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Hamm, Joshua N., Susanne Erdmann, Emiley A. Eloe-Fadrosh, Allegra Angeloni, Ling Zhong, Christopher Brownlee, Timothy J. Williams, et al. "Unexpected host dependency of Antarctic Nanohaloarchaeota." Proceedings of the National Academy of Sciences 116, no. 29 (June 28, 2019): 14661–70. http://dx.doi.org/10.1073/pnas.1905179116.
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In hypersaline environments, Nanohaloarchaeota (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaeota [DPANN] superphylum) are thought to be free-living microorganisms. We report cultivation of 2 strains of Antarctic Nanohaloarchaeota and show that they require the haloarchaeon Halorubrum lacusprofundi for growth. By performing growth using enrichments and fluorescence-activated cell sorting, we demonstrated successful cultivation of Candidatus Nanohaloarchaeum antarcticus, purification of Ca. Nha. antarcticus away from other species, and growth and verification of Ca. Nha. antarcticus with Hrr. lacusprofundi; these findings are analogous to those required for fulfilling Koch’s postulates. We use fluorescent in situ hybridization and transmission electron microscopy to assess cell structures and interactions; metagenomics to characterize enrichment taxa, generate metagenome assembled genomes, and interrogate Antarctic communities; and proteomics to assess metabolic pathways and speculate about the roles of certain proteins. Metagenome analysis indicates the presence of a single species, which is endemic to Antarctic hypersaline systems that support the growth of haloarchaea. The presence of unusually large proteins predicted to function in attachment and invasion of hosts plus the absence of key biosynthetic pathways (e.g., lipids) in metagenome assembled genomes of globally distributed Nanohaloarchaeota indicate that all members of the lineage have evolved as symbionts. Our work expands the range of archaeal symbiotic lifestyles and provides a genetically tractable model system for advancing understanding of the factors controlling microbial symbiotic relationships.
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Verrier, Eloi R., Amélie Weiss, Charlotte Bach, Laura Heydmann, Vincent Turon-Lagot, Arnaud Kopp, Houssein El Saghire, et al. "Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets." Gut 69, no. 1 (March 4, 2019): 158–67. http://dx.doi.org/10.1136/gutjnl-2018-317065.
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ObjectiveHepatitis D virus (HDV) is a circular RNA virus coinfecting hepatocytes with hepatitis B virus. Chronic hepatitis D results in severe liver disease and an increased risk of liver cancer. Efficient therapeutic approaches against HDV are absent.DesignHere, we combined an RNAi loss-of-function and small molecule screen to uncover host-dependency factors for HDV infection.ResultsFunctional screening unravelled the hypoxia-inducible factor (HIF)-signalling and insulin-resistance pathways, RNA polymerase II, glycosaminoglycan biosynthesis and the pyrimidine metabolism as virus-hepatocyte dependency networks. Validation studies in primary human hepatocytes identified the carbamoyl-phosphatesynthetase 2, aspartate transcarbamylase and dihydroorotase (CAD) enzyme and estrogen receptor alpha (encoded by ESR1) as key host factors for HDV life cycle. Mechanistic studies revealed that the two host factors are required for viral replication. Inhibition studies using N-(phosphonoacetyl)-L-aspartic acid and fulvestrant, specific CAD and ESR1 inhibitors, respectively, uncovered their impact as antiviral targets.ConclusionThe discovery of HDV host-dependency factors elucidates the pathogenesis of viral disease biology and opens therapeutic strategies for HDV cure.
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Kanojia, Aditi, Mansi Sharma, Rishad Shiraz, and Shashank Tripathi. "Flavivirus–Host Interaction Landscape Visualized through Genome-Wide CRISPR Screens." Viruses 14, no. 10 (September 30, 2022): 2164. http://dx.doi.org/10.3390/v14102164.
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Flaviviruses comprise several important human pathogens which cause significant morbidity and mortality worldwide. Like any other virus, they are obligate intracellular parasites. Therefore, studying the host cellular factors that promote or restrict their replication and pathogenesis becomes vital. Since inhibiting the host dependency factors or activating the host restriction factors can suppress the viral replication and propagation in the cell, identifying them reveals potential targets for antiviral therapeutics. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has provided an effective means of producing customizable genetic modifications and performing forward genetic screens in a broad spectrum of cell types and organisms. The ease, rapidity, and high reproducibility of CRISPR technology have made it an excellent tool for carrying out genome-wide screens to identify and characterize viral host dependency factors systematically. Here, we review the insights from various Genome-wide CRISPR screens that have advanced our understanding of Flavivirus-Host interactions.
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Becker, Tanja, Vu Le-Trilling, and Mirko Trilling. "Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses." International Journal of Molecular Sciences 20, no. 7 (April 2, 2019): 1636. http://dx.doi.org/10.3390/ijms20071636.
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Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that frequently causes morbidity and mortality in individuals with insufficient immunity, such as transplant recipients, AIDS patients, and congenitally infected newborns. Several antiviral drugs are approved to treat HCMV infections. However, resistant HCMV mutants can arise in patients receiving long-term therapy. Additionally, side effects and the risk to cause birth defects limit the use of currently approved antivirals against HCMV. Therefore, the identification of new drug targets is of clinical relevance. Recent work identified DNA-damage binding protein 1 (DDB1) and the family of the cellular cullin (Cul) RING ubiquitin (Ub) ligases (CRLs) as host-derived factors that are relevant for the replication of human and mouse cytomegaloviruses. The first-in-class CRL inhibitory compound Pevonedistat (also called MLN4924) is currently under investigation as an anti-tumor drug in several clinical trials. Cytomegaloviruses exploit CRLs to regulate the abundance of viral proteins, and to induce the proteasomal degradation of host restriction factors involved in innate and intrinsic immunity. Accordingly, pharmacological blockade of CRL activity diminishes viral replication in cell culture. In this review, we summarize the current knowledge concerning the relevance of DDB1 and CRLs during cytomegalovirus replication and discuss chances and drawbacks of CRL inhibitory drugs as potential antiviral treatment against HCMV.
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Aromolaran, Olufemi, Thomas Beder, Eunice Adedeji, Yvonne Ajamma, Jelili Oyelade, Ezekiel Adebiyi, and Rainer Koenig. "Predicting host dependency factors of pathogens in Drosophila melanogaster using machine learning." Computational and Structural Biotechnology Journal 19 (2021): 4581–92. http://dx.doi.org/10.1016/j.csbj.2021.08.010.
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Petrova, Evgeniya, Ségolène Gracias, Guillaume Beauclair, Frédéric Tangy, and Nolwenn Jouvenet. "Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen." Viruses 11, no. 1 (January 15, 2019): 68. http://dx.doi.org/10.3390/v11010068.
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Flaviviruses, such as dengue (DENV), West Nile (WNV), yellow fever (YFV) and Zika (ZIKV) viruses, are mosquito-borne pathogens that present a major risk to global public health. To identify host factors that promote flavivirus replication, we performed a genome-wide gain-of-function cDNA screen for human genes that enhance the replication of flavivirus reporter particles in human cells. The screen recovered seventeen potential host proteins that promote viral replication, including the previously known dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit (DDOST). Using silencing approaches, we validated the role of four candidates in YFV and WNV replication: ribosomal protein L19 (RPL19), ribosomal protein S3 (RPS3), DDOST and importin 9 (IPO9). Applying a panel of virological, biochemical and microscopic methods, we validated further the role of RPL19 and DDOST as host factors required for optimal replication of YFV, WNV and ZIKV. The genome-wide gain-of-function screen is thus a valid approach to advance our understanding of flavivirus replication.
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Syarifuddin, Ferry. "The Dynamics of Foreign Portfolio Investment and Exchange Rates: An Interconnection Approach in ASEAN." Journal of Eurasian Economies 1, no. 2 (July 22, 2022): 1–12. http://dx.doi.org/10.36880/j01.2.0113.
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This paper examines the spatial dependence of foreign portfolio investment (FPI) inflows among ASEAN countries in 2002Q1-2018Q4 utilizing the spatial econometric approach. This paper adds clarity to the identification of the true nature of portfolio investment performances. I show a competitive relationship among ASEAN countries, indicating crowding out of FPI in the host country is most likely to occur when the neighboring country is experiencing a crowding out. I also show that exchange rate volatility and changes, both in the host country and neighboring country, do not significantly affect FPI in the host country. Furthermore, I find that, aside from macroeconomic factors of the host country, foreign investors also consider the macroeconomic conditions in the neighboring country, suggesting the existence of spatial dependency. Robustness checks are conducted to confirm the main findings of this study.
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Rother, Marion, Christiane Dimmler, Friderike Weege, Hans-Joachim Mollenkopf, Thomas F. Meyer, and Michael Naumann. "Discovery of Zika virus host dependency factors in trophoblasts using CRISPR/Cas9 screening." Journal of Virological Methods 290 (April 2021): 114085. http://dx.doi.org/10.1016/j.jviromet.2021.114085.
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King, Cason R., and Andrew Mehle. "The later stages of viral infection: An undiscovered country of host dependency factors." PLOS Pathogens 16, no. 8 (August 25, 2020): e1008777. http://dx.doi.org/10.1371/journal.ppat.1008777.
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Ma, Yijie, Michael J. Walsh, Katharina Bernhardt, Camille W. Ashbaugh, Stephen J. Trudeau, Isabelle Y. Ashbaugh, Sizun Jiang, et al. "CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors." Cell Host & Microbe 21, no. 5 (May 2017): 580–91. http://dx.doi.org/10.1016/j.chom.2017.04.005.
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Roesmann, Fabian, Lisa Müller, Katleen Klaassen, Stefanie Heß, and Marek Widera. "Interferon-Regulated Expression of Cellular Splicing Factors Modulates Multiple Levels of HIV-1 Gene Expression and Replication." Viruses 16, no. 6 (June 11, 2024): 938. http://dx.doi.org/10.3390/v16060938.
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Type I interferons (IFN-Is) are pivotal in innate immunity against human immunodeficiency virus I (HIV-1) by eliciting the expression of IFN-stimulated genes (ISGs), which encompass potent host restriction factors. While ISGs restrict the viral replication within the host cell by targeting various stages of the viral life cycle, the lesser-known IFN-repressed genes (IRepGs), including RNA-binding proteins (RBPs), affect the viral replication by altering the expression of the host dependency factors that are essential for efficient HIV-1 gene expression. Both the host restriction and dependency factors determine the viral replication efficiency; however, the understanding of the IRepGs implicated in HIV-1 infection remains greatly limited at present. This review provides a comprehensive overview of the current understanding regarding the impact of the RNA-binding protein families, specifically the two families of splicing-associated proteins SRSF and hnRNP, on HIV-1 gene expression and viral replication. Since the recent findings show specifically that SRSF1 and hnRNP A0 are regulated by IFN-I in various cell lines and primary cells, including intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs), we particularly discuss their role in the context of the innate immunity affecting HIV-1 replication.
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Park, Ryan J., Tim Wang, Dylan Koundakjian, Judd F. Hultquist, Pedro Lamothe-Molina, Blandine Monel, Kathrin Schumann, et al. "A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors." Nature Genetics 49, no. 2 (December 19, 2016): 193–203. http://dx.doi.org/10.1038/ng.3741.
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Zhang, Xi, Hin Chu, Lei Wen, Huiping Shuai, Dong Yang, Yixin Wang, Yuxin Hou, et al. "Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation." Emerging Microbes & Infections 9, no. 1 (January 1, 2020): 733–46. http://dx.doi.org/10.1080/22221751.2020.1738277.
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Hafer, Terry L., Abby Felton, Yennifer Delgado, Harini Srinivasan, and Michael Emerman. "A CRISPR Screen of HIV Dependency Factors Reveals That CCNT1 Is Non-Essential in T Cells but Required for HIV-1 Reactivation from Latency." Viruses 15, no. 9 (August 31, 2023): 1863. http://dx.doi.org/10.3390/v15091863.
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We sought to explore the hypothesis that host factors required for HIV-1 replication also play a role in latency reversal. Using a CRISPR gene library of putative HIV dependency factors, we performed a screen to identify genes required for latency reactivation. We identified several HIV-1 dependency factors that play a key role in HIV-1 latency reactivation including ELL, UBE2M, TBL1XR1, HDAC3, AMBRA1, and ALYREF. The knockout of Cyclin T1 (CCNT1), a component of the P-TEFb complex that is important for transcription elongation, was the top hit in the screen and had the largest effect on HIV latency reversal with a wide variety of latency reversal agents. Moreover, CCNT1 knockout prevents latency reactivation in a primary CD4+ T cell model of HIV latency without affecting the activation of these cells. RNA sequencing data showed that CCNT1 regulates HIV-1 proviral genes to a larger extent than any other host gene and had no significant effects on RNA transcripts in primary T cells after activation. We conclude that CCNT1 function is non-essential in T cells but is absolutely required for HIV latency reversal.
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Hafirassou, Mohamed Lamine, Laurent Meertens, Claudia Umaña-Diaz, Athena Labeau, Ophelie Dejarnac, Lucie Bonnet-Madin, Beate M. Kümmerer, et al. "A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors." Cell Reports 21, no. 13 (December 2017): 3900–3913. http://dx.doi.org/10.1016/j.celrep.2017.11.094.
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Hafirassou, Mohamed Lamine, Laurent Meertens, Claudia Umaña-Diaz, Athena Labeau, Ophelie Dejarnac, Lucie Bonnet-Madin, Beate M. Kümmerer, et al. "A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors." Cell Reports 22, no. 5 (January 2018): 1364. http://dx.doi.org/10.1016/j.celrep.2018.01.038.
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Aldamen, Yasmin. "Understanding Social Media Dependency, and Uses and Gratifications as a Communication System in the Migration Era: Syrian Refugees in Host Countries as a Case Study." Social Sciences 12, no. 6 (May 30, 2023): 322. http://dx.doi.org/10.3390/socsci12060322.
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Through the theoretical frameworks of the media system dependency model and uses and gratifications theory, this study examined the uses of social media by Syrian refugees in Jordan and Turkey. A mixed-methods approach was used to increase the credibility and validity of the study’s findings by combining a qualitative method with quantitative data. The findings show that there were some factors that affected the Syrian refugees’ use of social media before seeking refuge in Jordan and Turkey, which were mainly its ban due to the regime’s censorship and a bad Internet connection due to the bad infrastructure. The absence of these two factors led to an increase in their social media dependency after seeking refuge. There are variances in which social media sites Syrian refugees use the most and why. The majority relied on Facebook for various reasons, and this dependency had varying repercussions on individuals. Furthermore, many immigrants were acquainted with new platforms, implying that refugees became social-media-literate and participated in the updates of the new platforms, even if such sites were not well known to the general public. The Syrian refugees’ dependency on social media varies from person to person due to differences in personal goals, social status, locations, living characteristics, and easy access to the Internet. Furthermore, this dependency on social media has different effects on them according to the media system dependency model. The refugees become increasingly dependent on social media to satisfy their needs and, because of that, social media dependency will become more important in their lives and will increase its influence and effects on them. Furthermore, the study found that the Syrian refugees depended on social media for various gratifications, such as educational, work, and business; information access; cultural and social aspects; connecting with networks and families; establishing friendships; learning new skills; self-expression; making business; and finding work, in addition to reaching routes and contacting smugglers to help them leave the country.
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Mosbah, Aissa, Jaithen Alharbi, Abdulla Fetais, and Ibrahim Alkandi. "The Role of the Manager in the Middle East: An Empirical Study of Multinational Companies." Global Business Review 20, no. 4 (May 23, 2019): 887–900. http://dx.doi.org/10.1177/0972150919844892.
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This article is an empirical investigation into the role of the CEO manager in the affiliates of multinational corporations operating in the Middle East. Grounded in a literature review of the reasons for employing either parent country nationals (PCNs) or host country nationals (HCNs) in top management position in foreign subsidiaries, a number of factors influencing the choice between these alternatives are identified. Using a data collected from 147 multinational companies (MNCs) operating in the Kingdom of Saudi Arabia (KSA), the influence of each of these factors on this selection is empirically tested with the help of primary data. The study proposed that the relationship between the home and host country managers could be linked to agency theory (with the ‘classical’ principal–agent relationship) and to resource dependency theory (implying relations between the branch and other partners based on interdependence). Our results show that the agency and resource dependency mechanisms are indeed used side by side and complementary to each other to exercise control. Home country managers can strategize to implement control by the informal and social means by positioning a sizeable number of managers from the home country within the subsidiary. Indeed, our results revealed this as true.
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Kratzel, Annika, Jenna N. Kelly, Philip V’kovski, Jasmine Portmann, Yannick Brüggemann, Daniel Todt, Nadine Ebert, et al. "A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets." PLOS Biology 19, no. 12 (December 28, 2021): e3001490. http://dx.doi.org/10.1371/journal.pbio.3001490.
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Over the past 20 years, 3 highly pathogenic human coronaviruses (HCoVs) have emerged—Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and, most recently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)—demonstrating that coronaviruses (CoVs) pose a serious threat to human health and highlighting the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycles. Herein, we conducted 2 independent genome-wide CRISPR/Cas-9 knockout (KO) screens to identify MERS-CoV and HCoV-229E host dependency factors (HDFs) required for HCoV replication in the human Huh7 cell line. Top scoring genes were further validated and assessed in the context of MERS-CoV and HCoV-229E infection as well as SARS-CoV and SARS-CoV-2 infection. Strikingly, we found that several autophagy-related genes, including TMEM41B, MINAR1, and the immunophilin FKBP8, were common host factors required for pan-CoV replication. Importantly, inhibition of the immunophilin protein family with the compounds cyclosporine A, and the nonimmunosuppressive derivative alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures, which recapitulate the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrated that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.
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Diana Uwaila Oboite. "Perceived impact of volunteer tourism on host communities in Lubbock, United States: A qualitative exploration." World Journal of Advanced Research and Reviews 23, no. 2 (August 30, 2024): 1501–14. http://dx.doi.org/10.30574/wjarr.2024.23.2.2445.
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Volunteer tourism is a popular trend with millions of people participating in various volunteer activities. Although volunteer tourism is frequently promoted as a way to improve host communities, little is known about how it is perceived to impact host communities. Hence this study explored the perceptions of volunteer tourists regarding the impact of their activities on the host community; investigated the alignment between volunteer tourists’ perceptions of impact and the actual needs and concerns of the host community; gathered insights into the factors influencing volunteer tourists’ perceptions of impact. The Qualitative study sampled ten voluntourists through purposive and snowballing sampling techniques. Findings revealed that, Volunteers reported both positive and negative effects of voluntourism, including community bonding, environmental conservation, dependency, and cultural insensitivity. This study highlights a critical tension between voluntourism’s potential for positive community engagement and its susceptibility to perpetuating neocolonial narratives evidenced by uneven power dynamics and cultural imposition.
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Kokkonos, Konstantinos G., Nicolas Fossat, Louise Nielsen, Christina Holm, Wytske M. Hepkema, Jens Bukh, and Troels K. H. Scheel. "Evolutionary selection of pestivirus variants with altered or no microRNA dependency." Nucleic Acids Research 48, no. 10 (May 6, 2020): 5555–71. http://dx.doi.org/10.1093/nar/gkaa300.
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Abstract Host microRNA (miRNA) dependency is a hallmark of the human pathogen hepatitis C virus (HCV) and was also described for the related pestiviruses, which are important livestock pathogens. The liver-specific miR-122 binds within the HCV 5′ untranslated region (UTR), whereas the broadly expressed let-7 and miR-17 families bind two sites (S1 and S2, respectively) in the pestiviral 3′ UTR. Here, we dissected the mechanism of miRNA dependency of the pestivirus bovine viral diarrhea virus (BVDV). Argonaute 2 (AGO2) and miR-17 binding were essential for viral replication, whereas let-7 binding was mainly required for full translational efficiency. Furthermore, using seed site randomized genomes and evolutionary selection experiments, we found that tropism could be redirected to different miRNAs. AGO cross-linking and immunoprecipitation (CLIP) experiments and miRNA antagonism demonstrated that these alternative variants bound and depended on the corresponding miRNAs. Interestingly, we also identified miRNA-independent variants that were obtained through acquisition of compensatory mutations near the genomic 3′ terminus. Rescue experiments demonstrated that miRNA binding and 3′ mutagenesis contribute to replication through mutually exclusive mechanisms. Altogether, our findings suggest that pestiviruses, although capable of miRNA-independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation.
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Schmidt, Nora, and Mathias Munschauer. "Atlas der SARS-CoV-2-RNA-Protein-Interaktionen in infizierten Zellen." BIOspektrum 27, no. 4 (June 2021): 376–79. http://dx.doi.org/10.1007/s12268-021-1587-3.
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AbstractUsing RNA antisense purification and mass spectrometry, we identified more than 100 human proteins that directly and specifically bind SARS-CoV-2 RNA in infected cells. To gain insights into the functions of selected RNA interactors, we applied genetic perturbation and pharmacological inhibition experiments, and mapped the contact sites on the viral RNA. This led to the identification of host dependency factors and defense strategies, which can guide the design of novel therapeutics against SARS-CoV-2.
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Bao, Yanqing, Lin Wang, and Jianjun Sun. "A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction." Cells 10, no. 7 (June 30, 2021): 1645. http://dx.doi.org/10.3390/cells10071645.
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As a major effector of the ESX-1 secretion system, EsxA is essential for the virulence of pathogenic mycobacteria, such as Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). EsxA possesses an acidic pH-dependent membrane permeabilizing activity and plays an essential role by mediating mycobacterial escape from the phagosome and translocation to the cytosol for intracellular replication. Moreover, EsxA regulates host immune responses as a potent T-cell antigen and a strong immunoregulator. EsxA interacts with multiple cellular proteins and stimulates several signal pathways, such as necrosis, apoptosis, autophagy, and antigen presentation. Interestingly, there is a co-dependency in the expression and secretion of EsxA and other mycobacterial factors, which greatly increases the complexity of dissecting the precise roles of EsxA and other factors in mycobacterium–host interaction. In this review, we summarize the current understandings of the roles and functions of EsxA in mycobacterial infection and discuss the challenges and future directions.
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Chai, Haiting, Quan Gu, Joseph Hughes, and David L. Robertson. "In silico prediction of HIV-1-host molecular interactions and their directionality." PLOS Computational Biology 18, no. 2 (February 8, 2022): e1009720. http://dx.doi.org/10.1371/journal.pcbi.1009720.
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Human immunodeficiency virus type 1 (HIV-1) continues to be a major cause of disease and premature death. As with all viruses, HIV-1 exploits a host cell to replicate. Improving our understanding of the molecular interactions between virus and human host proteins is crucial for a mechanistic understanding of virus biology, infection and host antiviral activities. This knowledge will potentially permit the identification of host molecules for targeting by drugs with antiviral properties. Here, we propose a data-driven approach for the analysis and prediction of the HIV-1 interacting proteins (VIPs) with a focus on the directionality of the interaction: host-dependency versus antiviral factors. Using support vector machine learning models and features encompassing genetic, proteomic and network properties, our results reveal some significant differences between the VIPs and non-HIV-1 interacting human proteins (non-VIPs). As assessed by comparison with the HIV-1 infection pathway data in the Reactome database (sensitivity > 90%, threshold = 0.5), we demonstrate these models have good generalization properties. We find that the ‘direction’ of the HIV-1-host molecular interactions is also predictable due to different characteristics of ‘forward’/pro-viral versus ‘backward’/pro-host proteins. Additionally, we infer the previously unknown direction of the interactions between HIV-1 and 1351 human host proteins. A web server for performing predictions is available at http://hivpre.cvr.gla.ac.uk/.
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Ligat, Gaëtan, Kaku Goto, Eloi Verrier, and Thomas F. Baumert. "Targeting Viral cccDNA for Cure of Chronic Hepatitis B." Current Hepatology Reports 19, no. 3 (July 10, 2020): 235–44. http://dx.doi.org/10.1007/s11901-020-00534-w.
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Abstract Purpose of Review Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a major cause of advanced liver disease and hepatocellular carcinoma (HCC) worldwide. HBV replication is characterized by the synthesis of covalently closed circular (ccc) DNA which is not targeted by antiviral nucleos(t)ide analogues (NUCs) the key modality of standard of care. While HBV replication is successfully suppressed in treated patients, they remain at risk for developing HCC. While functional cure, characterized by loss of HBsAg, is the first goal of novel antiviral therapies, curative treatments eliminating cccDNA remain the ultimate goal. This review summarizes recent advances in the discovery and development of novel therapeutic strategies and their impact on cccDNA biology. Recent Findings Within the last decade, substantial progress has been made in the understanding of cccDNA biology including the discovery of host dependency factors, epigenetic regulation of cccDNA transcription and immune-mediated degradation. Several approaches targeting cccDNA either in a direct or indirect manner are currently at the stage of discovery, preclinical or early clinical development. Examples include genome-editing approaches, strategies targeting host dependency factors or epigenetic gene regulation, nucleocapsid modulators and immune-mediated degradation. Summary While direct-targeting cccDNA strategies are still largely at the preclinical stage of development, capsid assembly modulators and immune-based approaches have reached the clinical phase. Clinical trials are ongoing to assess their efficacy and safety in patients including their impact on viral cccDNA. Combination therapies provide additional opportunities to overcome current limitations of individual approaches.
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Pitoyo, Agus Joko. "COMBATTING SEXUAL HARASSMENT AGAINST WOMEN MIGRANT WORKERS OVERSEAS: LOOKING AT THE CONTEXTUAL FACTORS." Populasi 24, no. 1 (April 3, 2016): 36–56. http://dx.doi.org/10.22146/jp.23694.
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Violence against women is a criminal act. It involves not only in personal domain, but also within social arenas. It could be happened in social life, such as the fact of sexual harassment at work. Through qualitative retrospective cross-sectional methods, the study aimed to explore the contextual factors of sexual harassment which have occurred overseas among women migrant workers from Ponorogo, East Java, Indonesia. Several factors altogether were identi ed as logical elements contributing to the existence of sexual harassment, composed of personal factors, relationship, working environment and structural regulation. The poor mechanism of placing Indonesian workers overseas was also perceived as an exacerbating factor to the presence of the conducts. Sexual harassment was more likely happened for female migrants in young age, low skill, and poor language in host countries. Several kinds of dependencies upon employers, such as administrative dependency, social and economic dependencies, and the existence of con ict at work were identi ed as other precipitating factors to the malpractice.
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Jühling, Frank, Antonio Saviano, Clara Ponsolles, Laura Heydmann, Emilie Crouchet, Sarah C. Durand, Houssein El Saghire, et al. "Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma." Life Science Alliance 4, no. 9 (July 21, 2021): e202101036. http://dx.doi.org/10.26508/lsa.202101036.
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Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) world-wide. The molecular mechanisms of viral hepatocarcinogenesis are still partially understood. Here, we applied two complementary single-cell RNA-sequencing protocols to investigate HBV–HCC host cell interactions at the single cell level of patient-derived HCC. Computational analyses revealed a marked HCC heterogeneity with a robust and significant correlation between HBV reads and cancer cell differentiation. Viral reads significantly correlated with the expression of HBV-dependency factors such as HLF in different tumor compartments. Analyses of virus-induced host responses identified previously undiscovered pathways mediating viral carcinogenesis, such as E2F- and MYC targets as well as adipogenesis. Mapping of fused HBV–host cell transcripts allowed the characterization of integration sites in individual cancer cells. Collectively, single-cell RNA-Seq unravels heterogeneity and compartmentalization of both, virus and cancer identifying new candidate pathways for viral hepatocarcinogenesis. The perturbation of pro-carcinogenic gene expression even at low HBV levels highlights the need of HBV cure to eliminate HCC risk.
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Isenberg, H. D. "Pathogenicity and virulence: another view." Clinical Microbiology Reviews 1, no. 1 (January 1988): 40–53. http://dx.doi.org/10.1128/cmr.1.1.40.
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The concepts of pathogenicity and virulence have governed our perception of microbial harmfulness since the time of Pasteur and Koch. These concepts resulted in the recognition and identification of numerous etiological agents and provided natural and synthetic agents effective in therapy and prevention of diseases. However, Koch's postulates--the premier product of this view--place the onus of harmfulness solely on the microbial world. Our recent experiences with polymicrobic and nosocomial infections, legionellosis, and acquired immunodeficiency syndrome point to the host as the major determinant of disease. The principles of parasitism, enunciated by Theobold Smith, approximate more accurately the disturbances of the host-parasite equilibrium we designate as infection. Many complex attributes of microbial anatomy and physiology have been obscured by our dependency on the pure-culture technique. For example, bacterial attachment organelles and the production of exopolysaccharides enable microorganisms to interact with mammalian glycocalyces and specific receptors. In addition, selection, through the use of therapeutic agents, aids in the progression of environmental organisms to members of the intimate human biosphere, with the potential to complicate the recovery of patients. These factors emphasize further the pivotal significance of host reactions in infections. Parasitism, in its negative aspects, explains the emergence of "new" infections that involve harm to more than host organs and cells: we may encounter subtler infections that reveal parasitic and host cell nucleic acid interactions in a form of genomic parasitism.
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Vitetta, Luis, Matthew Bambling, and Esben Strodl. "Probiotics and Commensal Bacteria Metabolites Trigger Epigenetic Changes in the Gut and Influence Beneficial Mood Dispositions." Microorganisms 11, no. 5 (May 18, 2023): 1334. http://dx.doi.org/10.3390/microorganisms11051334.
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The effect of the intestinal microbiome on the gut–brain axis has received considerable attention, strengthening the evidence that intestinal bacteria influence emotions and behavior. The colonic microbiome is important to health and the pattern of composition and concentration varies extensively in complexity from birth to adulthood. That is, host genetics and environmental factors are complicit in shaping the development of the intestinal microbiome to achieve immunological tolerance and metabolic homeostasis from birth. Given that the intestinal microbiome perseveres to maintain gut homeostasis throughout the life cycle, epigenetic actions may determine the effect on the gut–brain axis and the beneficial outcomes on mood. Probiotics are postulated to exhibit a range of positive health benefits including immunomodulating capabilities. Lactobacillus and Bifidobacterium are genera of bacteria found in the intestines and so far, the benefits afforded by ingesting bacteria such as these as probiotics to people with mood disorders have varied in efficacy. Most likely, the efficacy of probiotic bacteria at improving mood has a multifactorial dependency, relying namely on several factors that include the agents used, the dose, the pattern of dosing, the pharmacotherapy used, the characteristics of the host and the underlying luminal microbial environment (e.g., gut dysbiosis). Clarifying the pathways linking probiotics with improvements in mood may help identify the factors that efficacy is dependent upon. Adjunctive therapies with probiotics for mood disorders could, through DNA methylation molecular mechanisms, augment the intestinal microbial active cohort and endow its mammalian host with important and critical co-evolutionary redox signaling metabolic interactions, that are embedded in bacterial genomes, and that in turn can enhance beneficial mood dispositions.
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LAM, RUO YI, MING SHE SEE, FAIZAH SHAROM-HARRISON, HAZLINA AHAMAD ZAKERI, and NOR OMAIMA HARUN. "HOST SPECIFICITY, INFECTION DYNAMICS, AND ALLERGENICITY IN Anisakis SPP. INFESTATION: A REVIEW." Universiti Malaysia Terengganu Journal of Undergraduate Research 6, no. 2 (April 29, 2024): 62–75. http://dx.doi.org/10.46754/umtjur.v6i2.459.
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Fish and seafood are important in providing protein to human diets. However, they are susceptible to contamination by various parasites, such as nematodes, cestodes, and trematodes. Among these, Anisakis spp. and other species of trematodes belonging to the Anisakidae family are commonly identified in fish and shellfish, posing a significant health risk. This contamination poses a substantial risk to public health, particularly with the increasing prevalence of these parasites in marine fish. The globalisation of cuisines, including sushi, is one of the factors causing this development. The risk of Anisakis contamination has increased due to the global popularity of sushi, a form of Japanese food that features raw or undercooked fish. Gastric anisakiasis is the primary infection in humans, caused by the penetration of L3 larvae into the gastric wall. However, the indefinite symptoms associated with anisakiasis make precise identification challenging, complicating efforts to effectively treat this health issue. This study reviewed the host specificity, risk factors, infection mechanisms, and infestation areas of Anisakis spp. Various reputable sources, including Google Scholar, PubMed Central, ScienceDirect, Springer Link, and the Wiley Online Library, were used to explore the diverse host preferences and the impact of environmental changes. The larvae of Anisakis spp. exhibit diverse host preferences and environmental changes like global warming make hosts more vulnerable. Inadvertent exposure to these parasites occurs when individuals consume raw or undercooked fish and seafood. An extremely serious threat is posed by allergic anisakiasis, characterised by severe symptoms such as respiratory arrest, shock, and collapse. Research focusing on bioactive substances capable of blocking or neutralising the excretions and secretions of Anisakis sp. should be encouraged. Metalloproteinases (MMPs) and serine proteases, in particular, show promise for minimising adverse effects and reducing dependency on medication in treating allergic anisakiasis. Further research and intervention techniques are essential if health issues associated with Anisakis exist.
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Miljan, Merilin, and Ronnie Cann. "Rethinking case marking and case alternation in Estonian." Nordic Journal of Linguistics 36, no. 3 (October 25, 2013): 333–79. http://dx.doi.org/10.1017/s0332586513000309.
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In this paper, we argue for a view of case marking that does not treat case as the passive realisation of other morpho-syntactic properties of a construction but as independently bringing information to a clause. This different view of case entails that precise functions of case-marked expressions may be determined by the interaction of the case marking, the meaning of the host noun, the semantics of any predicate of which it is an argument and other contextually given factors. With respect to Estonian, it is argued that there is only one ‘structural’ case, the genitive, and this case marks non-subject, or oblique, dependency on some head. The partitive case, we argue, is semantically partitive in all its uses, except that the partitive meaning can be obscured or even eliminated depending on contextual factors. The nominative is merely the absence of case, associated with no specific positions or semantic effects.
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Lee, Jiae, Katelyn G. L. Ng, Kenneth M. Dombek, Dae Seok Eom, and Young V. Kwon. "Tumors overcome the action of the wasting factor ImpL2 by locally elevating Wnt/Wingless." Proceedings of the National Academy of Sciences 118, no. 23 (June 2, 2021): e2020120118. http://dx.doi.org/10.1073/pnas.2020120118.
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Tumors often secrete wasting factors associated with atrophy and the degeneration of host tissues. If tumors were to be affected by the wasting factors, mechanisms allowing tumors to evade the adverse effects of the wasting factors must exist, and impairing such mechanisms may attenuate tumors. We use Drosophila midgut tumor models to show that tumors up-regulate Wingless (Wg) to oppose the growth-impeding effects caused by the wasting factor, ImpL2 (insulin-like growth factor binding protein [IGFBP]-related protein). Growth of Yorkie (Yki)-induced tumors is dependent on Wg while either elimination of ImpL2 or elevation of insulin/insulin-like growth factor signaling in tumors revokes this dependency. Notably, Wg augmentation could be a general mechanism for supporting the growth of tumors with elevated ImpL2 and exploited to attenuate muscle degeneration during wasting. Our study elucidates the mechanism by which tumors negate the action of ImpL2 to uphold their growth during cachexia-like wasting and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.
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Kok, Laurence M. C., Laura Bungener, Geertruida H. de Bock, Anouschka Biswana, Geertiena van der Wal, Gustaaf W. van Imhoff, and Mar Bellido. "Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS." Human Cell 33, no. 1 (November 15, 2019): 243–51. http://dx.doi.org/10.1007/s13577-019-00297-7.
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AbstractModerate to severe chronic graft-versus-host disease (cGVHD) is associated with high morbidity, hospital dependency and poor quality of life. In this study, we analyzed a well-defined consecutive series of 98 patients with acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) who received allogeneic stem cell transplantation with non-myeloablative (NMA) conditioning to determine risk factors associated with the severity of cGVHD. cGVHD was defined according to the 2005 National Institute of Health consensus criteria. Transfusions before transplantation, presence of HLA antibodies, composition of the graft (CD3+, CD19+, CD34+ cells), sibling or matched unrelated donor, female donor to male recipient, CMV serology and the development of acute GVHD (aGVHD), were considered potential risk factors. Multivariate Cox regression analysis identified the number of CD19+ 106/kg (HR 2.79; 95% CI 1.35–5.74), CD3+ 106/kg (HR 2.18; 95% CI 1.04–4.59) infused cells and the presence of patient HLA antibodies before transplantation (HR 2.34; CI 1.11–4.95) as significant risk factors for the development of moderate to severe cGVHD. In summary, we identified in a small, but well-defined cohort, 3 risk factors associated with the severity of cGVHD that should be validated in a larger multi-center study.
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Sultana, Rafia, Ateeb Ahmad Parray, Muhammad Riaz Hossain, Bachera Aktar, and Sabina Faiz Rashid. "“We are invisible to them”—Identifying the most vulnerable groups in humanitarian crises during the COVID-19 pandemic: The case of Rohingyas and the Host communities of Cox’s Bazar." PLOS Global Public Health 3, no. 6 (June 8, 2023): e0000451. http://dx.doi.org/10.1371/journal.pgph.0000451.
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The COVID-19 pandemic has had an adverse impact on the Rohingya and the Bangladeshi host communities, which have been well documented in the literature. However, the specific groups of people rendered most vulnerable and marginalized during the pandemic have not been studied comprehensively. This paper draws on data to identify the most vulnerable groups of people within the Rohingya and the host communities of Cox’s Bazar, Bangladesh, during the COVID-19 pandemic. This study employed a systematic sequential method to identify the most vulnerable groups in the context of Rohingya and Host communities of Cox’s Bazar. We conducted a rapid literature review (n = 14 articles) to list down Most vulnerable groups (MVGs) in the studied contexts during the COVID-19 pandemic and conducted four (04) group sessions with humanitarian providers and relevant stakeholders in a research design workshop to refine the list. We also conducted field visits to both communities and interviewed community people using In-depth interviews (n = 16), Key-informant Interviews (n = 8), and several informal discussions to identify the most vulnerable groups within them and their social drivers of vulnerabilities. Based on the feedback received from the community, we finalized our MVGs criteria. The data collection commenced from November 2020 to March 2021. Informed consent was sought from all participants, and ethical clearance for this study was obtained from the IRB of BRAC JPGSPH. The most vulnerable groups identified in this study were: single female household heads, pregnant and lactating mothers, persons with disability, older adults, and adolescents. Our analysis also found some factors that may determine the different levels of vulnerabilities and risks faced by some groups more than others in the Rohingya and host communities during the pandemic. Some of these factors include economic constraints, gender norms, food security, social safety-security, psychosocial well-being, access to healthcare services, mobility, dependency, and a sudden halt in education. One of the most significant impacts of COVID-19 was the loss of earning sources, especially for the already economically vulnerable; this had far-reaching consequences on individuals’ food security and food consumption. Across the communities, it was found that the economically most affected group was single female household heads. The elderly and pregnant and lactating mothers face challenges seeking health services due to their restricted mobility and dependency on other family members. Persons living with disabilities from both contexts reported feelings of inadequacy in their families, exacerbated during the pandemic. Additionally, the shutdown in the formal education, and informal learning centres in both communities had the most significant impact on the adolescents during the COVID-19 lockdown. This study identifies the most vulnerable groups and their vulnerabilities amid the COVID-19 pandemic in the Rohingya and Host communities of Cox’s Bazar. The reasons behind their vulnerabilities are intersectional and represent deeply embedded patriarchal norms that exist in both communities. The findings are essential for the humanitarian aid agencies and policymakers for evidence-based decision-making and service provisions for addressing the vulnerabilities of the most vulnerable groups.
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Surahio, Muhammad Kashan, Shengyu Gu, Hakim Ali Mahesar, and Mansoor Mumtaz Soomro. "China–Pakistan Economic Corridor: Macro Environmental Factors and Security Challenges." SAGE Open 12, no. 1 (January 2022): 215824402210798. http://dx.doi.org/10.1177/21582440221079821.
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Pakistan, excepting external issues, has been enduring from chronic problems, that is, political-military anarchy, bad-governance, interprovincial conflicts, social divisions, sectarian influence, and terrorism resulting negatively on inland politics, economics, socioculture, and techno-industry (PEST). This amplified domestic instability and governmental dependency toward external support. Appropriately, China’s recent FDI for CPEC is aimed to revive Pakistan’s energy, transport, infrastructure, industries and also procure China’s energy and trade transmission, and opportunities. So far, some studies separately have reported favorable and unfavorable effects emerged between projects and local PEST domains. Apart from numerous advantages, the drawbacks are also found many that are not limited to institutional concerns, project misappropriations, ethnic and provincial reservations, opposition, and targeted terrorism. Therefore, current study systematically revolves around exploring, comparing, and analyzing the cross-impact among CPEC, PEST, and Security concomitantly. Employing qualitative interviews, all-round literature, and statistical index datasets, study determines that the security risk is critical for Chinese manpower whereas the concerns of inter-government, projects, institutions, civil-military, and ethnicities are somehow manageable. Results show positive trend in Pakistan’s many PEST indicators except political violence, corruption, security costs and threats, electricity costs and supply, debts, imports, and forestry that are in continuous negative impact. Moreover, opposition, trust-deficit, and attacks against CPEC are yet unchanged factors. The study, therefore, argues that if negative impact factors are recognized for elimination, the CPEC as a result will improve the both host and investor environments with promised socioeconomic advantages, and minimize challenges including terrorism. In last, study also suggests various practical and policy implications.
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Bates, C. J., D. M. O'Doherty, and D. Williams. "Flow instabilities in a graft anastomosis: A study of the instantaneous velocity fields." Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine 215, no. 6 (June 1, 2001): 579–87. http://dx.doi.org/10.1243/0954411011536181.
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The major cause of arterial bypass graft failure is intimal hyperplasia. Fluctuating wall shear stresses in the graft, which are associated with disturbed flow, are believed to be important factors in the development and localization of intimal hyperplasia. This study, based upon water as the working fluid, has investigated the flow structure inside a 30° Y-junction with different fillet radii at the intersection between the graft and the host artery at various Reynolds numbers and distal outlet segment (DOS) to proximal outlet segment (POS) flow ratios. The structure of the flow has been investigated experimentally using particle image velocimetry (PIV). The two-dimensional instantaneous velocity fields confirm the existence of a very complex flow, especially in the toe and heel regions for the different fillet radii and clearly identify features such as sinks, sources, vortices and strong time dependency.
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Ortiz-Cobo, Monica, Jose Garcia-Martin, and Rosella Bianco. "Will the “normality” times come back? L2 learning motivation between immigrants and refugees before Covid-19." XLinguae 14, no. 1 (January 2021): 182–96. http://dx.doi.org/10.18355/xl.2021.14.01.15.
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In these turbulent times of changes and transformations where educational processes are being virtualized due to the pandemic, we must not forget the difficulties that this implies for certain vulnerable learners and some learning contexts. That is the case of the L2 learning by immigrants and refugees. Such learners already have a starting difficulty, both for not mastering the language of learning and for the digital divide, which is increased by the migration variable. This work analyses, within a context of “normality”, the motivation of immigrants and refugees, in the light of their links and expectations. The differences in the relation with the Italian language are shown. The results show that the dependency on the host society, the uncertainty of the future and the absence of family ties are influential factors for refugees learning motivation. On the contrary, immigrants are not subjected to these factors, and therefore their Italian L2 learning motivations are different. By this research we conclude that adult refugees and immigrant students have different attitudes through the residency country language learning.
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Hao, Zhipeng, Wei Xie, Xuelian Jiang, Zhaoxiang Wu, Xin Zhang, and Baodong Chen. "Arbuscular Mycorrhizal Fungus Improves Rhizobium–Glycyrrhiza Seedling Symbiosis under Drought Stress." Agronomy 9, no. 10 (September 23, 2019): 572. http://dx.doi.org/10.3390/agronomy9100572.
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Rhizobia and arbuscular mycorrhizal (AM) fungi can potentially alleviate the abiotic stress on the legume Glycyrrhiza (licorice), while the potential benefits these symbiotic microbes offer to their host plant are strongly influenced by environmental factors. A greenhouse pot experiment was conducted to investigate the effects of single and combined inoculation with a rhizobium Mesorhizobium tianshanense Chen and an AM fungus Rhizophagus irregularis Walker & Schuessler on Glycyrrhiza uralensis Fisch. seedling performance under different water regimes. Drought stress inhibited rhizobium nodulation but increased mycorrhizal colonization. Furthermore, co-inoculation of rhizobium and AM fungus favored nodulation under both well-watered and drought stress conditions. Glycyrrhiza seedling growth showed a high mycorrhizal dependency. The seedlings showed a negative growth dependency to rhizobium under well-watered conditions but showed a positive response under drought stress. R. irregularis-inoculated plants showed a much higher stress tolerance index (STI) value than M. tianshanense-inoculated plants. STI value was more pronounced when plants were co-inoculated with R. irregularis and M. tianshanense compared with single-inoculated plants. Plant nitrogen concentration and contents were significantly influenced by inoculation treatments and water regimes. R. irregularis inoculation significantly increased plant shoot and root phosphorus contents. AM fungus inoculation could improve Glycyrrhiza plant–rhizobium symbiosis under drought stress, thereby suggesting that tripartite symbiotic relationships were more effective for promoting plant growth and enhancing drought tolerance.
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Lin, Wen-Ting. "Market distance and insider-ownership strategies: a resource-dependence perspective." Management Decision 57, no. 11 (November 12, 2019): 2958–77. http://dx.doi.org/10.1108/md-07-2017-0681.
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Purpose Ownership issues are an important feature of corporate governance when firms focus on global expansion in multiple and diverse regions. Drawing on resource dependence theory (RDT), the purpose of this paper is to address the phenomenon regarding the extent to which international market distance affects equity stakes in group-affiliated firms held by business group headquarters. Design/methodology/approach This study uses longitudinal data on foreign direct investments by 106 business groups (BGs), including 561 group-affiliated firms, from Taiwan over a five-year period from 2006 to 2010. Findings The results show that the equity stakes of the BG headquarters in the group-affiliated firms in foreign markets were positively associated with the geographic distance between the country of the BG headquarters and the host country of the foreign group-affiliated firms, the cultural distance between the country of the BG headquarters and the host country of the foreign group-affiliated firms and institutional distance between the country of the BG headquarters and the host country of the foreign group-affiliated firms. Research limitations/implications Most studies of corporate governance and international business are based on a transaction cost economics approach, a resource-based perspective and agency and institutional theories. In contrast, this study, by using RDT, provides an alternative explanation regarding the factors that affect the equity stakes of parent firms in group-affiliated firms. Practical implications This study presents two basic pieces of advice for consideration. First, at the managerial level, group-affiliated firms should develop their own resources and capabilities in order to become more autonomous in pursuing advantageous international activities that the parent firms may not foresee. Second, and again at the managerial level, business group headquarters should adopt a strategy to balance the dependency relationship between group-affiliated firms and business group headquarters. Originality/value This study provides the most finely grained analysis, to date, regarding how international market distance affects business group headquarters from newly industrialized economies in terms of diverse equity stakes in foreign affiliates, the unique attributes of BGs and international market distances’ relationship with both the operations and the expansion opportunities of BGs.
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Bellamine, Aouatef, Tram N. Q. Pham, Jaspreet Jain, Jacob Wilson, Kazim Sahin, Frederic Dallaire, Nabil G. Seidah, Shane Durkee, Katarina Radošević, and Éric A. Cohen. "L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection." Nutrients 13, no. 4 (April 14, 2021): 1297. http://dx.doi.org/10.3390/nu13041297.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.
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Soeharto, Dyah Nurnaningtyas. "Kekuatan Politik & Hukum PT Freeport Indonesia atas Kasus Pemblokiran Jaminan Kesehatan Pekerja Tahun 2018." Politeia: Jurnal Ilmu Politik 13, no. 2 (July 19, 2021): 61–75. http://dx.doi.org/10.32734/politeia.v13i2.6189.
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Abstrak Perusahaan multinasional di negara berkembang menciptakan hubungan ketergantungan. Secara ekonomi, korporasi memainkan peran penting bagi perkembangan negara tuan rumah tetapi tidak jarang terjadi penyimpangan yang bersinggungan dengan isu hak asasi manusia. Ketergantungan negara tuan rumah memberikan peluang bagi perusahaan untuk mendapatkan keuntungan ekonomi dan politik yang terakumulasi menjadi kekuatan perusahaan. Ada dua aspek kekuatan korporasi, yaitu aliansi politik bisnis dengan elitis dan peran pembangunan daerah. Kekuatan ini memudahkan korporasi untuk bebas dari jeratan tuntutan hukum. Penelitian ini berupaya menjawab upaya perusahaan terhadap gugatan negara penerima dan faktor-faktor yang mengindikasikan kekuatan korporasi dengan menggunakan indikator kekuatan korporasi menurut Ted Nace. Studi kasus yang penulis angkat adalah kasus PT Freeport Indonesia yang secara sepihak menerapkan kebijakan pencabutan status jaminan kesehatan BPJS pekerja. Namun dalam persidangan PTFI dinyatakan tidak bersalah. Penulis berpendapat bahwa lepasnya PTFI dari jerat hukum pelanggaran hak-hak pekerja karena adanya kedekatan dengan elitis politik dan dominasi pembangunan daerah yang membuat PTFI bebas dari tuntutan hukum. Kata Kunci : PT.Freeport Indonesia, BPJS, Kekuatan Korporasi, Hak Pekerja, Kebijakan Fulrough Abstrak Multinational corporations in developing countries creates dependency relations. Economically, corporations play an important role for the development of host countries but it is not uncommon for corporate irregularities to intersect with human rights issues. The dependency of host country provides opportunities for corporations to gain profits and political interests accumulated into corporate power. There are two aspects of corporate power, namely business political alliances with elitists and the role of regional development. This corporate power makes it easy for corporations to be free from ensnaring legal charges. This study seeks to answer the company's efforts against the recipient's state lawsuit and factors indicating the strength of the corporation by using indicators of corporate power by Ted Nace. The case study that the author raised was a case of PT Freeport Indonesia unilaterally implemented a furlough policy and terminated BPJS health insurance status of workers. However, in the trial PTFI was found not guilty. The author argues that PTFI's release from the legal snare of violations of workers' rights is due to proximity to political elitists and dominance in regional development that makes PTFI free from lawsuits. Keywords : PT.Freeport Indonesia,BPJS,Corporation Power, Worker Rights, Furlogh Policy
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Veltrop, M. H. A. M., H. Beekhuizen, and J. Thompson. "Bacterial Species- and Strain-Dependent Induction of Tissue Factor in Human Vascular Endothelial Cells." Infection and Immunity 67, no. 11 (November 1, 1999): 6130–38. http://dx.doi.org/10.1128/iai.67.11.6130-6138.1999.
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ABSTRACT A cardinal process in bacterial endocarditis (BE) is the activation of the clotting system and the formation of a fibrin clot on the inner surface of the heart, the so-called endocardial vegetation. The processes that lead to the activation of the clotting system on endothelial surfaces upon exposure to bacteria are largely unknown. In the present study, we investigated in an in vitro model whether infection of human endothelial cells (EC) with bacteria that are relevant to BE, such as Staphylococcus aureus,Streptococcus sanguis, and Staphylococcus epidermidis, leads to induction of tissue factor (TF)-dependent procoagulant activity (TFA) and whether this process is influenced by host factors, such as interleukin-1 (IL-1), that are produced in response to the bacteremia in vivo. The results show that S. aureus binds to and is internalized by EC, resulting in expression of TF mRNA and TF surface protein as well as generation of TFA within 4 to 8 h after infection. No TFA was found when EC were exposed to UV-irradiated S. aureus or bacterial cell wall fragments. S. sanguis and S. epidermidis, although also binding to EC, did not induce endothelial TFA. This indicates a species and strain dependency. EC also expressed TFA after exposure to IL-1. The enhanced TFA of EC after exposure to S. aureus was not prevented by IL-1 receptor antagonist, arguing against an auto- or paracrine contribution of endogenous IL-1. When IL-1 was applied together with bacteria, this had a synergistic effect on the induction of EC TFA. This was found in particular with S. aureus but also, although to a lesser degree, with S. sanguis and S. epidermidis. This influence of IL-1 on the species- and strain-dependent induction of EC TFA suggests that bacterial factors as well as host factors orchestrate the induction of coagulation in an early stage in the pathogenesis of endovascular disease, such as BE.
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Cippà, Pietro E., Federica Cugnata, Paolo Ferrari, Chiara Brombin, Lorenzo Ruinelli, Giorgia Bianchi, Nicola Beria, et al. "A data-driven approach to identify risk profiles and protective drugs in COVID-19." Proceedings of the National Academy of Sciences 118, no. 1 (December 10, 2020): e2016877118. http://dx.doi.org/10.1073/pnas.2016877118.
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As the COVID-19 pandemic is spreading around the world, increasing evidence highlights the role of cardiometabolic risk factors in determining the susceptibility to the disease. The fragmented data collected during the initial emergency limited the possibility of investigating the effect of highly correlated covariates and of modeling the interplay between risk factors and medication. The present study is based on comprehensive monitoring of 576 COVID-19 patients. Different statistical approaches were applied to gain a comprehensive insight in terms of both the identification of risk factors and the analysis of dependency structure among clinical and demographic characteristics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells by binding to the angiotensin-converting enzyme 2 (ACE2), but whether or not renin−angiotensin−aldosterone system inhibitors (RAASi) would be beneficial to COVID-19 cases remains controversial. The survival tree approach was applied to define a multilayer risk stratification and better profile patient survival with respect to drug regimens, showing a significant protective effect of RAASi with a reduced risk of in-hospital death. Bayesian networks were estimated, to uncover complex interrelationships and confounding effects. The results confirmed the role of RAASi in reducing the risk of death in COVID-19 patients. De novo treatment with RAASi in patients hospitalized with COVID-19 should be prospectively investigated in a randomized controlled trial to ascertain the extent of risk reduction for in-hospital death in COVID-19.
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Chaloner, Thomas M., Helen N. Fones, Varun Varma, Daniel P. Bebber, and Sarah J. Gurr. "A new mechanistic model of weather-dependent Septoria tritici blotch disease risk." Philosophical Transactions of the Royal Society B: Biological Sciences 374, no. 1775 (May 6, 2019): 20180266. http://dx.doi.org/10.1098/rstb.2018.0266.
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We present a new mechanistic model for predicting Septoria tritici blotch (STB) disease, parameterized with experimentally derived data for temperature- and wetness-dependent germination, growth and death of the causal agent, Zymoseptoria tritici . The output of this model (A) was compared with observed disease data for UK wheat over the period 2002–2016. In addition, we compared the output of a second model (B), in which experimentally derived parameters were replaced by a modified version of a published Z. tritici thermal performance equation, with the same observed disease data. Neither model predicted observed annual disease, but model A was able to differentiate UK regions with differing average disease risks over the entire period. The greatest limitations of both models are: broad spatial resolution of the climate data, and lack of host parameters. Model B is further limited by its lack of explicitly defined pathogen death, leading to a cumulative overestimation of disease over the course of the growing season. Comparison of models A and B demonstrates the importance of accounting for the temperature-dependency of pathogen processes important in the initiation and progression of disease. However, effective modelling of STB will probably require similar experimentally derived parameters for host and environmental factors, completing the disease triangle. This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
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Li, Jianhong, Ekkehard Werner, Manfred Hergenhahn, Rémy Poirey, Zuyu Luo, Jean Rommelaere, and Jean-Claude Jauniaux. "Expression Profiling of Human Hepatoma Cells Reveals Global Repression of Genes Involved in Cell Proliferation, Growth, and Apoptosis upon Infection with Parvovirus H-1." Journal of Virology 79, no. 4 (February 15, 2005): 2274–86. http://dx.doi.org/10.1128/jvi.79.4.2274-2286.2005.
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ABSTRACT Autonomous parvoviruses are characterized by their stringent dependency on host cell S phase and their cytopathic effects on neoplastic cells. To better understand the interactions between the virus and its host cell, we used oligonucleotide arrays that carry more than 19,000 unique human gene sequences to profile the gene expression of the human hepatocellular carcinoma cell line QGY-7703 at two time points after parvovirus H-1 infection. At the 6-h time point, a single gene was differentially expressed with a >2.5-fold change. At 12 h, 105 distinct genes were differentially expressed in virus-infected cells compared to mock-treated cells, with 93% of these genes being down-regulated. These repressed genes clustered mainly into classes involved in transcriptional regulation, signal transduction, immune and stress response, and apoptosis, as exemplified by genes encoding the transcription factors Myc, Jun, Fos, Ids, and CEBPs. Quantitative real-time reverse transcription-PCR analysis on selected genes validated the array data and allowed the changes in cellular gene expression to be correlated with the accumulation of viral transcripts and NS1 protein. Western blot analysis of several cellular proteins supported the array results and substantiated the evidence given by these and other data to suggest that the H-1 virus kills QGY-7703 cells by a nonapoptotic process. The promoter regions of most of the differentially expressed genes analyzed fail to harbor any motif for sequence-specific binding of NS1, suggesting that direct binding of NS1 to cellular promoters may not participate in the modulation of cellular gene expression in H-1 virus-infected cells.
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Montoya, Vanessa R., Trine M. Ready, Abby Felton, Sydney R. Fine, Molly OhAinle, and Michael Emerman. "A Virus-Packageable CRISPR System Identifies Host Dependency Factors Co-Opted by Multiple HIV-1 Strains." mBio, February 6, 2023. http://dx.doi.org/10.1128/mbio.00009-23.
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With a small genome of ~9.2 kb that encodes 14 major proteins, HIV must hijack host cellular machinery to successfully establish infection. These host proteins necessary for HIV replication are called “dependency factors.” Whole-genome, and then targeted screens were done to try to comprehensively identify all dependency factors acting throughout the HIV replication cycle.
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Yin, Peiqi, Xia Jian, Yihan Liu, Yuwen Liu, Lu Lv, Haoran Cui, and Leiliang Zhang. "Elucidating cellular interactome of chikungunya virus identifies host dependency factors." Virologica Sinica, May 2023. http://dx.doi.org/10.1016/j.virs.2023.05.007.
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Farley, Scotland E., Jennifer E. Kyle, Hans C. Leier, Lisa M. Bramer, Jules B. Weinstein, Timothy A. Bates, Joon-Yong Lee, Thomas O. Metz, Carsten Schultz, and Fikadu G. Tafesse. "A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants." Nature Communications 13, no. 1 (June 17, 2022). http://dx.doi.org/10.1038/s41467-022-31097-7.
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AbstractA comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We find that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.
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Brugier, Alexis, Mohamed Lamine Hafirrassou, Marie Pourcelot, Morgane Baldaccini, Vasiliya Kril, Laurine Couture, Beate M. Kümmerer, et al. "RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication." Journal of Virology 96, no. 7 (April 13, 2022). http://dx.doi.org/10.1128/jvi.01962-21.
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We recently identified the scaffolding RACK1 protein as an important host-dependency factor for dengue virus (DENV), a positive-stranded RNA virus responsible for the most prevalent mosquito-borne viral disease worldwide. Here, we have performed the first RACK1 interactome in human cells and identified Vigilin and SERBP1 as DENV host-dependency factors.
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Fu, Chen, Shiping Yang, Xiaodi Yang, Xianyi Lian, Yan Huang, Xiaobao Dong, and Ziding Zhang. "Human Gene Functional Network-Informed Prediction of HIV-1 Host Dependency Factors." mSystems 5, no. 6 (November 3, 2020). http://dx.doi.org/10.1128/msystems.00960-20.
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ABSTRACT Human immunodeficiency virus type 1 (HIV-1) depends on a class of host proteins called host dependency factors (HDFs) to facilitate its infection. So far experimental efforts have detected a certain number of HDFs, but the gene inventory of HIV-1 HDFs remains incomplete. Here, we implemented an existing network-based gene discovery strategy to predict HIV-1 HDFs. First, an encoding scheme based on a publicly available human tissue-specific gene functional network (GIANT; http://giant.princeton.edu/) was designed to convert each human gene into a 25,825-dimensional feature vector. Then, a random forest-based predictive model was trained on a data set containing 868 known HDFs and 1,736 non-HDFs. Through 5-fold cross-validation, an independent test, and comparison with one existing method, the proposed prediction method consistently revealed accurate and competitive performance. The highlight of our method should be ascribed to the introduction of the GIANT encoding scheme, which contains rich information regarding gene interactions. By merging known HDFs and genome-wide HDF prediction results, network analysis was conducted to catch the common patterns of HDFs in the context of the GIANT network. Interestingly, HDFs reveal significantly lower betweenness than HIV-1-interacting human proteins (i.e., HIV targets). In the meantime, the functional roles of HDFs were also examined by mapping all the HDF candidates into human protein complexes. Especially, we observed the frequent co-occurrence of HDFs and HIV targets at the protein complex level. Collectively, we hope the proposed prediction method not only can accelerate the HDF identification and antiviral drug target discovery, but also can provide some mechanistic insights into human-virus relationships. IMPORTANCE Identification of HIV-1 HDFs remains a crucial step to understand the complicated relationships between human and HIV-1. To complement the experimental identification of HDFs, we have implemented an existing network-based gene discovery strategy to predict HDFs from the human genome. The core idea of the proposed method is that the rich information deposited in host gene functional networks can be effectively utilized to infer the potential HDFs. We hope the proposed prediction method could further guide hypothesis-driven experimental efforts to interrogate human–HIV-1 relationships and provide new hints for the development of antiviral drugs to combat HIV-1 infection.