bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical Modeling Identifies the Role of Adaptive Immunity as a Key Controller of Respiratory Syncytial Virus (RSV) Titer in Cotton Rats
Authors: Wethington Darren , Harder Olivia , Uppulury Karthik , Stewart William C. L. , Chen Phylip , King Tiffany , Reynolds Susan D. , Peeples Mark E. , Niewiesk Stefan , Das Jayajit 
Published: October 2018

AbstractRespiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modeling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well differentiated human airway epithelial (HAE) culturesin vitroand in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titer kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titer kinetic features including a faster time scale of viral titer clearance than viral production, and a monotonic decrease in the peak RSV titer with decreasing inoculum dose. Parameter estimation in the ODE model using a non-linear mixed effects approach revealed a very low rate (average single cell lifetime > 10 days) of cell lysis by RSV before the adaptive immune response is initiated. Our model predicted negligible changes in the RSV titer kinetics on earlier days (< 5 d.p.i) but a slower decay in RSV titer in immunosuppressed cotton rats compared to that in non-suppressed cotton rats at later days (>5 d.p.i)in silico.These predictions were in excellent agreement with the experimental results. Our combined approach quantified the importance of the adaptive immune response in suppressing RSV infection in cotton rats, which could be useful in testing RSV vaccine candidates.ImportanceA major difficulty in developing vaccines against RSV infection is our rudimentary understanding of the mechanisms that underlie RSV infection. We addressed this challenge by developing a mechanistic computational model with predictive powers for describing RSV infection kinetics in cotton rats. The model was constructed synergistically within vitroandin vivomeasurements. The combined framework determined an important role for CD8+ T cells responses in reducing RSV titers in cotton rats. The framework can be used to design future experiments to elucidate mechanisms underlying RSV infection and test outcomes for potential vaccine candidates. In addition, estimation of the model parameters provides quantitative values for parameters of biological and clinical interest such as the replication rate of RSV, the death rate of infected cells, and the average number of new infections initiated by a single infected cell.
Metagenomic characterization of the viral community of the South Scotia Ridge
Authors: Yang Qingwei , Gao Chen , Jiang Yong , Wang Min , Zhou Xinhao , Shao Hongbing , Gong Zheng , McMinn Andrew 
Published: October 2018

AbstractViruses are the most abundant biological entities in aquatic ecosystems and harbor an enormous genetic diversity. While their great influence on the marine ecosystems is widely acknowledged, current information about their diversity remains scarce. Aviral metagenomic analysis of two surfaces and one bottom water sample was conducted from sites on the South Scotia Ridge (SSR) near the Antarctic Peninsula, during the austral summer 2016. The taxonomic composition and diversity of the viral communities were investigated and a functional assessment of the sequences was determined. Phylotypic analysis showed that most viruses belonging to the order Caudovirales, in particular, the family Podoviridae (41.92-48.7%), which is similar to the viral communities from the Pacific Ocean. Functional analysis revealed a relatively high frequency of phage-associated and metabolism genes. Phylogenetic analyses of phage TerL and Capsid_NCLDV (nucleocytoplasmic large DNA viruses) marker genes indicated that many of the sequences associated with Caudovirales and NCLDV were novel and distinct from known complete phage genomes. High Phaeocystis globosa virus virophage (Pgvv) signatures were found in SSR area and complete and partial Pgvv-like were obtained which may have an influence on host-virus interactions in the area during summer. Our study expands the existing knowledge of viral communities and their diversities from the Antarctic region and provides basic data for further exploring polar microbiomes.ImportanceIn this study, we used high-throughput sequencing and bioinformatics analysis to analyze the viral community structure and biodiversity of SSR in the open sea near the Antarctic Peninsula. The results showed that the SSR viromes are novel, oceanic-related viromes and a high proportion of sequence reads was classified as unknown. Among known virus counterparts, members of the order Caudovirales were most abundant which is consistent with viromes from the Pacific Ocean. In addition, phylogenetic analyses based on the viral marker genes (TerL and MCP) illustrate the high diversity among Caudovirales and NCLDV. Combining deep sequencing and a random subsampling assembly approach, a new Pgvv-like group was also found in this region, which may a signification factor regulating virus-host interactions.
Gut microbiota and phytoestrogen-associated infertility in southern white rhinoceros
Authors: Williams Candace L. , Ybarra Alexis R. , Meredith Ashley N. , Durrant Barbara S. , Tubbs Christopher W. 
Published: October 2018

AbstractWith recent poaching of southern white rhinoceros (Ceratotherium simum simum; SWR) reaching record levels, the need for a robust assurance population is urgent. However, the global captive SWR population is not currently self-sustaining due to the reproductive failure of captive-born females. Dietary phytoestrogens have been proposed to play a role in this phenomenon, and recent work has demonstrated a negative relationship between diet estrogenicity and fertility of captive-born female SWR. To further examine this relationship, we compared gut microbial communities, fecal phytoestrogens, and fertility of SWR to another rhinoceros species–the greater one-horned rhinoceros (Rhinoceros unicornis; GOHR), which consumes a similar diet but exhibits high levels of fertility in captivity. Using 16S rRNA amplicon sequencing and mass spectrometry, we identified a species-specific fecal microbiota and three dominant fecal phytoestrogen profiles. These profiles exhibited varying levels of estrogenicity when tested in an in vitro estrogen receptor activation assay for both rhinoceros species, with profiles dominated by the microbial metabolite, equol, stimulating the highest levels of receptor activation. Finally, we found that SWR fertility varies significantly with respect to phytoestrogen profile, but also with the abundance of several bacterial taxa and microbially-derived phytoestrogen metabolites. Taken together, these data suggest that in addition to species differences in estrogen receptor sensitivity to phytoestrogens, reproductive outcomes may be driven by gut microbiota’s transformation of dietary phytoestrogens in captive SWR females.
A small RNA controls bacterial resistance to gentamicin during iron starvation
Authors: Chareyre Sylvia , Barras Frédéric , Mandin Pierre 
Published: October 2018

ABSTRACTPhenotypic resistance describes a bacterial population that becomes transiently resistant to an antibiotic without requiring a genetic change. We here investigated the role of the small regulatory RNA (sRNA) RyhB, a key contributor to iron homeostasis, in the phenotypic resistance ofEscherichia colito various classes of antibiotics. We found that RyhB induces resistance to gentamicin, an aminoglycoside that targets the ribosome, when iron is scarce. RyhB induced resistance is due to the inhibition of respiratory complexes Nuo and Sdh activities. These complexes, which contain numerous Fe-S clusters, are crucial for generating a proton motive force (pmf) that allows gentamicin uptake. RyhB directly represses the expression ofnuoandsdhoperons by binding to their mRNAs, thereby inhibiting their translation. Indirectly, RyhB also inhibits the maturation of Nuo and Sdh by repressing synthesis of the Isc Fe-S biogenesis machinery. Notably, our study identifiesnuoas a new direct RyhB target and shows that respiratory complexes activity levels are predictive of the bacterial sensitivity to gentamicin. Altogether, these results unveil a new role for RyhB in the adaptation to antibiotic stress, an unprecedented consequences of its role in iron starvation stress response.AUTHOR’S SUMMARYUnderstanding the mechanisms at work behind bacterial antibiotic resistance has become a major health issue in the face of the antibiotics crisis. Here, we show that RyhB, a bacterial small regulatory RNA, induces resistance ofEscherichia colito the antibiotic gentamicin when iron is scarce, an environmental situation prevalent during host-pathogen interactions. This resistance is due to RyhB repression of the synthesis and post-translational maturation of the respiratory complexes Nuo and Sdh. These complexes are crucial in producing the proton motive force that allows uptake of the antibiotics in the cell. Altogether, these data point out to a major role for RyhB in escaping antibacterial action.
Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration
Authors: Garcia Sandra Ruiz , Deprez Marie , Lebrigand Kevin , Paquet Agnès , Cavard Amélie , Arguel Marie-Jeanne , Magnone Virginie , Caballero Ignacio , Leroy Sylvie , Marquette Charles-Hugo , Marcet Brice , Barbry Pascal , Zaragosi Laure-Emmanuelle 
Published: October 2018

AbstractBackgroundIt is usually considered that the upper airway epithelium is composed of multiciliated, goblet, secretory and basal cells, which collectively constitute an efficient first line of defense against inhalation of noxious substances. Upon injury, regeneration of this epithelium through proliferation and differentiation can restore a proper mucociliary function. However, in chronic airway diseases, the injured epithelium frequently displays defective repair leading to tissue remodeling, characterized by a loss of multiciliated cells and mucus hyper-secretion. Delineating drivers of differentiation dynamics and cell fate in the human airway epithelium is important to preserve homeostasis.ResultsWe have used single cell transcriptomics to characterize the sequence of cellular and molecular processes taking place during human airway epithelium regeneration. We have characterized airway subpopulations with high resolution and lineage inference algorithms have unraveled cell trajectories from basal to luminal cells, providing markers for specific cell populations, such as deuterosomal cells, i.e. precursors of multiciliated cells. We report that goblet cells, like secretory cells, can act as precursors of multiciliated cells. Our study provides a repertoire of molecules involved in key steps of the regeneration process, either keratins or components of the Notch, Wnt or BMP/TGFβ signaling pathways. Our findings were confirmed in independent experiments performed on fresh human and pig airway samples, and on mouse tracheal epithelial cells.ConclusionsOur single-cell RNA-seq study provides novel insights about airway epithelium differentiation dynamics, clarifies cell trajectories between secretory, goblet and multiciliated cells, identifies novel cell subpopulations, and maps the activation and repression of key signaling pathways.
A Machine Learning Approach to Map Tropical Selective Logging
Authors: Hethcoat MG , Edwards DP , Carreiras JMB , Bryant RG , França FM , Quegan S 
Published: October 2018

AbstractHundreds of millions of hectares of tropical forest have been selectively logged, either legally or illegally. Methods for detecting and monitoring tropical selective logging using satellite data are at an early stage, with current methods only able to detect more intensive timber harvest (>20 m3 ha−1). The spatial resolution of widely available datasets, like Landsat, have previously been considered too coarse to measure the subtle changes in forests associated with less intensive selective logging, yet most present-day logging is at low intensity. We utilized a detailed selective logging dataset from over 11,000 ha of forest in Rondônia, southern Brazilian Amazon, to develop a Random Forest machine-learning algorithm for detecting low-intensity selective logging (< 15 m3 ha−1). We show that Landsat imagery acquired before the cessation of logging activities (i.e. the final cloud-free image of the dry season during logging) was better at detecting selective logging than imagery acquired at the start of the following dry season (i.e. the first cloud-free image of the next dry season). Within our study area the detection rate of logged pixels was approximately 90% (with roughly 20% commission and 8% omission error rates) and approximately 40% of the area inside low-intensity selective logging tracts were labelled as logged. Application of the algorithm to 6152 ha of selectively logged forest at a second site in Pará, northeast Brazilian Amazon, resulted in the detection of 2316 ha (38%) of selective logging (with 20% commission and 7% omission error rates). This suggests that our method can detect low-intensity selective logging across large areas of the Amazon. It is thus an important step forward in developing systems for detecting selective logging pan-tropically with freely available data sets, and has key implications for monitoring logging and implementing carbon-based payments for ecosystem service schemes.
Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation ofhmx3aexpression
Authors: Hartwell Ryan D. , England Samantha J. , Monk Nicholas A. M. , van Hateren Nicholas J. , Baxendale Sarah , Marzo Mar , Lewis Katharine E. , Whitfield Tanya T. 
Published: October 2018

AbstractIn the zebrafish, Fgf and Hh signalling assign anterior and posterior identity, respectively, to the poles of the developing ear. Mis-expression offgf3or inhibition of Hh signalling results in double-anterior ears, including ectopic expression ofhmx3a. To understand how this double-anterior pattern is established, we characterised transcriptional responses in Fgf gain-of-signalling or Hh loss-of-signalling backgrounds. Mis-expression offgf3resulted in rapid expansion of anterior otic markers, refining over time to give the duplicated pattern. Response to Hh inhibition was very different: initial anteroposterior asymmetry was retained, with de novo duplicate expression domains appearing later. We show that Hmx3a is required for normal anterior otic patterning, but neither loss nor gain ofhmx3afunction was sufficient to generate ear duplications. Using our data to infer a transcriptional regulatory network required for acquisition of otic anterior identity, we can recapitulate both the wild-type and the double-anterior pattern in a mathematical model.
Connecting the Microenvironmental Niche to Treatment Response in Ovarian Cancer
Authors: Strobl Maximilian , Wicker Matthew , Adhikarla Vikram , Shockey W. Andrew , Lakatos Eszter , Pooladvand Pantea , Schenk Ryan , Saputro Linggih , Gatenbee Chandler , Koppens Martijn , García Salvador Cruz , Wenham Robert , Damaghi Mehdi , Gallaher Jill A. 
Published: October 2018

AbstractOvarian cancer has the highest mortality rate of all gynecologic cancers, which may be attributed to an often late stage diagnosis, when the cancer is already metastatic, and rapid development of treatment resistance. We propose that the metastatic disease could be better characterized by observing interactions within the microenvironmental niche of the primary site that shapes the tumor’s early phenotypic progression. We present a mechanistic mathematical model of ovarian cancer that considers spatial interactions between tumor cells and several key stromal components. We demonstrate how spatial biomarker imaging data from the primary tumor can be analyzed to define a patient-specific microenvironment in the mathematical model. We then show preliminary results, using this model, that demonstrate how differences in the niche composition of a tumor affects phenotypic evolution and treatment response.
A Novel analog approach for fast evaluation of affinity between ligand and receptor in scaled up molecular models
Authors: Tavousi Pouya , Shahbazmohamadi Sina 
Published: October 2018

AbstractRational structure based drug design aims at identifying ligand molecules that bind to the active site of a target molecule with high affinity (low binding free energy), to promote or inhibit certain biofunctions. Thus, it is absolutely essential that one can evaluate such affinity for the predicted molecular complexes in order to design drugs effectively. A key observation is that, binding affinity is proportional to the geometric fit between the two molecules. Having a way to assess the quality of the fit enables one to rank the quality of potential drug solutions. Other than experimental methods that are associated with excessive time, labor and cost, several in silico methods have been developed in this regard. However, a main challenge of any computation-based method is that, no matter how efficient the technique is, the trade-off between accuracy and speed is inevitable. Therefore, given today’s existing computational power, one or both is often compromised. In this paper, we propose a novel analog approach, to address the aforementioned limitation of computation-based algorithms by simply taking advantage of Kirchhoff’s circuit laws. Ligand and receptor are represented with 3D printed molecular models that account for the flexibility of the ligand. Upon the contact between the ligand and the receptor, an electrical current will be produced that is proportional to the number of representative contact points between the two scaled up molecular models. The affinity between the two molecules is then assessed by identifying the number of representative contact points obtainable from the measured total electrical current. The simple yet accurate proposed technique, in combination with our previously developed model, Assemble-And-Match, can be a breakthrough in development of tools for drug design. Furthermore, the proposed technique can be more broadly practiced in any application that involves assessing the quality of geometric match between two physical objects.
The impact of human activities on Australian wildlife
Authors: Taylor-Brown Alyce , Booth Rosie , Gillett Amber , Mealy Erica , Ogbourne Steven , Polkinghorne Adam , Conroy Gabriel C. 
Published: October 2018

AbstractIncreasing human population size and the concomitant expansion of urbanisation significantly impact natural ecosystems and native fauna globally. Successful conservation management relies on precise information on the factors associated with wildlife population decline, which are challenging to acquire from natural populations. Wildlife Rehabilitation Centres (WRC) provide a rich source of this information. However, few researchers have conducted large-scale longitudinal studies, with most focussing on narrow taxonomic ranges, suggesting that WRC-associated data remains an underutilised resource, and may provide a fuller understanding of the anthropogenic threats facing native fauna.We analysed admissions and outcomes data from a WRC in Queensland, Australia Zoo Wildlife Hospital, to determine the major factors driving admissions and morbidity of native animals in a region experiencing rapid and prolonged urban expansion.We studied 31,626 admissions of 83 different species of native birds, reptiles, amphibians, marsupials and eutherian mammals from 2006 to 2017. While marsupial admissions were highest (41.3%), admissions increased over time for all species and exhibited seasonal variation (highest in Spring to Summer), consistent with known breeding seasons.Causes for admission typically associated with human influenced activities were dominant and exhibited the highest mortality rates. Car strikes were the most common reason for admission (34.7%), with dog attacks (9.2%), entanglements (7.2%), and cat attacks (5.3% also high. Admissions of orphaned young and overt signs of disease were significant at 24.6% and 9.7%, respectively. Mortality rates were highest following dog attacks (72.7%) and car strikes (69.1%) and lowest in orphaned animals (22.1%).Our results show that WRC databases offer rich opportunities for wildlife monitoring and provide quantification of the negative impacts of human activities on ecosystem stability and wildlife health. The imminent need for urgent, proactive conservation management to ameliorate the negative impacts of human activities on wildlife is clearly evident from our results.
Rapid clearing of biological organs by using phosphoric acid, a hydrophilic solution with high refractive index
Authors: Umezawa Masakazu , Haruguchi Shinsuke , Fukushima Rihito , Sekiyama Shota , Kamimura Masao , Soga Kohei 
Published: October 2018

AbstractTissue clearing is a fundamental challenge in biology and medicine to achieve high-resolution optical imaging of tissues deep inside intact organs. The clearing methods, reported up to now, require long incubation time or physical/electrical pressure to achieve tissue clearing, which is done by matching the refractive indices of the whole sample and medium to that of the lipid layer. Here we show that phosphoric acid increases the refractive index of the medium and can increase the transparency of formalin-fixed tissue samples rapidly. Immersion of fixed tissues of mice in phosphoric acid solutions increased their transparency within 60 min in the case of 3-mm-thick fixed tissue specimens. While phosphoric acid suppresses bright signals on the boundary of cells in their phase-contrast images, it does not damage the morphology of cell membrane with phospholipid bilayer. The protocol presented herein may contribute to develop better and faster soaking methods for tissue clearing than previously reported protocols.Highlights▪ Phosphoric acid can reduce light scattering by tissue samples.▪ Tissue clearing effect of phosphoric acid is fast and needs only 60-min incubation.▪ Cell membrane was preserved during incubation using phosphoric acid.