bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming sustainable aquaculture by applying circularity principles
Authors: Chary Killian , van Riel Anne‐Jo , Muscat Abigail , Wilfart Aurélie , Harchaoui Souhil , Verdegem Marc , Filgueira Ramón , Troell Max , Henriksson Patrik J. G. , de Boer Imke J. M. , Wiegertjes Geert F. 
Published: September 2023

AbstractA circular economy is considered one way to reduce environmental impacts of human activities, by more efficient use of resources and recovery, resulting in less waste and emissions compared to linear take‐make‐dispose systems. Muscat et al. developed five ecological principles to guide biomass use towards a circular economy. A few studies have demonstrated environmental benefits of applying these principles to land‐based food systems, but to date, these principles have not been explored in aquaculture. The current study expands on these principles and provides a narrative review to (i) translate them to aquaculture, while identifying implications for the main species and production systems, and (ii) identify the main pathways to make aquaculture more circular. We show that the underlying concepts of the ‘safeguard’, ‘entropy’, and ‘recycle’ principles have been well researched and sometimes well implemented. In contrast, the ‘avoid’ and ‘prioritise’ principles have been explored much less; doing so would provide an opportunity to decrease environmental impacts of aquaculture at the food‐system level. One example is prioritising the production of species that contribute to food and nutrition security, have low environmental impacts and thinking at wider food system scale to avoid feed‐food competition in aquaculture. We identified six priorities that could make aquaculture more circular: (i) increase production and demand for the most essential species, (ii) decrease food loss and waste at farm and post‐harvest stages, (iii) support nutrient recycling practices at multiple scales, (iv) adapt aquafeed formulations, (v) inform consumers about benefits of species of low trophic levels and other environmentally friendly aquatic foods, and (vi) address urgent research gaps.
PPARγ regulates lipid metabolism and viability of sheep trophoblast cells
Authors: Hao Kexing , Liu Xiuxia , Chen Yan , Zeng Weibin , Chen Lei , Wang Jing , Hu Guangdong 
Published: September 2023

AbstractPeroxisome proliferator‐activated receptor γ (PPARγ) is highly expressed in trophoblast tissues in pregnancy during which the protein participates in diverse events, including embryo implantation and placental formation. However, little is known about the role of PPARγ in embryonic development. This study investigated the function of PPARγ in sheep trophoblast cells. The coding sequence of sheep PPARγ encoded 475 amino acids and included one synonymou mutation compared with the sheep reference sequence for PPARγ. The PPARγ protein was localized in the nucleus and cytoplasm of sheep trophoblasts. The relative expression of PPARγ was elevated in cells treated with rosiglitazone and reduced following administration of GW9662. Activation of PPARγ promoted cell proliferation and mobility, but inhibited apoptosis. In addition, stimulation of PPARγ promoted the expression of lipid metabolism‐related genes FABP4 and PLIN2. The expression of prostaglandin metabolism‐related genes PLA2G4A, PTGS2 and PTGES also was upregulated significantly in trophoblast cells when PPARγ was activated. In contrast, activation of PPARγ did not impact expression of the prostaglandin‐related genes PGFS and SLCO2A1. At the same time, activation of PPARγ activity increased the ratio of PGE2 to PGF2α. Furthermore, fluorescence labelling showed that the numbers of cell lipid droplets increased after stimulation of PPARγ activity, but decreased when PPARγ was inhibited. In conclusion, PPARγ is critical for the regulation of lipid metabolism and prostaglandin synthesis and secretion in sheep trophoblast cells and also has a potent effect on cell proliferation and viability.
Short‐term function and immune‐protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non‐human primates without systemic immune suppression: A pilot study
Authors: Sremac Marinko , Luo Hao , Deng Hongping , Parr Madeline F. E. , Hutcheson Jessica , Verde Pushkar S. , Alagpulinsa David A. , Kitzmann Jenna Miner , Papas Klearchos K. , Brauns Timothy , Markmann James F. , Lei Ji , Poznansky Mark C. 
Published: September 2023

AbstractReplacement of insulin‐producing pancreatic beta‐cells by islet transplantation offers a functional cure for type‐1 diabetes (T1D). We recently demonstrated that a clinical grade alginate micro‐encapsulant incorporating the immune‐repellent chemokine and pro‐survival factor CXCL12 could protect and sustain the integrity and function of autologous islets in healthy non‐human primates (NHPs) without systemic immune suppression. In this pilot study, we examined the impact of the CXCL12 micro encapsulant on the function and inflammatory and immune responses of xenogeneic islets transplanted into the omental tissue bilayer sac (OB; n = 4) and diabetic (n = 1) NHPs. Changes in the expression of cytokines after implantation were limited to 2–6‐fold changes in blood, most of which did not persist over the first 4 weeks after implantation. Flow cytometry of PBMCs following transplantation showed minimal changes in IFNγ or TNFα expression on xenoantigen‐specific CD4+ or CD8+ T cells compared to unstimulated cells, and these occurred mainly in the first 4 weeks. Microbeads were readily retrievable for assessment at day 90 and day 180 and at retrieval were without microscopic signs of degradation or foreign body responses (FBR). In vitro and immunohistochemistry studies of explanted microbeads indicated the presence of functional xenogeneic islets at day 30 post transplantation in all biopsied NHPs. These results from a small pilot study revealed that CXCL12‐microencapsulated xenogeneic islets abrogate inflammatory and adaptive immune responses to the xenograft. This work paves the way toward future larger scale studies of the transplantation of alginate microbeads with CXCL12 and porcine or human stem cell‐derived beta cells or allogeneic islets into diabetic NHPs without systemic immunosuppression.
Models of palliative care for under-served populations in high-income countries: a scoping review protocol
Authors: Dadich Ann , van der Kruk Shannen , Cornell Victoria , Nobes Karen , Gunn Kate , Eliott Jaklin , Laurence Caroline 
Published: September 2023

Objective:The objective of this scoping review is to describe models of palliative care for under-served populations in high-income countries, defined as adults of culturally and linguistically diverse communities, low socioeconomic status, and/or residing in rural areas.Introduction:Models of palliative care are processual, referring to the way palliative care services are delivered as people experience a condition, injury, or event. The aim of these models is to ensure people get the right care, at the right time, by the right team, in the right place. Evidence suggests there is a wide variety of models of palliative care, but what is not known is how these models can vary to meet the needs of under-served populations.Inclusion criteria:This scoping review will consider articles that focus on models of palliative care for under-served populations, irrespective of sex, age, or primary diagnosis.Methods:MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), Emcare (Ovid), CINAHL (EBSCOhost), and Scopus will be searched for articles, irrespective of language, published from 2014. Two independent reviewers will screen titles and abstracts, followed by a full-text review of potentially relevant articles. Discrepancies will be reconciled with another reviewer. Two independent reviewers will extract data from included articles using a data extraction tool developed for this review. Results will be tabulated and/or presented diagrammatically, as well as summarized to explicitly address the objective of the review.Review registration:Open Science Framework osf.io/x4ky3
The matrix protein of respiratory syncytial virus suppresses interferon signaling via RACK1 association
Authors: Cao Jingjing , Shi Menghan , Zhu Lina , Li Xiangzhi , Li Aiying , Wu Shwu-Yuan , Chiang Cheng-Ming , Zhang Youming 
Published: September 2023

ABSTRACT
Respiratory syncytial virus (RSV) is a frequent cause of respiratory illness among pediatric and elderly populations. The severity of the respiratory disease is determined, in part, by RSV virulence and the host immune response, especially type I interferon (IFN) production. Using proteomics for the identification of partner proteins associated with RSV-encoded matrix (M) protein in transiently M-expressed and RSV-infected cells, we identified many M-interacting proteins involved in diverse biological processes including cell stress and innate immune response, highlighting M protein as a novel antagonist of IFN-β potentially accounting for limited IFN production in RSV-infected epithelial cells. To clarify the M antagonistic mechanism, we focused on M-interacting receptor of activated C kinase 1 (RACK1), which is an adaptor protein and a negative regulator of IRF3/7. Knockdown of RACK1 with small-interfering RNA attenuated the M-suppressed IFN-β response leading to increased IFN-β production and reduced RSV genome replication, confirming RACK1 as a critical host factor for efficient RSV infection. Our finding unravels an immune-intervening effect of RSV M protein on IFN response and further identifies RACK1 as a promising target for antiviral therapy.

IMPORTANCE
Respiratory syncytial virus (RSV) matrix (M) protein is indispensable for virion assembly and release. It is localized to the nucleus during early infection to perturb host transcription. However, the function of RSV M protein in other cellular activities remains poorly understood. In this study, several interferon response-associated host factors, including RACK1, were identified by proteomic analysis as RSV M interactors. Knockdown of RACK1 attenuates RSV-restricted IFN signaling leading to enhanced host defense against RSV infection, unraveling a role of M protein in antagonizing IFN response via association with RACK1. Our study uncovers a previously unrecognized mechanism of immune evasion by RSV M protein and identifies RACK1 as a novel host factor recruited by RSV, highlighting RACK1 as a potential new target for RSV therapeutics development.
Effects on exocytosis by two HSV-1 mutants unable to block autophagy
Authors: Waisner Hope , Lasnier Sarah , Suma Sreenath Muraleedharan , Kalamvoki Maria 
Published: September 2023

ABSTRACT
Herpes simplex virus 1 (HSV-1) is a prominent human pathogen that manipulates host responses to support the infection. HSV-1 infection triggers an increased release of extracellular vesicles (EVs) through the CD63 biogenesis pathway that contains the DNA sensor STING and exerts an antiviral effect on recipient cells. However, it is currently unknown how different viral proteins influence EV production. The viral proteins ICP0 and ICP34.5 are important for blocking host responses, including autophagy. Considering that autophagy and exocytosis are interwoven processes regulating intercellular communication, we sought to determine changes in EV biogenesis after infection with a ΔICP0 and a ΔICP34.5 virus that displayed defects in blocking autophagy compared with wild-type virus. ΔICP34.5 virus induced a greater release of EVs as compared to HSV-1(F), whereas ΔICP0 virus did not. EVs released by ΔICP34.5-infected cells differ in origin from those released by HSV-1(F)-infected cells as they contained markers of microvesicles and apoptotic bodies, but lacked major tetraspanins (CD63 or CD81) or lysosomal membrane proteins. EVs released by ΔICP0-infected cells are generated through the CD63 biogenesis pathway activated by HSV-1(F) but displayed reduced amounts of cargo. EVs released by these mutant viruses triggered robust innate immunity gene expression in uninfected recipient cells that exceeded host responses due to infection by these viruses. Overall, we have characterized how infection with viruses unable to block autophagy affects EV biogenesis, and their effect on recipient cells.

IMPORTANCE
Pathogens often hijack extracellular vesicle (EV) biogenesis pathways for assembly, egress, and cell-to-cell spread. Herpes simplex virus 1 (HSV-1) infection stimulated EV biogenesis through a CD63 tetraspanin biogenesis pathway and these EVs activated antiviral responses in recipient cells restricting the infection. HSV-1 inhibits autophagy to evade the host, and increased CD63 exocytosis could be a coping mechanism, as CD63 is involved in both cargo delivery to lysosomes during autophagy and exocytosis. We analyzed exocytosis after infection with two HSV-1 mutants, a ΔICP34.5 and a ΔICP0, that could not inhibit autophagy. Unlike HSV-1(F), neither of these viruses stimulated increased EV biogenesis through the CD63 pathway. ΔICP34.5 stimulated production of microvesicles and apoptotic bodies that were CD63-negative, while ΔICP0 displayed an overall reduced production of EVs. These EVs activated innate immunity gene expression in recipient cells. Given the potential use of these mutants for therapeutic purposes, the immunomodulatory properties of EVs associated with them may be beneficial.
Direct interaction with the BRD4 carboxyl-terminal motif (CTM) and TopBP1 is required for human papillomavirus 16 E2 association with mitotic chromatin and plasmid segregation function
Authors: Prabhakar Apurva T. , James Claire D. , Fontan Christian T. , Otoa Raymonde , Wang Xu , Bristol Molly L. , Yeager Calvin , Hill Ronald D. , Dubey Aanchal , Wu Shwu-Yuan , Chiang Cheng-Ming , Morgan Iain M. 
Published: September 2023

ABSTRACT

During the human papillomavirus 16 (HPV16) life cycle, the E2 protein binds simultaneously to the viral genome and host chromatin throughout mitosis, ensuring viral genomes reside in daughter cell nuclei following cell division. Previously, we demonstrated that CK2 phosphorylation of E2 on serine 23 promotes interaction with TopBP1, and that this interaction is required for optimum E2 mitotic chromatin association and plasmid segregation function. Others have implicated BRD4 in mediating the plasmid segregation function of E2 and we have demonstrated that there is a TopBP1-BRD4 complex in the cell. We therefore further investigated the role of the E2-BRD4 interaction in mediating E2 association with mitotic chromatin and plasmid segregation function. Using a combination of immunofluorescence and our novel plasmid segregation assay in U2OS and N/Tert-1 cells stably expressing a variety of E2 mutants, we report that direct interaction with the BRD4 carboxyl-terminal motif (CTM) and TopBP1 is required for E2 association with mitotic chromatin and plasmid segregation. We also identify a novel TopBP1-mediated interaction between E2 and the BRD4 extra-terminal domain
in vivo
. In addition, we demonstrate for the first time that E2 plasmid segregation function occurs in human foreskin keratinocytes immortalized by HPV16. Overall, the results demonstrate that direct interaction with TopBP1 and the BRD4 CTM is required for E2 mitotic chromatin association and plasmid segregation function. Disruption of this complex offers therapeutic options for targeting segregation of viral genomes into daughter cells, potentially combating HPV16 infections and cancers that retain episomal genomes.

Importance
Human papillomavirus 16 (HPV16) is a causative agent in around 3%–4% of all human cancers, and currently, there are no anti-viral therapeutics available for combating this disease burden. In order to identify new therapeutic targets, we must increase our understanding of the HPV16 life cycle. Previously, we demonstrated that an interaction between E2 and the cellular protein TopBP1 mediates the plasmid segregation function of E2, allowing distribution of viral genomes into daughter nuclei following cell division. Here, we demonstrate that E2 interaction with an additional host protein, BRD4, is also essential for E2 segregation function, and that BRD4 exists in a complex with TopBP1. Overall, these results enhance our understanding of a critical part of the HPV16 life cycle and presents several therapeutic targets for disruption of the viral life cycle.
Independent loss events of a functional
tetherin
gene in galliform birds
Authors: Krchlíková Veronika , Lotke Rishikesh , Haußmann Isabell , Reinišová Markéta , Kučerová Dana , Pecnová Ľubomíra , Ungrová Lenka , Hejnar Jiří , Sauter Daniel , Elleder Daniel 
Published: September 2023

ABSTRACT

The restriction factor tetherin (bone marrow stromal cell antigen 2) is an interferon-inducible protein preventing the release of newly formed viral particles from infected cells. Tetherin displays antiviral activity against a broad range of enveloped viruses, including retroviruses. While tetherin orthologs have been identified in several mammalian species, little is known about its expression and activity in non-mammalian vertebrates, including birds. We have previously described antiviral activity of chicken (
Gallus gallus
) tetherin against the prototypical avian retrovirus avian sarcoma and leukosis virus (ASLV). Here, we report the loss of functional tetherin orthologs in several galliform birds, including turkey (
Meleagris gallopavo
) and Mikado pheasant (
Syrmaticus mikado
). In both species, the
tetherin
coding sequence acquired inactivating mutations, including an in-frame stop codon and frameshifting deletions. Similar to the chicken tetherin ortholog, reconstituted turkey and Mikado pheasant tetherins restricted ASLV and HIV-1 indicating antiviral activity of the ancestor protein. Previous work revealed the presence of the
TMCC(aT
) gene in close proximity to tetherin, encoding a protein with tetherin-like structure in multiple vertebrates. Intriguingly, ectopic overexpression of chicken and turkey TMCC(aT) proteins in human cells decreased total HIV-1 yield. In contrast to tetherin, however, TMCC(aT) did not specifically restrict virion release, suggesting distinct antiviral mechanisms. In line with this, IFNα stimulation did not reduce the release of ASLV particles from infected turkey cells. Overall, our data describe the loss of functional
tetherin
genes in several galliform species and identify an antiviral activity of the related TMCC(aT) protein that is mechanistically different from that of tetherin.

IMPORTANCE

Birds represent important hosts for numerous viruses, including zoonotic viruses and pathogens with the potential to cause major economic losses to the poultry industry. Viral replication and transmission can be inhibited or blocked by the action of antiviral restriction factors (RFs) encoded by the host. One well-characterized RF is tetherin, a protein that directly blocks the release of newly formed viral particles from infected cells. Here, we describe the evolutionary loss of a functional tetherin gene in two galliform birds, turkey (
Meleagris gallopavo
) and Mikado pheasant (
Syrmaticus mikado
). Moreover, we demonstrate that the structurally related protein TMCC(aT) exerts antiviral activity in several birds, albeit by a mechanism different from that of tetherin. The evolutionary scenario described here represents the first documented loss-of-tetherin cases in vertebrates.
A disintegrin and metalloproteinase domain 9 facilitates SARS-CoV-2 entry into cells with low ACE2 expression
Authors: Melano Ivonne , Cheng Wei-Chung , Kuo Li-Lan , Liu Yuag-Meng , Chou Yu Chi , Hung Mien-Chie , Lai Michael M. C. , Sher Yuh-Pyng , Su Wen-Chi 
Published: September 2023

ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the Coronavirus disease-19 (COVID-19) pandemic, utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor for virus infection. However, the expression pattern of ACE2 does not coincide with the tissue tropism of SARS-CoV-2, hinting that other host proteins might be involved in facilitating SARS-CoV-2 entry. To explore potential host factors for SARS-CoV-2 entry, we performed an arrayed shRNA screen in H1650 and HEK293T cells. Here, we identified a disintegrin and a metalloproteinase domain 9 (ADAM9) protein as an important host factor for SARS-CoV-2 entry. Our data showed that silencing ADAM9 reduced virus entry, while its overexpression promoted infection. The knockdown of ADAM9 decreased the infectivity of the variants of concern tested—B.1.1.7 (alpha), B.1.617.2 (delta), and B.1.1.529 (omicron). Furthermore, mechanistic studies indicated that ADAM9 is involved in the binding and endocytosis stages of SARS-CoV-2 entry. Through immunoprecipitation experiments, we demonstrated that ADAM9 binds to the S1 subunit of the SARS-CoV-2 Spike. Additionally, ADAM9 can interact with ACE2, and co-expression of both proteins markedly enhances virus infection. Moreover, the enzymatic activity of ADAM9 facilitates virus entry. Our study reveals an insight into the mechanism of SARS-CoV-2 virus entry and elucidates the role of ADAM9 in virus infection.

IMPORTANCE
COVID-19, an infectious respiratory disease caused by SARS-CoV-2, has greatly impacted global public health and the economy. Extensive vaccination efforts have been launched worldwide over the last couple of years. However, several variants of concern that reduce the efficacy of vaccines have kept emerging. Thereby, further understanding of the mechanism of SARS-CoV-2 entry is indispensable, which will allow the development of an effective antiviral strategy. Here, we identify a disintegrin and metalloproteinase domain 9 (ADAM9) protein as a co-factor of ACE2 important for SARS-CoV-2 entry, even for the variants of concern, and show that ADAM9 interacts with Spike to aid virus entry. This virus-host interaction could be exploited to develop novel therapeutics against COVID-19.
Nanotopography by chromatic confocal microscopy of the endothelium in Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy and healthy corneas
Authors: Vaitinadapoulé Hanielle , Poinard Sylvain , He Zhiguo , Pascale-Hamri Alina , Thomas Justin , Gain Philippe , Thuret Jean-Yves , Mascarelli Frédéric , Thuret Gilles 
Published: September 2023

AimTo investigate the interest of chromatic confocal microscopy (CCM) to characterise guttae in Fuchs endothelial corneal dystrophy (FECD).MethodsDescemet’s membranes (DM) were obtained during endothelial keratoplasty in patients with FECD and pseudophakic bullous keratopathy (PBK). They were compared with healthy samples obtained from body donation to science. Samples were fixed in 0.5% paraformaldehyde and flat mounted. Surface roughness of DMs was quantified using CCM and the AltiMap software that provided the maximum peak (Sp) and valley (Sv) heights, the mean square roughness (Rq) and the asymmetry coefficient (Ssk).ResultsThe physiological roughness of healthy samples was characterised by an Rqof 0.12±0.05 µm, which was two times rougher than in PBK (Rq=0.06±0.03 µm), but both were still flat with a symmetrical distribution between peaks and valleys (Sskclose to 0, npeaks=nvalleys), smaller than 1 µm. In FECD, the maximum peak height was 5.10±2.40 µm, up to 5.8 and 8.3 times higher than the control and PBK, respectively. The maximum valley depth was half than the peak (2.28±0.89 µm). The surface with guttae was very rough (Rq=0.45±0.14 µm) and the Ssk=1.84± 0.43 µm, greater than 0, confirms an asymmetric surface with high peaks and low valleys (npeaks>nvalleys). Moreover, the CCM provided quantitative parameters allowing to distinguish different types of guttae from different patients.ConclusionsCCM is an innovative approach to describe and quantify different morphologies of guttae. It could be useful to analyse the different stages of FECD and define subgroups of patients.