bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients
Authors: Tracy Mary Fran , Chlan Linda , Savik Kay , Skaar Debra J. , Weinert Craig
Published: December 2018

Background

Although potent sedative and opioid drugs are some of the most commonly used medications to manage pain, anxiety, and discomfort in critically ill patients, conducting clinical trials where sedative and opioid medications are outcome variables within a longitudinal research design can be a methodological challenge.

Objectives

The purpose of this article is to provide in detail a conceptual discussion of the concept and analysis of sedative exposure: A novel research analysis method for aggregating sedative and opioid medication doses from disparate drug classes commonly administered to critically ill patients and used by our team in several clinical research studies.

Methods

Comparing the dose of each sedative and opioid administered to an individual patient (within a defined time interval) to all other patients in a research study receiving the same medications allows for ranking of dosages for each medication by quartiles. Rank values for all sedatives and opioids received can be summed to a single value resulting in a Sedation Intensity Score. In addition, a simple count of how many hours at least one dose of a sedative or opioid medication has been administered can determine sedation frequency.

Results

This method can allow for comparison of sedative exposure with medications from disparate drug classes and for analysis of estimates of change in medication use over time.

Discussion

This novel research analysis method can overcome the challenges and limitations of determining changes in sedative and opioid medication regimens in cohort and clinical trial study designs.
Use of Assistive Devices to Lift, Transfer, and Reposition Hospital Patients
Authors: Schoenfisch Ashley L. , Kucera Kristen L. , Lipscomb Hester J. , McIlvaine Jennifer , Becherer Lori , James Tamara , Avent Susan
Published: December 2018

Background

Devices to lift, transfer, and reposition patients are recommended for healthcare workers' and patients' safety, but their intended use has yet to be fully realized.

Objective

The aim of this study was to describe hospital nursing staff use of lift/transfer devices and the presence of factors at the time of lifts/transfers with potential to influence whether devices are used.

Methods

Participants were 108 US nursing staff in a university-based medical center and two community hospitals. A self-completed questionnaire was used to collect demographic and work characteristics, typical frequency of patient lifts/transfers, training in and typical use of lift equipment, and specific factors that could influence use. Proportional distributions of lifting/transferring and repositioning frequencies in a typical shift, amount of equipment use, and factors present were examined overall and across worker and work-related characteristics.

Results

Although trained in equipment use, only 40% used equipment for at least half of lifts/transfers. During lifts/transfers, factors often present included patient unable to help with lift/transfer (91.3%) or of a size/weight where participant needed assistance to help lift/transfer (87.5%); availability of others who could assist with manual lift (86.3%) or use of lift equipment (82.4%); and equipment functioning properly (86.4%), having supplies available (82.5%), and being easy to retrieve from storage (81.6%). During repositioning tasks, physical assistance was “always/almost always” provided from coworkers (83.3%) and often perceived as “very helpful” (92.6%) in reducing physical demands. Physical assistance from patients was less common (14.0% “always/almost always”) yet perceived as “very helpful” by 66.3%. One fifth always used friction-reducing devices.

Discussion

Despite training in their use, nursing staff use of available lift equipment and assistive devices is limited. Factors present at the time of lifts/transfers that may influence equipment/device use reflect a complex mix of patient, worker, equipment, and situational characteristics.
Gray-zone Lymphoma Between cHL and Large B-Cell Lymphoma
Authors: Sarkozy Clémentine , Copie-Bergman Christiane , Damotte Diane , Ben-Neriah Susana , Burroni Barbara , Cornillon Jérome , Lemal Richard , Golfier Camille , Fabiani Bettina , Chassagne-Clément Catherine , Parrens Marie , Herbaux Charles , Xerri Luc , Bossard Celine , Laurent Camille , Cheminant Morgane , Cartron Guillaume , Cabecadas Jose , Molina Thierry , Salles Gilles , Steidl Christian , Ghesquières Hervé , Mottok Anja , Traverse-Glehen Alexandra
Published: December 2018

Gray-zone lymphoma (GZL) with features intermediate between classic Hodgkin lymphoma (cHL) and large B-cell lymphoma (LBCL) was introduced as a provisional entity into the World Health Organization classification in 2008. However, as diagnostic criteria are imprecise, reliable identification of GZL cases remains challenging. Here, we describe the histopathologic features of 139 GZL cases from a retrospective Lymphoma Study Association (LYSA) study with the goal to improve classification accuracy. Inclusion criteria were based on literature review and an expert consensus opinion of the LYSA hematopathologist panel. We observed 86 cases with a morphology more closely related to cHL, but with an LBCL immunophenotype based on strong and homogenous B-cell marker expression (CD20 and/or CD79a, OCT2, BOB1, PAX5) on all tumor cells (cHL-like GZL). Fifty-three cases were morphologically more closely related to LBCL but harbored a cHL immunophenotype (LBCL-like GZL). Importantly, we observed a continuous morphologic and immunophenotypic spectrum within these 2 GZL categories. The majority of cases presented genetic immune escape features with CD274/PDCD1LG2 and/or CIITA structural variants by fluorescence in situ hybridization. Patients without mediastinal involvement at diagnosis (17%) were older than those with mediastinal tumors (median: 56 vs. 39 y). Cases associated with Epstein-Barr virus (24%) presented with similar patient characteristics and outcome as Epstein-Barr virus negative cases. In summary, we provide refined diagnostic criteria that contribute to a more precise pathologic and clinical characterization of GZL within a broad spectrum from cHL-like to LBCL-like disease.
Choice of Catheter Size for Infants in Continuous Renal Replacement Therapy: Bigger Is Not Always Better*
Authors: Garzotto Francesco , Zaccaria Marta , Vidal Enrico , Ricci Zaccaria , Lorenzin Anna , Neri Mauro , Murer Luisa , Nalesso Federico , Ruggeri Alfredo , Ronco Claudio
Published: December 2018

Objectives:

Renal replacement therapy in infants and small children is the treatment of choice for severe oligoanuric renal dysfunction, with an increasing consensus that early initiation might contribute to preventing acute kidney injury complications. Safer renal replacement therapy devices specifically designed for neonates may contribute to ameliorating outcomes and increasing chances of survival. One of the crucial factors to achieve an effective renal replacement therapy in small infants is adequate vascular access. The interaction of small size central vascular catheters with renal replacement therapy devices has never been investigated. The aim of this study was to characterize both the operating conditions and performance of three different central vascular catheters sizes (4F, 5F, and 7F) connected to two different extracorporeal blood circulation models (adult and pediatric). The rheologic performance of each vascular access size in combination with the adult and pediatric renal replacement therapy models was described.

Design:

Series of experimental extracorporeal circulation circuit tests were conducted with different setups. A two-roller pump was used to simulate a standard adult dialysis machine, whereas a small three-roller pump served as pediatric renal replacement therapy device.

Setting:

A pressure-flow setup aimed to collect pressure and flow values under different test conditions. A second experiment focused on hemolysis estimation induced by the extracorporeal system. Hemolysis exclusively induced by the 4F catheter was also evaluated. Finally, our data were applied to estimate the optimal catheter size theoretically capable of delivering adequate doses basing on anthropometric data (patient weight and cannulation site) in absence of direct ultrasound vessel measurement.

Subjects:

In vitro tests conducted on simulated extracorporeal circuit models of continuous pediatric and neonatal renal replacement therapy.

Interventions:

None.

Measurements and Main Results:

When 4F and 5F catheters are used, maximal blood flows within safe circuit pressures can be set at the values of 13 and 29 mL/min, respectively, when a small pump is used. Differently, when using adult roller pumps, only maximal flows of 10 and 20 mL/min are reached. However, hemolysis is higher when using a three-roller pump compared with the two-roller. The clinical impact of this increased hemolytic burden is likely not relevant.

Conclusions:

Small size central vascular catheters display optimal rheologic performances in terms of pressures and flows particularly when the renal replacement therapy device is equipped with pumps proportional to central vascular catheters sizes, and even when relatively high blood flows are set. This is achieved at the risk of a higher hemolysis rate.
Nonvascularized Bone Graft Reconstruction of the Irradiated Murine Mandible: An Analogue of Clinical Head and Neck Cancer Treatment
Authors: Urlaub Kevin M. , Ettinger Russell E. , Nelson Noah S. , Hoxie Jessie M. , Snider Alicia E. , Perosky Joseph E. , Polyatskaya Yekaterina , Donneys Alexis , Buchman Steven R.
Published: December 2018

Nonvascularized bone grafts (NBGs) represent a practical method of mandibular reconstruction that is precluded in head and neck cancer patients by the destructive effects of radiotherapy. Advances in tissue-engineering may restore NBGs as a viable surgical technique, but expeditious translation demands a small-animal model that approximates clinical practice. This study establishes a murine model of irradiated mandibular reconstruction using a segmental iliac crest NBG for the investigation of imperative bone healing strategies. Twenty-seven male isogenic Lewis rats were divided into 2 groups; control bone graft and irradiated bone graft (XBG). Additional Lewis rats served as graft donors. The XBG group was administered a fractionated dose of 35Gy. All rats underwent reconstruction of a segmental, critical-sized defect of the left hemi-mandible with a 5 mm NBG from the iliac crest, secured by a custom radiolucent plate. Following a 60-day recovery period, hemi-mandibles were evaluated for bony union, bone mineralization, and biomechanical strength (P < 0.05). Bony union rates were significantly reduced in the XBG group (42%) compared with controls (80%). Mandibles in the XBG group further demonstrated substantial radiation injury through significant reductions in all metrics of bone mineralization and biomechanical strength. These observations are consistent with the clinical sequelae of radiotherapy that limit NBGs to nonirradiated patients. This investigation provides a clinically relevant, quantitative model in which innovations in tissue engineering may be evaluated in the setting of radiotherapy to ultimately provide the advantages of NBGs to head and neck cancer patients and reconstructive surgeons.
A multiparametric, quantitative and high-throughput assay to quantify the influence of target size on phagocytic uptake
Authors: Montel Lorraine , Pinon Léa , Fattaccioli Jacques
Published: December 2018

Phagocytosis by macrophages represents a fundamental process essential for both immunity and tissue homeostasis. It consists in the uptake of pathogenic or cellular targets larger than 0.5μm. For the biggest particles, the phagocytic process involves a massive reorganization of membrane and actin cytoskeleton as well as an important intracellular deformation, all in a matter of minutes. The study of the role of the size of objects in their phagocytosis has lead to contradictory results in the last decades.
We designed a method using confocal microscopy, automated image analysis and databases for fast quantitative analysis of phagocytosis assays. It yields comprehensive data on the cells and targets geometric and fluorescence intensity parameters, automatically discriminates internalized from external targets, and stores the relationship between a cell and the targets it has engulfed. We used two types of targets, solid polystyrene beads and liquid lipid droplets, to investigate the influence of size on the phagocytic uptake of macrophages. The method made it possible, not only to perform phagocytic assays with functionalized droplets and beads of different sizes, but to use polydisperse particles to further our understanding of the role of size in phagocytosis.
The use of monodisperse and polydisperse objects shows that while smaller monodisperse objects are internalized in greater numbers, objects of different sizes presented simultaneously are internalized without preferred size. Throughout results, the total surface engulfed by the cell appeared to be the main factor limiting the uptake of particles, regardless of their nature or size. A meta-analysis of the literature reveals that this dependence in surface is consistently conserved throughout cell types, nature of targets or activated receptors.
High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine
Authors: Steinberg Asher Preska , Datta Sujit S. , Naragon Thomas , Rolando Justin C. , Bogatyrev Said R. , Ismagilov Rustem F.
Published: December 2018

The lumen of the small intestine (SI) is filled with particulates: microbes, therapeutic particles, and food granules. The structure of this particulate suspension could impact uptake of drugs and nutrients and the function of microorganisms; however, little is understood about how this suspension is re-structured as it transits the gut. Here, we demonstrate that particles spontaneously aggregate in SI luminal fluidex vivo. We find that mucins and immunoglobulins are not required for aggregation. Instead, aggregation can be controlled using polymers from dietary fiber in a manner that is qualitatively consistent with polymer-induced depletion interactions, which do not require specific chemical interactions. Furthermore, we find that aggregation is tunable; by feeding mice dietary fibers of different molecular weights, we can control aggregation in SI luminal fluid. This work suggests that the molecular weight and concentration of dietary polymers play an underappreciated role in shaping the physicochemical environment of the gut.
A probabilistic model to identify the core microbial community
Authors: Gumiere Thiago , Meyer Kyle M. , Burns Adam R. , Gumiere Silvio J. , Bohannan Brendan J. M. , Andreote Fernando D.
Published: December 2018

The core microbial community has been hypothesized to have essential functions ranging from maintaining health in animals to protection against plant disease. However, the identification of the core microbial community is frequently based on arbitrary thresholds, selecting only the most abundant microorganisms. Here, we developed and tested an approach to identify the core community based on a probabilistic model. The Poisson distribution was used to identify OTUs with a probable occurrence in every sample of a given dataset. We identified the core communities of four extensive microbial datasets, and compared the results with conventional, but arbitrary, methods. The datasets were composed of the microbiomes of humans (tongue, gut, and skin), mice (gut), plant (grapevine) tissue, and the maize rhizosphere. Our proposed method revealed core microbial communities with higher richness and diversity than those previously described. This method also includes a greater number of rare taxa in the core, which are often neglected by arbitrary threshold methods. We demonstrated that our proposed method revels a probable core microbial community for each different habitat, which extend our knowledge about shared microbial communities. Our proposed method may help the next steps proving the essential functions of core microbial communities.

Originality-Signifìcance Statement

More rigorous and less arbitrary statistical methods could increase knowledge regarding the role of microorganisms and their interactions. Here, we suggest a probabilistic method to identify the microbial core community across systems. Our method identifies a large proportion of the rare community that likely belongs to the microbial core community, which was not identified by conventional methods. Our probabilistic model is a non-arbitrary approach to defining the microbial core community, which may help in the next step of the microbial core community studies.
Structural Basis for Stereoselective Dehydration and Hydrogen-Bonding Catalysis by the SAM-Dependent Pericyclase LepI
Authors: Cai Yujuan , Hai Yang , Ohashi Masao , Jamieson Cooper S. , Garcia-Borras Marc , Houk K. N. , Zhou Jiahai , Tang Yi
Published: December 2018

LepI is an S-adenosylmethionine (SAM)-dependent pericyclase that catalyzes the formation of 2-pyridone natural product leporin C. Biochemical characterization showed LepI can catalyze the stereoselective dehydration to yield a reactive (E)-quinone methide which can undergo a bifurcating intramolecular Diels-Alder (IMDA) and hetero-Diels-Alder (HDA) cyclization from an ambimodal transition state, and a [3,3]-retro-Claisen rearrangement to recycle the IMDA product into leporin C. Here we solved the X-ray crystal structures of SAM-bound LepI, and in complex with a substrate analog, the product leporin C, and a retro-Claisen reaction transition-state analog to understand the structural basis for the multitude of reactions. Structural and mutational analysis revealed how Nature evolves a classic methyltransferase active site into one that can serve as a dehydratase and a multifunctional pericyclase. Catalysis of both sets of reactions employ His133 and Arg295, two active site residues that are not found in canonical methyltransferases. An alternative role of SAM, which is not found to be in direct contact of the substrate, is also proposed.
Virus-like vesicles expressing multiple antigens for immunotherapy of chronic hepatitis B
Authors: Yarovinsky Timur O. , Mason Stephen W. , Menon Manisha , Krady Marie M. , Haslip Maria , Madina Bhaskara R. , Ma Xianyong , Moshkani Safiehkhatoon , Chiale Carolina , Pal Anasuya Chattopadhyay , Almassian Bijan , Rose John K. , Robek Michael D. , Nakaar Valerian
Published: December 2018

Infection with hepatitis B virus (HBV) can initiate chronic hepatitis and liver injury, eventually progressing to liver fibrosis or cancer and causing more than 600,000 deaths each year worldwide. Current treatments for chronic hepatitis B, relying on nucleoside antivirals and interferon, are inadequate and leave an unmet need for immunotherapeutic approaches. This report describes virus-like vesicles (VLV), a form of self-amplifying RNA replicons, which express multiple HBV antigens (polymerase, core, and middle surface) from a single vector (HBV-VLV). The HBV-VLV induces HBV-specific T cell responses to all three HBV antigens. Immunization of naive mice with the multiantigen HBV-VLV renders them resistant to acute challenge with HBV delivered by adeno-associated virus (AAV). Using a chronic model of HBV infection by AAV delivery of HBV, we demonstrate immunotherapeutic potential of the multiantigen HBV-VLV in combination with DNA booster immunization, as 40% of the HBV-VLV-treated mice showed a decline of the serum HBV surface antigen below the detection limit and marked reduction in liver HBV RNA accompanied by induction of HBsAg-specific CD8 T cells. These results warrant further evaluation of multiantigen HBV-VLV for immunotherapy of chronic hepatitis B.

IMPORTANCE

More than 240 million people worldwide are chronically infected with hepatitis B virus. Current therapies are not sufficiently effective and are often beyond reach in the developing world. We describe a virus-like vesicle-based immunotherapeutic vaccine that expresses three major antigens of hepatitis B virus as a self-amplifying RNA replicon. By incorporating three HBV antigens in a single vaccine, we ensure broad T cell responses. We demonstrate that immunization with this vaccine protects mice from hepatitis B virus in a model of acute challenge. Importantly, treatment with this vaccine shows 40% efficacy in a mouse model of chronic hepatitis B. Thus, this study paves the way for evaluation of the multi-antigen virus-like vesicles as a tool for immunotherapy of chronic hepatitis B.
Cortical excitation:inhibition imbalance causes abnormal brain network dynamics as observed in neurodevelopmental disorders
Authors: Markicevic Marija , Fulcher Ben D. , Lewis Christopher , Helmchen Fritjof , Rudin Markus , Zerbi Valerio , Wenderoth Nicole
Published: December 2018

Abnormal brain development manifests itself at different spatial scales. However, whether abnormalities at the cellular level can be diagnosed from network activity measured withfunctional magnetic resonance imaging (fMRI) is largely unknown, yet of high clinical relevance. Here we applied fMRI while using chemogenetics to increase the excitation-to-inhibition ratio (E:I) within cortical microcircuits of the mouse brain, thereby mimicking a putative mechanism of neurodevelopmental disorders including autism. Increased E:I caused a significant reduction of long-range connectivity, irrespective of whether excitatory neurons were facilitated or inhibitory Parvalbumin interneurons were suppressed. Training a classifier on fMRI signals, we were able to accurately classify cortical areas exhibiting increased E:I. This classifier was validated in an independent cohort ofFmr1y/-knock-out mice, a model for autism with well-documented loss of Parvalbumin neurons and chronic alterations of E:I. Our findings demonstrate a promising novel approach towards inferring microcircuit abnormalities from macroscopic fMRI measurements.
Cryo-Electron tomography 3D structure and nanoscale model of Arabidopsis thaliana cell wall
Authors: Sarkar Purbasha , Kowalczyk Michal , Apte Salil , Yap Edgar G. , Das Jyotirmoy , Adams Paul D , Bajaj Chandrajit , Guindos Pablo , Auer Manfred
Published: December 2018

Using cryo-electron tomography of vitrified sections of one month-old Arabidopsis thaliana inflorescence stem tissue, we visualized primary and secondary cell walls of xylem tissue. Extensive quantitative and statistical analysis of segmented 3D tomographic data allowed geometrically idealized 3D-CAD model building of prototypic microfibrils, cross-links, and their supramolecular microfibril 3D organization. We propose a prototypic microfibril model where a cellulose core is heavily decorated by a thin sheath of hemicellulose with infrequent but sturdy hemicellulose-based cross-links. Such prototypic microfibrils then adopt a rather unexpected 3D supramolecular organization of high order and complexity. We discuss a possible new role for lignin in plant cell walls at low concentrations with lignin not acting as a matrix but rather as a reinforcement of microfibrils and cross-links. Extensive computational simulations of mechanical properties further revealed that this 3D organization of the cell wall is not optimized for load bearing but instead for flexibility and ductility.
Ecological specialization under multidimensional tradeoffs
Authors: Amado André , Campos Paulo R. A.
Published: December 2018

Although tradeoffs are expected to play an essential role in shaping the diversity in a community, their effects remain relatively nebulous and notoriously difficult to assess. This is especially true when multiple tradeoffs occur simultaneously. When dealing with single tradeoffs some information can be predicted based on their curvature. Does the same happen when dealing with multiple tradeoffs? What happens if the tradeoffs have opposing curvatures? To address these issues, we develop a resource-based model that encompasses multiple tradeoffs mediated by the acquisition and processing of the resources. The model considers a spatially structured population of microbial organisms that can grow on an arbitrary number of resources, which come into the system at a constant rate and diffuse through the environment. The individuals can adopt a variety of strategies through mutation constrained by tradeoffs, which renders the model adaptive. We assess population sizes and levels of ecological specialization. We find that when multiple tradeoffs are considered the classical intuition developed for single tradeoffs does not hold. The outcome can depend significantly not only on the curvature of the tradeoffs but also on resource availability.
The effect of tissue composition on gene co-expression
Authors: Zhang Yun , Cuerdo Jonavelle , Halushka Marc K , McCall Matthew N
Published: December 2018

Variable cellular composition of tissue samples represents a significant challenge for the interpretation of genomic profiling studies. Substantial effort has been devoted to modeling and adjusting for compositional differences when estimating differential expression between sample types. However, relatively little attention has been given to the effect of tissue composition on co-expression estimates. In this study, we illustrate the effect of variable cell type composition on correlation-based network estimation and provide a mathematical decomposition of the tissue-level correlation. We show that a class of deconvolution methods developed to separate tumor and stromal signatures can be applied to two component cell type mixtures. In simulated and real data, we identify conditions in which a deconvolution approach would be beneficial. Our results suggest that uncorrelated cell type specific markers are ideally suited to deconvolute both the expression and co expression patterns of an individual cell type. Finally, we provide a Shiny application for users to interactively explore the effect of cell type composition on correlation-based co-expression estimation for any cell types of interest.
Prediction of Hand Movement Speed and Force from Single-trial EEG with Convolutional Neural Networks
Authors: Gatti Ramiro , Atum Yanina , Schiaffino Luciano , Jochumsen Mads , Manresa José Biurrun
Published: December 2018

Building accurate movement decoding models from brain signals is crucial for many biomedical applications. Decoding specific movement features, such as speed and force, may provide additional useful information at the expense of increasing the complexity of the decoding problem. Recent attempts to predict movement speed and force from the electroencephalogram (EEG) achieved classification accuracy levels not better than chance, stressing the demand for more accurate prediction strategies. Thus, the aim of this study was to improve the prediction accuracy of hand movement speed and force from single-trial EEG signals recorded from healthy volunteers. A strategy based on convolutional neural networks (ConvNets) was tested, since it has previously shown good performance in the classification of EEG signals. ConvNets achieved an overall accuracy of 84% in the classification of two different levels of speed and force (4-class classification) from single-trial EEG. These results represent a substantial improvement over previously reported results, suggesting that hand movement speed and force can be accurately predicted from single-trial EEG.
Interpreting mosquito feeding patterns in Australia through an ecological lens; an analysis of blood meal studies.
Authors: Stephenson Eloise B , Murphy Amanda , Jansen Cassie C , Peel Alison J , McCallum Hamish
Published: December 2018

Mosquito-borne pathogens contribute significantly to the global burden of disease, infecting millions of people each year. Mosquito feeding is critical to the transmission dynamics of pathogens, and thus it is important to understanding and interpreting mosquito feeding patterns. In this paper we explore mosquito feeding patterns and their implications for disease ecology through a meta-analysis of published blood meal results collected across Australia from more than 12,000 blood meals from 22 species. To assess mosquito-vertebrate associations and identify mosquitoes on a spectrum of generalist or specialist feeders, we analysed blood meal data in two ways; first using a novel odds ratio analysis, and secondly by calculating Shannon diversity scores. We find that each mosquito species had a unique feeding association with different vertebrates, suggesting species-specific feeding patterns. Broadly, mosquito species could be grouped broadly into those that were primarily ornithophilic and those that fed more often on livestock. Aggregated feeding patterns observed across Australia were not explained by intrinsic variables such as mosquito genetics or larval habitats. We discuss the implications for disease transmission by vector mosquito species classified as generalist-feeders (such as Aedes vigilax and Culex annulirostris), or specialists (such as Aedes aegypti) in light of potential influences on mosquito host choice. Overall, we find that whilst existing blood meal studies in Australia are useful for investigating mosquito feeding patterns, standardisation of blood meal study methodologies and analyses, including the incorporation of vertebrate surveys, would improve predictions of the impact of vector-host interactions on disease ecology. Our analysis can also be used as a framework to explore mosquito-vertebrate associations, in which host availability data is unavailable, in other global systems.
Radial contractility of Actomyosin-II rings facilitates cargo trafficking and maintains axonal structural stability following cargo-induced transient axonal expansion
Authors: Wang Tong , Li Wei , Martin Sally , Papadopulos Andreas , Jiang Anmin , Shamsollahi Golnoosh , Amor Rumelo , Lanoue Vanessa , Padmanabhan Pranesh , Meunier Frederic A.
Published: December 2018

Most mammalian neurons have a narrow axon, which constrains the passage of large cargoes such as autophagosomes that can be larger than the axon diameter. Radial axonal expansion must therefore occur to ensure efficient axonal trafficking. In this study we consistently find that the trafficking speed of various large axonal cargoes is significantly slower than that of small ones, and reveal that the transit of diverse-sized cargoes causes an acute, albeit transient axonal radial expansion, which is immediately restored by constitutive contractility. Using live super-resolution microscopy, we demonstrate that actomyosin-II controls axonal radial contractility and local expansion, and that NM-II filaments associate with periodic F-actin rings via their head domains. Pharmacological inhibition of NM-II activity, significantly increases axon diameter by detaching the NM-II from F-actin, and impacts the trafficking speed, directionality, and overall efficiency of long-range retrograde trafficking. Consequently, prolonged disruption of NM-II activity leads to disruption of periodic actin rings and formation of focal axonal swellings, a hallmark of axonal degeneration.

Axonal radial contractility and local expansion control the retrograde trafficking of large cargoes. The periodic actomyosin-II network comprises of NM-II filaments and F-actin rings. Loss of actomyosin-II-mediated radial contractility causes defects in axonal trafficking and stability, leading to degeneration.
General characterization of regeneration in Aeolosoma viride
Authors: Chen Chiao-Ping , Fok Sheridan Ke-Wing , Hsieh Yu-Wen , Chen Cheng-Yi , Hsu Fei-Man , Chen Jiun-Hong
Published: December 2018

Regeneration has long attracted scientists for its potential to restore lost, damaged or aged tissues and organs. A wide range of studies have conducted on different model organisms on both cellular and molecular levels. Current evidences suggest that a variety of regenerative strategies are developed and used by different species, and their regenerative strategies are highly correlated to their reproductive methods. Our present work focused on the freshwater annelid Aeolosoma viride, which reproduces by paratonic fission and is capable of complete regeneration. We found out that A. viride can regenerate both anterior and posterior end, even with only 3 segments remained. This process is characterized by epimorphosis that involves large amount of cell proliferation which drives the formation of blastema. Cell proliferation and regeneration successful ratio were significantly decreased when treated with microtubule inhibitor taxol or Avi-tubulin dsRNA, which confirmed that cell proliferation served as a key event during regeneration. Together, our data described the regenerative processes of A. viride, which includes high level of cell proliferation and the formation of blastema. Furthermore, our findings demonstrated A. viride as a potential model for the study of regeneration.
Early maltreatment experience increases resting-state functional connectivity in the theory of mind (ToM) network
Authors: Boccadoro Sara , Siugzdaite Roma , Hudson Anna , Maeyens Lien , Van Hamme Charlotte , Mueller Sven
Published: December 2018

Background: Early life stressful events, such as childhood maltreatment, significantly increase risk for the development of psychopathology and are associated with impairments in socio-cognitive skills including theory-of-mind (ToM). However, to date, no study has examined the resting-state activity of the ToM network in adults with maltreatment history. Methods: Thirty-five women with a history of childhood maltreatment and 31 unaffected women completed a resting-state scan and a ToM localizer task. The peak coordinates from the localizer were used as the seed regions for the resting-state functional connectivity (RSFC) analyses (temporoparietal junction, dorsomedial prefrontal cortex, middle temporal gyrus and precuneus). Results: Child abuse was associated with increased RSFC between various ToM regions including the precuneus and the brainstem suggesting altered hierarchical processing in ToM regions. In addition, RSFC was also changed between the dorsomedial prefrontal cortex and the cerebellum. Limitations. A small and heterogeneous sample. Conclusions: The data indicate a lasting influence of early life stress on neural networks involved in social processing and may underlie the social difficulties reported by maltreated individuals.
Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspired Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
Authors: Perov Sergei , Lidor Ofir , Salinas Nir , Golan Nimrod , Tayeb-Fligelman Einav , Deshmukh Maya , Willbold Dieter , Landau Meytal
Published: December 2018

Curli amyloid fibrils secreted by Enterobacteriaceae mediate host cell adhesion and contribute to biofilm formation, thereby promoting bacterial resistance to environmental stressors. Here, we present crystal structures of amyloid-forming segments from the major curlin subunit, CsgA, revealing steric zipper fibrils of tightly mated β-sheets, demonstrating a structural link between curli and human pathological amyloids. We propose that these cross-β segments structure the highly robust curli amyloid core. D-enantiomeric peptides, originally developed to interfere with Alzheimer's disease-associated Amyloid-β, inhibited CsgA fibrillation and reduced biofilm formation in Salmonella typhimurium. Moreover, CsgA fibrils cross-seeded fibrillation of Amyloid-β, providing further support for the proposed structural resemblance and potential for cross-species amyloid interactions. In this study, we provide structural insights into curli formation, offer a novel strategy for disrupting amyloid-structured biofilms, and hypothesize on the formation of self-propagating prion-like species originating from a microbial source that could influence neurodegenerative diseases.
Degree of urbanization and predation pressure on artificial lepidopteran caterpillars in Cali, Colombia
Authors: Cupitra-Rodríguez Jefferson , Cruz-Bernate Lorena , Montoya-Lerma James
Published: December 2018

Growing urban expansion results in the alteration of ecological processes (i.e. predation) within trophic networks. Predation on herbivores is known to vary with the size of the area covered in vegetation, successional stage, altitude, and the structure of the predator community, but there are gaps in information regarding how this occurs in urban and suburban environments. The purpose of this study was to determine whether the predation pressure on artificial models of lepidopteran larvae varied with degree of urbanization, type of substrate, and group of predators (birds or arthropods) in Cali, Colombia. Five hundred and eighteen artificial larvae were placed in two areas of the city (urban vs. suburban) and in two types of substrate (leaf vs. stem) for 30 continuous days and with two replications over time. Total predation was measured as the number of models with evidence of attack by predators. The overall incidence of predation was 24.13%, and was significantly higher in the urban area (63.20%) when compared to the suburban area (36.80%). The leaf substrate was attacked significantly more than the stem (60% vs. 40%). The proportion of attacks carried out by birds was significantly higher (74.40%) than that carried out by arthropods (24.80%). Together, these results suggest that the incidence of predation varies with the disturbance caused by urbanization and by the type of substrate in which prey organisms are found. In addition, the study confirms that birds are the main controllers of herbivorous insects in urban environments.
Novel allelic variant of Lpa1 gene associated with a significant reduction in seed phytic acid content in rice (Oryza sativa L.)
Authors: Kishor D.S. , Lee Choonseok , Lee Dongryung , Venkatesh Jelli , Seo Jeonghwan , Chin Joong Hyoun , Jin Zhuo , Hong Soon-Kwan , Ham Jin-Kwan , Koh Hee-Jong
Published: December 2018

In plants, myo-inositol-1,2,3,4,5,6-hexakisphosphate (InsP6), also known as phytic acid (PA), is a major component of organic phosphorus (P), and accounts for up to 85% of the total P in seeds. In rice (Oryza sativa L.), PA mainly accumulates in rice bran, and chelates mineral cations, resulting in mineral deficiencies among brown rice consumers. Therefore, considerable efforts have been focused on the development of low PA (LPA) rice cultivars. In this study, we performed genetic and molecular analyses of OsLpa1, a major PA biosynthesis gene, in Sanggol, a low PA mutant variety developed via chemical mutagenesis of Ilpum rice cultivar. Genetic segregation and sequencing analyses revealed that a recessive allele, lpa1-3, at the OsLpa1 locus (Os02g0819400) was responsible for a significant reduction in seed PA content in Sanggol. The lpa1-3 gene harboured a point mutation (C623T) in the fourth exon of the predicted coding region, resulting in threonine (Thr) to isoleucine (Ile) amino acid substitution at position 208 (Thr208Ile). Three-dimensional analysis of Lpa1 protein structure indicated that myo-inositol 3-monophosphate [Ins(3)P1] kinase binds to the active site of Lpa1, with ATP as a cofactor for catalysis. Furthermore, the presence of Thr208 in the loop adjacent to the entry site of the binding pocket suggests that Thr208Ile substitution is involved in regulating enzyme activity via phosphorylation. Therefore, we propose that Thr208Ile substitution in lpa1-3 reduces Lpa1 enzyme activity in Sanggol, resulting in reduced PA biosynthesis.
Diffeomorphic registration with intensity transformation and missing data: Application to 3D digital pathology of Alzheimer's disease
Authors: Tward Daniel Jacob , Brown Timothy , Kageyama Yusuke , Patel Jaymin , Hou Zhipeng , Mori Susumu , Albert Marilyn , Troncoso Juan , Miller Michael
Published: December 2018

This paper examines the problem of diffeomorphic image mapping in the presence of differing image intensity profiles and missing data. Our motivation comes from the problem of aligning 3D brain MRI with 100 micron isotropic resolution, to histology sections with 1 micron in plane resolution. Multiple stains, as well as damaged, folded, or missing tissue are common in this situation. We overcome these challenges by introducing two new concepts. Cross modality image matching is achieved by jointly estimating polynomial transformations of the atlas intensity, together with pose and deformation parameters. Missing data is accommodated via a multiple atlas selection procedure where several atlases may be of homogeneous intensity and correspond to ''background'' or ''artifact''. The two concepts are combined within an Expectation Maximization algorithm, where atlas selection posteriors and deformation parameters are updated iteratively, and polynomial coefficients are computed in closed form. We show results for 3D reconstruction of digital pathology and MRI in standard atlas coordinates. In conjunction with convolutional neural networks, we quantify the 3D density distribution of tauopathy throughout the medial temporal lobe of an Alzheimer's disease postmortem specimen.
Characterisation of antigenic MHC Class I-restricted T cell epitopes in the glycoprotein of Ebolavirus
Authors: Powlson Jonathan , Wright Daniel , Zeltina Antra , Giza Mark , Nielsen Morten , Rampling Tommy , Venkatrakaman Navin , Ewer Katie J , Bowden Thomas A. , Hill Adrian V.S.
Published: December 2018

Ebolavirus is a pathogen capable of causing highly lethal haemorrhagic fever in humans. The envelope-displayed viral glycoprotein is the primary target of humoral immunity induced by both natural exposure and vaccination. The epitopes targeted by B cells have been thoroughly characterised by functional and structural analyses of the glycoprotein, GP, yet there is a paucity of information regarding the cellular immune response to Ebolavirus. To date, no T cell epitopes in the glycoprotein have been characterised in detail in humans.

A recent Phase I clinical trial of a heterologous prime-boost vaccination regime with viral vectors encoding filovirus antigens elicited strong humoral and T cell responses in vaccinees. Using samples from this trial, the most frequently recognised peptide pools were studied in more detail to identify the minimal epitopes recognised by antigen-specific T cells and associated HLA-restrictions.

Using IFNγ ELISPOT and flow cytometry, we characterised nine highly immunogenic T cell epitopes located on both the GP1 and GP2 subunits of the Ebolavirus GP. Epitope mapping revealed the location of these epitopes as presented on the mature virion. HLA-typing on all participants, combined with in silico epitope analysis, determined the likely MHC class I restriction elements. Thirteen HLA-A and -B alleles were predicted to present the identified epitopes, suggesting promiscuous recognition and induction of a broad immune response.

The glycoprotein of Ebolavirus is highly immunogenic, inducing both CD4+ and CD8+ T cell responses and we have shown here for the first time that these responses are associated with multiple HLA types. Delivery of this antigen using a heterologous prime-boost approach with ChAd3 and MVA is likely to be highly immunogenic in genetically diverse human populations, due to the induction of responses against multiple immunodominant epitopes.
Ulinastatin prevents hyperoxia-induced lung injury on newborn rats by downregulating TNF-α and inhibiting macrophage infiltration
Authors: Xu Fengdan , Deng Wenlong , Kong Xiangyong , Feng Zhichun
Published: December 2018

Ulinastatin (UTI) can support protection for several organs through inhibition of the release of inflammatory factors, absorbing oxygen radicals, and inhibition the progression of fibrosis. However, whether UTI has effect on hyperoxia-induced lung injury is still unclear. In this study, the effects of UTI treatment on newborn rats suffering hyperoxia-induced lung injury were examined. The results demonstrated that UTI treatment significantly attenuated the wet/dry weight ratio, downregulated the levels of tumor necrosis factor-α (TNF-α), inhibited macrophage infiltration, and improved the average weight of rats. The most significant changes were observed in high-dose UTI treatment group. However, UTI had no effect on pulmonary superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Our results suggested that Ulinastatin prevents hyperoxia-induced lung injury on newborn rats by downregulating TNF-α and inhibiting macrophage infiltration.
Relationship of drought severity index with climatic factors on the Tibetan Plateau
Authors: Wang Xiangtao
Published: December 2018

It remains unclear how drought is varying under climatic change. Quantifying the relationship between drought and climatic factors is crucial for predicting future drought risk under global climatic change. Correlations of annual drought severity index (DSI) with climatic factors were examined from 2000 to 2011 on the Tibetan Plateau. Spatially averaged DSI increased with increasing precipitation and minimum relative humidity, but decreased with increasing sunshine. The degrees of correlation between DSI and climatic factors varied with vegetation types. The change magnitude of DSI decreased with increasing temperature, precipitation and vapor pressure, but increased with increasing wind speed and sunshine. Therefore, clarifying the correlation between drought and climatic change need consider ecosystem types and their local climate on the Tibetan Plateau.
A new framework for the study of apicomplexan diversity across environments
Authors: del Campo Javier , Heger Thierry , Rodríguez-Martínez Raquel , Worden Alexandra Z. , Richards Thomas A. , Massana Ramon , Keeling Patrick J.
Published: December 2018

Apicomplexans are a group of microbial eukaryotes that contain some of the most well-studied parasites, including widespread intracellular pathogens of mammals such as Toxoplasma and Plasmodium (the agent of malaria), and emergent pathogens like Cryptosporidium and Babesia. Decades of research have illuminated the pathogenic mechanisms, molecular biology, and genomics of model apicomplexans, but we know surprisingly little about their diversity and distribution in natural environments. In this study we analyze the distribution of apicomplexans across a range of both host-associated and free-living environments, covering animal hosts from cnidarians to mammals, and ecosystems from soils to fresh and marine waters. Using publicly available small subunit (SSU) rRNA gene databases, high-throughput environmental sequencing (HTES) surveys such as Tara Oceans and VAMPS, as well as our own generated HTES data, we developed an apicomplexan reference database, which includes the largest apicomplexan SSU rRNA tree available to date and encompasses comprehensive sampling of this group and their closest relatives. This tree allowed us to identify and correct incongruences in the molecular identification of sequences, particularly within the hematozoans and the gregarines. Analyzing the diversity and distribution of apicomplexans in HTES studies with this curated reference database also showed a widespread, and quantitatively important, presence of apicomplexans across a variety of free-living environments. These data allow us to describe a remarkable molecular diversity of this group compared with our current knowledge, especially when compared with that identified from described apicomplexan species. This revision is most striking in marine environments, where potentially the most diverse apicomplexans apparently exist, but have not yet been formally recognized. The new database will be useful for both microbial ecology and epidemiological studies, and provide valuable reference for medical and veterinary diagnosis especially in cases of emerging, zoonotic, and cryptic infections.