bluuebunny/crossref_metadata_2025_split huggingface dataset:
RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during CNS viral infection
Authors: Estevez Irving , Buckley Benjamin D. , Panzera Nicholas , Lindman Marissa , Chou Tsui-Wen , McCourt Micheal , Vaglio Brandon J. , Atkins Colm , Firestein Bonnie L. , Daniels Brian P. 
Published: April 2024

SummaryWhile recent work has identified roles for immune mediators in the regulation of neural activity, the capacity for cell intrinsic innate immune signaling within neurons to influence neurotransmission remains poorly understood. However, the existing evidence linking immune signaling with neuronal function suggests that modulation of neurotransmission may serve previously undefined roles in host protection during infection of the central nervous system. Here, we identify a specialized function for RIPK3, a kinase traditionally associated with necroptotic cell death, in preserving neuronal survival during neurotropic flavivirus infection through the suppression of excitatory neurotransmission. We show that RIPK3 coordinates transcriptomic changes in neurons that suppress neuronal glutamate signaling, thereby desensitizing neurons to excitotoxic cell death. These effects occur independently of the traditional functions of RIPK3 in promoting necroptosis and inflammatory transcription. Instead, RIPK3 promotes phosphorylation of the key neuronal regulatory kinase CaMKII, which in turn activates the transcription factor CREB to drive a neuroprotective transcriptional program and suppress deleterious glutamatergic signaling. These findings identify an unexpected function for a canonical cell death protein in promoting neuronal survival during viral infection through the modulation of neuronal activity, highlighting new mechanisms of neuroimmune crosstalk.
Unraveling the Molecular Landscape of Uterine Fibroids, Insights intoHMGA2and Stem Cell Involvement
Authors: Paul Emmanuel N. , Carpenter Tyler J. , Pavliscak Laura A. , Bennett Abigail Z. , Ochoa-Bernal Maria Ariadna , Fazleabas Asgerally T. , Teixeira Jose M. 
Published: April 2024

AbstractUterine fibroids are prevalent benign tumors in women that exhibit considerable heterogeneity in clinical presentation and molecular characteristics, necessitating a deeper understanding of their etiology and pathogenesis.HMGA2overexpression has been associated with fibroid development, yet its precise role remains elusive. Mutations in fibroids are mutually exclusive and largely clonal, suggesting that tumors originate from a single mutant cell. We explored a possible role forHMGA2overexpression in differentiated myometrial cells, hypothesizing its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development. Myometrial cells were immortalized and transduced with anHMGA2lentivirus to produce HMGA2hi cells.In vitrostem cell assays were conducted and RNA from HMGA2hi and control cells and fibroid-free myometrial and HMGA2 fibroid (HMGA2F) tissues were submitted for RNA-sequencing. HMGA2hi cells have enhanced self-renewal capacity, decreased proliferation, and have a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibit a stem cell-like signature and share transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways are observed in both HMGA2hi cells and HMGA2F. Our findings suggest that HMGA2 overexpression drives myometrial cells to dedifferentiate into a more plastic phenotype and underscore a pivotal role for HMGA2 in fibroid pathogenesis.
A strong priority effect in the assembly of a specialized insect-microbe symbiosis
Authors: Chen Jason Z. , Junker Anthony , Zheng Iris , Gerardo Nicole M. , Vega Nic M. 
Published: April 2024

AbstractMicrobial community assembly is determined in part by interactions between taxa that colonize ecological niches available within habitat patches. The outcomes of these interactions, and by extension the trajectory of community assembly, can display priority effects - dependency on the order in which taxa first occupy these niches. The underlying mechanisms of these phenomena vary from system to system and are often not well resolved.Here, we characterize priority effects in colonization of the squash bug (Anasa tristis) by bacterial symbionts from the genusCaballeronia, using pairs of strains that are known to strongly compete during host colonization, as well as strains that are isogenic and thus functionally identical. By introducing symbiont strains into individual bugs in a sequential manner, we show that within-host populations established by the first colonist are extremely resistant to invasion, regardless of strain identity and competitive interactions. By knocking down the population of an initial colonist with antibiotics, we further show that colonization success by the second symbiont is still diminished even when space in the symbiotic organ is available and physically accessible for colonization. We propose a paradigm in which resident symbionts exclude subsequent infections by manipulating the host environment, partially but not exclusively by eliciting tissue remodeling of the symbiont organ.ImportanceHost-associated microbial communities underpin critical ecosystem processes and human health, and their ability to do so is determined in turn by the various processes that shape their composition. While natural selection acts on competing genotypes and species during community assembly, the manner by which selection determines the trajectory of community assembly can differ depending on the sequence by which taxa establish within that community. We document this phenomenon, known as a priority effect, during experimental colonization of a North American insect pest, the squash bugAnasa tristis, by its betaproteobacterial symbionts in the genusCaballeronia. Our study demonstrates how stark, strain-level variation can emerge in specialized host-microbe symbioses simply through differences in the order by which strains colonize the host. Understanding the mechanistic drivers of community structure in host-associated microbiomes can highlight both pitfalls and opportunities for the engineering of these communities and their constituent taxa for societal benefit.
Interplay between particle size and microbial ecology in the gut microbiome
Authors: Letourneau Jeffrey , Carrion Verónica M , Jiang Sharon , Osborne Olivia W , Holmes Zachary C , Fox Aiden , Epstein Piper , Tan Chin Yee , Kirtley Michelle , Surana Neeraj K , David Lawrence A 
Published: April 2024

ABSTRACTPhysical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Surprisingly, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that mammalian and human gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally,ex vivoculture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion, and that the microbiomes of individuals vary in this capacity. These new insights also suggest FPS in humans to be governed by processes beyond those found in other mammals and emphasize the importance of gut microbiota in shaping their own abiotic environment.
Human polymerase theta helicase positions DNA microhomologies for double-strand break repair
Authors: Zerio Christopher J. , Bai Yonghong , Sosa-Alvarado Brian A. , Guzi Timothy , Lander Gabriel C. 
Published: April 2024

AbstractDNA double-strand breaks occur in all human cells on a daily basis and must be repaired with high fidelity to minimize genomic instability1. Deficiencies in high-fidelity DNA repair by homologous recombination lead to dependence on DNA polymerase theta, which identifies DNA microhomologies in 3’ single-stranded DNA overhangs and anneals them to initiate error-prone double-strand break repair. The resulting genomic instability is associated with numerous cancers, thereby making this polymerase an attractive therapeutic target2,3. However, despite the biomedical importance of polymerase theta, the molecular details of how it initiates DNA break repair remain unclear4,5. Here we present cryo-electron microscopy structures of the polymerase theta helicase domain bound to microhomology-containing DNA, revealing DNA-induced rearrangements of the helicase that enable DNA repair. Our structures show that DNA-bound helicase dimers facilitate a microhomology search that positions 3’ single-stranded DNA ends in proximity to align complementary base pairs and anneal DNA microhomology. We define the molecular determinants that enable the polymerase theta helicase domain to identify and pair DNA microhomologies to initiate mutagenic DNA repair, providing mechanistic insights into therapeutic targeting of these interactions.
The enhancement of electricity generation using cellulose based on ternary microbial consortium
Authors: Gao Shengchao , Mai Tingfang , Ding Yi , Wang Zhiwei , Fan Xinxin , Zhang Yue , Liu Gongwei , Liu Ying 
Published: April 2024

ABSTRACTCooperation between microorganisms is crucial to design an efficient inoculum for enhancing the electricity-producing ability of carboxymethyl cellulose (CMC) fed bioreactors. In the present study, the influence of microbial mutualistic interactions and electricity generation capability were investigated by designing several co-culture and ternary culture systems. It was found that a ternary culture system ofCellulomonasLsc-8,Bacillus subtilisC9 andGeobacter sulfurreducensPCA was used to efficiently convert cellulose into electricity. The maximum current density of 796 ± 30 µA·cm-2were achieved by the ternary culture, which were much higher than thatGeobacter sulfurreducensPCA using acetate and co-culture systems to utilize CMC in bioreactors, respectively. In this consortium,CellulomonasLsc-8, andBacillus subtilisC9 simultaneously digested CMC to produce acetate and secreted riboflavin as an electron shuttle;Geobacter sulfurreducensPCA utilized acetate to generate electricity. The introduction ofBacillus subtilisC9 further promoted the degradation of CMC and secreted more riboflavin to enhance electricity generation of the ternary culture. This work suggested that the synergistic interaction between interspecies in microbial consortia is emergent in designing specific community for achieving maximum power generation using CMC as substrate. This research shows new insight into the design of more efficient, stable, and robust microbial consortia applicable in waste treatment and power generation.IMPORTANCEMicrobial fuel cells (MFCs) may benefit from microbial consortia that efficiently convert carbon sources to electricity. A key challenge with this system is how to manage microbial community assembly to maximize electricity generation. Herein, we constructed and tested a three-species microbial consortium to enhance conversion of cellulose to electricity.CellulomonasLsc-8 andBacillus subtilisC9 efficiently converted cellulose to acetate (electron donor) and riboflavin (electron shuttle), which enabledGeobacter sulfurreducensto generate electricity. This study laid the foundation for design of more efficient, stable, and robust microbial consortia for waste treatment and energy applications.
Splenic red pulp macrophages eliminate the liver-resistantStreptococcus pneumoniaeduring bloodstream infection
Authors: Huang Yijia , Zhao Zhifeng , Li Kunpeng , Huang Xueting , Tian Xianbin , Meng Jingjing , Zhou Hongyu , Wu Jiamin , Dai Qionghai , Zhang Jing-Ren , An Haoran 
Published: April 2024

ABSTRACTThe spleen is well-known for defense against invasive infections of encapsulated bacteria, particularlyStreptococcus pneumoniae(pneumococcus). However, the precise mechanism of the splenic anti-bacterial immunity remains elusive. Here we report that red pulp (RP) macrophages execute the splenic defense againstS. pneumoniaein mice, with the help of natural antibodies (nAbs) and complement system. The spleen slowly but substantially cleared encapsulated pneumococci from the bloodstream in the early phase of blood infection, especially the serotypes that resist to liver filtration. Among splenic macrophage subpopulations, only the lack of RP macrophages led to the complete loss of the splenic immunity. Intravital microscopy detected direct capture and phagocytic killing of circulating pneumococci by RP macrophages in the absence of neutrophils and inflammatory monocytes. Likewise, plasma nAbs targeting pneumococcal cell wall phosphocholine and complement protein C3 were essential for RP macrophage-mediated immune clearance. Our findings have thus uncovered the long-sought immune pathway against invasive pneumococcal infections in the spleen.Short summaryThe spleen plays a crucial role in defending against invasive infections caused byStreptococcus pneumoniae(pneumococcus) and other encapsulated bacteria in humans, but the mechanisms underlying this organ-specific immunity remain largely elusive. This study has revealed that the spleen eliminates pneumococci through a coordinated interplay among red pulp macrophages, serum nAbs targeting phosphocholine and the complement system.
High-resolution atlas of the developing human heart and the great vessels
Authors: Bayraktar Semih , Cranley James , Kanemaru Kazumasa , Knight-Schrijver Vincent , Colzani Maria , Davaapil Hongorzul , Lee Jonathan Chuo Min , Polanski Krzysztof , Richardson Laura , Semprich Claudia I. , Kapuge Rakeshlal , Dabrowska Monika , Mulas Ilaria , Perera Shani , Patel Minal , Ho Siew Yen , He Xiaoling , Tyser Richard , Gambardella Laure , Teichmann Sarah A. , Sinha Sanjay 
Published: April 2024

AbstractThe human heart and adjoining great vessels consist of multiple cell types vital for life, yet many remain uncharacterised molecularly during development. Here, we performed a high-resolution profiling of the heart and great vessels during the first and second trimesters, defining 63 cell types with distinct identity and location-specific signatures. We reveal previously unreported cell types, including for the pericardium and the ductus arteriosus. At the ventricles, we identified signatures involved in establishing the trabeculation-compaction and right-left axes of ventricular cardiomyocytes. At the vessels, we distinguished the constituents belonging to either coronary or great vessels. We confirmed our findings and revealed nuanced signatures with specific zonation patterns. Collectively, we provide a comprehensive human cardiac developmental atlas for enhanced understanding of function in health and disease.
The under-recognized dominance of magnetosome gene cluster-containing bacteria in oxygen-stratified freshwater ecosystems
Authors: Ji Runjia , Wan Juan , Goswami Pranami , Shen Jianxun , Pan Yonxin , Lin Wei 
Published: April 2024

AbstractMagnetotactic bacteria (MTB) capable of magnetosome organelle biomineralization and magnetotaxis are widespread in chemically stratified aquatic environments. Conventionally, it has long been considered that the overall abundance of MTB in microbiota is not very high and that Magnetococcia is the most frequently identified and predominant MTB members. However, the diversity and distribution of MTB in chemically stratified environments remain elusive due to the lack of large-scale systematic analyses. Here we conduct a comprehensive survey of genomes containing magnetosome gene clusters (MGCs), a group of genes responsible for magnetosome biomineralization and magnetotaxis, in 267 metagenomes from 38 oxygen-stratified freshwater environments. A total of 63 MGC-containing genomes belonging to eight bacterial phyla are reconstructed, including the newly identified Myxococcota. We discover an unexpectedly high relative abundance of putative MTB (up to 15.4% of metagenomic reads) in hypoxic and anoxic water columns, in which Deltaproteobacteria, rather than traditionally considered Magnetococcia, are the most ubiquitous and predominant MGC-containing bacteria. Our analysis reveals a depth-specific taxonomy and function of MGC-containing bacteria in stratified water columns shaped by physicochemical conditions. These findings underscore the unrecognized ecophysiological importance of MTB in freshwater ecosystems.
Design and synthesis of DNA origami nanostructures to control TNF receptor activation
Authors: Aba Göktuğ , Scheeren Ferenc A. , Sharp Thomas H. 
Published: April 2024

AbstractClustering of type II tumour necrosis factor (TNF) receptors (TNFRs) is essential for their activation, yet currently available drugs fail to activate signalling. Some strategies aim to cluster TNFR by using multivalent streptavidin or scaffolds based on dextran or graphene. However, these strategies do not allow for control of the valency or spatial organisation of the ligands, and consequently control of the TNFR activation is not optimal. DNA origami nanostructures allow nanometre-precise control of the spatial organization of molecules and complexes, with defined spacing, number and valency. Here, we demonstrate the design and characterisation of a DNA origami nanostructure that can be decorated with an engineered single-chain TNF-related apoptosis-inducing ligand (SC-TRAIL) complexes, which show increased cell killing compared to SC-TRAIL alone on Jurkat cells. The information in this chapter can be used as a basis to decorate DNA origami nanostructures with various proteins, complexes or other biomolecules.
Direct and indirect regulation of β-glucocerebrosidase by the transcription factorsUSF2andONECUT2
Authors: Ging Kathi , Frick Lukas , Schlachetzki Johannes , Armani Andrea , Zhu Yanping , Gilormini Pierre-André , Marques Ana , Dhingra Ashutosh , Böck Desirée , Deen Matthew , Chen Xi , Serdiuk Tetiana , Trevisan Chiara , Sellitto Stefano , Pisano Claudio , Glass Christopher K , Heutink Peter , Yin Jiang-An , Vocadlo David J , Aguzzi Adriano 
Published: April 2024

AbstractMutations in theGBAgene, which encodes the lysosomal enzyme β-glucocerebrosidase (GCase), are the most prevalent genetic susceptibility factor for Parkinson’s disease (PD). However, only approximately 20% of carriers develop the disease, suggesting the presence of genetic modifiers influencing the risk of developing PD in the presence ofGBAmutations. Here we screened 1,634 human transcription factors (TFs) for their effect on GCase activity in cell lysates of the human glioblastoma line LN-229, into which we introduced the pathogenicGBAL444P variant via adenine base editing. Using a novel arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity. Among these, activation ofMITFandTFECincreased lysosomal GCase activity in live cells, while activation ofONECUT2andUSF2decreased it. Conversely, ablating USF2 increasedGBAmRNA and led to enhanced levels of GCase protein and activity. While MITF, TFEC, and USF2 affectedGBAtranscription, ONECUT2 was found to control GCase trafficking by modulating the guanine exchange factors PLEKHG4 and PLEKHG4B. Hence, our study provides a systematic approach to identifying modulators of GCase activity, expands the transcriptional landscape ofGBAregulation, and deepens our understanding of the mechanisms involved in influencing GCase activity.
Proteomic Dynamics and Heat Stress Response inArabidopsisSeedlings
Authors: Fan Kai-Ting , Xu Yuan 
Published: May 2024

AbstractGlobal warming poses a grave threat to plant survival, adversely affecting growth and agricultural productivity. To develop thermotolerant crops, a profound comprehension of plant responses to heat stress at the molecular level is imperative. Leveraging a novel fusion of 15N-stable isotope labeling and the ProteinTurnover algorithm, we meticulously investigated proteome dynamics in Arabidopsis thaliana seedlings subjected to moderate heat stress (30°C). This innovative approach facilitated a comprehensive analysis of proteomic changes across diverse cellular fractions. Our study unveiled significant turnover rate alterations in 571 proteins, with a median increase of 1.4-fold, indicative of accelerated protein dynamics under heat stress. Notably, root soluble proteins exhibited more subdued changes, suggesting tissue-specific adaptations. Moreover, we observed noteworthy turnover variations in proteins associated with redox signaling, stress response, and metabolism, underscoring the complexity of the response network. Conversely, proteins involved in carbohydrate metabolism and mitochondrial ATP synthesis displayed minimal turnover changes, signifying their stability. This exhaustive examination sheds light on the proteomic adjustments of Arabidopsis seedlings to moderate heat stress, elucidating the delicate balance between proteome stability and adaptability. These findings significantly augment our understanding of plant thermal resilience and offer crucial insights for the development of crops endowed with enhanced thermotolerance.
Developing a decision model for risks associated with using social media in operation and supply chain management
Authors: Yildiz Çankaya Sibel , Can Saglam Yesim , Sezen Bulent 
Published: May 2024

PurposeWith the increasing use of social media in operation and supply chain management (OSCM), it is of great importance for managers to consider risks in advance and take precautions against the risks that might arise from social media usage among supply chain members. The aim of this research is to identify and evaluate the risks related to the use of social media in OSCM.Design/methodology/approachAn initial research of the literature revealed that there is no detailed risk categorization in this area. Current taxonomies on the business risks of social media usage were examined and integrated with classifications identified in a Delphi study. The authors empirically demonstrate how the determined risks are prioritized and how decision-makers may decide to manage risks effectively based on the analytical hierarchy process (AHP) method.FindingsThe findings of the research showed that reputation-associated risks such as criticism, language and loss of confidence should be prioritized over human, content and technical-associated risks.Originality/valueTo date, a comprehensive approach to determine risks arising from using social media in OSCM is missing. With the Delphi and AHP techniques, the authors provide a novel insight for managers to mitigate risks. The outcomes of this study may assist executives in achieving successful management of social media usage in OSCM. Besides, the proposed AHP model may provide guidelines and direction in this regard.