bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the phycosphere of Emiliania huxleyi: from bloom dynamics to microbiome assembly experiments
Authors: Câmara dos Reis Mariana , Romac Sarah , Le Gall Florence , Marie Dominique , Frada Miguel J. , Koplovitz Gil , Cariou Thierry , Henry Nicolas , de Vargas Colomban , Jeanthon Christian 
Published: February 2022

AbstractCoccolithophores have global ecological and biogeochemical significance as the most important calcifying marine phytoplankton group. The structure and selection of prokaryotic communities associated with the most abundant coccolithophore and bloom-forming species, Emiliania huxleyi, are still poorly known. In this study, we assessed the diversity of bacterial communities associated with an E. huxleyi bloom in the Celtic Sea, exposed axenic E. huxleyi cultures to prokaryotic communities derived from bloom and non-bloom conditions and followed the dynamics of their microbiome composition over one year. Bloom-associated prokaryotic communities were dominated by SAR11, Marine group II Euryarchaeota, Rhodobacterales and contained substantial proportions of known indicators of phytoplankton bloom demises such as Flavobacteriaceae and Pseudoalteromonadaceae. Taxonomic richness of replicated co-cultures resulting from natural communities with axenic E. huxleyi rapidly shifted and then stabilized over time, presumably by ecological selection favoring more beneficial populations. Recruited microbiomes from the environment were consistently dependent on the composition of the initial bacterioplankton community. Phycosphere-associated communities derived from the E. huxleyi bloom depth were highly similar to one another, suggesting deterministic processes, whereas cultures from non-bloom conditions show an effect of both deterministic processes and stochasticity. Overall, this work sheds new light on the importance of the initial inoculum composition in microbiome recruitment and elucidates the temporal dynamics of its composition and long-term stability.
A phospholipase assay screen identifies synergistic inhibitors of the P. aeruginosa toxin ExoU
Authors: Foulkes Daniel M. , McLean Keri , Hermann Anne , Johnson James , Winstanley Craig , Berry Neil , Fernig David G. , Kaye Stephen B. 
Published: February 2022

AbstractThe opportunistic pathogen Pseudomonas aeruginosa is a leading cause of disability and mortality worldwide and the World Health Organisation has listed it with the highest priority for the need of new therapies. P. aeruginosa strains that express ExoU are implicated in the worst clinical outcomes. ExoU is phospholipase that is secreted by P. aeruginosa directly into the cytoplasm of target host cells, where its catalytic activity, directed towards plasma membranes, causes rapid cell lysis. Inhibition of ExoU may be a novel strategy to combat acutely cytotoxic ExoU expressing P. aeruginosa infections. Using an in vitro phospholipase assay, we performed a high throughput screen to identify compounds that might be repurposed as therapeutic ExoU inhibitors. We discovered a panel of compounds that appeared to inhibit ExoU through distinct mechanisms. Compound C prevented ExoU membrane localisation in HEK293T cells and caused colocalization with lysosomes, whereas compound D prevented PIP2 dependent oligomerisation of ExoU in vitro suggestive of synergistic action. Indeed, the concentrations required by compounds C and D to inhibit in vitro ExoU catalytic activity, when used in combination, was in the nanomolar region. In corneal scratch and infection assays, these compounds reduced ExoU mediated cytotoxicity, as assessed by fluorescence microscopy and lactate dehydrogenase release assays.
Visual and auditory cortices represent acoustic speech-related information during silent lip reading
Authors: Bröhl Felix , Keitel Anne , Kayser Christoph 
Published: February 2022

AbstractSpeech is an intrinsically multisensory signal and seeing the speaker’s lips forms a cornerstone of communication in acoustically impoverished environments. Still, it remains unclear how the brain exploits visual speech for comprehension and previous work debated whether lip signals are mainly processed along the auditory pathways or whether the visual system directly implements speech-related processes. To probe this question, we systematically characterized dynamic representations of multiple acoustic and visual speech-derived features in source localized MEG recordings that were obtained while participants listened to speech or viewed silent speech. Using a mutual-information framework we provide a comprehensive assessment of how well temporal and occipital cortices reflect the physically presented signals and speech-related features that were physically absent but may still be critical for comprehension. Our results demonstrate that both cortices are capable of a functionally specific form of multisensory restoration: during lip reading both reflect unheard acoustic features, with occipital regions emphasizing spectral information and temporal regions emphasizing the speech envelope. Importantly, the degree of envelope restoration was predictive of lip reading performance. These findings suggest that when seeing the speaker’s lips the brain engages both visual and auditory pathways to support comprehension by exploiting multisensory correspondences between lip movements and spectro-temporal acoustic cues.HighlightsVisual and auditory cortex represent unheard acoustic information during lip readingAuditory cortex emphasizes the acoustic envelopeVisual cortex emphasizes a pitch signatureTracking of unheard features in auditory cortex is associated with behavior
Proteasomal downregulation of the pro-apoptotic MST2 pathway contributes to BRAF inhibitor resistance in melanoma
Authors: Romano David , García-Gutiérrez Lucia , Duffy David J. , Flaherty Keith T. , Frederick Dennie T. , Kolch Walter , Matallanas David 
Published: February 2022

AbstractThe RAS-RAF-MEK-ERK pathway is hyperactivated in almost all malignant melanomas, and mutations in BRAF or NRAS account for most of these cases. BRAF inhibitors are highly efficient for treating patients with BRAFV600E mutations, but tumours frequently acquire resistance within a few months. Multiple resistance mechanisms have been identified, due to mutations or network adaptations that revive ERK signalling. We have previously shown that RAF proteins inhibit the MST2 proapoptotic pathway in a kinase independent fashion. Here, we have investigated the role of the MST2 pathway in mediating resistance to BRAF inhibitors. We show that the BRAFV600E mutant protein, but not the wildtype BRAF protein, strongly binds to MST2 and inhibits MST2 pro-apoptotic signalling. Downregulation of MST2 reduces BRAF inhibitor induced apoptosis. In BRAF inhibitor resistant cell lines MST2 pathway proteins are downregulated by ubiquitination and subsequent proteasomal degradation rendering cells refractory to MST2 pathway induced apoptosis. Restoration of apoptosis can be achieved by increasing MST2 pathway protein expression using proteasome inhibitors. In summary, we show that the MST2 pathway plays a role in the acquisition of BRAF inhibitor resistance in melanoma.
Reactive astrocytes transduce blood-brain barrier dysfunction through a TNFα-STAT3 signaling axis and secretion of alpha 1-antichymotrypsin
Authors: Kim Hyosung , Leng Kun , Park Jinhee , Sorets Alexander G. , Kim Suil , Shostak Alena , Sturgeon Sarah M. , Neal Emma H. , McMahon Douglas G. , Schrag Matthew S. , Kampmann Martin , Lippmann Ethan S. 
Published: February 2022

AbstractAstrocytes are critical components of the neurovascular unit that support blood-brain barrier (BBB) function in brain microvascular endothelial cells (BMECs). Transformation of astrocytes to a reactive state in response to injury and disease can be protective or harmful to BBB function, but the underlying mechanisms for these effects remain mostly unclear. Using a human induced pluripotent stem cell (iPSC)-derived coculture model of BMEC-like cells and astrocytes, we found that tumor necrosis factor alpha (TNFα) transitions astrocytes to an inflammatory reactive state through activated STAT3 signaling, whereby the resultant astrocytes disrupt passive BBB function and induce vascular cell adhesion molecule 1 (VCAM-1) expression in the BMEC-like cells. These associations between inflammatory reactive astrocytes, STAT3 activation, and vascular VCAM-1 expression were corroborated in human postmortem tissue. Bioinformatic analyses coupled with CRISPR interference techniques in the iPSC model revealed that inflammatory reactive astrocytes transduce BBB disruption in part through SERPINA3, which encodes alpha 1-antichymotrypsin (α1ACT), a secreted serine protease inhibitor associated with aging, neuroinflammation, and Alzheimer’s disease. In murine ex vivo cortical explant cultures, shRNA-mediated silencing of Serpina3n in astrocytes reduced vascular VCAM-1 expression after TNFα challenge. Further, direct treatment with recombinant Serpina3n in both ex vivo explant cultures and the brain in vivo (via intracerebroventricular injection into wild-type mice) was sufficient to induce vascular VCAM-1 expression and reduce tight junction integrity. Overall, our results define the TNFα-STAT3 signaling axis as a driver of an inflammatory reactive astrocyte subtype responsible for BBB dysfunction. Our results also identify α1ACT as an explicit mediator of BBB damage and suggest that inhibition of α1ACT expression or activity could represent a therapeutic avenue for reversing BBB deficits in aging and neurodegenerative disease.
Epstein-Barr virus latency programs dynamically sensitize B-cells to ferroptosis
Authors: Burton Eric M. , Voyer Jewel , Gewurz Benjamin E. 
Published: February 2022

AbstractEpstein-Barr virus (EBV) causes 200,000 cancers annually. Upon B-cell infection, EBV induces lipid metabolism to support B-cell proliferation. Yet, little is known about how latent EBV infection, or human B-cell stimulation more generally, alter sensitivity to ferroptosis, a non-apoptotic form of programmed cell death driven by iron-dependent lipid peroxidation and membrane damage. To gain insights, we analyzed lipid reactive oxygen species (ROS) levels and ferroptosis vulnerability in primary human CD19+ B-cells infected by EBV or stimulated by key B-cell receptors. Prior to the first mitosis, EBV-infected cells were exquisitely sensitive to blockade of glutathione biosynthesis, a phenomenon not observed with B-cell receptor stimulation. Subsequently, EBV-mediated Burkitt-like hyper-proliferation generated elevated levels of lipid ROS, which necessitated SLC7A11-mediated cystine import and glutathione peroxidase 4 (GPX4) activity to prevent ferroptosis. By comparison, B-cells were sensitized to ferroptosis induction by combinatorial CD40-ligand and interleukin-4 stimulation or anti-B-cell receptor and Toll-like receptor 9 stimulation upon GPX4 inhibition, but not with SLC7A11 blockade. EBV transforming B-cells became progressively resistant to ferroptosis induction upon switching to the latency III program and lymphoblastoid physiology. Similarly, latency I Burkitt cells were particularly vulnerable to blockade of SLC7A11 or GPX4 or cystine withdrawal, while latency III Burkitt and lymphoblastoid cells were comparatively resistant. The selenocysteine biosynthesis kinase PSTK was newly implicated as a cellular target for ferroptosis induction including in Burkitt cells, likely due to roles in GPX4 biosynthesis. These results highlight ferroptosis as an intriguing therapeutic target for the prevention or treatment of particular EBV-driven B-cell malignancies.SignificanceEBV contributes to B-cell Burkitt and post-transplant lymphoproliferative disease (PTLD). EBV transforming programs activate lipid metabolism to convert B-cells into immortalized lymphoblastoid cell lines (LCL), a PTLD model. We found that stages of EBV transformation generate lipid reactive oxygen species (ROS) byproducts to varying degrees, and that a Burkitt-like phase of B-cell outgrowth is dependent on lipid ROS detoxification by glutathione peroxidase 4 and its cofactor glutathione. Perturbation of this redox defense in early stages of B-cell transformation or in Burkitt cells triggered ferroptosis, a programmed cell death pathway. LCLs were less dependent on this defense, a distinction tied to EBV latency programs. This highlights ferroptosis induction as a novel therapeutic approach for prevention or treatment of EBV+ lymphomas.
Zebrafish fin regeneration requires generic and regeneration-specific responses of osteoblasts to trauma
Authors: Sehring Ivonne , Haffner-Luntzer Melanie , Ignatius Anita , Huber-Lang Markus , Weidinger Gilbert 
Published: February 2022

AbstractSuccessful regeneration requires the coordinated execution of multiple cellular responses to injury. In amputated zebrafish fins, mature osteoblasts dedifferentiate, migrate towards the injury and form proliferative osteogenic blastema cells. We show that osteoblast migration is preceded by cell elongation and alignment along the proximodistal axis, which require actomyosin, but not microtubule turnover. Surprisingly, osteoblast dedifferentiation and migration can be uncoupled. Using pharmacological and genetic interventions, we found that NF-κB and retinoic acid signalling regulate dedifferentiation without affecting migration, while the complement system and actomyosin dynamics are required for migration but not dedifferentiation. Furthermore, by removing bone at two locations within a fin ray, we established a trauma model containing two injury sites. We found that osteoblasts dedifferentiate at and migrate towards both sites, while accumulation of osteogenic progenitor cells and regenerative bone formation only occur at the distal-facing injury. Together, these data indicate that osteoblast dedifferentiation and migration represent generic injury responses that are differentially regulated and can occur independently of each other and of regenerative growth. Successful bone regeneration appears to require the coordinated execution of generic and regeneration-specific responses of osteoblast to trauma.Abstract Figure
Enablers for facilitating life cycle assessment: key stakeholder perspectives of Sri Lankan construction industry
Authors: Amarasinghe Isuri Anuradha , Hadiwattege Chandanie 
Published: February 2022

PurposeDespite the desire to improve the sustainability of the construction industry, Sri Lanka is still plagued by the low-level adoption of essential methods such as Life Cycle Assessment (LCA) in building and infrastructure delivery. It is indispensable to investigate enablers for facilitating LCA because identification of enablers is a crucial step in the implementation of LCA. This study aims to analyze internal and external enablers for facilitating LCA for the Sri Lankan construction industry from the perspective of five stakeholder categories (academia, government, construction industry, society and environmentalists) and also aims to develop strategies to strengthen the enablers.Design/methodology/approachAn explanatory research design was used. The five stakeholder categories identified above, whose contribution is essential for implementing LCA in Sri Lanka, were selected for data collection. A total of 20 semi-structured interviews were held representing each stakeholder category. The Repertory Grid Interview (RGI) technique was utilized and data analysis was performed using content analysis.FindingsThe results revealed that “ability to identify opportunities for environmental improvements as an extremely important internal enabler for all stakeholder categories” and “the positive growth in the country to achieve environmental sustainability”, “the availability of standardized LCA guides and handbooks” as extremely important external enablers for all stakeholder categories for facilitating LCA in the Sri Lankan construction industry. Further, strategies including making people aware of the LCA concept and development of the LCA database, etc. were proposed to strengthen the enablers.Practical implicationsKnowledge generated through this study would enable the abovementioned stakeholders to make informed decisions to promote the implementation of LCA in the Sri Lankan construction industry. Further, the results of this study have raised awareness of the issues that Sri Lanka will need to solve to expand the LCA applications.Originality/valueSo far, research on LCA has not looked into enablers that can facilitate the implementation of LCA in the Sri Lankan construction industry. This research provides a comprehensive view of the internal and external enablers for facilitating LCA from the perspective of five stakeholder categories and identifies enablers that led the abovementioned stakeholders to pursue the implementation of LCA in the Sri Lankan construction industry. The study also proposes strategies for strengthening the enablers.
Openness strategies and the success of international entrepreneurship
Authors: Gimenez-Fernandez Elena M. , Ferraris Alberto , Troise Ciro , Sandulli Francesco Domenico 
Published: February 2022

PurposeExternal knowledge is a key resource for the success and the survival of born global firms; however, existing models provide minimal evidence on how these firms should source this knowledge resource. Thus, the purpose of this research is to increase understanding on the impact of diverse knowledge search and knowledge formal protection in international new ventures (INVs).Design/methodology/approachThe study uses a quantitative methodology based on a sample of start-ups from the Spanish Community Innovation Survey data. Using ordinary least squares regressions on a 10-year period panel data, this research tests the moderator role of a heterogeneous base of international partners and formal knowledge appropriation strategy on the relationship between start-ups and their export performance.FindingsThe results show that compared to non-born global start-ups, born global firms benefit more from establishing relationships with a set of heterogeneous international partners. By contrast, all start-ups benefit from an extensive appropriation strategy if they establish such alliances with diverse international partners.Originality/valueThe study extends current theory on international entrepreneurship by providing a new theoretical framework for INVs of both the extensive use of formal mechanisms of knowledge protection and the access to heterogeneous and distant knowledge. This study has also several implications for knowledge management domain.
Do global factors drive the interconnectedness among green, Islamic and conventional financial markets?
Authors: Karim Sitara , Naeem Muhammad Abubakr 
Published: February 2022

PurposeThis study aims to examine the connectedness among green, Islamic and conventional financial markets from December 2008 to May 2021. Moreover, the impact of global factors on the connectedness of given financial markets is also observed.Design/methodology/approachThis study first employed the time-varying parameter vector autoregressions (TVP-VAR) technique to explore the connectedness of markets. Second, This study utilized the wavelet coherence analysis to test the time-frequency impact of global factors in terms of implied volatilities of stock, oil, gold, currency and bond on the connectedness across financial markets.FindingsThis study finds Islamic stocks, sustainability index and S&P500 composite index are the net transmitters, whereas Sukuk, commodity index, bond market, clean energy and green bonds are the net recipient of spillovers. Time-varying features of green, Islamic and conventional financial markets are evident in system-wide connectedness. This study further evidenced that global factors drive the connectedness of financial markets, particularly during stressful times.Practical implicationsThe findings of this study furnish significant implications for policymakers, regulatory authorities, investors, financial market participants and portfolio managers in terms of carefully assessing the unique characteristics offered by each financial market in terms of risk mitigation and diversifying the portfolios.Originality/valueUsing a portfolio of green, Islamic and conventional financial markets, the uniqueness of this study lies in the examination of the connectedness of these markets by deploying the TVP-VAR technique. In addition, wavelet analysis offers a significant contribution in terms of global factors driving the connectedness of green, Islamic and conventional markets.
Impact of coupling of technological innovation and standardisation on industrial development
Authors: Yang Jing , Shao Lushen , Jin Xiang , Zhou Lijun 
Published: February 2022

PurposeUsing the industrial data between 2000 and 2016, this study analysed the process of coupling and coordinated development of technological innovation and standardisation. Accordingly, the study considered the high-tech industry (five sub-sectors) in China as the research object.Design/methodology/approachBased on the summary of innovation and standardisation literature review, this study constructed a theoretical model of the influence of technological innovation and standardisation on industrial development from the perspective of the coupling system. Furthermore, the study employed multivariate linear regression analysis to explore coupling coordination relationships.FindingsThe study results revealed that high coupling coordination between technological innovation and standardisation is highly conducive to industrial development. Moreover, requirements for standardisation levels differ owing to different stages and characteristics in each segmented industry.Originality/valueThis study primarily contributes to the literature by using a bibliometrics tool to summarise related literature on innovation and standardisation and provides a new perspective of reviewing, and it also offers new evidence on the coupling coordination relationship between innovation and standardisation in the high-tech industry.
Communication and leadership in times of crisis: analyzing the cultural competency of US state governors during the vaccine administration phase of the COVID-19 pandemic
Authors: Lofaro Ryan J. , Sapat Alka 
Published: February 2022

PurposeThe purpose of this article is to analyze the common vaccine equity practices expressed by United States (US) governors in their COVID-19 press conferences—with a specific focus on equitable vaccine distribution and overcoming vaccine hesitancy—in order to provide an understanding of gubernatorial cultural competency during the vaccine administration phase of the pandemic.Design/methodology/approachThis article employs a qualitative content analysis of the COVID-19 press conferences held by US governors from November 1, 2020, to August 14, 2021, to inductively identify themes in socially equitable and culturally competent vaccine administration strategies and rhetoric.FindingsThe article finds that common strategies aimed at providing equitable access to vaccines and combating vaccine hesitancy in communities of color include utilizing data to target communities where vaccines are needed, meeting people where they are at by working with community leaders and organizations, addressing language concerns, educating skeptics and appealing to communitarian and familial values. The findings also show that US governors tended to embrace a general prioritization lens rather than focusing on the unique needs of communities of color, with scant attention paid to the historical instances of public health discrimination that have influenced vaccine hesitancy within such communities.Originality/valueThis article provides an understanding of the equitable and culturally competent messages and strategies conveyed by sub-national leaders during the vaccination phase of the COVID-19 pandemic.