bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streptococcus pyogenes infects human endometrium by limiting its immune response
Authors: Weckel Antonin , Guilbert Thomas , Lambert Clara , Plainvert Céline , Goffinet François , Poyart Claire , Méhats Céline , Fouet Agnès 
Published: July 2019

AbstractGroup A Streptococcus (GAS), a Gram-positive human-specific pathogen yields 517,000 deaths annually worldwide, including 163,000 due to invasive infections and among them puerperal fever. GAS is their most feared etiologic agent. Puerperal fever still accounts for more than 75,000 maternal deaths annually and before the introduction of efficient prophylactic measures 10% childbirths were followed by the mother’s death. Yet little is known regarding GAS invasive infection establishment or GAS efficiency in causing postpartum infection. To characterize its early steps, we set up coordinated analyses of ex vivo infection of the human decidua, the puerperal fever portal of entry. We analyzed GAS behavior and the immune response triggered. We demonstrate that GAS (i) benefits from tissue secreted products to multiply; (ii) invades the tissue and leads to the death of half the cells within two hours via SpeB protease and Streptolysin O activities, respectively; (iii) impairs the tissue immune response. Immune impairment occurs both at the RNA level, with the induction of only a restricted immediate innate immune response, and at the protein level, in a SLO- and SpeB-dependent manner. Our study indicates that GAS efficient decidua invasion and immune response restraint favor its propensity to develop rapid invasive infections in a gynecological-obstetrical context.
Biosynthesis of alkylcitric acids inAspergillus nigerinvolves both co-localized and unlinked genes
Authors: Palys Sylvester , Pham Thi Thanh My , Tsang Adrian 
Published: July 2019

AbstractFilamentous fungi are an abundant source of bioactive secondary metabolites (SMs). In many cases, the biosynthetic processes of SMs are not well understood. This work focuses on a group of SMs, the alkylcitric acids, each of which contains a saturated alkyl “tail” and a citrate-derived “head”. We initially identified their biosynthetic gene cluster and the transcriptional regulator (akcR) involved in the biosynthesis of alkylcitrates in the filamentous fungusAspergillus nigerby examining the functional annotation of SM gene clusters predicted from genomic data. We overexpressed the transcription regulator geneakcRand obtained from a litre of culture filtrate 8.5 grams of extract containing seven alkylcitric acids as determined by NMR. Hexylaconitic acid A comprised ~ 95% of the total production, and four of the seven identified alkylcitrates have not been reported previously. Analysis of orthologous alkylcitrate gene clusters in the Aspergilli revealed an in-cluster cis-aconitate decarboxylase gene (cadA) inA. oryzaeandA. flavus, which inA. nigeris located on a different chromosome. Overexpression of theA. niger cadAandakcRgenes together shifted the profile of alkylcitrates production from primarily hexylaconitic acids to mainly hexylitaconic acids. We also detected two additional, previously unreported, alkylcitric acids in the double overexpression strain. This study shows that phylogenomic analysis together with experimental manipulations can be used to reconstruct a more complete biosynthetic pathway in generating a broader spectrum of alkylcitric compounds. The approach adopted here has the potential of elucidating the complexity of other SM biosynthetic pathways in fungi.
Matrix-Assisted Laser Desorption-Ionization Time-of-Flight mass spectrometry using a custom-made database, biomarker assignment, or mathematical classifiers does not differentiate Shigella spp. and Escherichia coli
Authors: van den Beld Maaike J.C. , Rossen John W.A. , Evers Arie , Kooistra-Smid A.M.D. (Mirjam) , Reubsaet Frans A.G. 
Published: July 2019

AbstractPurposeShigella spp. and E. coli are closely related and cannot be distinguished using Matrix-Assisted Laser Desorption-Ionization Time-of-Flight mass spectrometry (MALDI-TOF MS) with commercially available databases. Here, three alternative approaches using MALDI-TOF MS to identify and distinguish Shigella spp., E. coli, and its pathotype EIEC were explored.MethodsA custom-made database was developed, biomarkers were assigned, and classification models using machine learning were designed and evaluated using spectra of 456 Shigella spp., 42 E. coli, and 61 EIEC isolates, obtained by the direct smear method and the ethanol-formic acid extraction method. The isolates were identified using ipaH PCR and phenotypic and serological typing.ResultsIdentification with a custom-made database resulted in >94% Shigella identified at the genus level and >91% S. sonnei and S. flexneri at the species level, but distinction of S. dysenteriae, S. boydii, and E. coli was poor. Moreover, 10-15% of duplicates rendered discrepant results. With biomarker assignment, 98% S. sonnei isolates were correctly identified, although the S. sonnei biomarkers were not specific as other species, for instance S. boydii and E. coli were also identified as S. sonnei. Discriminating markers for S. dysenteriae, S. boydii, and E. coli were not assigned at all. Classifiers identified Shigella in 96% of isolates correctly, but most E. coli isolates were also assigned to Shigella.ConclusionNone of the proposed alternative approaches is suitable for use in clinical diagnostics for the identification of Shigella spp., E. coli, and EIEC, reflecting their relatedness and problematic taxonomical classification. We suggest the use of MALDI-TOF MS for the identification of the Shigella spp./E. coli complex, but other tests should be used for distinction.
Drifting codes within a stable coding scheme for working memory
Authors: Wolff M. J. , Jochim J. , Akyürek E. G. , Buschman T. J. , Stokes M. G. 
Published: July 2019

AbstractWorking memory (WM) is important to maintain information over short time periods to provide some stability in a constantly changing environment. However, brain activity is inherently dynamic, raising a challenge for maintaining stable mental states. To investigate the relationship between WM stability and neural dynamics, we used electroencephalography to measure the neural response to impulse stimuli during a WM delay. Multivariate pattern analysis revealed representations were both stable and dynamic: there was a clear difference in neural states between time-specific impulse responses, reflecting dynamic changes, yet the coding scheme for memorized orientations was stable. This suggests that a stable subcomponent in WM enables stable maintenance within a dynamic system. A stable coding scheme simplifies readout for WM-guided behaviour, whereas the low-dimensional dynamic component could provide additional temporal information. Despite having a stable subspace, WM is clearly not perfect – memory performance still degrades over time. Indeed, we find that even within the stable coding scheme, memories drift during maintenance. When averaged across trials, such drift contributes to the width of the error distribution.
Better tired than lost: turtle ant trail networks favor coherence over short edges
Authors: Chandrasekhar Arjun , Marshall James A. R. , Austin Cortnea , Navlakha Saket , Gordon Deborah M. 
Published: July 2019

AbstractCreating a routing backbone is a fundamental problem in both biology and engineering. The routing backbone of the trail networks of arboreal turtle ants (Cephalotes goniodontus) connects many nests and food sources using trail pheromone deposited by ants as they walk. Unlike species that forage on the ground, the trail networks of arboreal ants are constrained by the vegetation. We examined what objectives the trail networks meet by comparing the observed ant trail networks with networks of random, hypothetical trail networks in the same surrounding vegetation and with trails optimized for four objectives: minimizing path length, minimizing average edge length, minimizing number of nodes, and minimizing opportunities to get lost. The ants’ trails minimized path length by minimizing the number of nodes traversed rather than choosing short edges. In addition, the ants’ trails reduced the opportunity for ants to get lost at each node, favoring nodes with 3D configurations most likely to be reinforced by pheromone. Thus, rather than finding the shortest edges, turtle ant trail networks take advantage of natural variation in the environment to favor coherence, keeping the ants together on the trails.Author SummaryWe investigated the trail networks of arboreal turtle ants in the canopy of the tropical forest, to ask what characterizes the colony’s choice of foraging paths within the vegetation. We monitored day to day changes in the junctions and edges of trail networks of colonies in the dry forest of western Mexico. We compared the paths used by the ants to simulated random paths in the surrounding vegetation. We found that the paths of turtle ants prioritize coherence, keeping ants together on the trail, over minimizing the average edge length. The choice of paths reduces the number of junctions in the trail where ants could get lost, and favors junctions with a physical configuration that makes it likely that successive ants will reinforce the same path. Our work suggests that design principles that emphasize keeping information flow constrained to streamlined, coherent trails may be useful in human-designed distributed routing and transport networks or robot swarms.
Reconstructing the Evolutionary History of Nitrogenases: Evidence for Ancestral Molybdenum-Cofactor Utilization
Authors: Garcia Amanda K. , McShea Hanon , Kolaczkowski Bryan , Kaçar Betül 
Published: July 2019

ABSTRACTThe nitrogenase metalloenzyme family, essential for supplying fixed nitrogen to the biosphere, is one of life’s key biogeochemical innovations. The three isozymes of nitrogenase differ in their metal dependence, each binding either a FeMo-, FeV-, or FeFe-cofactor where the reduction of dinitrogen takes place. The history of nitrogenase metal dependence has been of particular interest due to the possible implication that ancient marine metal availabilities have significantly constrained nitrogenase evolution over geologic time. Here, we reconstructed the evolutionary history of nitrogenases, and combined phylogenetic reconstruction, ancestral sequence inference, and structural homology modeling to evaluate the potential metal dependence of ancient nitrogenases. We find that active-site sequence features can reliably distinguish extant Mo-nitrogenases from V- and Fe-nitrogenases, and that inferred ancestral sequences at the deepest nodes of the phylogeny suggest these ancient proteins most resemble modern Mo-nitrogenases. Taxa representing early-branching nitrogenase lineages lack one or more biosyntheticnifEandnifNgenes that both contribute to the assembly of the FeMo-cofactor in studied organisms, suggesting that early Mo-nitrogenases may have utilized an alternate and/or simplified pathway for cofactor biosynthesis. Our results underscore the profound impacts that protein-level innovations likely had on shaping global biogeochemical cycles throughout the Precambrian, in contrast to organism-level innovations that characterize the Phanerozoic Eon.
Control strategies for the timing of intracellular events
Authors: Cao Mengfang , Qiu Baohua , Zhang Jiajun , Zhou Tianshou 
Published: July 2019

AbstractWhile the timing of intracellular events is essential for many cellular processes, gene expression inside a cell can exhibit substantial cell-to-cell variability, raising the question of how cells ensure precision in the event timing despite such stochasticity. We address this question by analyzing a biologically reasonable model of gene expression in the context of first passage time (FPT), focusing on two experimentally measurable statistics: mean FPT (MFPT) and timing variability (TV). We show that: (1) transcriptional burst size (BS) and burst frequency (BF) can minimize the TV; (2) translational BS monotonically reduces the MFPT to a nonzero low bound and can minimize the TV; (3) the timescale of promoter kinetics can minimize both the MFPT and the TV, depending on the ratio of the off-switching rate over the on-switching rate; and (4) positive feedback regulation of any form can all minimize the TV, whereas negative feedback regulation of transcriptional BF or BS always enhances the TV. These control strategies can have broad implications for diverse cellular processes relying on precise temporal triggering of events.
Limited intra-host diversity and background evolution accompany 40 years of canine parvovirus host adaptation and spread
Authors: Voorhees Ian E.H. , Lee Hyunwook , Allison Andrew B. , Lopez-Astacio Robert , Goodman Laura B. , Oyesola Oyebola O. , Omobowale Olutayo , Fagbohun Olusegun , Dubovi Edward J. , Hafenstein Susan L. , Holmes Edward C. , Parrish Colin R. 
Published: July 2019

ABSTRACTCanine parvovirus (CPV) is a highly successful pathogen that has sustained pandemic circulation in dogs for more than 40 years. Here, integrating full-genome and deep sequencing analyses, structural information, andin vitroexperimentation, we describe the macro- and micro-scale features that have accompanied CPV’s evolutionary success. Despite 40 years of viral evolution, all CPV variants are >∼99% identical in nucleotide sequence, with only a limited number (<40) of mutations becoming fixed or widespread during this time. Notably, most changes in the major capsid protein (VP2) are nonsynonymous and fall within, or adjacent to, the overlapping receptor footprint or antigenic regions, suggesting competitive selective pressures have played a key role in CPV evolution and likely constrained its evolutionary trajectory. Moreover, among the limited number of variable sites, CPV genomes exhibit complex patterns of variation that likely include parallel evolution, reversion, and recombination, making phylogenetic inference difficult. Additionally, deep sequencing of viral DNA in original clinical samples collected from dogs and other host species sampled between 1978 and 2018 revealed few sub-consensus single nucleotide variants (SNVs) above ∼0.5%, and experimental passages demonstrate that substantial pre-existing genetic variation is not necessarily required for rapid host receptor driven adaptation. Together, these findings suggest that although CPV is capable of rapid host adaptation, relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since its initial emergence have reduced the long-term genetic diversity accumulation and evolutionary rate. Hence, continuously high levels of inter- and intra-host diversity are not intrinsic to highly adaptable viruses.IMPORTANCERapid mutation rates and correspondingly high levels of standing intra-host diversity and accumulated inter-host diversity over epidemic scales are often cited as key features of viruses with the capacity for emergence and sustained transmission in a new host species. However, most of this information comes from studies of RNA viruses, with relatively little being known about that evolutionary processes that occur for viruses with DNA genomes. Here we provide a unique model of virus evolution, integrating both long-term global-scale and short-term intra-host evolutionary processes of a virus in a new host animal. Our analysis reveals that successful host jumping and sustained onward transmission does not necessarily depend on a high level of intra-host diversity or result in the continued accumulation of high levels of long-term evolution change. These findings indicate that all aspects of a virus’s biology and ecology are relevant when considering their adaptability.
Modulation of Voltage-Gated Sodium Channel (VGSC) Activity in Human Dorsal Root Ganglion (DRG) Neurons by Herpesvirus Quiescent Infection
Authors: Zhang Qiaojuan , Chen Feng , Martin-Caraballo Miguel , Hsia Shaochung V. 
Published: July 2019

AbstractThe molecular mechanisms of pain associated with alphaherpesvirus latency are not clear. We hypothesize that the voltage-gated sodium channels (VGSC) on dorsal root ganglion (DRG) neurons controlling electrical impulses may have abnormal activity during viral latent infection and reactivation. We used HSV-1 to infect human DRG-derived neuronal cell line HD10.6 to study viral latency establishment, maintenance and reactivation as well as changes of VGSC functional expression. Differentiated cells exhibited robust tetrodotoxin (TTX) sensitive sodium currents and acute infection significantly reduced the VGSC functional expression within 24 hours, and completely abolished the VGSC activity within three days lytic infection. A quiescent state of infection mimicking latency can be achieved by HSV infection in the presence of acyclovir (ACV) for 7 days followed by 5 days of ACV washout and the viruses can remain dormant for another three weeks. It was noted that during HSV-1 latency establishment, the loss of VGSC activity caused by HSV-1 infection could not be blocked by ACV treatment within 3 days infection. However, neurons with continued treatment of ACV for another 4 days showed a gradual recovery of VGSC functional expression. Furthermore, the latent neurons exhibited higher VGSC activity in comparison to controls. The overall regulation of VGSC by HSV-1 during its quiescent infection was proved by increased transcription and possible translation of Nav1.7. Together these observations demonstrated a very complex pattern of electrophysiological changes during HSV infection of DRG neurons, which may have implication for understanding the mechanisms of virus-mediated pain linked to latency and reactivation.ImportanceThe reactivation of the herpesvirus from ganglionic neurons may cause cranial nerve disorders and unbearable pain. It is unclear why normal stimuli would trigger enhanced pain sensation in these patients. The current work meticulously studies the functional expression profile changes of VGSC during the process of latency establishment using anin vitromodel. Our results indicated that VGSC activity was eliminated upon infection but steadily recovered during the latency establishment and the latent neurons exhibited even higher VGSC activity. This finding advances our knowledge of how ganglion neurons generated uncharacteristic electrical impulses due to abnormal VGSC functional expression influenced by latent virus.
Assessment of a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of pathogenic bacteria from respiratory samples in patients with hospital-acquired pneumonia
Authors: Vergara Andrea , Boutal Hervé , Ceccato Adrián , López Míriam , Cruells Adrià , Bueno-Freire Leticia , Moreno Javier , de la Bellacasa Jorge Puig , Castro Pedro , Torres Antoni , Marco Francesc , Casals-Pascual Climent , Vila Jordi 
Published: July 2019

AbstractIntroductionHospital-acquired pneumonia (HAP) is the one that presents clinically two or more days after admission into the hospital. Rapid identification of the causative agent of HAP will allow an earlier administration of a more appropriate antibiotic therapy and could lead to an improved outcome of patients with HAP.MethodsFirst of all, a rapid procedure (< 30 min) to extract the DNA from bronchoalveolar lavage (BAL), endotracheal aspirate (EA) or bronchoaspirate (BAS) was set up. A loop-mediated isothermal amplification reaction (LAMP) specific for Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii was carried out with the extracted solution. The reaction was performed at 65ºC for 30-40 min. LAMP was compared with bacterial culture method.ResultsOverall, 58 positive BAL and 83 EA/BAS samples were tested. The limits of detection varied according to the microorganism detected and to the respiratory sample analyzed. Validation of the LAMP assay with BAL samples showed that the assay was 100% specific and 86.3% sensitive (positive predictive value of 100% and a negative predictive value of 50%). Meanwhile for BAS/EA samples, the assay rendered the following statistical parameters: 100% specificity, 94.6% sensitivity, 100% positive predictive value and 69.2% negative predictive value. These scores were obtained including minor errors as correct. The turnaround time including preparation of the sample and LAMP was circa 1 hour.ConclusionsLAMP method may be used to detect the most frequent bacteria causing HAP. It is a simple, cheap, sensitive, specific and rapid assay.
Teichoic acids anchor distinct cell wall lamellae in an apically growing bacterium
Authors: Ultee Eveline , van der Aart Lizah T. , van Dissel Dino , Diebolder Christoph A. , van Wezel Gilles P. , Claessen Dennis , Briegel Ariane 
Published: July 2019

AbstractThe bacterial cell wall is a dynamic, multicomponent structure that provides structural support for cell shape and physical protection from the environment. In monoderm species, the thick cell wall is made up predominantly of peptidoglycan, teichoic acids and a variety of capsular glycans. Filamentous monoderm Actinobacteria, such asStreptomyces coelicolor, incorporate new cell wall material at the apex of their hyphal cells during growth. In this study we use cryo-electron tomography to reveal the structural architecture of the cell wall of this bacterium. Our data shows a density difference between the apex and subapical regions of chemically isolated sacculi. Removal of the teichoic acids with hydrofluoric acid reveals a rough and patchy cell wall and distinct lamellae in a number of sacculi. Absence of the extracellular glycans poly-β-1,6-𝒩-acetylglucosamine and a cellulose-like polymer, produced by the MatAB and CslA proteins respectively, results in a thinner sacculus and absence of lamellae and patches. Extracellular glycans might thus form or lead to the formation of the outer cell wall lamella. Based on these findings we propose a revisited model for the complex cell wall architecture of an apically growing bacterium, in which the network of peptidoglycan together with extracellular polymers is structurally supported by teichoic acids.
Generation and quality control of maternal plasma lipidomics data associated with preterm birth
Authors: Mei ZhanLong , Ye Lingfei , Huang Kang , Yang Xi , Chen Xiaomin , Cen Miaolan , Chen Yuan , Zhu Sujun , Zeng Juan , Roy Bhaskar , Jiang Hui , Wang Wen-Jing 
Published: July 2019

AbstractPreterm birth is not only one of the most common causes of infant deaths but also a great risk for them to have severe subsequent health problems. The causes of preterm birth may be due to a combination of genetic and environmental factors, however, it remains largely unknown. Here we report an untargeted lipidomics dataset of plasma specimens from 258 pregnant women at the stage of twelve to twenty-five gestational weeks. Among them, 44 had extremely to very preterm births, 54 had moderate preterm births, 71 had late preterm births and 89 had full-term deliveries. The metabolomic profiling was generated with an UPLC-MS in both the positive and negative mode, and putative identification of all the metabolites was provided by searching against online databases. The quality assessment performed on quality control samples showed that the data is reproducible, robust and reliable. Both the raw data files, the raw and processed data matrix were available on MetaboLights, which may be used as a valuable validation dataset for new findings and a test dataset for novel algorithms.