bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malt1 blocks IL-1β production by macrophages in vitro and limits dextran sodium sulfate-induced intestinal inflammation in vivo
Authors: Monajemi Mahdis , Pang Yvonne C F , Bjornson Saelin , Menzies Susan C , van Rooijen Nico , Sly Laura M 
Published: June 2018

Abstract
This study tested the hypothesis that Malt1 deficiency in macrophages contributes to dextran sodium sulfate (DSS)-induced intestinal inflammation in Malt1-deficient mice. In people, combined immunodeficiency caused by a homozygous mutation in the MALT1 gene is associated with increased susceptibility to bacterial infections and chronic inflammation, including severe inflammation along the gastrointestinal tract. The consequences of Malt1 deficiency have largely been attributed to its role in lymphocytes, but Malt1 is also expressed in macrophages, where it is activated downstream of TLR4 and dectin-1. The effect of Malt1 deficiency in murine macrophages and its contribution to DSS-induced colitis have not been investigated. Our objectives were to compare the susceptibility of Malt1+/+ and Malt1−/− mice to DSS-induced colitis, to determine the contribution of macrophages to DSS-induced colitis in Malt1−/− mice, and to assess the effect of innate immune stimuli on Malt1−/− macrophage inflammatory responses. We found that Malt1 deficiency exacerbates DSS-induced colitis in mice, accompanied by higher levels of IL-1β, and that macrophages and IL-1 signaling contribute to pathology in Malt1−/− mice. Malt1−/− macrophages produce more IL-1β in response to either TLR4 or dectin-1 ligation, whereas inhibition of Malt1 proteolytic (paracaspase) activity blocked IL-1β production. TLR4 or dectin-1 stimulation induced Malt1 protein levels but decreased its paracaspase activity. Taken together, these data support the hypothesis that Malt1−/− macrophages contribute to increased susceptibility of Malt1−/− mice to DSS-induced colitis, which is dependent on IL-1 signaling. Increased IL-1β production by MALT1-deficient macrophages may also contribute to chronic inflammation in people deficient in MALT1.
Innate immune stimuli up-regulate Malt1 protein expression and block Malt1 paracaspase activity in macrophages permitting IL-1β production in vitro and in vivo.
Dose‐escalation strategies which use subgroup information
Authors: Cotterill Amy , Jaki Thomas 
Published: June 2018

Dose‐escalation trials commonly assume a homogeneous trial population to identify a single recommended dose of the experimental treatment for use in future trials. Wrongly assuming a homogeneous population can lead to a diluted treatment effect. Equally, exclusion of a subgroup that could in fact benefit from the treatment can cause a beneficial treatment effect to be missed. Accounting for a potential subgroup effect (ie, difference in reaction to the treatment between subgroups) in dose‐escalation can increase the chance of finding the treatment to be efficacious in a larger patient population.A standard Bayesian model‐based method of dose‐escalation is extended to account for a subgroup effect by including covariates for subgroup membership in the dose‐toxicity model. A stratified design performs well but uses available data inefficiently and makes no inferences concerning presence of a subgroup effect. A hypothesis test could potentially rectify this problem but the small sample sizes result in a low‐powered test. As an alternative, the use of spike and slab priors for variable selection is proposed. This method continually assesses the presence of a subgroup effect, enabling efficient use of the available trial data throughout escalation and in identifying the recommended dose(s). A simulation study, based on real trial data, was conducted and this design was found to be both promising and feasible.
Attitudes of emergency department physicians and nurses toward implementation of an early warning score to identify critically ill patients: qualitative explanations for failed implementation
Authors: Bigham Blair L. , Chan Teresa , Skitch Steven , Fox-Robichaud Alison 
Published: June 2018

AbstractBackgroundSepsis, a common, time-sensitive condition, is sometimes not identified at emergency department (ED) triage. The use of early warning scores has been shown to improve sepsis-related screening in other settings.ObjectivesOur objective was to elucidate nurse and physician perceptions with the Hamilton Early Warning Score (HEWS) in combination with the Canadian Triage Acuity Scale.MethodSemi-structured interviews were conducted with nurses, resident physicians and attending physicians to explore perceived feasibility, utility, comfort, barriers, successes, opportunities and accuracy. A constructivist grounded theory approach was used. Transcripts were coded into thematic coding trees.ResultsThe twelve participants did not value the HEWS in the ED because they felt it was not helpful in identifying critically ill patients. We identified five themes; knowledge of sepsis and HEWS, utility of HEWS in emergency triage, utility of HEWS at the bedside, utility in communicating acuity and deterioration, and feasibility and accuracy of data collection. We also found 9 barriers and 7 enablers to the use of early warning score in the ED.ConclusionsIn our emergency departments, we identified potential barriers to implementation of an early warning score. A pre-existing expertise and lexicon related to critically ill patients lessens the perceived utility of an EWS in the ED. Understanding these cultural barriers needs to be addressed through change theory and implementation science.
Recent advances in trypanosomatid research: genome organization, expression, metabolism, taxonomy and evolution
Authors: Maslov Dmitri A. , Opperdoes Fred R. , Kostygov Alexei Y. , Hashimi Hassan , Lukeš Julius , Yurchenko Vyacheslav 
Published: June 2018

AbstractUnicellular flagellates of the family Trypanosomatidae are obligatory parasites of invertebrates, vertebrates and plants. Dixenous species are aetiological agents of a number of diseases in humans, domestic animals and plants. Their monoxenous relatives are restricted to insects. Because of the high biological diversity, adaptability to dramatically different environmental conditions, and omnipresence, these protists have major impact on all biotic communities that still needs to be fully elucidated. In addition, as these organisms represent a highly divergent evolutionary lineage, they are strikingly different from the common ‘model system’ eukaryotes, such as some mammals, plants or fungi. A number of excellent reviews, published over the past decade, were dedicated to specialized topics from the areas of trypanosomatid molecular and cell biology, biochemistry, host–parasite relationships or other aspects of these fascinating organisms. However, there is a need for a more comprehensive review that summarizing recent advances in the studies of trypanosomatids in the last 30 years, a task, which we tried to accomplish with the current paper.
Trematode cercariae as prey for zooplankton: effect on fitness traits of predators
Authors: Mironova Ekaterina , Gopko Mikhail , Pasternak Anna , Mikheev Viktor , Taskinen Jouni 
Published: June 2018

AbstractRemoval of parasite free-living stages by predators has previously been suggested an important factor controlling parasite transmission in aquatic habitats. Experimental studies of zooplankton predation on macroparasite larvae are, however, scarce. We tested whether trematode cercariae, which are often numerous in shallow waters, are suitable prey for syntopic zooplankters. Feeding rates and survival of freshwater cyclopoids (Megacyclops viridis,Macrocyclops distinctus), calanoids (Arctodiaptomus paulseni), cladocerans (Sida crystallina) and rotifersAsplanchnaspp., fed with cercariae ofDiplostomum pseudospathaceum, a common fish trematode, were studied. In additional long-term experiments, we studied reproduction of cyclopoids fed with cercariae. All tested zooplankton species consumed cercariae. The highest feeding rates were observed for cyclopoids (33 ± 12 cercariae ind−1h−1), which actively reproduced (up to one egg clutch day−1) when fedad libitumwith cercariae. Their reproductive characteristics did not change significantly with time, indicating that cercariae supported cyclopoids’ dietary needs. Mortality of rotifers and cladocerans was high (25–28% individuals) when exposed to cercariae in contrast to cyclopoids and calanoids (<2%). Cercariae clogged the filtration apparatus of cladocerans and caused internal injuries in predatory rotifers, which ingested cercariae. Observed trophic links between common freshwater zooplankters and cercariae may significantly influence food webs and parasite transmission in lentic ecosystems.
Investigating pathogen burden in relation to a cumulative deficits index in a representative sample of US adults
Authors: Noppert G. A. , Aiello A. E. , O'Rand A. M. , Cohen H. J. 
Published: June 2018

AbstractPathogen burden is a construct developed to assess the cumulative effects of multiple, persistent pathogens on morbidity and mortality. Despite the likely biological wear and tear on multiple body systems caused by persistent infections, few studies have examined the impact of total pathogen burden on such outcomes and specifically on preclinical markers of dysfunction. Using data from two waves of the National Health and Nutrition Examination Survey, we compared three alternative methods for measuring pathogen burden, composed of mainly persistent viral infections, using a cumulative deficits index (CDI) as an outcome: single pathogen associations, a pathogen burden summary score and latent class analyses. We found significant heterogeneity in the distribution of the CDI by age, sex, race/ethnicity and education. There was an association between pathogen burden and the CDI by all three metrics. The latent class classification of pathogen burden showed particularly strong associations with the CDI; these associations remained after controlling for age, sex, body mass index, smoking, race/ethnicity and education. Our results suggest that pathogen burden may influence early clinical indicators of poor health as measured by the CDI. Our results are salient since we were able to detect these associations in a relatively young population. These findings suggest that reducing pathogen burden and the specific pathogens that drive the CDI may provide a target for preventing the early development of age-related physiological changes.
Occurrence, antimicrobial susceptibility patterns and genotypic relatedness of Salmonella spp. isolates from captive wildlife, their caretakers, feed and water in India
Authors: Milton Arockiasamy Arun Prince , Agarwal Rajesh Kumar , Priya Govindarajan Bhuvana , Athira Cheruplackal Karunakaran , Saminathan Mani , Reddy Avinash , Aravind Manivasagam , Kumar Ashok 
Published: June 2018

AbstractOccurrence of Salmonella spp. in captive wild animal species in India is largely unknown. The purpose of this study was to determine the occurrence of different Salmonella serotypes, antimicrobial resistance patterns and genotypic relatedness of recovered isolates. A total of 370 samples including faecal (n = 314), feed and water (n = 26) and caretakers stool swabs (n = 30) were collected from 40 different wild animal species in captivity, their caretakers, feed and water in four zoological gardens and wildlife enclosures in India. Salmonellae were isolated using conventional culture methods and tested for antimicrobial susceptibility with the Kirby–Bauer disc diffusion method. Salmonella isolates were serotyped and genotyping was performed using enterobacterial repetitive intergenic consensus (ERIC) PCR and 16S rRNA sequencing. Animal faecal samples were also subjected to direct PCR assay. Salmonella was detected in 10 of 314 (3.1%) faecal samples by isolation and 18 of 314 (5.7%) samples by direct PCR assay; one of 26 (3.8%) feed and water samples and five of 30 (16.7%) caretakers stool swabs by isolation. Salmonella was more commonly isolated in faecal samples from golden pheasants (25%; 2/8) and leopard (10%; 2/20). Salmonella enterica serotypes of known public health significance including S. Typhimurium (37.5%; 6/14), S. Kentucky (28.5%; 4/14) and S. Enteritidis (14.3%; 2/14) were identified. While the majority of the Salmonella isolates were pan-susceptible to the commonly used antibiotics. Seven (43.7%; 7/16) of the isolates were resistant to at least one antibiotic and one isolate each among them exhibited penta and tetra multidrug-resistant types. Three S. Kentucky serotype were identified in a same golden pheasants cage, two from the birds and one from the feed. This serotype was also isolated from its caretaker. Similarly, one isolate each of S. Typhimurium were recovered from ostrich and its caretaker. These isolates were found to be clonally related suggesting that wildlife may serve as reservoir for infections to humans and vice versa. These results emphasise the transmission of Salmonella among hosts via environmental contamination of feces to workers, visitors and other wildlife.
A serological survey of anthrax in domestic dogs in Zimbabwe: a potential tool for anthrax surveillance
Authors: Mukarati N. L. , Ndumnego O. , van Heerden H. , Ndhlovu D. N. , Matope G. , Caron A. , de Garine-Wichatitsky M. , Pfukenyi D. M. 
Published: June 2018

AbstractAnthrax is an important disease caused by the bacteriumBacillus anthracisaffecting both domestic and wild animals at the wildlife/livestock interface, defined here as a physical space in which wild and domestic species overlap in range and potentially interact. In endemic regions, sporadic anthrax outbreaks occur, causing significant deaths of both wildlife and livestock and sporadically, humans. However, it may also occur as isolated outbreaks with a few animals affected. Such isolated anthrax outbreaks maybe missed. High seroprevalence among carnivores suggests either regular non-fatal exposure to the pathogen circulating in a given environment, or contact with missed cases through consumption of anthrax carcases. To investigate the relevance of this potential indicator, a cross-sectional study was conducted to determine anthrax seroprevalence in domestic dogs (Canis lupus familiaris)from selected interface and non-interface areas of Zimbabwe with known history of anthrax outbreaks. Based on past anthrax outbreaks in the respective areas, the sites were further classified as high or low risk areas for anthrax outbreaks. Sera were collected from domestic dogs (n= 186) and tested for antibodies againstB. anthracisprotective antigens (PA) using an ELISA test. The overall seroprevalence was 51.6% (96/186; 95% CI 44.2–59.0). Sites from the non-interface areas recorded a significantly (P< 0.001) higher (72.1%) anthrax seroprevalence compared with those from the wildlife –livestock interface (41.5%). The results demonstrated a strong association (χ2= 14.3; OR = 3.2, 1.6 < OR < 6.2,P< 0.001) between anthrax seropositivity and interface type. Low-risk sites (42.5%) had a significantly (P= 0.044) lower seroprevalence compared with high-risk sites (58.5%) but still demonstrated high seroprevalence for areas where anthrax was last reported more than 20 years back. Dogs from Tsholotsho South were more than 90-times (OR = 96.5, 13.5 < OR < 690.8) more likely to be seropositive compared with those from Hwange. The study demonstrated the potential to use domestic dogs as indicators of anthrax in the study areas to survey anthrax circulation in supposed low-risk areas and calls for a redefinition of both low and high risk areas for anthrax in Zimbabwe based on an improved surveillance.
Global Plate Motions and Earthquake Cycle Effects
Authors: Graham Shannon E. , Loveless John P. , Meade Brendan J. 
Published: June 2018

AbstractThe rotations of tectonic plates provide a partial description of the total observed displacements at the Earth's surface. The estimated number of kinematically distinct plates has increased from 12 in 1990 to 56 in 2010 as a result of the increase in the number of kinematic observables. At length scales <1,000 km, rotation‐only plate models are inaccurate because geodetic signals of long‐term plate motions are complicated by earthquake cycle effects. Here we present results from a global block model that unifies large‐scale plate motions and local earthquake cycle effects at plate boundaries. Incorporating the rotations of 307 distinct plates, elastic strain accumulation from 16 subduction zones and 1.59 × 107 km2 of fault system area, this model explains 19,664 interseismic GPS velocities at a resolution of 2.2 mm/year. Geodetically constrained fault slip deficit rates yield a cumulative global moment accumulation rate of 1.09 × 1022 N·m/year, 12% larger than the average annual coseismic moment release rate from 1900 to 2013. The potential contribution to the total moment rate budget can be estimated from the frequency distribution of the modeled fault slip‐deficit rates, which follow an exponential distribution. Integrating this frequency distribution over all possible slip rates indicates that the geologic structures included in this reference global block model account for 98% of the global moment budget. Comparing our results with population distribution, we find that ∼50% of the world's population lives within 200 km of an active fault with a slip rate >2 mm/year.
Cultural conformity generates extremely stable traditions in bird song
Authors: Lachlan Robert F. , Ratmann Oliver , Nowicki Stephen 
Published: June 2018

AbstractCultural traditions have been observed in a wide variety of animal species. It remains unclear, however, what is required for social learning to give rise to stable traditions: what level of precision and what learning strategies are required. We address these questions by fitting models of cultural evolution to learned bird song. We recorded 615 swamp sparrow (Melospiza georgiana) song repertoires, and compared syllable frequency distributions to the output of individual-based simulations. We find that syllables are learned with an estimated error rate of 1.85% and with a conformist bias in learning. This bias is consistent with a simple mechanism of overproduction and selective attrition. Finally, we estimate that syllable types could frequently persist for more than 500 years. Our results demonstrate conformist bias in natural animal behaviour and show that this, along with moderately precise learning, may support traditions whose stability rivals those of humans.
miR-143/145 differentially regulate hematopoietic stem and progenitor activity through suppression of canonical TGFβ signaling
Authors: Lam Jeffrey , van den Bosch Marion , Wegrzyn Joanna , Parker Jeremy , Ibrahim Rawa , Slowski Kate , Chang Linda , Martinez-Høyer Sergio , Condorelli Gianluigi , Boldin Mark , Deng Yu , Umlandt Patricia , Fuller Megan , Karsan Aly 
Published: June 2018

AbstractExpression of miR-143 and miR-145 is reduced in hematopoietic stem/progenitor cells (HSPCs) of myelodysplastic syndrome patients with a deletion in the long arm of chromosome 5. Here we show that mice lacking miR-143/145 have impaired HSPC activity with depletion of functional hematopoietic stem cells (HSCs), but activation of progenitor cells (HPCs). We identify components of the transforming growth factor β (TGFβ) pathway as key targets of miR-143/145. Enforced expression of the TGFβ adaptor protein and miR-145 target, Disabled-2 (DAB2), recapitulates the HSC defect seen in miR-143/145−/− mice. Despite reduced HSC activity, older miR-143/145−/− and DAB2-expressing mice show elevated leukocyte counts associated with increased HPC activity. A subset of mice develop a serially transplantable myeloid malignancy, associated with expansion of HPC. Thus, miR-143/145 play a cell context-dependent role in HSPC function through regulation of TGFβ/DAB2 activation, and loss of these miRNAs creates a preleukemic state.
Three-photon tissue imaging using moxifloxacin
Authors: Lee Seunghun , Lee Jun Ho , Wang Taejun , Jang Won Hyuk , Yoon Yeoreum , Kim Bumju , Jun Yong Woong , Kim Myoung Joon , Kim Ki Hean 
Published: June 2018

AbstractMoxifloxacin is an antibiotic used in clinics and has recently been used as a clinically compatible cell-labeling agent for two-photon (2P) imaging. Although 2P imaging with moxifloxacin labeling visualized cells inside tissues using enhanced fluorescence, the imaging depth was quite limited because of the relatively short excitation wavelength (<800 nm) used. In this study, the feasibility of three-photon (3P) excitation of moxifloxacin using a longer excitation wavelength and moxifloxacin-based 3P imaging were tested to increase the imaging depth. Moxifloxacin fluorescence via 3P excitation was detected at a >1000 nm excitation wavelength. After obtaining the excitation and emission spectra of moxifloxacin, moxifloxacin-based 3P imaging was applied to ex vivo mouse bladder and ex vivo mouse small intestine tissues and compared with moxifloxacin-based 2P imaging by switching the excitation wavelength of a Ti:sapphire oscillator between near 1030 and 780 nm. Both moxifloxacin-based 2P and 3P imaging visualized cellular structures in the tissues via moxifloxacin labeling, but the image contrast was better with 3P imaging than with 2P imaging at the same imaging depths. The imaging speed and imaging depth of moxifloxacin-based 3P imaging using a Ti:sapphire oscillator were limited by insufficient excitation power. Therefore, we constructed a new system for moxifloxacin-based 3P imaging using a high-energy Yb fiber laser at 1030 nm and used it for in vivo deep tissue imaging of a mouse small intestine. Moxifloxacin-based 3P imaging could be useful for clinical applications with enhanced imaging depth.
Thermal carbonization in nanoscale reactors: controlled formation of carbon nanodots inside porous CaCO3 microparticles
Authors: Vostrikova Anna V. , Prikhozhdenko Ekaterina S. , Mayorova Oksana A. , Goryacheva Irina Yu. , Tarakina Nadezda V. , Sukhorukov Gleb B. , Sapelkin Andrei V. 
Published: June 2018

AbstractSynthesis of carbon nanodots (CNDs) in confined geometry via incorporation of dextran sulphate into pores of CaCO3 microparticles is demonstrated. The preparation process included three steps: co-precipitation of solutions of inorganic salts and carbon source, thermal treatment and CaCO3 matrix removal. We show that geometric constraints can be used to precisely control the amount of source material and to avoid formation of large carbon particles. Analysis of TEM data shows particle size of ~3.7 nm with narrow size distribution. Furthermore, we found that variation in pore morphology has a clear effect on CNDs structure and optical properties. CNDs with graphene oxide like structure were obtained in the nanoporous outer shell layer of CaCO3 microparticles, while less ordered CNDs with the evidence of complex disordered carbons were extracted from the inner microcavity. These results suggest that confined volume synthesis route in CaCO3 nanopores can be used to precisely control the structure and optical properties of CNDs.