bluuebunny/crossref_metadata_2025_split huggingface dataset:
How does fertilization impact the wild blueberry microbiome ?
Authors: Morvan Simon , Paré Maxime C. , Lafond Jean , Hijri Mohamed 
Published: July 2023

AbstractWild blueberries production is regarded as less intensive than other agricultural systems, although several agricultural practices are commonly implemented to increase crop yields and to mitigate pets and pathogen attacks. Fertilization, organic or mineral, is used to increase soil nutrient availability and improve fruit yield. Wild blueberry plants are also known to depend on their microbiome to overcome the lack of nutrient availability in the soil and their symbiosis with ericoid mycorrhizal fungi is thought to be crucial in that regard. As fertilization can alter crop microbial communities, our study aimed to measure the impact of this practice in a wild blueberry setting, focusing on the bacterial and fungal communities found in the roots and rhizosphere ofVaccinium angustifoliumAit., both at the time of application and more than year later during the harvest season. Our study indicates that fertilization, whether mineral or organic, has a minimal effect on microbial communities. One year after application, fertilization does not seem to have a negative repercussion on the ericoid mycorrhizal (ErM) fungal community as no significant differences were observed in terms of relative abundance on known and putative ErM taxa between the control and the two fertilizer treatments. The fact that fertilization is applied at a low rate could explain this absence of effect on the microbial communities. However, longer-term studies are needed to ensure that repeated fertilization does not cause any shifts in microbial communities that could be detrimental to the wild blueberry nutrition.ImportanceThis study examines the impact of fertilization, whether organic or mineral, on microbial communities in the roots and rhizosphere of wild blueberry (Vaccinium angustifoliumAit.). both Fertilization is commonly used to enhance soil nutrient availability and improve fruit yield, but its effects on the plant’s microbiome, particularly on the ericoid mycorrhizal fungi (ErM), are not well understood. The samples were taken both during the pruning season, 3 months after the treatment, and one year later, during harvest season. The results suggest that fertilization has minimal impact on the microbial communities. One year after application, no significant differences were observed in the relative abundance of known and putative ErM taxa between the control group and the two fertilizer-treated groups. The low amount of fertilization applied could explain these results. However, longer-term research are needed to ensure that repeated fertilization does not lead to detrimental shifts in microbial communities affecting wild blueberry nutrition.
Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in Acute Viral Infections
Authors: Li Gong-Hua , Han Feifei , Luo Rong-Hua , Li Peng , Chang Chia-Jung , Xu Weihong , Long Xin-Yan , Huang Jing-Fei , Zheng Yong-Tang , Kong Qing-Peng , Xiao Wenzhong 
Published: July 2023

AbstractBackgroundHost response is critical to the onset, progression, and outcome of viral infections. Since viruses hijack the host cellular metabolism for their replications, we hypothesized that restoring host cell metabolism can efficiently reduce viral production.ResultsHere, we present a viral-host Metabolic Modeling (vhMM) method to systematically evaluate the disturbances in host metabolism in viral infection and computationally identify targets for modulation by integrating genome-wide precision metabolic modeling and cheminformatics. We applied vhMM to SARS-CoV-2 infections and identified consistent changes in host metabolism and gene and endogenous metabolite targets between the original SARS-COV-2 and different variants (Alpha, Delta, and Omicron). Among six compounds predicted for repurposing,methotrexate, cinnamaldehyde, anddeferipronewere testedin vitroand effective in inhibiting viral production with IC50 less than 4uM. Further, an analysis of real-world patient data showed that cinnamon usage significantly reduced the SARS-CoV-2 infection rate with an odds ratio of 0.65 [95%CI: 0.55∼0.75].ConclusionsThese results demonstrated that vhMM is an efficient method for predicting targets and drugs for viral infections.
Gas vesicle-blood interactions enhance ultrasound imaging contrast
Authors: Ling Bill , Ko Jeong Hoon , Stordy Benjamin , Zhang Yuwei , Didden Tighe F. , Malounda Dina , Swift Margaret B. , Chan Warren C.W. , Shapiro Mikhail G. 
Published: July 2023

ABSTRACTGas vesicles (GVs) are genetically encoded, air-filled protein nanostructures of broad interest for biomedical research and clinical applications, acting as imaging and therapeutic agents for ultrasound, magnetic resonance, and optical techniques. However, the biomedical applications of GVs as a systemically injectable nanomaterial have been hindered by a lack of understanding of GVs’ interactions with blood components, which can significantly impactin vivoperformance. Here, we investigate the dynamics of GVs in the bloodstream using a combination of ultrasound and optical imaging, surface functionalization, flow cytometry, and mass spectrometry. We find that erythrocytes and serum proteins bind to GVs and shape their acoustic response, circulation time, and immunogenicity. We show that by modifying the GV surface, we can alter these interactions and thereby modify GVs’in vivoperformance. These results provide critical insights for the development of GVs as agents for nanomedicine.
The long non-coding RNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation
Authors: Morgenstern Eva , Schwartz Uwe , Graf Johannes , Bruckmann Astrid , Kretz Markus 
Published: July 2023

AbstractNumerous long non-coding RNAs (lncRNAs) were shown to have functional impact on cellular processes such as human epidermal homeostasis. However, the mechanism of action for many lncRNAs remains unclear to date. Here, we report that lncRNA LINC00941 regulates keratinocyte differentiation on an epigenetic level through association with the NuRD complex, one of the major chromatin remodelers in cells. We find that LINC00941 interacts with NuRD-associated MTA2 in human primary keratinocytes. LINC00941 perturbation changes MTA2/NuRD occupancy at bivalent chromatin domains in close proximity to transcriptional regulator genes, including theEGR3gene coding for a transcription factor regulating epidermal differentiation. Notably, LINC00941 depletion resulted in reduced NuRD occupancy at theEGR3gene locus, increased EGR3 expression in human primary keratinocytes, as well as increased abundance of EGR3-regulated epidermal differentiation genes in cells and human organotypic epidermal tissue. Our results therefore indicate a role for LINC00941/NuRD in repressing EGR3 expression in non-differentiated keratinocytes, consequentially preventing premature differentiation of human epidermal tissue.
Same same but different – The global response ofEscherichia colito five different LpxC inhibitors
Authors: Möller Anna-Maria , Vázquez-Hernández Melissa , Kutscher Blanka , Brysch Raffael , Brückner Simon , Marino Emily , Kleetz Julia , Senges Christoph HR , Schäkermann Sina , Bandow Julia E , Narberhaus Franz 
Published: July 2023

AbstractA promising but yet clinically unexploited antibiotic target in difficult-to-treat Gram-negative bacteria is LpxC, the key enzyme in the biosynthesis of lipopolysaccharides (LPS), which are the major constituents of the outer membrane. To gain insights into the mode of action of five different LpxC inhibitors, we conducted a comparative phenotypic and proteomic analysis. All five compounds bound to purified LpxC fromEscherichia coli. Treatment ofE. coliwith these compounds changed the cell shape and stabilized LpxC suggesting that the FtsH-mediated turnover is impaired. LpxC inhibition sensitizedE. colito the cell wall antibiotic vancomycin, which typically does not cross the outer membrane. Four of the five compounds led to an accumulation of lyso-PE, a cleavage product of phosphatidylethanolamine (PE), generated by the phospholipase PldA. The combined results suggested an imbalance in phospholipid (PL) and LPS biosynthesis, which was corroborated by the global proteome response to treatment with the LpxC inhibitors. Apart from LpxC itself, FabA and FabB responsible for the biosynthesis of unsaturated fatty acids, were consistently upregulated. Our work also shows that antibiotics targeting the same enzyme do not necessarily elicit identical cellular responses. Compound-specific marker proteins belonged to different functional categories, like stress responses, nucleotide or amino acid metabolism and quorum sensing. These findings provide new insights into common and distinct cellular defense mechanisms against LpxC inhibition. Moreover, they support a delicate balance between LPS and PL biosynthesis with great potential as point of attack for antimicrobial intervention.ImportanceThe alarming spread of antimicrobial resistance among Gram-negative bacteria calls for novel intervention strategies. Inhibitors of LpxC, the first committed enzyme of lipopolysaccharide biosynthesis have been recognized as promising broad-spectrum antibiotics against Gram-negative pathogens. Despite the development of dozens of chemically diverse LpxC inhibitor molecules, it is essentially unknown how bacteria counteract LpxC inhibition. Our study provides comprehensive insights into the bacterial defense strategies against five different LpxC inhibitors. We show that the cellular response ofEscherichia coliis compound-specific but shares a common pattern. Inhibition of LpxC is toxic, disrupts membrane integrity, and elicits a stress response, including upregulation of fatty acid biosynthesis proteins. Pre-treatment ofE. coliwith low doses of LpxC inhibitors increased the sensitivity to the cell wall antibiotic vancomycin suggesting new directions in combination therapies.
Comprehensive catalogs for microbial genes and metagenome-assembled genomes of the swine lower respiratory tract microbiome identify the relationship of microbial species with lung lesions
Authors: Li Jingquan , Huang Fei , Zhou Yunyan , Huang Tao , Tong Xinkai , Zhang Mingpeng , Chen Jiaqi , Zhang Zhou , Du Huipeng , Liu Zifeng , Zhou Meng , Xiahou Yiwen , Ai Huashui , Chen Congying , Huang Lusheng 
Published: July 2023

AbstractUnderstanding the community structure and functional capacity of the lower respiratory tract microbiome is crucial for elucidating its roles in respiratory tract diseases. However, there are few studies about it owing to the difficulty in obtaining microbial samples from the lower respiratory tract. Here we collected 745 microbial samples from the porcine lower respiratory tract by harvesting 675 pigs, and constructed a gene catalog containing 10,337,194 nonredundant genes, of which only 30% could be annotated taxonomically. We obtained 397 metagenome-assembled genomes (MAGs) including 111 MAGs with high-quality. These 397 MAGs were further clustered into 292 species-level genome bins (SGBs), among which 56% SGBs are unknown with current databases. Combining with the lung lesion phenotype, we found thatMycoplasma hyopneumoniaestrains and the adhesion-related virulence factors harboring in their genomes were significantly associated with porcine lung lesions, implying the role of adhesion and overgrowth of pathogenicM. hyopneumoniaein host lung diseases. This study provided important resources for the study of porcine lower respiratory tract microbiome and lung health.
RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors
Authors: Dou Dan , Aiken Jayne , Holzbaur Erika L.F. 
Published: July 2023

ABSTRACTGain-of-function mutations in theLRRK2gene cause Parkinson’s disease (PD), characterized by debilitating motor and non-motor symptoms. Increased phosphorylation of a subset of RAB GTPases by LRRK2 is implicated in PD pathogenesis. We find that increased phosphorylation of RAB3A, a cardinal synaptic vesicle precursor (SVP) protein, disrupts anterograde axonal transport of SVPs in iPSC-derived human neurons (iNeurons) expressing hyperactiveLRRK2-p.R1441H. Knockout of the opposing protein phosphatase 1H (PPM1H) in iNeurons phenocopies this effect. In these models, the compartmental distribution of synaptic proteins is altered; synaptophysin and synaptobrevin-2 become sequestered in the neuronal soma with decreased delivery to presynaptic sites along the axon. We find that RAB3A phosphorylation disrupts binding to the motor adapter MADD, potentially preventing formation of the RAB3A-MADD-KIF1A/1Bβ complex driving anterograde SVP transport. RAB3A hyperphosphorylation also disrupts interactions with RAB3GAP and RAB-GDI1. Our results reveal a mechanism by which pathogenic hyperactive LRRK2 may contribute to the altered synaptic homeostasis associated with characteristic non-motor and cognitive manifestations of PD.SUMMARYDou et al. demonstrate that Parkinson’s disease-associated hyperactive LRRK2 decreases trafficking of synaptic vesicle proteins within neurons by disrupting regulation of the synaptic vesicle precursor protein RAB3A. Impaired delivery of synaptic proteins to presynaptic sites could contribute to progression of debilitating non-motor PD symptoms.
Ribosome Heterogeneity in Development and Disease
Authors: Gao Yuen , Wang Hongbing 
Published: July 2023

ABSTRACTThe functional ribosome is composed of ∼80 ribosome proteins. With the intensity-based absolute quantification (iBAQ) value, we calculate the stoichiometry ratio of each ribosome protein. We analyze the ribosome ratio-omics (RibosomeR), which reflects the holistic signature of ribosome composition, in various biological samples with distinct functions, developmental stages, and pathological outcomes. The RibosomeRreveals significant ribosome heterogeneity among different tissues of fat, spleen, liver, kidney, heart, and skeletal muscles. During tissue development, testes at various stages of spermatogenesis show distinct RibosomeRsignatures. Duringin vitroneuronal maturation, the RibosomeRchanges reveal functional association with certain molecular aspects of neurodevelopment. Regarding ribosome heterogeneity associated with pathological conditions, the RibosomeRsignature of gastric tumors is functionally linked to pathways associated with tumorigenesis. Moreover, the RibosomeRundergoes dynamic changes in macrophages following immune challenges. Taken together, with the examination of a broad spectrum of biological samples, the RibosomeRbarcode reveals ribosome heterogeneity and specialization in cell function, development, and disease.One-Sentence SummaryRatio-omics signature of ribosome deciphers functionally relevant heterogeneity in development and disease.
Histidine and its uptake are essential for the growth ofStaphylococcus aureusat low pH
Authors: Beetham Catrin M. , Schuster Christopher F. , Santiago Marina , Walker Suzanne , Gründling Angelika 
Published: July 2023

AbstractStaphylococcus aureusis an opportunistic pathogen capable of causing many different human diseases. During colonization and infection,S. aureuswill encounter a range of hostile environments, including acidic conditions such as those found on the skin and within macrophages. However, little is known about the mechanisms thatS. aureususes to detect and respond to low pH. Here, we employed a transposon sequencing approach to determine on a genome-wide level the genes required or detrimental for growth at low pH. We identified 31 genes that were essential for the growth ofS. aureusat pH 4.5 and confirmed the importance of many of them through follow up experiments using mutant strains inactivated for individual genes. Most of the genes identified code for proteins with functions in cell wall assembly and maintenance. These data suggest that the cell wall has a more important role than previously appreciated in promoting bacterial survival when under acid stress. We also identified several novel processes previously not linked to the acid stress response inS. aureus. These include aerobic respiration and histidine transport, the latter by showing that one of the most important genes,SAUSA300_0846, codes for a previously uncharacterized histidine transporter. We show that anS. aureus SAUSA300_0846mutant is unable to maintain its cytosolic pH, thereby revealing an important function for histidine and its transport in buffering the intracellular pH in bacteria.Author summaryStaphylococcus aureusis an important human bacterial pathogen that can cause a range of diseases. During infection, the pathogen will encounter a hostile environment within the human host, including acidic conditions such as those found on the skin and within macrophages. The bacterium has developed sophisticated strategies to survive and grow under such harsh conditions. Here we performed a genome wide screen to identify factors that are required by this pathogen to survive under acid stress conditions and identified several novel processes including histidine uptake. Understanding the response ofS. aureusto deal with acid stress conditions will help us better manage infections.
The Hippo kinase cascade regulates a contractile cell behavior and cell density in a close unicellular relative of animals
Authors: Phillips Jonathan E , Pan Duojia 
Published: July 2023

ABSTRACTThe genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organismCapsaspora owczarzaki. We previously showed that theCapsasporaortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology ofCapsasporacell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki inCapsaspora, remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts inCapsasporaby generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing withinCapsasporaaggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing incoHpoandcoWtsmutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway kinase cascade and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.
Anti-CD47 immunotherapy as a therapeutic strategy for the treatment of breast cancer brain metastasis
Authors: Mackert Jessica D. , Stirling Elizabeth R. , Wilson Adam S. , Westwood Brian , Zhao Dawen , Lo Hui-Wen , Metheny-Barlow Linda , Cook Katherine L. , Lesser Glenn J. , Soto-Pantoja David R. 
Published: July 2023

AbstractThe presence of cell surface protein CD47 allows cancer cells to evade innate and adaptive immune surveillance resulting in metastatic spread. CD47 binds to and activates SIRPα on the surface of myeloid cells, inhibiting their phagocytic activity. On the other hand, CD47 binds the matricellular protein Thrombospondin-1, limiting T-cell activation. Thus, blocking CD47 is a potential therapeutic strategy for preventing brain metastasis. To test this hypothesis, breast cancer patient biopsies were stained with antibodies against CD47 to determine differences in protein expression. An anti-CD47 antibody was used in a syngeneic orthotopic triple-negative breast cancer model, and CD47 null mice were used in a breast cancer brain metastasis model by intracardiac injection of the E0771-Br-Luc cell line. Immunohistochemical staining of patient biopsies revealed an 89% increase in CD47 expression in metastatic brain tumors compared to normal adjacent tissue (p ≤ 0.05). Anti-CD47 treatment in mice bearing brain metastatic 4T1br3 orthotopic tumors reduced tumor volume and tumor weight by over 50% compared to control mice (p ≤ 0.05) and increased IBA1 macrophage/microglia marker 5-fold in tumors compared to control (p ≤ 0.05). Additionally, CD47 blockade increased the M1/M2 macrophage ratio in tumors 2.5-fold (p ≤ 0.05). CD47 null mice had an 89% decrease in metastatic brain burden (p ≤ 0.05) compared to control mice in a brain metastasis model. Additionally, RNA sequencing revealed several uniquely expressed genes and significantly enriched genes related to tissue development, cell death, and cell migration tumors treated with anti-CD47 antibodies. Thus, demonstrating that CD47 blockade affects cancer cell and tumor microenvironment signaling to limit metastatic spread and may be an effective therapeutic for triple-negative breast cancer brain metastasis.
Poly(dA:dT) tracts differentially modulate nucleosome remodeling activity of RSC and ISW1a complexes, exerting tract orientation-dependent and -independent effects
Authors: Amigo Roberto , Raiqueo Fernanda , Tarifeño Estefanía , Farkas Carlos , Gutiérrez José L. 
Published: July 2023

AbstractThe establishment and maintenance of nucleosome-free regions (NFRs) are prominent processes within chromatin dynamics. Transcription factors, ATP-dependent chromatin remodeling complexes (CRCs) and DNA sequences are the main factors involved. InSaccharomyces cerevisiae, CRCs such as RSC contribute to chromatin opening at NFRs, while other complexes, including ISW1a, contribute to NFR shrinking. Regarding DNA sequences, growing evidence point to poly(dA:dT) tracts as playing a direct role in the active processes involved in nucleosome positioning dynamics. Intriguingly, poly(dA:dT) tract-containing NFRs span asymmetrically relative to the location of the tract, by a currently unknown mechanism. In order to get insight into the role of poly(dA:dT) tracts in nucleosome remodeling, we performed a systematic analysis of their influence on the activity of ISW1a and RSC complexes, with focus on their effect when located on linker DNA. Our findings revealed that poly(dA:dT) tracts differentially affect the activity of these CRCs. Moreover, we found differences between the effects exerted by the two alternative tract orientations. Our results support a model for the asymmetric chromatin opening that take place around these sequences.