bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the dynamics of microbial consortia in spatially structured environments
Authors: Gupta Sonali , Ross Tyler D. , Gomez Marcella M. , Grant Job L. , Romero Philip A. , Venturelli Ophelia S.
Published: May 2020

The spatial organization of microbial communities arises from a complex interplay of biotic and abiotic interactions, and is a major determinant of ecosystem functions. Here we design a microfluidic platform to investigate how the spatial arrangement of microbes impacts gene expression and growth. We elucidate key biochemical parameters that dictate the mapping between spatial positioning and gene expression patterns. We show that distance can establish a low-pass filter to periodic inputs and can enhance the fidelity of information processing. Positive and negative feedback can play disparate roles in the synchronization and robustness of a genetic oscillator distributed between two strains to spatial separation. Quantification of growth and metabolite release in an amino-acid auxotroph community demonstrates that the interaction network and stability of the community are highly sensitive to temporal perturbations and spatial arrangements. In sum, our microfluidic platform can quantify spatiotemporal parameters influencing diffusion-mediated interactions in microbial consortia.
Representation of probabilistic outcomes during risky decision-making
Authors: Castegnetti Giuseppe , Tzovara Athina , Khemka Saurabh , Melinščak Filip , Barnes Gareth R. , Dolan Raymond J. , Bach Dominik R.
Published: May 2020

Goal-directed behaviour requires prospectively retrieving and evaluating multiple possible action outcomes. While a plethora of studies suggested sequential retrieval for deterministic choice outcomes, it remains unclear whether this is also the case when integrating multiple probabilistic outcomes of the same action. We address this question by capitalising on magnetoencephalography (MEG) in humans who made choices in a risky foraging task. We train classifiers to distinguish MEG field patterns during presentation of two probabilistic outcomes (reward, loss), and then apply these to decode such patterns during deliberation. First, decoded outcome representations have a temporal structure, suggesting alternating retrieval of the outcomes. Moreover, the probability that one or the other outcome is being represented depends on loss magnitude, but not on loss probability, and it predicts the chosen action. In summary, we demonstrate decodable outcome representations during probabilistic decision-making, which are sequentially structured, depend on task features, and predict subsequent action.
Immune-profiling of ZIKV-infected patients identifies a distinct function of plasmacytoid dendritic cells for immune cross-regulation
Authors: Sun Xiaoming , Hua Stephane , Gao Ce , Blackmer Jane E. , Ouyang Zhengyu , Ard Kevin , Ciaranello Andrea , Yawetz Sigal , Sax Paul E. , Rosenberg Eric S. , Lichterfeld Mathias , Yu Xu G.
Published: May 2020

Zika virus (ZIKV) is a mosquito-borne pathogen with increasing public health significance. To characterize immune responses to ZIKV, here we examine transcriptional signatures of CD4 T, CD8 T, B, and NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with ZIKV infection. While gene expression patterns from most cell subsets display signs of impaired antiviral immune activity, pDCs from infected host have distinct transcriptional response associated with activation of innate immune recognition and type I interferon signaling pathways, but downregulation of key host factors known to support ZIKV replication steps; meanwhile, pDCs exhibit a unique expression pattern of gene modules that are correlated with alternative cell populations, suggesting collaborative interactions between pDCs and other immune cells, particularly B cells. Together, these results point towards a discrete but integrative function of pDCs in the human immune responses to ZIKV infection.
HIV-associated gut dysbiosis is independent of sexual practice and correlates with noncommunicable diseases
Authors: Vujkovic-Cvijin I. , Sortino O. , Verheij E. , Sklar J. , Wit F. W. , Kootstra N. A. , Sellers B. , Brenchley J. M. , Ananworanich J. , Loeff M. Schim van der , Belkaid Y. , Reiss P. , Sereti I.
Published: May 2020

Loss of gut mucosal integrity and an aberrant gut microbiota are proposed mechanisms contributing to chronic inflammation and increased morbidity and mortality during antiretroviral-treated HIV disease. Sexual practice has recently been uncovered as a major source of microbiota variation, potentially confounding prior observations of gut microbiota alterations among persons with HIV (PWH). To overcome this and other confounding factors, we examine a well-powered subset of AGEhIV Cohort participants comprising antiretroviral-treated PWH and seronegative controls matched for age, body-mass index, sex, and sexual practice. We report significant gut microbiota differences in PWH regardless of sex and sexual practice including Gammaproteobacteria enrichment, Lachnospiraceae and Ruminococcaceae depletion, and decreased alpha diversity. Men who have sex with men (MSM) exhibit a distinct microbiota signature characterized by Prevotella enrichment and increased alpha diversity, which is linked with receptive anal intercourse in both males and females. Finally, the HIV-associated microbiota signature correlates with inflammatory markers including suPAR, nadir CD4 count, and prevalence of age-associated noncommunicable comorbidities.
Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease
Authors: Tiklová Katarína , Nolbrant Sara , Fiorenzano Alessandro , Björklund Åsa K. , Sharma Yogita , Heuer Andreas , Gillberg Linda , Hoban Deirdre B. , Cardoso Tiago , Adler Andrew F. , Birtele Marcella , Lundén-Miguel Hilda , Volakakis Nikolaos , Kirkeby Agnete , Perlmann Thomas , Parmar Malin
Published: May 2020

Cell replacement is a long-standing and realistic goal for the treatment of Parkinsonʼs disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.
Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver
Authors: Miao Lei , Lin Jiaqi , Huang Yuxuan , Li Linxian , Delcassian Derfogail , Ge Yifan , Shi Yunhua , Anderson Daniel G.
Published: May 2020

Lipid-like nanoparticles (LNPs) have potential as non-viral delivery systems for mRNA therapies. However, repeated administrations of LNPs may lead to accumulation of delivery materials and associated toxicity. To address this challenge, we have developed biodegradable lipids which improve LNPs clearance and reduce toxicity. We modify the backbone structure of Dlin-MC3-DMA by introducing alkyne and ester groups into the lipid tails. We evaluate the performance of these lipids when co-formulated with other amine containing lipid-like materials. We demonstrate that these formulations synergistically facilitate robust mRNA delivery with improved tolerability after single and repeated administrations. We further identify albumin-associated macropinocytosis and endocytosis as an ApoE-independent LNP cellular uptake pathway in the liver. Separately, the inclusion of alkyne lipids significantly increases membrane fusion to enhance mRNA release, leading to synergistic improvement of mRNA delivery. We believe that the rational design of LNPs with multiple amine-lipids increases the material space for mRNA delivery.
A redox-based electrogenetic CRISPR system to connect with and control biological information networks
Authors: Bhokisham Narendranath , VanArsdale Eric , Stephens Kristina T. , Hauk Pricila , Payne Gregory F. , Bentley William E.
Published: May 2020

Electronic information can be transmitted to cells directly from microelectronics via electrode-activated redox mediators. These transmissions are decoded by redox-responsive promoters which enable user-specified control over biological function. Here, we build on this redox communication modality by establishing an electronic eCRISPR conduit of information exchange. This system acts as a biological signal processor, amplifying signal reception and filtering biological noise. We electronically amplify bacterial quorum sensing (QS) signaling by activating LasI, the autoinducer-1 synthase. Similarly, we filter out unintended noise by inhibiting the native SoxRS-mediated oxidative stress response regulon. We then construct an eCRISPR based redox conduit in both E. coli and Salmonella enterica. Finally, we display eCRISPR based information processing that allows transmission of spatiotemporal redox commands which are then decoded by gelatin-encapsulated E. coli. We anticipate that redox communication channels will enable biohybrid microelectronic devices that could transform our abilities to electronically interpret and control biological function.
Conserved protein Pir2ARS2 mediates gene repression through cryptic introns in lncRNAs
Authors: Thillainadesan Gobi , Xiao Hua , Holla Sahana , Dhakshnamoorthy Jothy , Jenkins Lisa M. Miller , Wheeler David , Grewal Shiv I. S.
Published: May 2020

Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here, we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2ARS2 protein in association with splicing factors, which recruit RNA processing and chromatin-modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs.
Split Intein-Mediated Protein Ligation for detecting protein-protein interactions and their inhibition
Authors: Yao Zhong , Aboualizadeh Farzaneh , Kroll Jason , Akula Indira , Snider Jamie , Lyakisheva Anna , Tang Priscilla , Kotlyar Max , Jurisica Igor , Boxem Mike , Stagljar Igor
Published: May 2020

Here, to overcome many limitations accompanying current available methods to detect protein-protein interactions (PPIs), we develop a live cell method called Split Intein-Mediated Protein Ligation (SIMPL). In this approach, bait and prey proteins are respectively fused to an intein N-terminal fragment (IN) and C-terminal fragment (IC) derived from a re-engineered split intein GP41-1. The bait/prey binding reconstitutes the intein, which splices the bait and prey peptides into a single intact protein that can be detected by regular protein detection methods such as Western blot analysis and ELISA, serving as readouts of PPIs. The method is robust and can be applied not only in mammalian cell lines but in animal models such as C. elegans. SIMPL demonstrates high sensitivity and specificity, and enables exploration of PPIs in different cellular compartments and tracking of kinetic interactions. Additionally, we establish a SIMPL ELISA platform that enables high-throughput screening of PPIs and their inhibitors.
Observation of an acoustic octupole topological insulator
Authors: Xue Haoran , Ge Yong , Sun Hong-Xiang , Wang Qiang , Jia Ding , Guan Yi-Jun , Yuan Shou-Qi , Chong Yidong , Zhang Baile
Published: May 2020

Berry phase associated with energy bands in crystals can lead to quantised observables like quantised dipole polarizations in one-dimensional topological insulators. Recent theories have generalised the concept of quantised dipoles to multipoles, resulting in the discovery of multipole topological insulators which exhibit a hierarchy of multipole topology: a quantised octupole moment in a three-dimensional bulk induces quantised quadrupole moments on its two-dimensional surfaces, which in turn induce quantised dipole moments on one-dimensional hinges. Here, we report on the realisation of an octupole topological insulator in a three-dimensional acoustic metamaterial. We observe zero-dimensional topological corner states, one-dimensional gapped hinge states, two-dimensional gapped surface states, and three-dimensional gapped bulk states, representing the hierarchy of octupole, quadrupole and dipole moments. Conditions for forming a nontrivial octupole moment are demonstrated by comparisons with two different lattice configurations having trivial octupole moments. Our work establishes the multipole topology and its full hierarchy in three-dimensional geometries.
The route to transcription initiation determines the mode of transcriptional bursting in E. coli
Authors: Engl Christoph , Jovanovic Goran , Brackston Rowan D. , Kotta-Loizou Ioly , Buck Martin
Published: May 2020

Abstract

Transcription is fundamentally noisy, leading to significant heterogeneity across bacterial populations. Noise is often attributed to burstiness, but the underlying mechanisms and their dependence on the mode of promotor regulation remain unclear. Here, we measure E. coli single cell mRNA levels for two stress responses that depend on bacterial sigma factors with different mode of transcription initiation (σ70 and σ54). By fitting a stochastic model to the observed mRNA distributions, we show that the transition from low to high expression of the σ70-controlled stress response is regulated via the burst size, while that of the σ54-controlled stress response is regulated via the burst frequency. Therefore, transcription initiation involving σ54 differs from other bacterial systems, and yields bursting kinetics characteristic of eukaryotic systems.
Vulnerable window of yield strength for swelling-driven fracture of phase-transforming battery materials
Authors: Mesgarnejad Ataollah , Karma Alain
Published: May 2020

Despite numerous experimental and theoretical investigations of the mechanical behavior of high-capacity Si and Ge Li-ion battery anodes, our basic understanding of swelling-driven fracture in these materials remains limited. Existing theoretical studies have provided insights into elasto-plastic deformations caused by large volume change phase transformations, but have not modeled fracture explicitly beyond Griffith’s criterion. Here, we use a multi-physics phase-field approach to model self-consistently anisotropic phase transformation, elasto-plastic deformation, and crack initiation and propagation during lithiation of Si nanopillars. Our computational results reveal that fracture occurs within a “vulnerable window” inside the two-dimensional parameter space of yield strength and fracture energy and highlight the importance of taking into account the surface localization of plastic deformation to accurately predict the magnitude of tensile stresses at the onset of fracture. They further demonstrate how the increased robustness of hollow nanopillars can be understood as a direct effect of anode geometry on the size of this vulnerable window. Those insights provide an improved theoretical basis for designing next-generation mechanically stable phase-transforming battery materials undergoing large volume changes.
The SIRS criteria have better performance for predicting infection than qSOFA scores in the emergency department
Authors: Gando Satoshi , Shiraishi Atsushi , Abe Toshikazu , Kushimoto Shigeki , Mayumi Toshihiko , Fujishima Seitaro , Hagiwara Akiyoshi , Shiino Yasukazu , Shiraishi Shin-ichiro , Hifumi Toru , Otomo Yasuhiro , Okamoto Kohji , Sasaki Junichi , Takuma Kiyotsugu , Yamakawa Kazuma ,   The Japanese Association for Acute Medicine (JAAM) Sepsis Prognostication in Intensive Care Unit and Emergency Room (SPICE) (JAAM SPICE) Study Group, Hoshino Atsumi , Shiraishi Atsushi , Abe Toshiaki , Sugita Manabu , Hanaki Yoshihiro , Hagiwara Akiyoshi , Shiraishi Shin-ichiro , Shiino Yasukazu , Harada Masahiro , Yoshihara Hideaki , Takuma Kiyotsugu , Otomo Yasuhiro , Morino Kazuma , Shimizu Yoshihiro , Ishikura Hiroyasu , Hifumi Toru , Deguchi Yoshizumi , Nachi Sho , Gando Satoshi , Okamoto Kohji , Kawakami Masato , Fujishima Seitaro , Sasaki Junichi , Maehara Junichi , Okada Kunihiko , Yamakawa Kazuma , Kiyota Kazuya , Miki Yasuo , Koike Kaoru , Muroya Takashi , Yamashita Hisashi , Mayumi Toshihiko , Anan Hideaki , Kaneko Tadashi , Kittaka Hirotada , Yamaguchi Hiroyuki
Published: May 2020

Systemic inflammatory response syndrome (SIRS) reportedly has a low performance for distinguishing infection from non-infection. We explored the distribution of the patients diagnosed by SIRS (SIRS patients) or a quick sequential organ failure assessment (qSOFA) (qSOFA patients) and confirmed the performance of the both for predicting ultimate infection after hospital admission. We retrospectively analyzed the data from a multicenter prospective study. When emergency physicians suspected infection, SIRS or the qSOFA were applied. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the SIRS and qSOFA for predicting established infection. A total of 1,045 patients were eligible for this study. The SIRS patients accounted for 91.6% of qSOFA patients and they showed a higher rate of final infection than that of non-SIRS patients irrespective of the qSOFA diagnosis. The AUCs for predicting infection with SIRS and a qSOFA were 0.647 and 0.582, respectively. The SIRS significantly predicted an ultimate infection (AUC, 0.675; p = 0.018) in patients who met the SIRS and qSOFA simultaneously. In conclusion, the SIRS patients included almost all qSOFA patients. SIRS showed a better performance for predicting infection for qSOFA in those who met both definitions.
Salivary proteome signatures in the early and middle stages of human pregnancy with term birth outcome
Authors: Dey Amit Kumar , Kumar Bhoj , Singh Abhishek Kumar , Ranjan Prakash , Thiruvengadam Ramachandran , Desiraju Bapu Koundinya , Kshetrapal Pallavi , Wadhwa Nitya , Bhatnagar Shinjini , Rashid Faraz , Malakar Dipankar , Salunke Dinakar M. , Maiti Tushar Kanti ,   GARBH-Ini Study Group*, Das Bhabatosh , Misra Sumit , Nair Balakrish G. , Natchu Uma Chandra Mouli , Rath Satyajit , Sachdeva Kanika , Sopory Shailaja , Singh Amanpreet , Sharma Dharmendra , Bal Vineeta , Maitra Arindam , Majumder Partha P. , Bahl Monika , Sharma Sunita , Mehta Umesh , Sindhu Brahmdeep , Arya Sugandha , Bharti Rekha , Chellani Harish , Mittal Pratima , Ramji Siddarth , Tripathi Reva , Garg Anju , Khurana Ashok , Hari Smriti , Gupta Yashdeep , Tandon Nikhil , Gupta Rakesh
Published: May 2020

The establishment and maintenance of pregnancy in humans proceed through a continuous change of biochemical and biophysical processes. It requires a constant interaction between the fetus and the maternal system. The present prospective study aims to elucidate changes in salivary proteome from the early to middle stages of term pregnancy, and establishing an expressional trajectory for modulated proteins. To date, a comprehensive characterization of the longitudinal salivary proteome in pregnancy has not been performed and it is our immediate interest. In the discovery phase, maternal saliva (N = 20) at 6–13, 18–21, and 26–29 weeks of gestation was analyzed using level-free proteomics (SWATH-MS) approach. The expression levels of 65 proteins were found to change significantly with gestational age and distributed into two distinct clusters with a unique expression trajectory. The results revealed that altered proteins are involved in maternal immune modulation, metabolism, and host defense mechanism. Further, verification of 12 proteins was employed using targeted mass spectrometry (MRM-MS) in a separate subset of saliva (N = 14). The MRM results of 12 selected proteins confirmed a similar expression pattern as in SWATH-MS analysis. Overall, the results not only demonstrate the longitudinal maternal saliva proteome for the first time but also set the groundwork for comparative analysis between term birth and adverse pregnancy outcomes.
The Role of European Starlings (Sturnus vulgaris) in the Dissemination of Multidrug-Resistant Escherichia coli among Concentrated Animal Feeding Operations
Authors: Chandler Jeffrey C. , Anders Jennifer E. , Blouin Nicolas A. , Carlson James C. , LeJeune Jeffrey T. , Goodridge Lawrence D. , Wang Baolin , Day Leslie A. , Mangan Anna M. , Reid Dustin A. , Coleman Shannon M. , Hopken Matthew W. , Bisha Bledar
Published: May 2020

Antimicrobial use in livestock production is a driver for the development and proliferation of antimicrobial resistance (AMR). Wildlife interactions with livestock, acquiring associated AMR bacteria and genes, and wildlife’s subsequent dispersal across the landscape are hypothesized to play an important role in the ecology of AMR. Here, we examined priority AMR phenotypes and genotypes of Escherichia coli isolated from the gastrointestinal tracts of European starlings (Sturnus vulgaris) found on concentrated animal feeding operations (CAFOs). European starlings may be present in high numbers on CAFOs (>100,000 birds), interact with urban environments, and can migrate distances exceeding 1,500 km in North America. In this study, 1,477 European starlings from 31 feedlots in five U.S. states were sampled for E. coli resistant to third generation cephalosporins (3G-C) and fluoroquinolones. The prevalence of 3G-C and fluoroquinolone-resistant E. coli was 4% and 10%, respectively. Multidrug resistance in the E. coli isolates collected (n = 236) was common, with the majority of isolates displaying resistance to six or more classes of antibiotics. Genetic analyses of a subset of these isolates identified 94 genes putatively contributing to AMR, including seven class A and C β-lactamases as well as mutations in gyrA and parC recognized to confer resistance to quinolones. Phylogenetic and subtyping assessments showed that highly similar isolates (≥99.4% shared core genome, ≥99.6% shared coding sequence) with priority AMR were found in birds on feedlots separated by distances exceeding 150 km, suggesting that European starlings could be involved in the interstate dissemination of priority AMR bacteria.
Structure evolution during deposition and thermal annealing of amorphous carbon ultrathin films investigated by molecular dynamics simulations
Authors: Wang Shengxi , Komvopoulos Kyriakos
Published: May 2020

The evolution of the structure of amorphous carbon (a-C) films during deposition and thermal annealing is of significant interest from both the materials science and application perspectives. However, despite the voluminous literature of studies dealing with the deposition and physical properties of a-C films, basic understanding of the structure evolution due to phase change during film growth and heating is fairly sparse and empirical, presumably due to the lack of high-resolution instruments that can probe structural changes at the atomic and molecular levels in real time. Molecular dynamics (MD) is a powerful computational method for studying atomic/molecular-scale movement and interactions. Thus, the objective of this study was to perform MD simulations that provide insight into changes in the structure of ultrathin a-C films during deposition and annealing. Simulation results reveal a multi-layer film structure, even for a-C films as thin as ~20 Å, the existence of a deposition energy that yields a-C films with the highest sp3 content, the transient and steady-state stages of the structure evolution during annealing at different temperatures, and the changes in the hybridization state (mainly in the bulk layer) encountered during annealing at elevated temperatures. The MD results of this study are of particular importance to applications where the deposition conditions and operation temperature affect the structure and, in turn, the physical properties of ultrathin a-C films used as protective overcoats.
Dyspnea perception during the inspiratory resistive loads test in obese subjects waiting bariatric surgery
Authors: Tomasini Karina , Ziegler Bruna , Sanches Paulo Roberto Stefani , da Silva Junior Danton Pereira , Thomé Paulo Ricardo , Dalcin Paulo de Tarso Roth
Published: May 2020

Identification of low dyspnea perception is relevant, since this condition is significantly associated with worse outcomes. We investigated dyspnea perception during the inspiratory resistive loads test on obese subjects waiting bariatric surgery in comparison with normal subjects. Secondarily, we analysed the proportion of obese subjects with low, moderate and high dyspnea perception. This observational study included subjects with body mass index (BMI) ≥ 35 kg/m2, compared to healthy subjects with BMI ≥ 18 and <25 kg/m2. Subject underwent clinical evaluation, inspiratory test with progressive resistive loads and spirometry. We studied 23 obese subjects (mean BMI = 51.9 ± 9.3 kg/m2) and 25 normal subjects (mean BMI = 24.3 ± 2.3 kg/m2). With the increase magnitude of resistive loads there was a significant increase in dyspnea score (p < 0.001) and progressive increase of the generated inspiratory pressure (p < 0.001), but there was no difference between the groups in terms of dyspnea score (p = 0.191) and no interaction effect (p = 0.372). Among the obese subjects, 4 individuals were classified as low perception, 11 as moderate and 8 as high. In conclusion, the degree of dyspnea perception during the inspiratory progressive resistive loads test did not differ between obese and normal subjects. Among obese subjects, only 17% were classified as low dyspnea perception.
Distinguishing the taphonomic signature of wolves from humans and other predators on small prey assemblages
Authors: Lloveras Lluís , Nadal Jordi , Fullola Josep Maria
Published: May 2020

The study of human subsistence strategies in prehistoric hunter-gatherer communities is essential to understanding the evolution of human behaviour. An important topic of interest is the expansion of dietary breadth, resulting in the procurement of a larger number of small game species. However, to make accurate interpretations of human subsistence, the correct identification of the agents responsible for archaeofaunal assemblages is crucial, and actualistic studies that establish the taphonomic signature of the different predators are indispensable. Despite being one of the most ubiquitous carnivores in prehistoric archaeological sites, the role of wolves (Canis lupus) as agents responsible for small-prey accumulations has never been examined. The aims of this study are to analyse the taphonomic patterns left by wolves on rabbit remains and to put forward a series of criteria that can help distinguish assemblages produced by this carnivore from those accumulated by people or by other predators. Our results reveal that wolves ingest and consume the whole rabbit carcass, with the consequence that all rabbit remains accumulated by wolves come from the scats. The referential framework provided in this study will make it possible to discriminate wolves as agents of fossil rabbit accumulations.
Digital Proxy of a Bio-Reactor (DIYBOT) combines sensor data and data analytics to improve greywater treatment and wastewater management systems
Authors: McLamore Eric S. , Huffaker Ray , Shupler Matthew , Ward Katelyn , Datta Shoumen Palit Austin , Katherine Banks M. , Casaburi Giorgio , Babilonia Joany , Foster Jamie S.
Published: May 2020

Technologies to treat wastewater in decentralized systems are critical for sustainable development. Bioreactors are suitable for low-energy removal of inorganic and organic compounds, particularly for non-potable applications where a small footprint is required. One of the main problems associated with bioreactor use is sporadic spikes of chemical toxins, including nanoparticles. Here, we describe the development of DIYBOT (Digital Proxy of a Bio-Reactor), which enables remote monitoring of bioreactors and uses the data to inform decisions related to systems management. To test DIYBOT, a household-scale membrane aerated bioreactor with real-time water quality sensors was used to treat household greywater simulant. After reaching steady-state, silver nanoparticles (AgNP) representative of the mixture found in laundry wastewater were injected into the system to represent a chemical contamination. Measurements of carbon metabolism, effluent water quality, biofilm sloughing rate, and microbial diversity were characterized after nanoparticle exposure. Real-time sensor data were analyzed to reconstruct phase-space dynamics and extrapolate a phenomenological digital proxy to evaluate system performance. The management implication of the stable-focus dynamics, reconstructed from observed data, is that the bioreactor self-corrects in response to contamination spikes at AgNP levels below 2.0 mg/L. DIYBOT may help reduce the frequency of human-in-the-loop corrective management actions for wastewater processing.
Performance of four platforms for KRAS mutation detection in plasma cell-free DNA: ddPCR, Idylla, COBAS z480 and BEAMing
Authors: Vessies D. C. L. , Greuter M. J. E. , van Rooijen K. L. , Linders T. C. , Lanfermeijer M. , Ramkisoensing K. L. , Meijer G. A. , Koopman M. , Coupé V. M. H. , Vink G. R. , Fijneman R. J. A. , van den Broek D.
Published: May 2020

Multiple platforms are commercially available for the detection of circulating cell-free tumour DNA (ctDNA) from liquid biopsies. Since platforms have different input and output variables, deciding what platform to use for a given clinical or research question can be daunting. This study aimed to provide insight in platform selection criteria by comparing four commercial platforms that detect KRAS ctDNA hotspot mutations: Bio-Rad droplet digital PCR (ddPCR), BioCartis Idylla, Roche COBAS z480 and Sysmex BEAMing. Platform sensitivities were determined using plasma samples from metastatic colorectal cancer (mCRC) patients and synthetic reference samples, thereby eliminating variability in amount of plasma analysed and ctDNA isolation methods. The prevalence of KRAS nucleotide alterations was set against platform-specific breadth of target. Platform comparisons revealed that ddPCR and BEAMing detect more KRAS mutations amongst mCRC patients than Idylla and COBAS z480. Maximum sample throughput was highest for ddPCR and COBAS z480. Total annual costs were highest for BEAMing and lowest for Idylla and ddPCR. In conclusion, when selecting a platform for detection of ctDNA hotspot mutations the desired test sensitivity, breadth of target, maximum sample throughput, and total annual costs are critical factors that should be taken into consideration. Based on the results of this study, laboratories will be able to select the optimal platform for their needs.
Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis
Authors: Tantivitayakul Pornpen , Ruangchai Wuthiwat , Juthayothin Tada , Smittipat Nat , Disratthakit Areeya , Mahasirimongkol Surakameth , Viratyosin Wasna , Tokunaga Katsushi , Palittapongarnpim Prasit
Published: May 2020

Homoplastic mutations are mutations independently occurring in different clades of an organism. The homoplastic changes may be a result of convergence evolution due to selective pressures. Reports on the analysis of homoplastic mutations in Mycobacterium tuberculosis have been limited. Here we characterized the distribution of homoplastic single nucleotide polymorphisms (SNPs) among genomes of 1,170 clinical M. tuberculosis isolates. They were present in all functional categories of genes, with pe/ppe gene family having the highest ratio of homoplastic SNPs compared to the total SNPs identified in the same functional category. Among the pe/ppe genes, the homoplastic SNPs were common in a relatively small number of homologous genes, including ppe18, the protein of which is a component of a promising candidate vaccine, M72/AS01E. The homoplastic SNPs in ppe18 were particularly common among M. tuberculosis Lineage 1 isolates, suggesting the need for caution in extrapolating the results of the vaccine trial to the population where L1 is endemic in Asia. As expected, homoplastic SNPs strongly associated with drug resistance. Most of these mutations are already well known. However, a number of novel mutations associated with streptomycin resistance were identified, which warrants further investigation. A SNP in the intergenic region upstream of Rv0079 (DATIN) was experimentally shown to increase transcriptional activity of the downstream gene, suggesting that intergenic homoplastic SNPs should have effects on the physiology of the bacterial cells. Our study highlights the potential of homoplastic mutations to produce phenotypic changes. Under selective pressure and during interaction with the host, homoplastic mutations may confer advantages to M. tuberculosis and deserve further characterization.
Composite Hydrogel Model of Cartilage Predicts Its Load-Bearing Ability
Authors: Horkay Ferenc , Basser Peter J.
Published: May 2020

Articular cartilage is a load-bearing tissue found in animal and human joints. It is a composite gel-like material in which a fibrous collagen network encapsulates large proteoglycan assemblies that imbibe fluid and “inflate” the network. Here we describe a composite hydrogel consisting of a cross-linked polyvinyl alcohol matrix filled with poly(acrylic acid) microparticles that mimics functional properties and biomechanical behavior of cartilage. The swelling and mechanical behaviors of this biomimetic model system are strikingly similar to that of human cartilage. The development of synthetic composite gel-based articular cartilage analog suggests new avenues to explore material properties, and their change in disease and degeneration, as well as novel strategies for developing composite tissue-engineered cartilage constructs for regenerative medicine applications.
Behavioural effects of the common brain-infecting parasite Pseudoloma neurophilia in laboratory zebrafish (Danio rerio)
Authors: Midttun Helene L. E. , Vindas Marco A. , Nadler Lauren E. , Øverli Øyvind , Johansen Ida B.
Published: May 2020

Research conducted on model organisms may be biased due to undetected pathogen infections. Recently, screening studies discovered high prevalence of the microsporidiumPseudoloma neurophiliain zebrafish (Danio rerio) facilities. This spore-forming unicellular parasite aggregates in brain regions associated with motor function and anxiety, and despite its high occurrence little is known about how sub-clinical infection affects behaviour. Here, we assessed howP. neurophiliainfection alters the zebrafish´s response to four commonly used neurobehavioral tests, namely: mirror biting, open field, light/dark preference and social preference, used to quantify aggression, exploration, anxiety, and sociability. Although sociability and aggression remained unaltered, infected hosts exhibited reduced activity, elevated rates of freezing behaviour, and sex-specific effects on exploration. These results indicate that caution is warranted in the interpretation of zebrafish behaviour, particularly since in most cases infection status is unknown. This highlights the importance of comprehensive monitoring procedures to detect sub-clinical infections in laboratory animals.
Consumption of Oleic Acid During Matriphagy in Free-Living Nematodes Alleviates the Toxic Effects of the Bacterial Metabolite Violacein
Authors: Yoon Kyoung-hye , Lee Tong Young , Moon Je-Hyun , Choi Seong Yeol , Choi Yun Ji , Mitchell Robert J. , Il Lee Jin
Published: May 2020

Maternal behaviors benefit the survival of young, contributing directly to the mother’s reproductive fitness. An extreme form of this is seen in matriphagy, when a mother performs the ultimate sacrifice and offers her body as a meal for her young. Whether matriphagy offers only a single energy-rich meal or another possible benefit to the young is unknown. Here, we characterized the toxicity of a bacterial secondary metabolite, namely, violacein, in Caenorhabditis elegans and found it is not only toxic towards adults, but also arrests growth and development of C. elegans larvae. To counteract this, C. elegans resorted to matriphagy, with the mothers holding their eggs within their bodies and hatching the young larvae internally, which eventually led to the mothers’ death. This violacein-induced matriphagy alleviated some of the toxic effects of violacein, allowing a portion of the internally-hatched young to bypass developmental arrest. Using genetic and pharmacological experiments, we found the consumption of oleate, a monounsaturated fatty acid produced by the mother, during matriphagy is partially responsible. As such, our study provides experimental evidence of why such a drastic and peculiar maternal behavior may have arisen in nematode natural habitats.
Genome-wide screens reveal Escherichia coli genes required for growth of T1-like phage LL5 and V5-like phage LL12
Authors: Piya Denish , Lessor Lauren , Koehler Brian , Stonecipher Ashley , Cahill Jesse , Gill Jason J.
Published: May 2020

The host factor requirements of phages and mechanisms of mutational phage insensitivity must be characterized for rational design of phage cocktails. To characterize host dependencies of two novel Escherichia coli phages, the T1-like siphophage LL5 and the V5-like myophage LL12, forward genetic screens were conducted against the Keio collection, a library of single non-essential gene deletions in E. coli str. BW25113. These screens and subsequent experiments identified genes required by phages LL5 and LL12. E. coli mutants deficient in heptose II and the phosphoryl substituent of heptose I of the inner core lipopolysaccharide (LPS) were unable to propagate phage LL5, as were mutants deficient in the outer membrane protein TolC. Mutants lacking glucose I of the LPS outer core failed to propagate LL12. Two additional genes encoding cytoplasmic chaperones, PpiB and SecB, were found to be required for efficient propagation of phage LL5, but not LL12. This screening approach may be useful for identifying host factors dependencies of phages, which would provide valuable information for their potential use as therapeutics and for phage engineering.
Effect of mechanical combined with electromagnetic stirring on the dispersity of carbon fibers in the aluminum matrix
Authors: Li Guanglong , Qu Yingdong , Yang Yaohua , Chen Ruirun , Zhou Qiwen , Li Rongde
Published: May 2020

In order to improve the uneven distribution of carbon fibers (CFs) in the matrix by traditional single mechanical stirring, mechanical combined with electromagnetic (M-E) stirring was used to prepare short carbon fibers reinforced aluminum matrix (Csf/Al) composites. The 3-D flow field of aluminum melt under mechanical/M-E stirring were calculated and compared. The calculation results show that the complexity of flow field under M-E stirring could be significantly enhanced relative to a single mechanical stirring, especially there was a strong melt flow near the crucible wall due to the skin effect. It was found that except the inertial force under mechanical stirring and the melt collision with the crucible walls, CFs were also subjected to the electromagnetic force and the oscillating flow between the eddy currents, which would promote the dispersity of the short CFs in the composites. The experimental results are consistent with the calculation results. The experimental results show that the distribution of CFs at each position in the composite samples prepared under M-E stirring was stable. The uniform distribution of CFs in the composites would play an important role in improving the overall performance of the Csf/Al composites.
Association between initial dialytic modalities and the risks of mortality, infection death, and cardiovascular events: A nationwide population-based cohort study
Authors: Tu Yi-Ran , Tsai Tsung-Yu , Lin Ming-Shyan , Tu Kun-Hua , Lee Cheng-Chia , Wu Victor Chien-Chia , Hsu Hsiang-Hao , Chang Ming-Yang , Tian Ya-Chung , Chang Chih-Hsiang
Published: May 2020

To date, few studies have been conducted to pairwise compare the prognosis of peritoneal dialysis (PD), unplanned PD, and unplanned hemodialysis (HD). We analyzed longitudinal data from Taiwan’s National Health Insurance Research Database. We included 45,165 patients whose initial dialytic modality was PD or unplanned HD between January 1, 2001 and December 31, 2013. We divided the patients into three groups according to their initial dialytic modalities. The primary outcomes were all-cause mortality and death from infection during 1-year follow up. The risks of all-cause mortality and infection death were higher in the unplanned PD group than in the planned PD group (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.28–1.60; HR 1.54, 95% CI 1.32–1.80). Likewise, the risks of all-cause mortality and infection death were higher in the unplanned HD group (HR 1.64, 95% CI 1.48–1.82; HR 1.85, 95% CI 1.61–2.13). Furthermore, the risks of all-cause mortality and infection death were also higher in the unplanned HD group than in the unplanned PD group (HR 1.15, 95% CI 1.07–1.23; HR 1.20, 95% CI 1.09–1.32). In conclusion, our study demonstrates that patients whose initial modality was planned PD or unplanned PD may have better clinical outcomes than those whose initial modality was unplanned HD.
A Novel Hydrogenation of Nitroarene Compounds with Multi Wall Carbon Nanotube Supported Palladium/Copper Nanoparticles (PdCu@MWCNT NPs) in Aqueous Medium
Authors: Göksu Haydar , Zengin Nursefa , Burhan Hakan , Cellat Kemal , Şen Fatih
Published: May 2020

A novel nanocatalyst, multi-wall carbon nanotube supported palladium/copper (PdCu@MWCNT) nanoparticles, was synthesized for the reduction of nitroarene compounds. Characterization of the nanocatalyst was achieved by XRD, XPS, TEM, and Raman spectroscopy analysis. In this study, the hydrogenation of nitroarenes to primary amine compounds was achieved in aqueous medium at room temperature. The aniline derivatives were synthesized with high yields at mild conditions via novel PdCu@MWCNT nanocatalyst. The conversion of nitroarenes to amine derivatives was accomplished at 99% efficiency. In addition to its high activity, the PdCu@MWCNT catalyst was determined to be stable and reusable after the 3rd consecutive use for the reaction and provided 99% conversion of various compounds in the reduction reaction.
Obesity and Diabetes in an Arab population: Role of Adenovirus 36 Infection
Authors: Lessan Nader , Saradalekshmi Koramannil R. , Alkaf Budour , Majeed Maria , Barakat Maha T. , Lee Zendra P. L. , Atkinson Richard L
Published: May 2020

Prior infection with adenovirus 36 (Adv36) has been associated with increased adiposity, improved insulin sensitivity, and a lower prevalence of diabetes. This study investigated the prevalence of Adv36 seropositivity and its association with obesity and diabetes among adults attending a diabetes centre in the UAE.Participants (N = 973) with different weight and glucose tolerance categories were recruited. Adv36 seropositivity (Adv36 + ) was assessed using ELISA. Differences among groups were analyzed using statistical tests as appropriate to the data. Prevalence of Adv36+ in the study population was 47%, with no significant difference in obese and non-obese subgroups (42.5% vs 49.6% respectively; p=non-significant). Females were more likely to be Adv36+ compared to males (odds ratio 1.78; 95% CI 1.36–2.32, p < 0.001). We found no significant association between Adv36 seropositivity and different BMI categories, or glucose tolerance status. In our population, the effect of Adv36 infection on lipid profile varied between healthy individuals and individuals with obesity. Adv36 infection is more prevalent in the UAE than in other countries but has no association with obesity. Our study found that females were more likely to be Adv36 positive regardless of weight or diabetes status.
Functional analysis of an essential Ran-binding protein gene, CpRbp1, from the chestnut blight fungus Cryphonectria parasitica using heterokaryon rescue
Authors: Ko Yo-Han , Choi So-Yeon , So Kum-Kang , Kim Jung-Mi , Chun Jeesun , Kim Dae-Hyuk
Published: May 2020

A Ran binding protein (RanBP) homolog, CpRbp1, from Cryphonectria parasitica, has been identified as a protein that is affected by hypovirus infection or tannic acid supplementation. In this study, functional analyses of CpRbp1 were performed by constructing a knockout mutant and analyzing the resulting heterokaryon. Transformation-mediated gene replacement resulted in two putative CpRbp1-null mutants and genotype analyses identified these two mutants as heterokaryotic transformants consisting of two types of nuclei, one with the wild-type CpRbp1 allele and another with the CpRbp1-null mutant allele. Although stable mycelial growth of the heterokaryotic transformant was observed on selective medium containing hygromycin B, neither germination nor growth of the resulting conidia, which were single-cell monokaryotic progeny, was observed on the medium. In trans complementation of heterokaryons using a full-length wild-type allele of the CpRbp1 gene resulted in complemented transformants. These transformants sporulated single-cell monokaryotic conidia that were able to grow on media selective for replacing and/or complementing markers. These results clearly indicate that CpRbp1 is an essential gene, and heterokaryons allowed the fungus to maintain lethal CpRbp1-null mutant nuclei. Moreover, in trans complementation of heterokaryons using chimeric structures of the CpRbp1 gene allowed for analysis of its functional domains, which was previously hampered due to the lethality of the gene. In addition, in trans complementation using heterologous RanBP genes from Aspergillus nidulans was successful, suggesting that the function of RanBP is conserved during evolution. Furthermore, in trans complementation allowed for functional analyses of lethal orthologs. This study demonstrates that our fungal heterokaryon system can be applied effectively to determine whether a gene of interest is essential, perform functional analyses of a lethal gene, and analyze corresponding heterologous genes.