bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial distribution ofSalmonella entericain poultry shed environments observed by intensive longitudinal environmental sampling
Authors: Crabb Helen K , Allen Joanne Lee , Devlin Joanne Maree , Wilks Colin Reginald , Gilkerson James Rudkin 
Published: February 2019

ABSTRACTDuring a series of epidemiological studies to investigate the transmission of salmonellae within poultry environments, intensive longitudinal sampling within caged sheds revealed that both the number and location of sample collection within this environment were important to ensure the best chance of detectingSalmonellaspp. Multiple serovars ofSalmonella entericasubspeciesentericawere detected in each shed; 5% of all samples contained more than one serovar. Samples collected on the north side of the shed (OR = 1.77, 95% CI [1.17, 2.68]), on the sheltered side of the shed (OR = 1.90, 95% CI [1.26, 2.89]) and during winter (OR = 48.41, 95%CI [23.56, 104.19]) were more likely to be positive for salmonellae. The distribution of salmonellae within a shed was not homogenous, as differences were identified in the within-shed distribution ofSalmonella entericasubspeciesentericaserovar Typhimurium (χ2(27, 1,538) = 54.4, P < 0.001), andSalmonella entericasubspeciesentericaserovar Infantis (χ2(27, 1,538) = 79.8, P < 0.0001). The difference in sample prevalence by serovar and spatial location within a shed indicates that there are important shed micro-environmental factors that influence survival and/or distribution of salmonellae. These factors should be taken into consideration when undertaking environmental surveillance for salmonellae in flocks housed in caged sheds.IMPORTANCERoutine epidemiological surveillance for salmonellae in poultry relies initially on environmental sampling. Our study confirmed that the sampling methodology conducted within a poultry environment is a non-trivial part of sampling design. The spatial locations of sample collection within a shed revealed differences in both the sample prevalence and serovar of salmonellae detected.
Cryptic inoviruses are pervasive in bacteria and archaea across Earth’s biomes
Authors: Roux Simon , Krupovic Mart , Daly Rebecca A. , Borges Adair L. , Nayfach Stephen , Schulz Frederik , Cheng Jan-Fang , Ivanova Natalia N. , Bondy-Denomy Joseph , Wrighton Kelly C. , Woyke Tanja , Visel Axel , Kyrpides Nikos C. , Eloe-Fadrosh Emiley A. 
Published: February 2019

AbstractBacteriophages from the Inoviridae family (inoviruses) are characterized by their unique morphology, genome content, and infection cycle. To date, a relatively small number of inovirus isolates have been extensively studied, either for biotechnological applications such as phage display, or because of their impact on the toxicity of known bacterial pathogens including Vibrio cholerae and Neisseria meningitidis. Here we show that the current 56 members of the Inoviridae family represent a minute fraction of a highly diverse group of inoviruses. Using a new machine learning approach leveraging a combination of marker gene and genome features, we identified 10,295 inovirus-like genomes from microbial genomes and metagenomes. Collectively, these represent six distinct proposed inovirus families infecting nearly all bacterial phyla across virtually every ecosystem. Putative inoviruses were also detected in several archaeal genomes, suggesting that these viruses may have occasionally transferred from bacterial to archaeal hosts. Finally, we identified an expansive diversity of inovirus-encoded toxin-antitoxin and gene expression modulation systems, alongside evidence of both synergistic (CRISPR evasion) and antagonistic (superinfection exclusion) interactions with co-infecting viruses which we experimentally validated in a Pseudomonas model. Capturing this previously obscured component of the global virosphere sparks new avenues for microbial manipulation approaches and innovative biotechnological applications.
Model ensembles with different response variables for base and meta models: malaria disaggregation regression combining prevalence and incidence data
Authors: Lucas Tim C. D. , Nandi Anita , Nguyen Michele , Rumisha Susan , E. Battle Katherine , E. Howes Rosalind , Hendriks Chantal , Python Andre , Hancock Penny , Cameron Ewan , Gething Pete , Weiss Daniel J. 
Published: February 2019

AbstractMaps of infection risk are a vital tool for the elimination of malaria. Routine surveillance data of malaria case counts, often aggregated over administrative regions, is becoming more widely available and can better measure low malaria risk than prevalence surveys. However, aggregation of case counts over large, heterogeneous areas means that these data are often underpowered for learning relationships between the environment and malaria risk. A model that combines point surveys and aggregated surveillance data could have the benefits of both but must be able to account for the fact that these two data types are different malariometric units. Here, we train multiple machine learning models on point surveys and then combine the predictions from these with a geostatistical disaggregation model that uses routine surveillance data. We find that, in tests using data from Colombia and Madagascar, using a disaggregation regression model to combine predictions from machine learning models trained on point surveys improves model accuracy relative to using the environmental covariates directly.
Competitive Inhibitors of Ras Effector Binding
Authors: Wiechmann Svenja , Maisonneuve Pierre , Grebbin Britta M. , Hoffmeister Meike , Kaulich Manuel , Clevers Hans , Rajalingam Krishnaraj , Kurinov Igor , Farin Henner F. , Sicheri Frank , Ernst Andreas 
Published: February 2019

AbstractThe small GTPases H, K and NRas are molecular switches that are indispensable for the correct regulation of cellular proliferation and growth. Mutations in Ras are associated with cancer and result in unwanted activation of signaling processes caused by aberrant recruitment of downstream effector proteins. In this study, we have engineered variants of the Ras-binding domain (RBD) of CRAF kinase that bind with highly improved affinity the effector binding site of Ras. Structural characterization demonstrates how the engineered RBD variants outcompete effector binding and inhibit Ras signaling in cells leading to apoptosis, growth arrest and senescence. The optimized RBD variants provide new insights in Ras biology and enabled the functional stratification of Ras dependency in patient-derived colorectal cancer organoids.One sentence summaryInhibition of effector kinase binding to Ras induces senescence in non-tumorigenic cells and reveals Ras dependency in patient-derived cancer organoids.
Global patterns of seed germination after ingestion by mammals
Authors: Torres Diego A. , Castaño John H. , Carranza-Quiceno Jaime A. 
Published: February 2019

AbstractSeed germination is the first step in seedling recruitment. Understanding what factors determine germination success allows some predictions of the effect of climate change or defaunation on the dynamics of plant communities. Mammals play an important role on seed germination through the ingestion of fruit and seeds. However, the populations of many mammal species have been reduced throughout the world, affecting in many ways the dynamics of plant communities. To understand how the loss of mammal populations might impact the dynamics of plant communities first requires us to collect and synthetize all the available evidence on the effects of mammals on seedling recruitment. Here, we used meta-analytical methods to describe the global patterns of the ingestion of seeds by mammals and their effect on seed germination. Our results showed a positive cumulative effect of mammals on seed germination. However, this effect was not the same for all the mammal orders; it varied depending on the plant family and the bioregion. Additionally, increased seed germination was related to rapid germination. These data highlight the important role that some mammals such as Primates and Elephants have on seed germination, and this poses many questions about the mechanisms behind seed germination patterns that will help to guide future research efforts.
Abstracted functions for engineering the autonomous growth and formation of patterns
Authors: Choksi Atri , Endy Drew 
Published: February 2019

ABSTRACTNatural biological patterns arise via the growth, differentiation, death, differential adhesion, communication, and movement of or among cells. Synthetic biologists typically impose explicit genetic control of cell-cell communication and programmable cell state to realize engineered biological patterns. Such engineering approaches do not usually consider the underlying physical properties of individual cells that inevitably contribute to pattern development. To better integrate synthetic genetic systems engineering with natural growth and patterning we derived abstract functions that relate how changes in basic cell properties such as growth rate, length, and radius of curvature result in differences in the curvature, end-point reliability, and texture of borders that define boundaries among growing cell lineages. Each abstracted border function is derived holistically as an emergent consequence of underlying cell physical properties. We experimentally demonstrate control of border curvature to angles of 60° from initial trajectories, control of end-point variability to within 15° of desired target endpoints, and control of border texture between 10 to 60 unit cell lengths. In combination with synthetic genetic control systems, we grow arbitrary two-dimensional patterns including phases of the moon, PacMen, and a yinyang-like pattern. Differences between the idealized and observed behavior of abstracted border functions highlight opportunities for realizing more precise control of growth and form, including better integration of synthetic genetic systems with native cellular properties and processes.
Comparison Between UMAP and t-SNE for Multiplex-Immunofluorescence Derived Single-Cell Data from Tissue Sections
Authors: Wu Duoduo , Poh Sheng Joe Yeong , Su-En Grace Tan , Chevrier Marion , Jie Hua Josh Loh , Kiat Hon Tony Lim , Chen Jinmiao 
Published: February 2019

AbstractUsing human hepatocellular carcinoma (HCC) tissue samples stained with seven immune markers including one nuclear counterstain, we compared and evaluated the use of a new dimensionality reduction technique called Uniform Manifold Approximation and Projection (UMAP), as an alternative to t-Distributed Stochastic Neighbor Embedding (t-SNE) in analysing multiplex-immunofluorescence (mIF) derived single-cell data. We adopted an unsupervised clustering algorithm called FlowSOM to identify eight major cell types present in human HCC tissues. UMAP and t-SNE were ran independently on the dataset to qualitatively compare the distribution of clustered cell types in both reduced dimensions. Our comparison shows that UMAP is superior in runtime. Both techniques provide similar arrangements of cell clusters, with the key difference being UMAP’s extensive characteristic branching. Most interestingly, UMAP’s branching was able to highlight biological lineages, especially in identifying potential hybrid tumour cells (HTC). Survival analysis shows patients with higher proportion of HTC have a worse prognosis (p-value = 0.019). We conclude that both techniques are similar in their visualisation capabilities, but UMAP has a clear advantage over t-SNE in runtime, making it highly plausible to employ UMAP as an alternative to t-SNE in mIF data analysis.
PhotorhabdusVirulence Cassettes: extracellular multi-protein needle complexes for delivery of small protein effectors into host cells
Authors: Vlisidou Isabella , Hapeshi Alexia , Healey Joseph R. J. , Smart Katie , Yang Guowei , Waterfield Nicholas R. 
Published: February 2019

AbstractPhotorhabdusis a highly effective insect pathogen and symbiont of insecticidal nematodes. To exert its potent insecticidal effects, it elaborates a myriad of toxins and small molecule effectors. Among these, thePhotorhabdusVirulence Cassettes (PVCs) represent an elegant self-contained delivery mechanism for diverse protein toxins. Importantly, these self-contained nanosyringes overcome host cell membrane barriers, and act independently, at a distance from the bacteria itself. In this study, we demonstrate that Pnf, a PVC needle complex associated toxin, is a Rho-GTPase, which acts via deamidation and transglutamination to disrupt the cytoskeleton. TEM and Western blots have shown a physical association between Pnf and its cognate PVC delivery mechanism. We demonstrate that for Pnf to exert its effect, translocation across the cell membrane is absolutely essential.SIGNIFICANCE STATEMENTHere we provide an up to date analysis of the nano-scale syringe-like molecular devices thatPhotorhabdususe to manipulate invertebrate hosts, the PVC system. They are related to theSerratiaAnti-Feeding Prophage and the Psuedoalteromonas MAC system. All these systems are in turn more distantly related to the well characterized Type VI secretion system currently receiving a great deal of attention. We demonstrate for the first time that the PVC nanosyringes are physically “loaded” with an effector protein payload before being freely released. The PVCs therefore represent bacterial molecular machines that are used as “long-range” protein delivery systems. This widespread class of toxin delivery system will likely prove of great significance in understanding many diverse bacteria/host interactions in future.
An Exclusively Skewed Distribution of Pediatric Immune Reconstitution Inflammatory Syndrome Towards the Female Sex is Associated with Advanced Acquired Immune Deficiency Syndrome
Authors: de Souza Campos Fernandes Regina Célia , Louvain de Souza Thaís , da Silva Barcellos Thiago , Medina-Acosta Enrique 
Published: February 2019

AbstractIn human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) patients with very low CD4 cell counts, there is a temporal relationship between administration of antiretroviral therapy (ART) and an increased inflammatory response state known as the immune reconstitution inflammatory syndrome (IRIS). The predominant clinical presentation of IRIS is an infectious disease that can be life-threatening. IRIS-related infectious events are distributed similarly between adult males and females, albeit a few studies have shown a skewing towards the male sex in pediatric IRIS. Here, we assessed sex-specific differences in the causes and extent of IRIS infectious events in HIV-infected pediatric patients on ART. We carried out a prospective clinical analysis (from 2000 to 2018) of IRIS-related infectious events after ART in a cohort of 82 Brazilian children and adolescents infected with HIV-1 through mother-to-child transmission as well as a comprehensive cross-referencing with public records on IRIS-related infectious causes in pediatric HIV/AIDS. Twelve events fulfilling the criteria of IRIS occurred exclusively in eleven females in our cohort. The median age at IRIS events was 3.6 years. The infectious causes included Mycobacterium bovis, varicella-zoster virus, molluscum contagiosum virus, human papillomavirus, cytomegalovirus, and Mycobacterium tuberculosis. In one female, there was regional bacillus Calmette-Guérin dissemination and cytomegalovirus esophagitis. There was complete health recovery after ten IRIS events without the use of corticosteroids or ART interruption. One case of IRIS-associated miliary tuberculosis was fatal. The biological female sex was a significant risk factor for IRIS events (odds ratio: 23.67; 95% confidence interval 95%: 1.341 – 417.7; P = 0.0016). We observed an effect of the advanced HIV/AIDS variable in IRIS females as compared with non-IRIS females (mean CD4+ T cell percentage 13.36% versus 18.63%; P = 0.0489), underpinning the exclusively skewed distribution towards the female sex of this cohort. Moreover, the IRIS females in our cohort had higher mean CD4+ T cell percentages before (13.36%) and after IRIS (26.56%) than those of the IRIS females (before IRIS, 4.978%; after IRIS, 13.81%) in previous studies conducted worldwide. We concluded that the exclusively skewed distribution of pediatric IRIS towards females is associated with more advanced AIDS.
Robust 3D Bloch-Siegert based B1+ mapping using Multi-Echo General Linear Modelling
Authors: Corbin Nadège , Acosta-Cabronero Julio , Malik Shaihan J. , Callaghan Martina F. 
Published: February 2019

AbstractPurposeQuantitative MRI applications, such as mapping the T1 time of tissue, puts high demands on the accuracy and precision of transmit field (B1+) estimation. A candidate approach to satisfy these requirements exploits the difference in phase induced by the Bloch-Siegert Shift (BSS) of two acquisitions with opposite off-resonance frequency RF pulses. Interleaving these RF pulses ensures robustness to motion and scanner drifts, however, here we demonstrate that doing so also introduces a bias in the B1+ estimates.MethodsWe show via simulation and experiments that the amplitude of the error depends on MR pulse sequence parameters, such as TR and RF spoiling increment, but more problematically, on the intrinsic properties, T1 and T2, of the investigated tissue. To solve these problems, we present a new approach to BSS-based B1+ estimation that uses a multi-echo acquisition and a general linear model (GLM) to estimate the correct BSS-induced phase.ResultsIn line with simulations, phantom and in-vivo experiments confirmed that the GLM-based method removed the dependency on tissue properties and pulse sequence settings. It also showed greater robustness to hardware imperfections.ConclusionThe GLM-based method is recommended as a more accurate approach to BSS-based B1+ mapping.
Attacked from above and below, new observations of cooperative and solitary predators on roosting cave bats
Authors: Tanalgo Krizler Cejuela. , Waldien Dave L. , Monfort Norma , Hughes Alice Catherine 
Published: February 2019

AbstractPredation of bats in their roosts has previously only been attributed to a limited number of species such as various raptors, owls, and snakes. However, in situations where due to over-crowding and limited roost space, some individuals may be forced to roost in suboptimal conditions, such as around the entrances of caves and may thus be vulnerable to predation by species which would normally be unlikely to predate bats whilst roosting inside caves. Here, we describe the first documented cooperative hunting of the Large-billed Crow, Corvus macrorhynchos Wagler, 1827 (Passeriformes: Corvidae) and opportunistic predation by the Yellow-headed water monitor, Varanus cumingi Martin, 1839 (Squamata: Varanidae) in the world’s largest colony of Geoffroy’s Rousette, Rousettus amplexicaudatus (É. Geoffroy Saint-Hilaire, 1810) (Chiroptera: Pteropidae) in the Island of Samal, Mindanao, Philippines.
LatentToxoplasma gondiiinfection increases soluble mutant huntingtin and promotes neurodegeneration in the YAC128 mouse model of Huntington’s disease
Authors: Donley David W. , Jenkins Teal , Deiter Cailin , Campbell Reed , Realing Marley , Chopra Vanita , Hersch Stephen , Gigley Jason P. , Fox Jonathan H. 
Published: February 2019

AbstractToxoplasma gondiicauses a prevalent neuroinvasive protozoal pathogen that in immune competent individuals results in latent infection characterized by intra-cellular parasite cysts in brain. Despite life-long infection, the role of latent toxoplasmosis on chronic neurodegenerative processes is poorly understood. Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a dominant CAG repeat expansion in the huntingtin gene (HTT) that results in the expression and accumulation of mutant huntingtin protein (mHTT). The mutant HD gene is fully penetrant. However, there is significant variability in disease progression that is in part explained by as yet unidentified environmental factors. The kynurenine pathway of tryptophan metabolism (KP) is an inflammatory pathway and its activation is implicated in HD pathogenesis. KP upregulation also occurs in response to infection withToxoplasma gondiisuggesting that the latent infection may promote HD. We discovered that mice on the FVB/NJ background develop latent toxoplasmosis following infection with the ME49 strain ofT. gondii. This finding enabled us to address the hypothesis that latent toxoplasmosis potentiates disease in the YAC128 mouse model of HD, as these mice are maintained on the FVB/NJ background. Wild-type and HD mice were infected at 2-months of age. During the 10-month follow-up, infection had adverse effects on mice of both genotypes. However, YAC128 HD mice demonstrated specific vulnerability to latent toxoplasmosis, as demonstrated by the presence of increased striatal degeneration, high levels of the blood neurodegeneration marker neurofilament light protein, and elevated brain soluble mHTT. Our studies have uncovered a novel HD-infection interaction in mice that provides insights into the large variability of the human HD phenotype.
Evaluating the stoichiometric trait distributions of cultured bacterial populations and uncultured microbial communities
Authors: Manzella Michael , Geiss Roy , Hall E.K. 
Published: February 2019

Originality StatementThe ecological stoichiometry of microbial biomass has most often focused on the ratio of the biologically-important elements carbon (C), nitrogen (N), and phosphorus (P) and has primarily been examined at a resolution where the contribution of the individual is masked by the reported population or community average. However, reporting population or community averages makes it difficult to assess phenotypic plasticity and stochasticity and mask important information required to understand both the drivers and implications of microbial biomass stoichiometry in nature. One way to assess the diversity of individual microbial phenotypes is through the use of single-cell techniques such as energy dispersive spectroscopy (EDS). EDS reports cellular quotas for the majority of elements composing microbial biomass including C, N, and P. In this study, by measuring individual cells within a microbial community or population, we describe for the first time the stoichiometry of microbial biomass as a distribution instead of an average. Exploration of stoichiometric trait distributions (as presented here) has the potential to improve our understanding of how nutrients interact with individual microorganisms to structure the elemental content of bacterial biomass and better describe how bacterial community biomass affects the ecosystems within which these organisms exist.SummaryTo assess the potential for EDS to describe the stoichiometric variance within populations and communities we measured the stoichiometric trait distribution of cultured freshwater bacterial populations under different resource conditions and compared them to natural microbial communities sampled from three lakes. Mean biomass C:N:P values obtained by EDS matched closely to those obtained by bulk measures using traditional analytical techniques for each freshwater isolate. However, we observed pronounced differences in the stoichiometric trait distributions of freshwater bacterial isolates compared to the stoichiometric trait distributions of natural communities. The stoichiometric trait distribution of the environmental isolates changed with P availability, growth phase, and genotype, with P availability having the strongest effect. The distribution of biomass ratios within each isolate growth experiment were the most constrained during stages of rapid growth and commonly had unimodal distributions. In contrast to the population distributions, the distribution of N:P and C:P for a similar number of cells from each of the mixed lake communities had narrower stoichiometric distributions and more commonly exhibited multiple modes.