bluuebunny/crossref_metadata_2025_split huggingface dataset:
IbpAB small heat shock proteins are not host factors for bacteriophage ϕX174 replication
Authors: Zhu Hannah X , Wright Bradley W , Logel Dominic Y , Molloy Mark P , Jaschke Paul R 
Published: October 2022

AbstractBacteriophages exploit host proteins for successful infection. Small heat shock proteins are a universally conserved family of stress-induced molecular chaperones that prevent irreversible aggregation of proteins. Two small heat shock proteins, IbpA and IbpB, are a class of holding modulators or “holdases”, which bind partially folded proteins and await ATP-driven folding chaperones for refolding. Bacteriophage ϕX174 is a small, icosahedral, and non-tailed virus belonging to theMicroviridae. During ϕX174 infection ofEscherichia coliC122, IbpA and IbpB were previously found to be the most highly upregulated host proteins, with expression levels comparable to ϕX174 proteins. In this work, to understand the role of IbpA and IbpB during ϕX174 infection, we used a hybrid approach of CRISPR interference and genomic knockouts to disrupt theibpAandibpBgenes. We show that these two proteins do not appear to be necessary for efficient ϕX174 replication, and moreover, their absence has no effect on ϕX174 fecundity.ImportanceThe small heat shock proteins (sHsps) are universally conserved family of stress-induced molecular chaperones that prevent irreversible protein aggregation. InE. coli, the IbpA/B sHsps work together, and separately, to bind partially folded proteins and await ATP-driven folding chaperones for refolding. These proteins are highly upregulated during protein overexpression and bacteriophage infection, but their collective role in bacteriophage infection has not been investigated. Here, we show that theibpA/Bgenes are dispensable for bacteriophage ϕX174 infection, and are likely not essential host factors despite their abundance during diverse phage infections. Instead, this work points towards their role as cell wall integrity sensors, similar to the phage shock protein system, in addition to their canonical role as holdases of cytoplasmic protein.
Bows and swords: why bacteria carry short and long-range weapons
Authors: Booth Sean C. , Smith William P.J. , Foster Kevin R. 
Published: October 2022

AbstractBacteria possess a diverse range of mechanisms for inhibiting competitors, including bacteriocins, tailocins, the type VI secretion system, and contact-dependent inhibition. Why bacteria have evolved such a wide array of weapon systems remains a mystery. Here we develop an agent-based model to compare short-range weapons that require cell-cell contact, with long-range weapons that rely on diffusion. Our models predict that contact weapons are useful when an attacking strain is outnumbered, facilitating invasion and establishment. By contrast, ranged weapons tend to only be effective when attackers are abundant. We test our predictions with the opportunistic pathogenPseudomonas aeruginosa, which naturally carries multiple weapons, including contact-dependent inhibition (CDI) and diffusing tailocins. As predicted, short-range CDI functions better at low frequency, while long-range tailocins require high frequency and cell density to function effectively. Head-to-head competitions between the two weapon types further support our predictions: a tailocin attacker only defeats CDI when it is numerically dominant, but then we find it can be devastating. Finally, we show that the two weapons work well together when one strain employs both. We conclude that short and long-range weapons serve different functions and allow bacteria to fight both as individuals and as a group.
Water mass age structures the auxiliary metabolic gene content of free-living and particle-attached deep ocean viral communities
Authors: Coutinho Felipe H , Silveira Cynthia B , Sebastián Marta , Sánchez Pablo , Duarte Carlos M , Vaqué Dolors , Gasol Josep M , Acinas Silvia G 
Published: October 2022

AbstractViruses play important roles on the biogeochemical cycles that take place in the ocean.Yet, deep ocean viruses are one of the most under-explored fractions of the global biosphere. Little is known about the environmental factors that control the composition and functioning of their communities, or how they interact with their free-living or particle-attached microbial hosts. Thus, we analysed 58 viral communities associated to size fractionated free-living (0.2–0.8 μm) and particle-attached (0.8–20 μm) cellular metagenomes from bathypelagic (2,150-4,018 m deep) microbiomes obtained during the Malaspina expedition. These metagenomes yielded 6,631 viral sequences, 91% of which were novel, and 67 represented high-quality genomes. Taxonomic classification assigned 53% of the viral sequences to families of tailed viruses from the order Caudovirales. Computational host prediction associated 886 viral sequences to dominant members of the deep ocean microbiome, such as Alphaproteobacteria (284), Gammaproteobacteria (241), SAR324 (23), Marinisomatota (39), and Chloroflexota (61). Free-living and particle-attached viral communities had markedly distinct taxonomic composition, host prevalence, and auxiliary metabolic gene content, which led to the discovery of novel viral encoded metabolic genes involved in the folate and nucleotide metabolisms. Water mass age emerged as an important factor driving viral community composition. We postulated this was due to changes in quality and concentration of dissolved organic matter acting on the host communities, leading to an increase of viral auxiliary metabolic genes associated with energy metabolism among older water masses. These results shed light on the mechanisms by which environmental gradients of deep ocean ecosystems structure the composition and functioning of free-living and particle-attached viral communities.
Stress-Induced Mucin 13 Reductions Drive Intestinal Microbiome Shifts and Despair Behaviors
Authors: Rivet-Noor Courtney R. , Merchak Andrea R. , Render Caroline , Gay Naudia , Beiter Rebecca M. , Brown Ryan , Keeler Austin , Moreau G. Brett , Li Sihan , Olgun Deniz E. , Steigmeyer Alexandra D. , Ofer Rachel , Phan Tobey Mihn Huu , Vemuri Kiranmayi , Chen Lei , Mahoney Keira E. , Shin Jung-Bum , Malaker Stacy A. , Deppmann Chris , Verzi Michael , Gaultier Alban 
Published: October 2022

AbstractDepression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in the microbiome are associated with disease pathology. In depression, stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is then known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes. Using a model of chronic stress, we show that the mucosal protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction ofMuc13is mediated by theHnf4transcription factor family. Finally, we determine that deletingMuc13is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a regulator of mucin 13 expression.SummaryIn this paper, authors identified a pathway by which stress induces microbiome shifts. They found that psychological stress selectively alters a key mucosal protein, mucin 13, which in turn modifies the microbial niche to induce changes in bacterial composition.
STAMP-Based Digital CRISPR-Cas13a (STAMP-dCRISPR) for Amplification-Free Quantification of HIV-1 Plasma Viral Load
Authors: Nouri Reza , Jiang Yuqian , Politza Anthony J. , Liu Tianyi , Greene Wallace , Nunez Jonathan , Lian Xiaojun Lance , Guan Weihua 
Published: October 2022

ABSTRACTThe development of new nucleic acid techniques to quantify HIV RNA in plasma is critical for identifying the disease progression and monitoring the effectiveness of antiretroviral therapy. While RT-qPCR has been the gold standard for HIV viral load quantification, digital assays could provide an alternative calibration-free absolute quantification method. Here, we report the development of aself-digitalizationthroughautomatedmembrane-basedpartitioning (STAMP) technique to digitalize the CRISPR-Cas13 assay (dCRISPR) for amplification-free and absolute quantification of HIV-1 viral RNAs. The analytical performances of STAMP-dCRISPR were evaluated with synthetic HIV-1 RNA, and it was found samples spanning 4 orders of dynamic range between 100 aM to 1 pM can be quantified as fast as 30 min. We also examined the overall assay from RNA extraction to STAMP-dCRISPR quantification with spiked plasma samples. The overall assay showed a resolution of 42 aM at a 90% confidence level. Finally, a total of 20 clinical plasma samples from patients were evaluated with STAMP-dCRISPR. The obtained results agreed well with the RT-qPCR. Our result demonstrates a new type of easy-to-use, scalable, and highly specific digital platform that would offer a simple and accessible platform for amplification-free quantification of viral RNAs, which could be exploited for the quantitative determination of viral load for an array of infectious diseases.
Human gut Actinobacteria boost drug absorption by secreting P-glycoprotein ATPase inhibitors
Authors: Kyaw Than S , Sandy Moriah , Trepka Kai , Goh Janice JN , Yu Kristie , Dimassa Vincent , Bess Elizabeth N. , Bisanz Jordan E , Turnbaugh Peter J 
Published: October 2022

SUMMARYDrug efflux transporters are a major determinant of drug efficacy and toxicity. A canonical example is P-glycoprotein (P-gp), an efflux transporter that controls the intestinal absorption of diverse compounds. Despite reports that P-gp expression depends on the microbiome, the mechanisms responsible and their physiological relevance remain unclear. Surprisingly, we found that the cardiac drug-metabolizing gut ActinobacteriumEggerthella lentaincreases drug absorption in mice through post-translational inhibition of P-gp ATPase efflux activity. P-gp inhibition is conserved in theEggerthellaceaefamily but absent in other Actinobacteria. Comparative genomics identified genes associated with P-gp inhibition. Finally, activity-guided biochemical fractionation coupled to metabolomics identified a cluster of isoflavonoids produced byE. lentarelated to plant-derived P-gp inhibitors. These results highlight the unexpected overlap between diet- and microbiome-derived compounds, and the importance of considering the broader relevance of the gut microbiome for drug disposition beyond first-pass metabolism.One Sentence SummaryThe gut bacteriumEggerthella lentasecretes inhibitors of P-glycoprotein ATPase activity, accelerating drug absorption.
Sporodochia formed byFusarium oxysporumf. sp.fragariaeproduce airborne conidia and are ubiquitous on diseased strawberry plants in California
Authors: Henry Peter M. , Dilla-Ermita Christine J. , Goldman Polly , Jaime Jose , Ramos Gerardo 
Published: October 2022

AbstractSporodochia are dense masses of fungal hyphae bearing asexual conidia. ForFusarium oxysporum, sporodochia are known to produce airborne conidia and enhance the dissemination of this otherwise soilborne pathogen. Sporodochia are small and transient, and they are documented for only a fewformae specialesofFusarium oxysporum. This study reports airborne conidia and sporodochia produced byF. oxysporumf. sp.fragariae, the cause of Fusarium wilt of strawberry, in the Monterey Bay region of California. Sporodochia were consistently present in Fusarium wilt-afflicted strawberry fields and were discovered in 21 of 24 Fusarium wilt-diseased fields. Only necrotic tissues were observed bearing sporodochia, and they were most frequently observed on petioles and peduncles. Sporodochia grew significantly longer up peduncles than petioles, extending further away from the base of the plant and toward parts of the canopy more exposed to wind. A stolon hosted the longest stretch of sporodochial growth, found covering the stolon’s entire 35 cm length and also the base of the daughter plant. Macroconidia were produced by all sporodochia samples, and we did not find microconidia on any samples. An initial series of experiments confirmed the potential for conidia produced by sporodochia to disperse with wind over short distances. The prevalence of sporodochia producing airborne spores ofF. oxysporumf. sp.fragariaehas great importance for disease management and biosecurity.
Treatment of prostate cancer with CD46 targeted225Ac alpha particle radioimmunotherapy
Authors: Bidkar Anil P. , Wang Sinan , Bobba Kondapa Naidu , Chan Emily , Bidlingmaier Scott , Egusa Emily A. , Peter Robin , Ali Umama , Meher Niranjan , Wadhwa Anju , Dhrona Suchi , Beckford-Vera Denis , Su Yang , Tang Ryan , Zhang Li , He Jiang , Wilson David M. , Aggarwal Rahul , VanBrocklin Henry F. , Seo Youngho , Chou Jonathan , Liu Bin , Flavell Robert R. 
Published: October 2022

AbstractRadiopharmaceutical therapy is changing the standard of care in prostate cancer (PCa) and other malignancies. We previously reported high CD46 expression in PCa and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. Our radiolabeled antibody retains binding efficacy and shows a high tumor to background ratio in PCa xenografts. Furthermore, we show that radiolabeled antibody was able to suppress the growth of cell-derived and patient-derived xenografts, including PSMA-positive and deficient models. Nephrotoxicity, not seen at low radioactive doses, is evident at higher radioactivity dose levels, likely due to redistribution of daughter isotope213Bi. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46 targeted radioligand therapy in PCa.
Iron Inhibits Glioblastoma Cell Migration and Polarization
Authors: Shenoy Ganesh , Kheirabadi Sina , Ataie Zaman , Palsa Kondaiah , Wade Quinn , Khunsriraksakul Chachrit , Khristov Vladimir , Slagle-Webb Becky , Lathia Justin D. , Wang Hong-Gang , Sheikhi Amir , Connor James R. 
Published: October 2022

AbstractGlioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent disease faced by most patients. Although research into the impact of iron on glioblastoma has addressed proliferation, there has been little investigation into how cellular iron impacts the ability of glioblastoma cells to migrate - a key question especially in the context of the diffuse spread observed in these tumors. Herein, we show that increasing cellular iron content results in decreased migratory capacity of human glioblastoma cells. The decrease in migratory capacity was accompanied by a decrease in cellular polarization in the direction of movement. Expression of CDC42, a Rho GTPase that is essential for both cellular migration and establishment of polarity in the direction of cell movement, was reduced upon iron treatment. Bioinformatic analysis of CDC42 mRNA revealed a potential iron-responsive element that may contribute to the regulation of CDC42 by iron. We then analyzed a single-cell RNA-seq dataset of human glioblastoma samples and found that cells at the tumor periphery had a gene signature that is consistent with having lower levels of cellular iron. Altogether, our results suggest that cellular iron content is impacting glioblastoma cell migratory capacity and that cells with higher iron levels exhibit reduced motility.
A Transducing Bacteriophage InfectingStaphylococcus epidermidisContributes to the Expansion of a Novel Siphovirus Genus and Implies Genus is Inappropriate for Phage Therapy
Authors: Andrews Taylor , Hoyer Steen , Ficken Karolyn , Fey Paul , Duffy Siobain , Boyd Jeffrey 
Published: October 2022

ABSTRACTThe effort to discover novel phages infectingStaphylococcus epidermidiscontributes to both the development of phage therapy and the expansion of genome-based phage phylogeny. Here, we report the genome of anS. epidermidis–infecting phage SEP1 and compare its genome with five other sequenced phages with high sequence identity. These phages represent a novel siphovirus genus, which was recently reported in the literature. The published member of this group was favorably evaluated as a phage therapeutic agent, but SEP1 is capable of transducing antibiotic resistance. Members of this genus may be maintained within their host as extrachromosomal plasmid prophages, through stable lysogeny or pseudolysogeny. Therefore, we conclude that SEP1 may be temperate and members of this novel genus are not suitable for phage therapy.
Muscle stem cell function is impaired in absence of Talpid3 - a gene required for primary cilia formation
Authors: Martinez-Heredia Victor , Blackwell Danielle , Sebastian Sujith , Pearson Timothy , Mok Gi Fay , Mincarelli Laura , Utting Charlotte , Folkes Leighton , Poeschl Ernst , Macaulay Iain , Mayer Ulrike , Münsterberg Andrea 
Published: October 2022

AbstractSkeletal muscle stem cells (MuSC) are crucial for tissue homeostasis and repair after injury. Following activation, they proliferate to generate differentiating myoblasts. A proportion of cells selfrenew, re-enter the MuSC niche under the basal lamina outside the myofiber and become quiescent. Quiescent MuSC have a primary cilium, which is disassembled upon cell cycle entry.Ex vivoexperiments suggest cilia are important for MuSC self-renewal, however, their role in muscle regenerationin vivoremains poorly understood. Talpid3 (TA3) is essential for primary cilia formation and Hedgehog (Hh) signalling. Here we use tamoxifen-inducible conditional deletion of TA3in MuSC (iSC-KO) and show that regeneration is impaired in response to cytotoxic injury. Repeat injury exacerbates the regeneration phenotype in TA3iSC-KOmice, indicating depletion of MuSCs. Single cell transcriptomics of MuSC progeny isolated from myofibers identifies components of several signalling pathways, which are deregulated in absence of TA3, including Hh and Wnt. Pharmacological activation of Wnt restores muscle regeneration, while purmorphamine, an activator of the Smoothened (Smo) co-receptor in the Hh pathway, has no effect. Together, our data suggest that TA3and primary cilia are important for MuSC self-renewal, and that pharmacological treatment can efficiently restore muscle regeneration.
Flight testing verification of lateral-directional dynamic stability of gliding birds due to wing dihedral
Authors: Wei Chenhao , Lin Gang , Huang Jun , Song Lei , Smith Howard 
Published: October 2022

PurposeUnlike conventional aircraft, birds can glide without a vertical tail. The purpose of this paper is to analyse the influence of dihedral angle spanwise distribution on lateral-directional dynamic stability by the simulation, calculation in the development of the bird-inspired aircraft and the flight testing.Design/methodology/approachThe gliding magnificent frigatebird (Fregata magnificens) was selected as the study object. The geometric and mass model of the study object were developed. Stability derivatives and moments of inertia were obtained. The lateral-directional stability was assessed under different spanwise distributions of dihedral angle. A bird-inspired aircraft was developed, and a flight test was carried out to verify the analysed results.FindingsThe results show that spanwise distribution changing of dihedral angle has influence on the lateral-directional mode stability. All of the analysed configurations have convergent Dutch roll mode and rolling mode. The key role of dihedral angle changing is to achieve a convergent spiral mode. Flight test results show that the bird-inspired aircraft has a well-convergent Dutch roll mode.Practical implicationsThe theory that birds can achieve its lateral-directional stability by changing its dihedral angle spanwise distribution may explain the stability mechanism of gliding birds.Originality/valueThis paper helps to improve the understanding of bird gliding stability mechanism and provides bio-inspired solutions in aircraft designing.
A novel identification approach of Bouc–Wen model parameter for piezoelectric hysteresis characteristic based on a modified whale optimization algorithm
Authors: Wang Geng , Zhou Yongsheng 
Published: October 2022

Purpose
Due to the non-linear nature of the hysteresis behavior, the accurate identification of the parameters of the Bouc–Wen hysteresis model is still a challenging problem. The purpose of this paper is to explore the potential of a heuristic improved whale optimization algorithm (IWOA) to accurately identify the model parameters, which has never been applied to the field of piezoelectric hysteresis identification.

Design/methodology/approach
Based on the analysis of the Bouc–Wen model structure and WOA optimization process, an approach that can fully exploit the potential of WOA is proposed. In this work, the position updating formula is improved by introducing non-linear weights, and the convergence factor formula is modified. And thus, the iteration speed, accuracy and stability of the classical WOA can be improved.

Findings
The experimental results show that the model output is in good agreement with the response of the real piezoelectric platform. Compared with the standard WOA and particle swarm optimization algorithms, the search performance of the proposed IWOA is better than those two competitors in terms of convergence speed and identification accuracy.

Originality/value
An IWOA is proposed according to the properties of the Bouc–Wen model and piezoelectric hysteresis. It has been approved that the algorithm has a good prospect in the identification of piezoelectric hysteresis systems. Furthermore, this method is easy to implement and is a good candidate algorithm to identify Bouc–Wen model parameters.