elaborate strategies to adapt to environmental challenges. One means to prepare for unpredictable changes is for clonal populations to contain individuals with diverse physiological states. These subpopulations will differentially respond to new environmental conditions, ensuring that some cells will better adapt. However, for social bacteria physiological heterogeneity may impede the ability of a clonal population to synchronize their behaviors. By using a highly cooperative and synchronizable model organism,
M. xanthus
, we asked how physiological differences between interacting siblings impacted their collective behaviors. Physiological heterogeneity was experimentally designed such that one population starved while the other grew when mixed. We found that these differences led to social conflict where more-fit individuals killed their less-fit siblings. For the first time, we report that the T6SS nanoweapon mediates antagonism between siblings, resulting in myxobacterial populations becoming more synchronized to conduct social behaviors.
Layered Structure and Complex Mechanochemistry Underlie Strength and Versatility in a Bacterial Adhesive
Authors: Hernando-Pérez Mercedes , Setayeshgar Sima , Hou Yifeng , Temam Roger , Brun Yves V. , Dragnea Bogdan , Berne Cécile 
Published: February 2018

ABSTRACT

While designing synthetic adhesives that perform in aqueous environments has proven challenging, microorganisms commonly produce bioadhesives that efficiently attach to a variety of substrates, including wet surfaces. The aquatic bacterium
Caulobacter crescentus
uses a discrete polysaccharide complex, the holdfast, to strongly attach to surfaces and resist flow. The holdfast is extremely versatile and has impressive adhesive strength. Here, we used atomic force microscopy in conjunction with superresolution microscopy and enzymatic assays to unravel the complex structure of the holdfast and to characterize its chemical constituents and their role in adhesion. Our data support a model whereby the holdfast is a heterogeneous material organized as two layers: a stiffer nanoscopic core layer wrapped into a sparse, far-reaching, flexible brush layer. Moreover, we found that the elastic response of the holdfast evolves after surface contact from initially heterogeneous to more homogeneous. From a composition point of view, besides
N
-acetyl-

d

-glucosamine (NAG), the only component that had been identified to date, our data show that the holdfast contains peptides and DNA. We hypothesize that, while polypeptides are the most important components for adhesive force, the presence of DNA mainly impacts the brush layer and the strength of initial adhesion, with NAG playing a primarily structural role within the core. The unanticipated complexity of both the structure and composition of the holdfast likely underlies its versatility as a wet adhesive and its distinctive strength. Continued improvements in understanding of the mechanochemistry of this bioadhesive could provide new insights into how bacteria attach to surfaces and could inform the development of new adhesives.

IMPORTANCE
There is an urgent need for strong, biocompatible bioadhesives that perform underwater. To strongly adhere to surfaces and resist flow underwater, the bacterium
Caulobacter crescentus
produces an adhesive called the holdfast, the mechanochemistry of which remains undefined. We show that the holdfast is a layered structure with a stiff core layer and a polymeric brush layer and consists of polysaccharides, polypeptides, and DNA. The DNA appears to play a role in the structure of the brush layer and initial adhesion, the peptides in adhesive strength, and the polysaccharides in the structure of the core. The complex, multilayer organization and diverse chemistry described here underlie the distinctive adhesive properties of the holdfast and will provide important insights into the mechanisms of bacterial adhesion and bioadhesive applications.
The Viscoelastic Properties of the Fungal Cell Wall Allow Traffic of AmBisome as Intact Liposome Vesicles
Authors: Walker Louise , Sood Prashant , Lenardon Megan D. , Milne Gillian , Olson Jon , Jensen Gerard , Wolf Julie , Casadevall Arturo , Adler-Moore Jill , Gow Neil A. R. 
Published: February 2018

ABSTRACT

The fungal cell wall is a critically important structure that represents a permeability barrier and protective shield. We probed
Candida albicans
and
Cryptococcus neoformans
with liposomes containing amphotericin B (AmBisome), with or without 15-nm colloidal gold particles. The liposomes have a diameter of 60 to 80 nm, and yet their mode of action requires them to penetrate the fungal cell wall to deliver amphotericin B to the cell membrane, where it binds to ergosterol. Surprisingly, using cryofixation techniques with electron microscopy, we observed that the liposomes remained intact during transit through the cell wall of both yeast species, even though the predicted porosity of the cell wall (pore size, ~5.8 nm) is theoretically too small to allow these liposomes to pass through intact.
C. albicans
mutants with altered cell wall thickness and composition were similar in both their
in vitro
AmBisome susceptibility and the ability of liposomes to penetrate the cell wall. AmBisome exposed to ergosterol-deficient
C. albicans
failed to penetrate beyond the mannoprotein-rich outer cell wall layer. Melanization of
C. neoformans
and the absence of amphotericin B in the liposomes were also associated with a significant reduction in liposome penetration. Therefore, AmBisome can reach cell membranes intact, implying that fungal cell wall viscoelastic properties are permissive to vesicular structures. The fact that AmBisome can transit through chemically diverse cell wall matrices when these liposomes are larger than the theoretical cell wall porosity suggests that the wall is capable of rapid remodeling, which may also be the mechanism for release of extracellular vesicles.

IMPORTANCE
AmBisome is a broad-spectrum fungicidal antifungal agent in which the hydrophobic polyene antibiotic amphotericin B is packaged within a 60- to 80-nm liposome. The mode of action involves perturbation of the fungal cell membrane by selectively binding to ergosterol, thereby disrupting membrane function. We report that the AmBisome liposome transits through the cell walls of both
Candida albicans
and
Cryptococcus neoformans
intact, despite the fact that the liposome is larger than the theoretical cell wall porosity. This implies that the cell wall has deformable, viscoelastic properties that are permissive to transwall vesicular traffic. These observations help explain the low toxicity of AmBisome, which can deliver its payload directly to the cell membrane without unloading the polyene in the cell wall. In addition, these findings suggest that extracellular vesicles may also be able to pass through the cell wall to deliver soluble and membrane-bound effectors and other molecules to the extracellular space.
‘The industry must be inconspicuous’: Japan Tobacco’s corruption of science and health policy via the Smoking Research Foundation
Authors: Iida Kaori , Proctor Robert N 
Published: February 2018

ObjectiveTo investigate how and why Japan Tobacco, Inc. (JT) in 1986 established the Smoking Research Foundation (SRF), a research-funding institution, and to explore the extent to which SRF has influenced science and health policy in Japan.MethodsWe analysed documents in the Truth Tobacco Industry Documents archive, along with recent Japanese litigation documents and published documents.ResultsJT’s effort to combat effective tobacco control was strengthened in the mid-1980s, following privatisation of the company. While remaining under the protection of Japan’s Ministry of Finance, the semiprivatised company lost its ‘access to politicos’, opening up a perceived need for collaboration with global cigarette makers. One solution, arrived at through clandestine planning with American companies, was to establish a third-party organisation, SRF, with the hope of capturing scientific and medical authority for the industry. Guarded by powerful people in government and academia, SRF was launched with the covert goal of influencing tobacco policy both inside and outside Japan. Scholars funded by SRF have participated in international conferences, national advisory committees and tobacco litigation, in most instances helping the industry to maintain a favourable climate for the continued sale of cigarettes.ConclusionsContrary to industry claims, SRF was never meant to be independent or neutral. With active support from foreign cigarette manufacturers, SRF represents the expansion into Asia of the denialist campaign that began in the USA in 1953.
The biology and ecology of slimy sculpin: A recipe for effective environmental monitoring
Authors: Gray Michelle A. , Curry R. Allen , Arciszewski Tim J. , Munkittrick Kelly R. , Brasfield Sandra M. 
Published: February 2018

Recently, the use of small-bodied fish in environmental monitoring has increased, particularly within the Canadian environmental effects monitoring (EEM) and other adaptive programs. Although it is possible to measure changes with many small-bodied species, interpretation is often complicated by the absence of information on the biology and ecology of fish not of commercial, recreational, or traditional interest. Knowing and understanding the basic biology of these fishes aids in the sensitivity of study designs (i.e., ability to detect change) and the interpretation of all biological levels of responses (e.g., cellular to community). The increased use of slimy sculpin ( Cottus cognatus Richardson, 1836) in impact assessment studies in North America provides a considerable amount of information on life history aspects. The slimy sculpin has the most ubiquitous North American distribution among cottids but yet has a very small home range, thus integrating environmental conditions of localized areas. This paper describes aspects of slimy sculpin life cycle that affect collection efficiency and timing, and describes and provides data collected over more than 10 years of studies at more than 20 reference study sites. This overview provides a functional and informative compilation to support adaptive environmental monitoring and provide a baseline for comparative ecological study.
Silencing the Snail-Dependent RNA Splice Regulator ESRP1 Drives Malignant Transformation of Human Pulmonary Epithelial Cells
Authors: Walser Tonya C. , Jing Zhe , Tran Linh M. , Lin Ying Q. , Yakobian Natalie , Wang Gerald , Krysan Kostyantyn , Zhu Li X. , Sharma Sherven , Lee Mi-Heon , Belperio John A. , Ooi Aik T. , Gomperts Brigitte N. , Shay Jerry W. , Larsen Jill E. , Minna John D. , Hong Long-sheng , Fishbein Michael C. , Dubinett Steven M. 
Published: February 2018

Abstract
Epithelial-to-mesenchymal transition (EMT) is organized in cancer cells by a set of key transcription factors, but the significance of this process is still debated, including in non–small cell lung cancer (NSCLC). Here, we report increased expression of the EMT-inducing transcription factor Snail in premalignant pulmonary lesions, relative to histologically normal pulmonary epithelium. In immortalized human pulmonary epithelial cells and isogenic derivatives, we documented Snail-dependent anchorage-independent growth in vitro and primary tumor growth and metastatic behavior in vivo. Snail-mediated transformation relied upon silencing of the tumor-suppressive RNA splicing regulatory protein ESRP1. In clinical specimens of NSCLC, ESRP1 loss was documented in Snail-expressing premalignant pulmonary lesions. Mechanistic investigations showed that Snail drives malignant progression in an ALDH+CD44+CD24− pulmonary stem cell subset in which ESRP1 and stemness-repressing microRNAs are inhibited. Collectively, our results show how ESRP1 loss is a critical event in lung carcinogenesis, and they identify new candidate directions for targeted therapy of NSCLC.
Significance: This study defines a Snail-ESRP1 cancer axis that is crucial for human lung carcinogenesis, with implications for new intervention strategies and translational opportunities. Cancer Res; 78(8); 1986–99. ©2018 AACR.
S-Nitrosylation of cIAP1 Switches Cancer Cell Fate from TNFα/TNFR1-Mediated Cell Survival to Cell Death
Authors: Romagny Sabrina , Bouaouiche Sarra , Lucchi Géraldine , Ducoroy Patrick , Bertoldo Jean B. , Terenzi Hernan , Bettaieb Ali , Plenchette Stéphanie 
Published: February 2018

Abstract
TNFα is a prominent proinflammatory cytokine and a critical mediator for the development of many types of cancer such as breast, colon, prostate, cervical, skin, liver, and chronic lymphocytic leukemia. Binding of TNFα to TNFR1 can lead to divergent signaling pathways promoting predominantly NF-κB activation but also cell death. We report here that the nitric oxide (NO) donor glyceryl trinitrate (GTN) converts TNFα, generated from immune cells or cancer cells stimulated by chemotherapy, into a prodeath mediator in colon and mammary cancer cells. GTN-mediated S-nitrosylation of cIAP1 on cysteines 571 and 574 inhibited its E3 ubiquitin ligase activity, which in turn reduced Lys63-linked ubiquitination of RIP1 and initiated assembly of a death complex. These findings provide insights into how NO can harness advantageous aspects of inflammation in cancer and provide new therapeutic strategies.
Significance: Combination of an NO donor with chemotherapeutic drug–induced TNFα represents a potentially valuable anticancer strategy. Cancer Res; 78(8); 1948–57. ©2018 AACR.
Achieving the United Nations Sustainable Development Goals on Biological Diversity in Nigeria: Current Issues and Future Directions
Authors: Olawuyi Damilola S. , Olusegun Olaitan O. 
Published: February 2018

The aim of this article is to examine the application of the United Nations Sustainable Development Goals (sdgs) on biological diversity in Nigeria, emphasizing the preconditions for implementation and the barriers and difficulties for their realization.
Given Nigeria’s faltering attempts and failure to achieve the biodiversity goals in the Millennium Development Goals (mdgs), a predecessor to the sdgs, this article builds a profile of the salient law and institutional barriers to the implementation and attainment of the sdgs on biodiversity in Nigeria and proffers practical and normative solutions to those challenges. The methodology approach is based in an analytical and survey of the scope and status of the implementation of international law norms on biodiversity in Nigeria. The results indicate that archaic legislative provision on biodiversity; lack of coherent post-2015 biodiversity agenda; lack of institutional coordination; absence of political will; and inadequate stakeholder engagement in evolving national biodiversity plans are the main legal barriers that must be addressed if the sdgs are to be attained in Nigeria.
Improving the Global Environmental Rule of Law by Upholding Indigenous Rights: Examples from Aotearoa New Zealand
Authors: Iorns Magallanes Catherine J. 
Published: February 2018

A better recognition of the relationship between human rights and the environment facilitates good governance, holistic management and environmental justice. This relationship works two ways: the protection of the environment is necessary to uphold human rights and the protection of human rights is necessary to protect the environment. This article focuses on the latter aspect of this relationship, addressing in particular how the protection of indigenous rights can help protect the environment and contribute to better environmental management.
The relationships indigenous peoples have with the natural world, as well as their protective views in relation to its uses, often clash with the dominant worldviews espoused by nation states. The two can only be reconciled when governments make a concerted effort to incorporate indigenous thinking into law and policy. This article argues that it is in the interests of all peoples that they do so. When indigenous cosmologies are recognized and provided for, the benefits are felt far beyond indigenous communities and can help to generate better environmental outcomes for all peoples.
This article provides some examples from Aotearoa New Zealand, a nation which has consistently upheld (minority) indigenous Maori rights in legal and non-legal instruments. It will focus in particular on the incorporation of the Maori concepts of whanaungatanga (kinship) and kaitiakatanga (guardianship) into New Zealand law. The former envisages mankind as part of nature and nature as a ‘living ancestor’ to be revered, while the latter redefines humans (in particular, iwi or Maori tribal groups, hapu – tribal sub-groups – and whanau – family groups) as ‘guardians’ or stewards of the environment who carry certain responsibilities, rather than as managers who possess certain rights.
Financing Sustainable Landscapes through Innovative International Economic Law and Governance Instruments
Authors: Segger Marie-Claire Cordonier , Holmgren Peter , Wardell D. Andrew 
Published: February 2018

This article examines innovative ways to promote investment and financing of sustainable landscape initiatives in international law. It argues that increased flows of investment and finance for sustainable landscapes must be guided by a clear and comprehensive legal framework; better and more appropriate knowledge and technologies; more informed decision-making; and improved governance at all levels.
The article considers concerns and opportunities to support the financing of sustainable forestry and land-use programs, especially in developing countries. It reviews the key contributions of international investment instruments to sustainability landscapes financing, in light of recent decisions concerning International Investment Agreements (iias) by arbitral panels convened to hear disputes under the rules of the International Centre for Settlement of Investment Disputes (icsid) or the United Nations Commission on International Trade Law (uncitral). It then proposes innovative ways that investment and financing rules might foster more effective implementation of innovative financing instruments, such as Landscape Funds in developing countries.