bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Silencing of Quorum-Sensing Activity ProtectsVibrio parahaemolyticusfrom Lysis by an Autoinducer-Detecting Phage
Authors: Duddy Olivia P. , Silpe Justin E. , Fei Chenyi , Bassler Bonnie L. 
Published: June 2023

ABSTRACTQuorum sensing (QS) is a chemical communication process that bacteria use to track population density and orchestrate collective behaviors. QS relies on the production, accumulation, and group-wide detection of extracellular signal molecules called autoinducers. Vibriophage 882 (phage VP882), a bacterial virus, encodes a homolog of theVibrioQS receptor-transcription factor, called VqmA, that monitors theVibrioQS autoinducer DPO. Phage VqmA binds DPO at high host-cell density and activates transcription of the phage geneqtip. Qtip, an antirepressor, launches the phage lysis program. Phage-encoded VqmA when bound to DPO also manipulates host QS by activating transcription of the host genevqmR. VqmR is a small RNA that controls downstream QS target genes. Here, we sequenceVibrio parahaemolyticusstrain O3:K6 882, the strain from which phage VP882 was initially isolated. The chromosomal region normally encodingvqmRandvqmAharbors a deletion encompassingvqmRand a portion of thevqmApromoter, inactivating that QS system. We discover thatV. parahaemolyticusstrain O3:K6 882 is also defective in its other QS systems, due to a mutation inluxO, encoding the central QS transcriptional regulator LuxO. Both thevqmR-vqmAandluxOmutations lockV. parahaemolyticusstrain O3:K6 882 into the low-cell density QS state. Reparation of the QS defects inV. parahaemolyticusstrain O3:K6 882 promotes activation of phage VP882 lytic gene expression and LuxO is primarily responsible for this effect. Phage VP882-infected QS-competentV. parahaemolyticusstrain O3:K6 882 cells lyse more rapidly and produce more viral particles than the QS-deficient parent strain. We propose that, inV. parahaemolyticusstrain O3:K6 882, constitutive maintenance of the low-cell density QS state suppresses the launch of the phage VP882 lytic cascade, thereby protecting the bacterial host from phage-mediated lysis.
A mutation-mediated host shift drives Avian paramyxovirus type 1 evolution
Authors: Chang Han , Feng Shengyong , Tang Xiaolu , Wang Ziming , Su Wen , Han Shuyi , Li Guanghao , Hu Bin , Jing Shengfan , Wang Bo , Xiang Chen , Xing Yanan , Wang Ye , Lu Jian , He Hongxuan 
Published: June 2023

AbstractPPMV-1, an antigenic variant of APMV-1, associated with specific pigeon host species. However, its evolutionary strategy and underlying drivers of host specificity remain unknown. In this study, we collect the outbreak data on a global scale to investigate its evolutionary dynamics, and provide an evidence-supported analysis the host shift of PPMV-1 from chickens to pigeons, and this shift is driven by the P protein. Our data indicated that the viruses in the United States and China have undergone convergent evolution. We find that three mutations of P protein, especially R163G, can significantly affect the adaptation of APMV-1 in pigeons. Mechanistically, sensor LSm14A inhibits the replication APMV-1 in DF-1 cells, and R163G substitutionon P protein increase LSm14A degradation. We propose the host shift drive the evolution of PPMV-1 and the underlying mechanism, offering new insights into the adaptive evolutionary process of the virus.
Broaden the application ofYarrowia Lipolyticasynthetic biology tools to explore the potential of Yarrowia clade biodiversity
Authors: Park Young-Kyoung , Rossignol Tristan 
Published: June 2023

AbstractYeasts have established themselves as prominent microbial cell factories, and the availability of synthetic biology tools has led to breakthroughs in the rapid development of industrial chassis strains. The selection of a suitable microbial host is critical in metabolic engineering applications, but it has been largely limited to a few well-defined strains. However, there is growing consideration for evaluating strain diversity, as a wide range of specific traits and phenotypes have been reported even within a specific yeast genus or species. Moreover, with the advent of synthetic biology tools, non-type strains can now be easily and swiftly reshaped.The yeastYarrowia lipolyticahas been extensively studied for various applications such as fuels, chemicals, and food. Additionally, other members of the Yarrowia clade are currently being evaluated for their industrial potential. In this study, we demonstrate the versatility of synthetic biology tools originally developed forY. lipolyticaby repurposing them for engineering other yeasts belonging to the Yarrowia clade. Leveraging the GoldenGateY. lipolyticatool kit, we successfully expressed fluorescent proteins as well as the carotenoid pathway in at least six members of the clade, serving as proof of concept.This research lays the foundation for conducting more comprehensive investigations into the under-characterized strains within the Yarrowia clade and exploring their potential applications in biotechnology.
Stable Structures or poly(A)-binding protein loading protect cellular and viral RNAs against ISG20-mediated decay
Authors: Louvat Camille , Deymier Séverine , Nguyen Xuan-Nhi , Labaronne Emmanuel , Noy Kodie , Cariou Marie , Corbin Antoine , Mateo Mathieu , Ricci Emiliano P. , Fiorini Francesca , Cimarelli Andrea 
Published: June 2023

ABSTRACTISG20 is an interferon-induced 3’-to-5’ RNA exonuclease that acts as a broad antiviral factor. At present, the features that expose RNA to ISG20 remain unclear, although recent studies have pointed to the modulatory role of epitranscriptomic modifications in the susceptibility of target RNAs to ISG20. These findings raise the question as to how cellular RNAs, on which these modifications are abundant, cope with ISG20. To obtain an unbiased perspective on this topic, we used RNAseq and biochemical assays to identify elements that regulate the behavior of RNAs against ISG20. The results we have obtained indicate that poly(A)-binding protein (PABP1) loading on the RNA 3’ tail provides a primal protection against ISG20, easily explaining the overall protection of cellular mRNAs observed by RNAseq. The second element we uncovered is provided by terminal stem-loop RNA structures, that have been associated to ISG20 protection before, but that we re-examine here systematically to define the stabilities that tilt the balance between resistance and susceptibility to ISG20. Given that these elements are present on cellular mRNAs, but can be co-opted by viruses as well, these results shed new light on the complex interplay that regulates the susceptibility of different classes of viruses against ISG20.
Enhanced fungal specificity andin vivotherapeutic efficacy of a C-22 modified FK520 analog againstC. neoformans
Authors: Rivera Angela , Lim Won Young , Park Eunchong , Dome Patrick A. , Hoy Michael J. , Spasojevic Ivan , Sun Sheng , Averette Anna Floyd , Pina-Oviedo Sergio , Juvvadi Praveen R. , Steinbach William J. , Ciofani Maria , Hong Jiyong , Heitman Joseph 
Published: June 2023

AbstractFungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections byCryptococcus neoformansare associated with high mortality, emphasizing the need for novel therapeutic options. Calcineurin is a protein phosphatase that mediates fungal stress responses, and calcineurin inhibition by the natural product FK506 blocksC. neoformansgrowth at 37°C. Calcineurin is also required for pathogenesis. However, because calcineurin is conserved in humans, and inhibition with FK506 results in immunosuppression, the use of FK506 as an anti-infective agent is precluded. We previously elucidated the structures of multiple fungal calcineurin-FK506-FKBP12 complexes and implicated the C-22 position on FK506 as a key point for differential modification of ligand inhibition of the mammalian versus fungal target proteins. Throughin vitroantifungal and immunosuppressive testing of FK520 (a natural analog of FK506) derivatives, we identified JH-FK-08 as a lead candidate for further antifungal development. JH-FK-08 exhibited significantly reduced immunosuppressive activity and both reduced fungal burden and prolonged survival of infected animals. JH-FK-08 exhibited additive activity in combination with fluconazolein vivo. These findings further advance calcineurin inhibition as an antifungal therapeutic approach.ImportanceFungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited and development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human host. With rising resistance to the current antifungal arsenal and an increasing at-risk population, there is an urgent need for the development of new antifungal compounds. The FK520 analogs described in this study display potent antifungal activity as a novel class of antifungals centered on modifying an existing orally-active FDA approved therapy. This research advances the development of much needed newer antifungal treatment options with novel mechanisms of action.
A structural competition involving WDR5 times circadian oscillations
Authors: Börgel Arne , Rawleigh Audrey , Conrady Marcel , Hof Florian , Ricci Kyra , Brown Steven , Wolf Eva 
Published: June 2023

AbstractIn the mammalian circadian clock, the transcription factor BMAL1/CLOCK cycles between an active state recruiting co-activators like MLL1, and repressed states associated with the clock proteins Period1/2 (PER1/2) and Cryptochrome1/2 (CRY1/2). The MLL1 complex component WDR5 was also found in a repressive PER complex, but the roles of WDR5-PER interactions are unknown. Here we show that WDR5 directly binds to the C-terminal CRY binding domain (CBD) regions of PER1 and PER2. PER2 binds WDR5 via a WDR5 binding (WBM) motif within the PER2/CRY interface, imposing a molecular choice between PER2/WDR5- and PER2/CRY complexes. PER1 predominantly binds WDR5 via a WDR5 interacting (WIN) motif outside the CBD and exhibits a 15-fold higher WDR5 affinity than PER2. Thereby PER1 can form trimeric PER1WIN/WDR5/RbBP5WBM- and PER1/WDR5/CRY complexes as potential transition states between activating MLL1WIN/WDR5/RbBP5WBM- and repressive PER/CRY complexes. Overexpressing WDR5 in mammalian cells increases the circadian amplitude, whereas a compound targeting the WIN motif binding site of WDR5 weakens PER1-WDR5 interactions and shortens the circadian oscillation period by 2 to 3 hours. Together, our studies uncover WDR5 as direct PER interaction partner at the interface between active- and repressed states of BMAL1/CLOCK and suggest a functional role of WDR5 and its WIN site interactions in the mammalian clock by both enhancing circadian oscillations and creating a temporal delay.
Functional characterization of helminth-associated Clostridiales reveals covariates of Treg differentiation
Authors: Sargsian Shushan , Lejeune Alannah , Ercelen Defne , Jin Wen-Bing , Varghese Alan , Loke P’ng , Lim Yvonne A. L. , Guo Chun-Jun , Cadwell Ken 
Published: June 2023

AbstractParasitic helminths influence the composition of the gut microbiome. However, the microbiomes of individuals living in helminth-endemic regions are understudied. The Orang Asli, an indigenous population in Malaysia with high burdens of the helminthTrichuris trichiura, displayed microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes previously shown to have immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted theTrichurislife cycle. Here, we further characterized the functional properties of these bacteria. Enzymatic and metabolomic profiling revealed a range of activities associated with metabolism and host response. Consistent with this finding, monocolonization of mice with individual isolates identified bacteria that were potent inducers of regulatory T cell (Treg) differentiation in the colon. Comparisons between variables revealed by these studies identified enzymatic properties correlated with Treg induction andTrichurisegg hatching. These results provide functional insights into the microbiotas of an understudied population.
A Connectome of the MaleDrosophilaVentral Nerve Cord
Authors: Takemura Shin-ya , Hayworth Kenneth J , Huang Gary B , Januszewski Michal , Lu Zhiyuan , Marin Elizabeth C , Preibisch Stephan , Xu C Shan , Bogovic John , Champion Andrew S , Cheong Han SJ , Costa Marta , Eichler Katharina , Katz William , Knecht Christopher , Li Feng , Morris Billy J , Ordish Christopher , Rivlin Patricia K , Schlegel Philipp , Shinomiya Kazunori , Stürner Tomke , Zhao Ting , Badalamente Griffin , Bailey Dennis , Brooks Paul , Canino Brandon S , Clements Jody , Cook Michael , Duclos Octave , Dunne Christopher R , Fairbanks Kelli , Fang Siqi , Finley-May Samantha , Francis Audrey , George Reed , Gkantia Marina , Harrington Kyle , Hopkins Gary Patrick , Hsu Joseph , Hubbard Philip M , Javier Alexandre , Kainmueller Dagmar , Korff Wyatt , Kovalyak Julie , Krzemiński Dominik , Lauchie Shirley A , Lohff Alanna , Maldonado Charli , Manley Emily A , Mooney Caroline , Neace Erika , Nichols Matthew , Ogundeyi Omotara , Okeoma Nneoma , Paterson Tyler , Phillips Elliott , Phillips Emily M , Ribeiro Caitlin , Ryan Sean M , Rymer Jon Thomson , Scott Anne K , Scott Ashley L , Shepherd David , Shinomiya Aya , Smith Claire , Smith Natalie , Suleiman Alia , Takemura Satoko , Talebi Iris , Tamimi Imaan FM , Trautman Eric T , Umayam Lowell , Walsh John J , Yang Tansy , Rubin Gerald M , Scheffer Louis K , Funke Jan , Saalfeld Stephan , Hess Harald F , Plaza Stephen M , Card Gwyneth M , Jefferis Gregory SXE , Berg Stuart 
Published: June 2023

AbstractAnimal behavior is principally expressed through neural control of muscles. Therefore understanding how the brain controls behavior requires mapping neuronal circuits all the way to motor neurons. We have previously established technology to collect large-volume electron microscopy data sets of neural tissue and fully reconstruct the morphology of the neurons and their chemical synaptic connections throughout the volume. Using these tools we generated a dense wiring diagram, or connectome, for a large portion of theDrosophilacentral brain. However, in most animals, including the fly, the majority of motor neurons are located outside the brain in a neural center closer to the body, i.e. the mammalian spinal cord or insect ventral nerve cord (VNC). In this paper, we extend our effort to map full neural circuits for behavior by generating a connectome of the VNC of a male fly.
An obligate intracellular bacterial pathogen forms a direct, interkingdom membrane contact site
Authors: Acevedo-Sánchez Yamilex , Woida Patrick J. , Kraemer Stephan , Lamason Rebecca L. 
Published: June 2023

ABSTRACTInterorganelle communication regulates cellular homeostasis through the formation of tightly-associated membrane contact sites1–3. Prior work has identified several ways that intracellular pathogens alter contacts between eukaryotic membranes4–6, but there is no existing evidence for contact sites spanning eukaryotic and prokaryotic membranes. Here, using a combination of live-cell microscopy and transmission and focused-ion-beam scanning electron microscopy, we demonstrate that the intracellular bacterial pathogenRickettsia parkeriforms a direct membrane contact site between its bacterial outer membrane and the rough endoplasmic reticulum (ER), with tethers that are approximately 55 nm apart. Depletion of the ER-specific tethers VAPA and VAPB reduced the frequency of rickettsia-ER contacts, suggesting these interactions mimic organelle-ER contacts. Overall, our findings illuminate a direct, interkingdom membrane contact site uniquely mediated by rickettsia that seems to mimic traditional host MCSs.
Cas4/1 dual nuclease activities enable prespacer maturation and directional integration in a type I-G CRISPR-Cas system
Authors: Dhingra Yukti , Sashital Dipali G. 
Published: June 2023

AbstractCRISPR-Cas adaptive immune systems uptake short ‘spacer’ sequences from foreign DNA and incorporate them into the host genome to serve as templates for crRNAs that guide interference against future infections. Adaptation in CRISPR systems is mediated by Cas1-Cas2 complexes that catalyze integration of prespacer substrates into the CRISPR array. Many DNA targeting systems also require Cas4 endonucleases for functional spacer acquisition. Cas4 selects prespacers containing a protospacer adjacent motif (PAM) and removes the PAM prior to integration, both of which are required to ensure host immunization. Cas1 has also been shown to function as a nuclease in some systems, but a role for this nuclease activity in adaptation has not been demonstrated. We identified a type I-G Cas4/1 fusion with a nucleolytically active Cas1 domain that can directly participate in prespacer processing. The Cas1 domain is both an integrase and a sequence-independent nuclease that cleaves the non-PAM end of a prespacer, generating optimal overhang lengths that enable integration at the leader side. The Cas4 domain sequence-specifically cleaves the PAM end of the prespacer, ensuring integration of the PAM end at the spacer side. The two domains have varying metal ion requirements. While Cas4 activity is Mn2+dependent, Cas1 preferentially uses Mg2+over Mn2+. The dual nuclease activity of Cas4/1 eliminates the need for additional factors in prespacer processing, making the adaptation module self-reliant for prespacer maturation and directional integration.
Bacterial mimicry of eukaryotic HECT ubiquitin ligation
Authors: Franklin Tyler G. , Brzovic Peter S. , Pruneda Jonathan N. 
Published: June 2023

ABSTRACTHECT E3 ubiquitin (Ub) ligases direct their modified substrates toward a range of cellular fates dictated by the specific form of monomeric or polymeric Ub (polyUb) signal that is attached. How polyUb specificity is achieved has been a longstanding mystery, despite extensive study ranging from yeast to human. Two outlying examples of bacterial “HECT-like” (bHECT) E3 ligases have been reported in the human pathogens EnterohemorrhagicEscherichia coliandSalmonellaTyphimurium, but what parallels can be drawn to eukaryotic HECT (eHECT) mechanism and specificity had not been explored. Here, we expanded the bHECT family and identified catalytically active,bona fideexamples in both human and plant pathogens. By determining structures for three bHECT complexes in their primed, Ub-loaded states, we resolved key details of the full bHECT Ub ligation mechanism. One structure provided the first glimpse of a HECT E3 ligase in the act of ligating polyUb, yielding a means to rewire the polyUb specificity of both bHECT and eHECT ligases. Through studying this evolutionarily distinct bHECT family, we have not only gained insight into the function of key bacterial virulence factors but also revealed fundamental principles underlying HECT-type Ub ligation.
Monocyte Adhesion and Transmigration Through Endothelium Following Cardiopulmonary Bypass Shearing is Mediated by IL-8 Signaling
Authors: Zhou Hao , Tu Lan N , Giachelli Cecilia , Nigam Vishal , Scatena Marta 
Published: June 2023

BackgroundThe use of cardiopulmonary bypass (CPB) can induce sterile systemic inflammation that contributes to morbidity and mortality, especially in children. Patients have been found to have increased expression of cytokines and transmigration of leukocytes during and after CPB. Previous work has demonstrated that the supraphysiologic shear stresses present during CPB are sufficient to induce proinflammatory behavior in non-adherent monocytes. The interactions between shear stimulated monocytes and vascular endothelial cells have not been well studied and have important translational implications.MethodsTo test the hypothesis that non-physiological shear stress experienced by monocytes during CPB affects the integrity and function of the endothelial monolayer via IL-8 signaling pathway, we have used an in vitro CPB model to study the interaction between THP-1 monocyte-like cells and human neonatal dermal microvascular endothelial cells (HNDMVECs). THP-1 cells were sheared in polyvinyl chloride (PVC) tubing at 2.1 Pa, twice of physiological shear stress, for 2 hours. Interactions between THP-1 cells and HNDMVECs were characterized after coculture.ResultsWe found that sheared THP-1 cells adhered to and transmigrated through the HNDMVEC monolayer more readily than static controls. When co-culturing, sheared THP-1 cells also disrupted in the VE-cadherin and led to reorganization of cytoskeletal F-actin of HNDMVECs. Treating HNDMVECs with IL-8 resulted in upregulation of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) while also increasing the adherence of non-sheared THP-1 cells. Preincubating HNDMVECs with Reparixin, an inhibitor of CXCR2/IL-8 receptor inhibited sheared THP-1 cell adhesion to the HNDMVECs.ConclusionsThese results suggested that IL-8 not only increases the endothelium permeability during monocyte migration, but also affects the initial adhesion of monocytes in a CPB setup. This study revealed a novel mechanism of post-CPB inflammation and will contribute to the development of targeted therapeutics to prevent and repair the damage to neonatal patients.HighlightsShear stress in a CPB-like environment promoted the adhesion and transmigration of monocytes to and through endothelial monolayer.Treating endothelial monolayer with sheared monocytes led to disruption of VE-cadherin and reorganization of F-actin.Interaction between sheared monocytes resulted in a significant increase of IL-8 release.Inhibiting IL-8 receptor prevented sheared monocyte adhesion, while IL-8 promoted naive monocyte adhesion.
How streamer channels influence luxury brand sales in live streaming commerce: an empirical study
Authors: Li Guoxin , Tang Peiwen , Feng Jiao 
Published: June 2023

PurposeThis study aims to understand how different levels of streamer channels influence luxury brand sales in live streaming commerce. This study also seeks to understand the conditions under which luxury brands may benefit more from different level streamer channels.Design/methodology/approachPanel data were collected from 17 international luxury brands on the Douyin live streaming platform in an 18 week period from August to December 2020 and analyzed by using a two-way fixed effects model.FindingsThe authors compared different mega-, macro- and micro-streamer channels within live streaming commerce and found that the densities of mega- and macro-streamer channels had significant positive impacts on luxury brand sales in live streaming commerce. Moreover, the effects of the density of streamer channel on luxury brand sales were moderated by such variables as product line breadth, product line depth, product type (star/non-star) and product price (high/low). The authors found that product line breadth and depth could reduce the positive impact of the densities of mega- and macro-streamer channels on luxury brand sales. For star products and high-priced products, the relationship between the density of mega-streamer channel and luxury brand sales was more likely to be observed than for non-star products and low-priced products. The relationship between the density of macro-streamer channel and luxury brand sales was more likely to be observed in low-priced products than in high-priced products.Originality/valueThe findings make important contributions to the literature in that the authors expand the influencer-brand fit theory by proposing a new model of effects of the densities of mega-, macro- and micro-streamer channels on sales performance across different luxury products to improve our understanding of the fit among influencers, brands and products. This helps luxury brands make basic decisions of “who sells” and “sells what” when engaging in live streaming commerce.