bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation inEnsiferspecies during free-living growth and during nitrogen-fixing symbiosis withMedicagospp.
Authors: diCenzo George C. , Cangioli Lisa , Nicoud Quentin , Cheng Janis H.T. , Blow Matthew J. , Shapiro Nicole , Woyke Tanja , Biondi Emanuele G , Alunni Benoît , Mengoni Alessio , Mergaert Peter 
Published: March 2021

ABSTRACTMethylation of specific DNA sequences is ubiquitous in bacteria and has known roles in immunity and regulation of cellular processes, such as the cell cycle. Using single-molecule real-time sequencing, six genome-wide methylated motifs were identified across fourEnsiferstrains, five of which were strain-specific. Only the GANTC motif, recognized by the cell cycle-regulated CcrM methyltransferase, was methylated in all strains. In actively dividing cells, methylation of GANTC motifs increased progressively from theoritoterregions in each replicon, in agreement with a cell cycle-dependent regulation of CcrM. In contrast, there was near full genome-wide GANTC methylation in the early stage of symbiotic differentiation. This was followed by a moderate decrease in the overall extent methylation and a progressive decrease in chromosomal GANTC methylation from theoritoterregions in later stages of differentiation. We interpret these observations as evidence of dysregulated and constitutive CcrM activity during terminal differentiation, and we hypothesize that it is a driving factor for endoreduplication of terminally differentiated bacteroids.
Activation of a signaling pathway by the physical translocation of a chromosome
Authors: Guzzo Mathilde , Sanderlin Allen G. , Castro Lennice K. , Laub Michael T. 
Published: March 2021

AbstractIn every organism, the cell cycle requires the execution of multiple cellular processes in a strictly defined order. However, the mechanisms used to ensure such order remain poorly understood, particularly in bacteria. Here, we show that the activation of the essential CtrA signaling pathway that triggers cell division inCaulobacter crescentusis intrinsically coupled to the successful initiation of DNA replication via the physical translocation of a newly-replicated chromosome, powered by the ParABS system. We demonstrate that ParA accumulation at the new cell pole during chromosome segregation recruits ChpT, an intermediate component of the CtrA signaling pathway. ChpT is normally restricted from accessing the selective PopZ polar microdomain until the new chromosome and ParA arrive. Consequently, any disruption to DNA replication initiation prevents the recruitment of ChpT and, in turn, cell division. Collectively, our findings reveal how major cell-cycle events are coordinated inCaulobacterand, importantly, how the physical translocation of a chromosome triggers an essential signaling pathway.
Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity
Authors: Di Russo Jacopo , Young Jennifer L. , Wegner Julian W. R. , Steins Timmy , Kessler Horst , Spatz Joachim P. 
Published: March 2021

AbstractNanometer-scale properties of the extracellular matrix influence many biological processes, including cell motility. While much information is available for single cell migration, to date, no knowledge exists on how the nanoscale presentation of extracellular matrix receptors influences collective cell migration. In wound healing, basal keratinocytes collectively migrate on a fibronectin-rich provisional basement membrane to re-epithelialize the injured skin. Among other receptors, the fibronectin receptor integrin α5β1 plays a pivotal role in this process. Using a highly specific integrin α5β1 peptidomimetic combined with nanopatterned hydrogels, we show that keratinocyte sheets regulate their migration ability at an optimal integrin α5β1 nanospacing. This efficiency relies on the effective propagation of stresses within the cell monolayer independent of substrate stiffness. For the first time, this work highlights the importance of extracellular matrix receptor nanoscale organization required for efficient tissue regeneration.
HERMES: a molecular formula-oriented method to target the metabolome
Authors: Giné Roger , Capellades Jordi , Badia Josep M. , Vughs Dennis , Schwaiger-Haber Michaela , Vinaixa Maria , Brunner Andrea M. , Patti Gary J. , Yanes Oscar 
Published: March 2021

ABSTRACTComprehensive metabolome analyses are hampered by low identification rates of metabolites due to suboptimal strategies in MS and MS2 acquisition, and data analysis. Here we present a molecular formula-oriented and peak detection-free method, HERMES, that improves sensitivity and selectivity for metabolite profiling in MS and structural annotation in MS2. An analysis of environmental water,E. coli, and human plasma extracts by HERMES showed increased biological specificity of MS2 scans, leading to improved mass spectral similarity scoring and identification rates when compared to iterative data-dependent acquisition (DDA). HERMES is available as an R package with a user-friendly graphical interface to allow data analysis and interactive tracking of compound annotations.
Ecosystem size and complexity dictate riverine biodiversity
Authors: Terui Akira , Kim Seoghyun , Dolph Christine L. , Kadoya Taku , Miyazaki Yusuke 
Published: March 2021

AbstractLarger ecosystems support more species; this ubiquitous pattern is the foundation of current conservation schemes. However, many ecosystems possess a complex spatial structure that cannot be represented by area, and the role of such complexity in scaling biodiversity is largely unknown. Here, we use theory and extensive fish community data from two distinct geographic regions (Japan and United States) to show that ecosystem size and complexity dictate riverine biodiversity. We found that larger and more branched ‘complex’ river networks harbored greater species richness due to increased space and environmental heterogeneity. The complexity effect was comparable to the size effect, and this pattern has emerged regardless of ecological contexts. The dual control of biodiversity may be a pervasive feature that has far-reaching implications for biodiversity conservation.One sentence summaryThis study provides the first evidence that ecosystem size and complexity play comparable roles in regulating biodiversity.
Oncogenic ZMYND11-MBTD1 fusion protein anchors the NuA4/TIP60 histone acetyltransferase complex to the coding region of active gene
Authors: Devoucoux Maëva , Fort Victoire , Khelifi Gabriel , Xu Joshua , Alerasool Nader , Galloy Maxime , Wong Nicholas , Bourriquen Gaëlle , Fradet-Turcotte Amélie , Taipale Mikko , Hope Kristin , Hussein Samer M. I. , Côté Jacques 
Published: March 2021

ABSTRACTA chromosomal translocation found in cannibalistic acute myeloid leukemia (AML) leads to an in-frame fusion of the transcription elongation repressor ZMYND11 to MBTD1, a subunit of the NuA4/TIP60 histone acetyltransferase (HAT) complex. In contrast to the NuA4/TIP60 complex, ZMYND11 is linked to repression of actively transcribed genes through recognition of H3.3K36me3. To understand the abnormal molecular events that expression of this ZMYND11-MBTD1 fusion protein can create, we performed its biochemical and functional characterization in comparison to each individual fusion partner. ZMYND11-MBTD1 is stably incorporated into the endogenous NuA4/TIP60 complex but does not bring any additional interactors as the fusion lacks the MYND domain of ZMYND11. Nevertheless, this truncated ZMYND11 moiety in the fusion leads to mislocalization of the NuA4/TIP60 complex on the body of genes normally bound by ZMYND11 in the genome, in a PWWP-H3.3K36me3 interaction-dependent manner. This can be correlated to increased chromatin acetylation and altered gene transcription, most notably on theMYConcogene, and alternative splicing. Importantly, expression of ZMYND11-MBTD1, but not the individual fusion partners, during embryonic stem cell differentiation, leads to decreased expression of specific differentiation markers, while favoring Myc-driven pluripotency. It also favors self-renewal of hematopoietic stem/progenitor cells. Altogether, these results indicate that the ZMYND11-MBTD1 fusion protein functions primarily by mistargeting the NuA4/TIP60 complex to the body of genes, altering normal transcription of specific genes, likely driving oncogenesis in part through the Myc regulatory network.Highlights-A recurrent chromosomal translocation detected in cannibalistic acute myeloid leukemia leads to the production of a ZMYND11-MBTD1 fusion protein.-The ZMYND11-MBTD1 fusion protein is stably incorporated into the endogenous NuA4/TIP60 complex.-ZMYND11-MBTD1 leads to mistargeting of NuA4/TIP60 activity to the coding region of ZMYND11-target genes, altering gene expression and splicing.-ZMYND11-MBTD1 binds theMYCgene leading to its upregulation, favoring growth and pluripotency while inhibiting differentiation markers.
Destruction of DNA-binding proteins by programmable O’PROTAC: Oligonucleotide-based PROTAC
Authors: Shao Jingwei , Yan Yuqian , Ding Donglin , Wang Dejie , He Yundong , Pan Yunqian , Yan Wei , Kharbanda Anupreet , Li Hong-yu , Huang Haojie 
Published: March 2021

AbstractDNA-binding proteins including transcription factors (TFs) play essential roles in gene transcription and DNA replication and repair during normal organ development and pathogenesis of diseases such as cancer, cardiovascular disease and obesity, deeming to be a large repertoire of attractive therapeutic targets. However, this group of proteins are generally considered undruggable as they lack an enzymatic catalytic site or a ligand binding pocket. PROteolysis-TArgeting Chimera (PROTAC) technology has been developed by engineering a bifunctional small molecule chimera to bring a protein of interest (POI) to the proximity of an E3 ubiquitin ligase, thus inducing the ubiquitination of POI and further degradation through proteasome pathway. Here we report the development of Oligonucleotide-based PROTAC (O’PROTACs), a class of noncanonical PROTACs in which a TF-recognizing double-stranded oligonucleotide is incorporated as a binding moiety of POI. We demonstrate that O’PROTACs of ERG and LEF1, two highly cancer-related transcription factors selectively promote degradation of these proteins and inhibit their transcriptional activity in cancer cells. The programmable nature of O’PROTACs indicates that this approach is applicable to destruct other TFs. O’PROTACs not only can serve as a research tool, but also can be harnessed as a therapeutic arsenal to target DNA binding proteins for effective treatment of diseases such as cancer.
A Tail Fiber Protein and a Receptor-Binding Protein Mediate ICP2 Bacteriophage Interactions withVibrio choleraeOmpU
Authors: Lim Andrea N.W. , Yen Minmin , Seed Kimberley D. , Lazinski David W. , Camilli Andrew 
Published: March 2021

AbstractICP2 is a virulent bacteriophage (phage) that preys onVibrio cholerae. ICP2 was first isolated from cholera patient stool samples. Some of these stools also contained ICP2-resistant isogenicV. choleraestrains harboring missense mutations in the trimeric outer membrane porin protein OmpU, identifying it as the ICP2 receptor. In this study, we identify the ICP2 proteins that mediate interactions with OmpU by selecting for ICP2 host-range mutants within infant rabbits infected with a mixture of wild type and OmpU mutant strains. ICP2 host-range mutants had missense mutations in putative tail fiber genegp25and putative adhesingp23. Using site-specific mutagenesis we show that single or double mutations ingp25are sufficient to generate the host-range mutant phenotype. However, at least one additional mutation ingp23is required for robust plaque formation on specific OmpU mutants. Mutations ingp23alone were insufficient to give a host-range mutant phenotype. All ICP2 host-range mutants retained the ability to plaque on wild typeV. choleraecells. The strength of binding of host-range mutants toV. choleraecorrelated with plaque morphology, indicating that the selected mutations ingp25andgp23restore molecular interactions with the receptor. We propose that ICP2 host-range mutants evolve by a two-step process where, first,gp25mutations are selected for their broad host-range, albeit accompanied by low level phage adsorption. Subsequent selection occurs forgp23mutations that further increase productive binding to specific OmpU alleles, allowing for near wild type efficiencies of adsorption and subsequent phage multiplication.ImportanceConcern over multidrug-resistant bacterial pathogens, includingVibrio cholerae, has led to a renewed interest in phage biology and their potential for phage therapy. ICP2 is a genetically unique virulent phage isolated from cholera patient stool samples. It is also one of three phages in a prophylactic cocktail shown to be effective in animal models of infection and the only one of the three that requires a protein receptor (OmpU). This study identifies a ICP2 tail fiber and a receptor binding protein and examines how ICP2 responds to the selective pressures of phage-resistant OmpU mutants. We found that this particular co-evolutionary arms race presents fitness costs to both ICP2 andV. cholerae.
Complete genome sequence ofXylella taiwanensisand comparative analysis of virulence gene content withXylella fastidiosa
Authors: Weng Ling-Wei , Lin Yu-Chen , Su Chiou-Chu , Huang Ching-Ting , Cho Shu-Ting , Chen Ai-Ping , Chou Shu-Jen , Tsai Chi-Wei , Kuo Chih-Horng 
Published: March 2021

AbstractThe bacterial genusXylellacontains plant pathogens that are major threats to agriculture in America and Europe. Although extensive research was conducted to characterize different subspecies ofXylella fastidiosa(Xf), comparative analysis at above-species levels were lacking due to the unavailability of appropriate data sets. Recently, a bacterium that causes pear leaf scorch (PLS) in Taiwan was described as the secondXylellaspecies (i.e.,Xylella taiwanensis;Xt). In this work, we report the complete genome sequence ofXttype strain PLS229T. The genome-scale phylogeny provided strong support thatXfsubspeciespauca(Xfp) is the basal lineage of this species andXylellawas derived from the paraphyletic genusXanthomonas. Quantification of genomic divergence indicated that differentXfsubspecies share ∼87-95% of their chromosomal segments, while the twoXylellaspecies share only ∼66-70%. Analysis of overall gene content suggested thatXtis most similar toXfsubspeciessandyi(Xfs). Based on the existing knowledge ofXfvirulence genes, the homolog distribution among 28Xylellarepresentatives was examined. Among the 11 functional categories, those involved in secretion and metabolism are the most conserved ones with no copy number variation. In contrast, several genes related to adhesins, hydrolytic enzymes, and toxin-antitoxin systems are highly variable in their copy numbers. Those virulence genes with high levels of conservation or variation may be promising candidates for future studies. In summary, the new genome sequence and analysis reported in this work contributed to the study of several important pathogens in the family Xanthomonadaceae.Contribution to the FieldXylella fastidiosais a plant-pathogenic bacterium with multiple subspecies that are major threats to agriculture in America and Europe. Although extensive research has been conducted, comparative analysis of this species with other bacteria is lacking due to the unavailability of known close relatives. In this work, we report the complete genome sequence ofXylella taiwanensis, a newly described species within the same genus. This new data set and our focused analysis helped to better understand the evolutionary relationships among differentXylellalineages and their genomic diversity. Moreover, detailed examination of their virulence genes identified those that are either highly conserved or variable, providing promising candidates for future studies to further investigate the molecular mechanisms ofXylellavirulence.
Glucose decoration on wall-teichoic acid is required for phage adsorption and InlB-mediated virulence inListeria ivanovii
Authors: Sumrall Eric. T. , Schneider Stephan R. , Boulos Samy , Loessner Martin J. , Shen Yang 
Published: March 2021

AbstractListeria ivanovii(Liv) is an intracellular Gram-positive pathogen that primarily infects ruminants, but also occasionally causes enteric infections in humans. Albeit rare, this bacterium possesses the capacity to cross the intestinal epithelium of humans, similar to its more frequently pathogenic cousin,Listeria monocytogenes(Lmo). Recent studies inLmohave shown that specific glycosyl modifications on the cell wall-associated glycopolymers (termed wall-teichoic acid, or WTA) ofLmoare responsible for bacteriophage adsorption and retention of the major virulence factor, Internalin B (InlB). However, the relationship between InlB and WTA inLivremains unclear. Here, we report the identification of the unique gene,liv1070that encodes a putative glucosyltransferase in the polycistronic WTA gene cluster of the Liv WSLC 3009 genome. We found that in-frame deletion ofliv1070led to loss of the glucose substitution on WTA, as revealed by UPLC-MS analysis. Interestingly, the glucose-deficient mutant became resistant to phage B025 infection due to an inability of the phage to adsorb to the bacterial surface, a binding process mediated by the receptor-binding protein B025_Gp17. As expected, deletion ofliv1070led to loss of InlB retention to the bacterial cell wall, which corresponded to a drastic decrease in cellular invasion. Genetic complementation ofliv1070restored the characteristic phenotypes, including glucose decoration, phage adsorption, and cellular invasion. Taken together, our data demonstrate that an interplay between phage, bacteria, and host cells also exists inListeria ivanovii, suggesting the trade-off between phage resistance and virulence attenuation may be a general feature in theListeriagenus.ImportanceListeria ivanoviiis a Gram-positive bacterial pathogen known to cause enteric infection in rodents and ruminants, and occasionally in immunocompromised humans. Recent investigations revealed that, in its better-known cousinListeria monocytogenes, strains develop resistance to bacteriophage attack due to loss of glycosylated surface receptors, which subsequently resulting in disconnection of one of the bacterium’s major virulence factors, InlB. However, the situation inL. ivanoviiremains unclear. Here, we show thatL. ivanoviiacquires phage resistance following deletion of a unique glycosyltransferase. This deletion also leads to dysfunction of InlB, making the resulting strain unable to invade host cells. Overall, this study suggests that the interplay between phage, bacteria and the host may be a feature common to theListeriagenus.
Maternal cradling bias drives early handedness in infant monkeys: A longitudinal study of grasping lateralization in baboons
Authors: Boulinguez-Ambroise Grégoire , Pouydebat Emmanuelle , Disarbois Éloïse , Meguerditchian Adrien 
Published: March 2021

AbstractThe most emblematic behavioral manifestation of human brain asymmetries is handedness. While the precise mechanisms behind the development of handedness are still widely debated, empirical evidences highlight that besides genetic factors, environmental factors may play a crucial role. As one of these factors, maternal cradling behavior may play a key role in the emergence of early handedness in the offspring. In the present study we followed 41 olive baboon (Papio anubis) infants living in different social groups with their mother for which direction (e.g., left- or right-arm) and degree of maternal cradling-side bias were available from our previous published study. We assessed hand preferences for an unimanual grasping task at 3 developmental stages: (1) 0-4, (2) 4-6 and (3) 9-10 months of age. We found that individual hand preferences for grasping exist as soon as the first months of age, with a population-level left-handedness predominance, being stable until 6 months; to wit the period during which juveniles are mainly carried by their mothers. More importantly, this early postnatal handedness is positively correlated with maternal cradling lateralization. Interestingly, hand preferences assessed later in the development, once juveniles are no longer carried (i.e., from 9 to 10 months of age), are less consistent with the earlier developmental stages and no longer dependent from the maternal cradling bias. Our findings suggest that the ontogenetic dynamics of the infant’s hand preference and its changes might ultimately rely on the degree of infant dependence from the mother across development.Research HighlightsEarly postnatal individual hand preferences are detected for unimanual food grasping within the first four months of age.Earliest measures of infant hand preference are positively correlated with measures of maternal cradling lateralization.Hand preferences assessed later in the development, from 9 to 10 months of age are less consistent with the earlier developmental stages and independent from maternal cradling bias.
Chimpanzee pant-hoots encode information about individual but not group differences
Authors: Desai Nisarg P. , Fedurek Pawel , Slocombe Katie E. , Wilson Michael L. 
Published: March 2021

AbstractVocal learning, the ability to voluntarily modify the acoustic structure of vocalizations based on social cues, is a fundamental feature of speech in humans (Homo sapiens). While vocal learning is common in taxa such as songbirds and whales, the vocal learning capacities of nonhuman primates appear more limited. Intriguingly, evidence for vocal learning has been reported in chimpanzees (Pan troglodytes), for example in the form of regional variation (‘dialects’) in the ‘pant-hoot’ calls. This suggests that some capacity for vocal learning may be an ancient feature of thePan-Homoclade. Nonetheless, reported differences have been subtle, with inter-community variation representing only a small portion of the total acoustic variation. To gain further insights into the extent of regional variation in chimpanzee vocalizations, we performed an analysis of pant-hoots from chimpanzees in the neighboring Kasekela and Mitumba communities at Gombe National Park, Tanzania, and the geographically distant Kanyawara community at Kibale National Park, Uganda. We observed group differences only among the geographically isolated communities and did not find any differences between the neighboring communities at Gombe. Furthermore, we found differences among individuals in all communities. Hence, the variation in chimpanzee pant-hoots reflected individual differences, rather than group differences. The limited evidences for vocal learning inPansuggest that extensive vocal learning emerged in the human lineage after the divergence fromPan.