bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehension of Antimicrobial Peptides Modulation of the Type VI Secretion System inVibrio cholerae
Authors: Mathieu-Denoncourt Annabelle , Duperthuy Marylise 
Published: November 2022

AbstractThe Type VI secretion System (T6SS) is a versatile weapon used by bacteria for virulence, resistance to grazing and competition with other bacteria. We previously demonstrated that the role of the T6SS in interbacterial competition and in resistance to grazing is enhanced inVibrio choleraein the presence of subinhibitory concentrations of polymyxin B (PmB). In this study, we performed a global quantitative proteomic analysis by liquid chromatography coupled to mass spectrometry and a transcriptomic analysis by quantitative PCR of the T6SS known regulators inV. choleraegrown with and without PmB. The proteome ofV. choleraeis greatly modified in the presence of PmB at subinhibitory concentrations with more than 39 % of the identified cellular proteins displaying a difference in their abundance, including T6SS-related proteins (Hcp, VasC, TsaB and ClpV). We identified a regulator whose abundance and expression are increased in the presence of PmB,vxrB, the response regulator of the two-component system VxrAB. In avxrABdeficient mutant, the expression ofhcpmeasured by quantitative PCR, although globally reduced, was not modified in the presence of PmB, confirming its role inhcpupregulation with PmB. The upregulation of the T6SS in the presence of PmB appears to be, at least in part, due to the two-component system VxrAB.ImportanceThe type VI secretion system is important for bacterial competition, virulence and resistance to grazing by predators. In this study, we investigated the regulation leading to the type VI secretion system activation in the presence of polymyxin B (PmB), an antimicrobial used in veterinary and human health to treat infection caused by multi-resistant Gram-negative bacteria, inV. cholerae. In addition to making an overall portrait of the modifications to the proteome, we identified the VxrAB two-component system as the main regulator responsible for this activation. Our results provide evidence that subinhibitory concentrations of antimicrobials are responsible for important modifications of the proteome of pathogenic bacteria, inducing the production of proteins involved in virulence, host colonisation, resistance and environmental survival.
Characterization of HcaA, a novel autotransporter protein inHelicobacter cinaedi, and its role in host cell adhesion
Authors: Aoki Sae , Mori Shigetarou , Matsui Hidenori , Shibayama Keigo , Kenri Tsuyoshi , Rimbara Emiko 
Published: November 2022

ABSTRACTHelicobacter cinaediinfects the human gut and causes invasive infections such as bacteremia and cellulitis through bacterial translocation. However, the mechanism by whichH. cinaediattaches to host cells and establishes infection remains unclear. This study aimed to investigate the relationship between a novel putative autotransporter protein,H. cinaediautotransporter protein A (HcaA), and its role in pathogenicity. The cytotoxicity ofH. cinaediinfection in colon epithelial cell lines (Caco-2 and HT-29) was assessed using a lactate dehydrogenase assay, and it was found that cytotoxicity significantly decreased upon HcaA knockout. Adhesion assays further revealed that the HcaA-knockout strain showed significantly reduced attachment to the human epithelial colorectal adenocarcinoma cell line (Caco-2) compared to that of the wild-type strain. Moreover, the recombinant HcaA protein demonstrated strong adhesion properties to the human monocytic cell line (U937). The adhesive activity was diminished when the RGD motif in HcaA was replaced with RAD, indicating that the RGD motif in HcaA is crucial for host cell adhesion. To determine the role of HcaA inH. cinaediinfectionin vivo, C57BL/6 mice were orally infected with wild-type and HcaA-knockoutH. cinaedistrains. Bacterial colonization was assessed 7, 14, and 28 days post-infection. At 7 days post-infection, colonization was significantly lower in mice infected with the HcaA-knockout strain compared to those infected with the wild-type strain. In conclusion, our findings suggest that HcaA, a novel putative autotransporter protein inH. cinaedi, plays a significant role as an adhesin in establishing colonization.IMPORTANCEHelicobacterspecies are classified as gastric or enterohepatic according to their habitat. Among enterohepaticHelicobacterspecies, which inhabit the intestine, colon and liver,H. cinaedihas been most frequently isolated from humans.H. cinaedioften causes bacteremia and cellulitis in immunocompromised hosts. Here, we focused on theH. cinaediautotransporter protein A (HcaA), a novel virulence factor inH. cinaedi. We discovered that HcaA contributes to cell adhesion via its RGD motif. Furthermore, in animal experiments, bacterial colonization was reduced in mice infected with HcaA-knockout strains, supporting the hypothesis that HcaA contributes toH. cinaediadhesion to host cells. Our study provides a novel mechanism for the establishment ofH. cinaediinfections and provides new insights into the role of autotransporter proteins in the establishment ofHelicobacterinfection.
Taxonomic and carbon metabolic diversification of Bathyarchaeia during its co-evolution history with the early Earth surface environment
Authors: Hou Jialin , Wang Yinzhao , Zhu Pengfei , Yang Na , Liang Lewen , Yu Tiantian , Niu Mingyang , Konhauser Kurt , Wang Fengping 
Published: November 2022

AbstractBathyarchaeia, as one of the most abundant microorganisms on Earth, play vital roles in the global carbon cycle. However, our understanding of their origin, evolution and ecological functions remains poorly constrained. Based on the phylogeny of the present largest dataset of Bathyarchaeia metagenome assembled genome (MAG), we reclassified Bathyarchaeia into eight order-level units and corresponded to the former subgroup system. Highly diversified and versatile carbon metabolisms were discovered among different orders, particularly atypical C1 metabolic pathways, indicating that Bathyarchaeia represent overlooked important methylotrophs. Molecular dating results indicate that Bathyarchaeia diverged at ∼3.3 Ga, followed by three major diversifications at ∼3.0 Ga, ∼2.5 Ga and ∼1.8-1.7 Ga, likely driven by continental emergence, growth and intensive submarine volcanism, respectively. The lignin-degrading Bathyarchaeia clade emerged at ∼300 Ma and perhaps contributed to the sharply decreased carbon sequestration rate during the Late Carboniferous period. The evolutionary pathway of Bathyarchaeia potentially have been shaped by geological forces, which in turn impacted the Earth’s surface environment.TeaserThe origin and divergence of Bathyarchaeia linked to the early Earth tectonics and surface environment changes
Targeted degradation of PRC1 components, BMI1 and RING1B, via a novel protein complex degrader strategy
Authors: Park Kwang-Su , Qin Lihuai , Kabir Md , Luo Kaixiu , Dale Brandon , Zhong Yue , Kim Arum , Wang Gang Greg , Kaniskan H. Ümit , Jin Jian 
Published: November 2022

AbstractPolycomb repressive complex 1 (PRC1) is an essential epigenetic regulator that mainly controls histone H2A Lys119 mono-ubiquitination (H2AK119ub). BMI1 and RING1B are PRC1 core components and play critical roles in the development of various cancers. However, therapeutic agents targeting PRC1 are very limited, and small-molecule inhibitors of PRC1 displayed limited effectiveness in killing cancer cells. In this study, MS147, the first degrader of PRC1 core components, BMI1 and RING1B, was discovered via a novel protein complex degradation strategy that utilizes the target protein’s interacting partner protein (EED) to degrade BMI1 and RING1B. MS147, which comprises an EED small-molecule binder linked to a ligand of the E3 ligase VHL, degrades BMI1 and RING1B in an EED-, VHL-, ubiquitination- and time-dependent manner. MS147 is selective and preferentially degrades BMI1 and RING1B over PRC2 core components: EED, EZH2 and SUZ12. Consequently, MS147 effectively reduces H2AK119ub, but not H3K27me3, which is catalyzed by PRC2. Furthermore, MS147, but not the parent EED binder or known PRC2 degraders, effectively inhibits the proliferation of cancer cell lines that are insensitive to EZH2 knockout or PRC2 degraders. Overall, this study provides a novel degrader targeting BMI1 and RING1B, which is a useful chemical tool to further investigate the roles of PRC1 in cancer, and a novel protein complex degradation strategy, which could potentially expand the degradable human proteome.
Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution
Authors: Han Li , Wu Xinran , Wang Ou , Luan Xiao , Velander William H. , Aynardi Michael , Halstead E. Scott , Bonavia Anthony S. , Jin Rong , Li Guohong , Li Yulong , Wang Yong , Dong Cheng , Lei Yuguo 
Published: November 2022

AbstractTrauma, surgery, and infection can cause severe inflammation. Both dysregulated inflammation intensity and duration can lead to significant tissue injuries, organ dysfunction, mortality, and morbidity. Anti-inflammatory drugs such as steroids and immunosuppressants can dampen inflammation intensity, but they derail inflammation resolution, compromise normal immunity, and have significant adverse effects. The natural inflammation regulator mesenchymal stromal cells (MSCs) have high therapeutic potential because of their unique capabilities to mitigate inflammation intensity, enhance normal immunity, and accelerate inflammation resolution and tissue healing. Furthermore, clinical studies have shown that MSCs are safe and effective. However, they are not potent enough, alone, to completely resolve severe inflammation and injuries. One approach to boost the potency of MSCs is to combine them with synergistic agents. We hypothesized that alpha-1 antitrypsin (A1AT), a plasma protein used clinically and having an excellent safety profile, was a promising candidate for synergism. This investigation examined the efficacy and synergy of MSCs and A1AT to mitigate inflammation and to promote resolution, using in vitro cell cultures and a mouse acute lung injury and inflammation model. We found that the combination of MSCs and A1AT was much more effective than each component alone in i) modulating cytokine releases and inflammatory pathways, ii) inhibiting reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) production by neutrophils, iii) enhancing phagocytosis and, iv) promoting inflammation resolution, tissue healing, and animal survival. Our results support the combined use of MSCs and A1AT for managing severe, acute inflammation.
Nod1-dependent NF-kB activation initiates hematopoietic stem cell specification in response to small Rho GTPases
Authors: Cheng Xiaoyi , Barakat Radwa , Gorden Abigail , Snella Elizabeth , Zhang Yudi , Dorman Karin , Fidanza Antonella , Campbell Clyde , Espin-Palazon Raquel 
Published: November 2022

SummaryThe possibility of specifying functional hematopoietic stem and progenitor cells (HSPCs) from human pluripotent stem cells (hPSCs) would overcome current limitations related to HSPC transplantation. However, generating hPSC-derived HSPCs has been elusive, necessitating a better understanding of the native developmental mechanisms that trigger HSPC specification. Here, we revealedin vivoan intrinsic inflammatory mechanism triggered by Nod1 that drives early hemogenic endothelium (HE) patterning to specify HSPCs. Our genetic and chemical experiments showed that HSPCs failed to specify in the absence of Nod1 and its downstream kinase Ripk2. Rescue experiments demonstrated that Nod1 and Ripk2 acted through NF-kB, and that small Rho GTPases are at the apex of this mechanism. Manipulation of NOD1 in a human system of hPSCs differentiation towards the definitive hematopoietic lineage indicated functional conservation. This work establishes the RAC1-NOD1-RIPK2-NFkB axis as the earliest inflammatory inductor that intrinsically primes the HE for proper HSPC specification. Manipulation of this pathway could help derive a competent HE amenable to specify functional patient specific HSPCs for the treatment of blood disorders.HighlightsNod1 specifies HSPCsin vivothrough the early induction of hemogenic endothelium.Nod1-Ripk2 controls HSPC specification by activating the inflammatory master TF NF-kB.Nod1 links small Rho GTPases with pro-inflammatory signaling during the genesis of HSPCs.The function of NOD1 is conserved in the development of definitive human HSPCs.
Mesoscopic patterns of functional connectivity alterations in autism by contrast subgraphs
Authors: Lanciano Tommaso , Petri Giovanni , Gili Tommaso , Bonchi Francesco 
Published: November 2022

AbstractDespite the breakthrough achievements in understanding structural and functional connectivity alterations that underlie autism spectrum disorder (ASD), the exact nature and type of such alterations are not yet clear due to conflicting reports of hyper-connectivity, hypo-connectivity, and –in some cases– combinations of both. In this work, we approach the debate about hyper- vs hypoconnectivity in ASD using a novel network comparison technique designed to capture mesoscopic-scale differential structures. In particular, we build on recent algorithmic advances in the sparsification of functional connectivity matrices, in the extraction of contrast subgraphs, and in the computation of statistically significant maximal frequent itemsets, and develop a method to identify mesoscale structural subgraphs that are maximally dense and different in terms of connectivity levels between the different sets of networks.We apply our method to analyse brain networks of typically developed individuals and ASD patients across different developmental phases and find a set of altered cortical-subcortical circuits between healthy subjects and patients affected by ASD. Specifically, our analysis highlights in ASD patients a significantly larger number of functional connections among regions of the occipital cortex and between the left precuneus and the superior parietal gyrus. At the same time, reduced connectivity characterised the superior frontal gyrus and the temporal lobe regions. More importantly, we can simultaneously detect regions of the brain that show hyper and hypo-connectivity in ASD in children and adolescents, recapitulating within a single framework multiple previous separate observations.
Urine proteomic analysis of the rat startle model
Authors: Zhao Chenyang , Liu Yuqing , Gao Youhe 
Published: November 2022

AbstractUrine proteomics was applied to explore whether the effect of startle can be detected in urine. A combination of natural enemy odor and sound stimulation was used to establish the rat startle model. Urine samples were collected before and after startle, and urine proteomes before-after startle of each rat were compared individually. Regulatory subunits of glutamate-cysteine ligase was identified as the sole differential protein among all five startled rats. To our surprise, its functional partner catalytic subunits of glutamate-cysteine ligase was also identified in four out of five rats as differential protein. When comparing before-after startle as two groups, 22 differential proteins were identified which represent biological pathways including neurotransmitter transport and glucose transmembrane transport.
Optimising source identification from marmoset vocalisations with hierarchical machine learning classifiers
Authors: Phaniraj Nikhil , Wierucka Kaja , Zürcher Yvonne , Burkart Judith M. 
Published: November 2022

ABSTRACTMarmosets, with their highly social nature and complex vocal communication system, are important models for comparative studies of vocal communication and, eventually, language evolution. However, our knowledge about marmoset vocalisations predominantly originates from playback studies or vocal interactions between dyads, and there is a need to move towards studying group-level communication dynamics. Efficient source identification from marmoset vocalisations is essential for this challenge, and machine learning algorithms (MLAs) can aid it. Here we built a pipeline capable of plentiful feature extraction, meaningful feature selection, and supervised classification of vocalisations of up to 18 marmosets. We optimised the classifier by building a hierarchical MLA that first learned to determine the sex of the source, narrowed down the possible source individuals based on their sex, and then determined the source identity. We were able to correctly identify the source individual with high precisions (87.21% – 94.42%, depending on call type, and up to 97.79% after the removal of twins from the dataset). We also examine the robustness of identification across varying sample sizes. Our pipeline is a promising tool not only for source identification from marmoset vocalisations but also for analysing vocalisations and tracking vocal learning trajectories of other species.
Population genomics reveals mechanisms and dynamics ofde novoproto-gene emergence inDrosophila melanogaster
Authors: Grandchamp Anna , Kühl Lucas , Lebherz Marie , Brüggemann Kathrin , Parsch John , Bornberg-Bauer Erich 
Published: November 2022

Scientific AbstractNovel genes are essential for evolutionary innovations and differ substantially even between closely related species. Recently, multiple studies across many taxa have suggested that some novel genes arisede novo, i.e. from previously non-coding DNA. In order to characterise the underlying mutations that allowedde novogene emergence and their order of occurrence, homologous regions must be detected within non-coding sequences in closely related sister genomes. So far, most studies do not detect non-coding homologs ofde novogenes due to inconsistent data and long evolutionary distances separating genomes. Here we overcome these issues by searching for proto-genes, the not-yet fixed precursors ofde novogenes that emerged within a single species. We sequenced and assembled genomes with long-read technology and the corresponding transcriptomes from inbred lines ofDrosophila melanogaster, derived from seven geographically diverse populations. We found line-specific proto-genes in abundance but few proto-genes shared by lines, suggesting a rapid turnover. Gain and loss of transcription is more frequent than the creation of Open Reading Frames (ORFs), e.g. by forming new START- and STOP-codons. Consequently, the gain of ORFs becomes rate limiting and is frequently the initial step in proto-gene emergence. Furthermore, Transposable Elements (TEs) are major drivers for intra genomic duplications of proto-genes, yet TE insertions are less important for the emergence of proto-genes. However, highly mutable genomic regions around TEs provide new features that enable gene birth. In conclusion, proto-genes have a high birth-death rate, are rapidly purged, but surviving proto-genes spread neutrally through populations and within genomes.
Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides
Authors: Pandi Amir , Adam David , Zare Amir , Trinh Van Tuan , Schaefer Stefan L. , Wiegand Marie , Klabunde Björn , Bobkova Elizaveta , Kushwaha Manish , Foroughijabbari Yeganeh , Braun Peter , Spahn Christoph , Preußer Christian , von Strandmann Elke Pogge , Bode Helge B. , von Buttlar Heiner , Bertrams Wilhelm , Jung Anna Lena , Abendroth Frank , Schmeck Bernd , Hummer Gerhard , Vázquez Olalla , Erb Tobias J. 
Published: November 2022

AbstractBioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are required to validate candidates in high throughput and at low cost. Here, we established a cell- free protein synthesis (CFPS) pipeline for the rapid and inexpensive production of antimicrobial peptides (AMPs) directly from DNA templates. To validate our platform, we used deep learning to design thousands of AMPs de novo. Using computational methods, we prioritized 500 candidates that we produced and screened with our CFPS pipeline. We identified 30 functional AMPs, which we characterized further through molecular dynamics simulations, antimicrobial activity and toxicity. Notably, six de novo-AMPs feature broad-spectrum activity against multidrug-resistant pathogens and do not develop bacterial resistance. Our work demonstrates the potential of CFPS for production and testing of bioactive peptides within less than 24 hours and <10$ per screen.
Urine proteomic analysis of the rat e-cigarette model
Authors: Liu Yuqing , Shen Ziyun , Zhao Chenyang , Gao Youhe 
Published: November 2022

AbstractUrinary proteomics was used to investigate the potential effects of e-cigarettes on the human body. In this study, a rat e-cigarette model was constructed by smoking for two weeks and urine samples before, during, and after e-cigarette smoking were collected. Urine proteomes before-after smoking of each rat were compared individually, while the control group was set up to rule out differences caused by rat growth and development. After smoking, the differential proteins produced by rats shows strong individual variation. Fetuin-B, a biomarker of COPD, and annexin A2, which is recognized as a multiple tumor marker, were identified as the differential proteins in five out of six smoking rats on day 3. To our surprise, odorant-binding proteins expressed in the olfactory epithelium were also found and were significantly upregulated, which may help explain olfactory adaptation. Pathways enriched by the differential proteins shows the evidence that smoking e-cigarettes affects the immune system, cardiovascular system, respiratory system, etc., which provides clues for further exploration of the mechanism of e-cigarettes on the human body.
Exposure to environmental stress decreases the resistance of river microbial communities towards invasion by antimicrobial resistant bacteria
Authors: Bagra Kenyum , Bellanger Xavier , Merlin Christophe , Singh Gargi , Berendonk Thomas U. , Klümper Uli 
Published: November 2022

AbstractEnvironmental microbiomes are constantly exposed to invasion events through foreign, antibiotic resistant bacteria that were enriched in the anthropic sphere. However, the biotic and abiotic factors, as well as the natural barriers that determine the invasion success of these invader bacteria into the environmental microbiomes are poorly understood. A great example of such invasion events are river microbial communities constantly exposed to resistant bacteria originating from wastewater effluents. Here, we aim at gaining comprehensive insights into the key factors that determine their invasion success with a particular focus on the effects of environmental stressors, regularly co-released in wastewater effluents. Understanding invasion dynamics of resistant bacteria is crucial for limiting the environmental spread of antibiotic resistance. To achieve this, we grew natural microbial biofilms on glass slides in rivers for one month. The biofilms were then transferred to laboratory, recirculating flume systems and exposed to a single pulse of a model resistant invader bacterium (E. coli) either in presence or absence of stress induced by Cu2+. The invasion dynamics ofE. coliinto the biofilms were then monitored for 14 days. Despite an initially successful introduction ofE. coliinto the biofilms, independent of the imposed stress, over time the invader perished in absence of stress. However, under stress c the invading strain successfully established and proliferated in the biofilms. Noteworthy, the increased establishment success of the invader coincided with a loss in microbial community diversity under stress conditions, likely due to additional niche space becoming available for the invader.