bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal infection results in impaired lung innate immunity to secondary respiratory infection
Authors: Trivedi Shubhanshi , Grossmann Allie H. , Jensen Owen , Cody Mark J. , Wahlig Taylor A. , Serpa Paula Hayakawa , Langelier Charles , Warren Kristi J. , Yost Christian C. , Leung Daniel T. 
Published: August 2020

AbstractBackgroundPneumonia and diarrhea are among the leading causes of death worldwide, and epidemiological studies have demonstrated that diarrhea is associated with an increased risk of subsequent pneumonia. Our aim was to determine the impact of intestinal infection on innate immune responses in the lung.MethodsUsing a mouse model of intestinal infection bySalmonella entericaserovar Typhimurium (S. Typhimurium (ST)), we investigated how infection in the gut compartment can modulate immunity in the lungs and impact susceptibility to bacterial (Klebsiella pneumoniae(KP)) challenge.ResultsWe found alterations in frequencies of innate immune cells in lungs of intestinally-infected mice compared to uninfected mice. On subsequent challenge withK. pneumoniaewe found that mice with prior intestinal infection have higher lung bacterial burden and inflammation, increased neutrophil margination, and neutrophil extracellular traps (NETs), but lower overall numbers of neutrophils, compared to mice without prior intestinal infection. Total numbers of dendritic cells, innate-like T cells, and natural killer cells were not different between mice with and without prior intestinal infection.ConclusionsTogether, these results suggest that intestinal infection impacts lung innate immune responses, most notably neutrophil characteristics, potentially resulting in increased susceptibility to secondary pneumonia.Article summaryWe show, in a mouse model, that prior intestinal infection withSalmonella Typhimuriumleads to increased susceptibility to respiratoryKlebsiella pneumoniae infection, which is associated with altered neutrophil responses.
Cytidine monophosphate N-acetylneuraminic acid synthetase and solute carrier family 35 member A1 are required for reovirus binding and infection
Authors: Urbanek Kelly , Sutherland Danica M. , Orchard Robert C. , Wilen Craig B. , Knowlton Jonathan J. , Aravamudhan Pavithra , Taylor Gwen M. , Virgin Herbert W. , Dermody Terence S. 
Published: August 2020

ABSTRACTEngagement of cell-surface receptors by viruses is a critical determinant of viral tropism and disease. The reovirus attachment protein, σ1, binds sialylated glycans and proteinaceous receptors to mediate infection, but the specific requirements on different cell types are unknown. To identify host factors required for reovirus-induced cell death, we conducted a CRISPR-knockout screen targeting over 20,000 genes in murine microglial BV2 cells. Candidate genes identified as required for reovirus to cause cell death were highly enriched for sialic acid synthesis and transport. Two of the top candidates identified, cytidine monophosphate N-acetylneuraminic acid synthetase (Cmas) and solute carrier family 35 member A1 (Slc35a1), promote sialic acid expression on the cell surface. Two reovirus strains differing in the capacity to bind sialic acid, T3SA+ and T3SA-, were used to evaluateCmasandSlc35a1as potential host genes required for infection. Following CRISPR-Cas9 disruption of either gene, cell-surface expression of sialic acid was diminished. These results correlated with decreased binding of strain T3SA+, which is capable of engaging sialic acid. Disruption of either gene did not alter the low-level binding of T3SA-, which does not engage sialic acid. Infectivity of T3SA+ was diminished to levels of T3SA-in cells lackingCmasandSlc35a1by CRISPR ablation. However, exogenous expression ofCmasandSlc35a1into the respective null cells restored sialic acid expression and T3SA+ binding and infectivity. These results demonstrate thatCmasandSlc35a1, which mediate cell-surface expression of sialic acid, are required in murine microglial cells for efficient reovirus binding and infection.IMPORTANCEAttachment factors and receptors are important determinants of dissemination and tropism during reovirus-induced disease. In a CRISPR cell-survival screen, we discovered two genes,CmasandSlc35a1, which encode proteins required for sialic acid expression on the cell surface, that mediate reovirus infection of microglial cells. This work elucidates host genes that render microglial cells susceptible to reovirus infection and expands current understanding of the receptors on microglial cells that are engaged by reovirus. Such knowledge may lead to new strategies to selectively target microglial cells for oncolytic applications.
Illumina iSeq 100 and MiSeq exhibit similar performance in freshwater fish environmental DNA metabarcoding
Authors: Nakao Ryohei , Inui Ryutei , Akamatsu Yoshihisa , Goto Masuji , Doi Hideyuki , Matsuoka Shunsuke 
Published: August 2020

AbstractEnvironmental DNA (eDNA) analysis is a method of detecting DNA from environmental samples and is used as a biomonitoring tool. In recent studies, Illumina MiSeq has been the most extensively used tool for eDNA metabarcoding. The Illumina iSeq 100 (hereafter, iSeq), one of the high-throughput sequencers (HTS), has a relatively simple workflow and is potentially more affordable than other HTS. However, its utility in eDNA metabarcoding has still not been investigated. In the present study, we applied fish eDNA metabarcoding to 40 water samples from river and lake ecosystems to assess the difference in species detectability and composition between iSeq and MiSeq. To check differences in sequence quality and errors, we also assessed differences in read changes between the two HTS. There were similar sequence qualities between iSeq and MiSeq. Significant difference was observed in the number of species between two HTS, but no difference was observed in species composition between the two HTS. Additionally, the species compositions in common with the conventional method were the same between the two HTS. According to the results, using the same amplicon library for sequencing, two HTS would exhibit a similar performance of fish species detection using eDNA metabarcoding.
KRASG12D mutant cells are outcompeted by wild type neighbours in adult pancreas in an EPHA2-dependent manner
Authors: Hill William , Zaragkoulias Andreas , Salvador Beatriz , Parfitt Geraint , Alatsatianos Markella , Padilha Ana , Porazinski Sean , Woolley Thomas E. , Morton Jennifer P. , Sansom Owen J. , Hogan Catherine 
Published: August 2020

SummaryAs we age, our tissues are repeatedly challenged by mutational insult, yet cancer occurrence is a relatively rare event. Cells carrying cancer-causing genetic mutations compete with normal neighbours for space and survival in tissues. However, the mechanisms underlying mutant-normal competition in adult tissues and the relevance of this process to cancer remain incompletely understood. Here, we investigate how the adult pancreas maintains tissue healthin vivofollowing sporadic expression of oncogenicKras(KrasG12D), the key driver mutation in human pancreatic cancer. We find that when present in tissues in low numbers, KrasG12D mutant cells are outcompeted and cleared from exocrine and endocrine compartmentsin vivo. Using quantitative 3D tissue imaging, we show that prior to being cleared, KrasG12D cells lose cell volume, segregate from normal cells and decrease E-cadherin-based cell-cell adhesions with normal neighbours. We identify EphA2 receptor is an essential signal in the clearance of KrasG12D cells from exocrine and endocrine tissuesin vivo. In the absence of functional EphA2, KrasG12D cells no longer segregate, E-cadherin-based cell-cell adhesions increase and KrasG12D cells are retained in tissues. Retention of KRasG12D cells leads to an increased burden of premalignant pancreatic intraepithelial neoplasia (PanINs) in tissues. Our data show that adult pancreas tissues remodel to clear KrasG12D cells and maintain tissue health. This study provides evidence to support a conserved functional role of EphA2 in Ras-driven cell competition in epithelial tissues and suggests that EphA2 is a novel tumour suppressor in pancreatic cancer.
A Failure Mode and Effect Analysis of plant metabolism reveals why cytosolic fumarase is required for temperature acclimation in Arabidopsis
Authors: Herrmann Helena A. , Calzadilla Pablo I. , Schwartz Jean-Marc , Johnson Giles N. 
Published: August 2020

SummaryPlants acclimate their photosynthetic capacity in response to changing environmental conditions. InArabidopsis thaliana, photosynthetic acclimation to cold requires the accumulation of the organic acid fumarate, catalysed by a cytosolic fumarase FUM2, however the role of this is currently unclear.In this study, we use an integrated experimental and modelling approach to examine the role of FUM2 and fumarate across the physiological temperature range. Using physiological and biochemical analyses, we demonstrate that FUM2 is necessary for high as well as low temperature acclimation.To understand the role of FUM2 activity, we have adapted a reliability engineering technique, Failure Mode and Effect Analysis (FMEA), to formalize a rigorous approach for ranking metabolites according to the potential risk that they pose to the metabolic system. FMEA identifies fumarate as a low-risk metabolite. Its precursor, malate, is shown to be high-risk and liable to cause system instability. We conclude that the role of cytosolic fumarase, FUM2, is to provide a fail-safe, maintaining system stability under changing environmental conditions.We argue that FMEA is a technique which is not only useful in understanding plant metabolism, it can also be used to study reliability in other systems and aid the design of synthetic pathways.
Using a simple cellular assay to map NES motifs in cancer-related proteins, gain insight into CRM1-mediated NES export, and search for NES-harbouring micropeptides
Authors: Sendino Maria , Omaetxebarria Miren Josu , Prieto Gorka , Rodriguez Jose Antonio 
Published: August 2020

ABSTRACTThe nuclear export receptor CRM1 (XPO1) recognizes and binds specific sequence motifs termed nuclear export signals (NESs) in cargo proteins. About 200 NES motifs have been identified, but over a thousand human proteins are potential CRM1 cargos, and most of their NESs remain to be identified. On the other hand, the interaction of NES peptides with the “NES-binding groove” of CRM1 has been studied in detail using structural and biochemical analyses, but a better understanding of CRM1 function requires further investigation of how the results from these in vitro studies translate into actual NES export in a cellular context. Here we show that a simple cellular assay, based on a recently described reporter (SRVB/A), can be applied to identify novel potential NESs motifs, and to obtain relevant information on different aspects of CRM1-mediated NES export. Using cellular assays, we first map 19 new sequence motifs with nuclear export activity in 14 cancer-related proteins that are potential CRM1 cargos. Next, we investigate the effect of mutations in individual NES-binding groove residues, providing further insight into CRM1-mediated NES export. Finally, we extend the search for CRM1-dependent NESs to a recently uncovered, but potentially vast, set of small proteins called micropeptides. By doing so, we report the first NES-harbouring human micropeptides.
A valid protective immune response elicited in rhesus macaques by an inactivated vaccine is capable of defending against SARS-CoV-2 infection
Authors: Chen Hongbo , Xie Zhongping , Long Runxiang , Fan Shengtao , Li Heng , He Zhanlong , Xu Kanwei , Liao Yun , Wang Lichun , Zhang Ying , Li Xueqi , Dong Xingqi , Mou Tangwei , Zhou Xiaofang , Yang Yaoyun , Guo Lei , Yang Jianbo , Zheng Huiwen , Xu Xingli , Li Jing , Liang Yan , Li Dandan , Zhao Zhimei , Hong Chao , Zhao Heng , Jiang Guorun , Che Yanchun , Yang Fengmei , Hu Yunguang , Wang Xi , Pu Jing , Ma Kaili , Wang Lin , Chen Chen , Duan Weiguo , Shen Dong , Zhao Hongling , Jiang Ruiju , Deng Xinqiang , Li Yan , Zhu Hailian , Zhou Jian , Yu Li , Xu Mingjue , Yang Huijuan , Yi Li , Zhou Zhenxin , Yang Jiafang , Duan Nan , Yang Huan , Zhao Wangli , Yang Wei , Li Changgui , Liu Longding , Li Qihan 
Published: August 2020

AbstractWith the relatively serious global epidemic outbreak of SARS-CoV-2 infection, public concerns focus on not only clinical therapeutic measures and public quarantine for this disease but also the development of vaccines. The technical design of our SARS-CoV-2 inactivated vaccine provides a viral antigen that enables the exposure of more than one structural protein based upon the antibody composition of COVID-19 patients’ convalescent serum. This design led to valid immunity with increasing neutralizing antibody titers and a CTL response detected post-immunization of this vaccine by two injections in rhesus macaques. Further, this elicited immunoprotection in macaques enables not only to restrain completely viral replication in tissues of immunized animals, compared to the adjuvant control and those immunized by an RBD peptide vaccine, but also to significantly alleviate inflammatory lesion in lung tissues in histo-pathologic detection, compared to the adjuvant control with developed interstitial pneumonia. The data obtained from these macaques immunized with the inactivated vaccine or RBD peptide vaccine suggest that immunity with a clinically protective effect against SARS-CoV-2 infection should include not only specific neutralizing antibodies but also specific CTL responses against at least the S and N antigens.
Trypanosoma cruziamastigotes have a reduced replication rate during chronic stage infections
Authors: Ward Alexander I. , Olmo Francisco , Atherton Richard , Taylor Martin C. , Kelly John M. 
Published: August 2020

AbstractChronicTrypanosoma cruziinfections are typically life-long, with small numbers of parasites surviving in restricted tissue sites, which include the gastro-intestinal tract. There is considerable debate about the replicative status of these persistent parasites. Here, we investigatedT. cruziproliferation in the colon of chronically infected mice using 5-ethynyl-2’deoxyuridine incorporation into DNA to provide “snapshots” of parasite replication. Highly sensitive imaging of infection foci at single cell resolution revealed that parasites are three times more likely to be in S-phase during the acute stage than during the chronic stage. By implication, chronic infections are associated with a reduced rate of parasite replication. Despite this, very few host cells survive infection for >14 days, suggesting thatT. cruzipersistence continues to involve regular cycles of replication, host cell lysis and re-infection. Therefore, long-term persistence in the colon is more likely to be associated with reduced proliferation than with dormancy.
Machine Learning-Based Protein Microarray Digital Assay Analysis
Authors: Song Yujing , Zhao Jingyang , Cai Tao , Su Shiuan-Haur , Sandford Erin , Flora Christopher , Singer Benjamin H. , Ghosh Monalisa , Choi Sung Won , Tewari Muneesh , Kurabayashi Katsuo 
Published: August 2020

AbstractSerial measurement of a large panel of protein biomarkers near the bedside could provide a promising pathway to transform the critical care of acutely ill patients. However, attaining the combination of high sensitivity and multiplexity with a short assay turnaround poses a formidable technological challenge. Here, we developed a rapid, accurate, and highly multiplexed microfluidic digital immunoassay by incorporating machine learning-based autonomous image analysis. The assay achieved 14-plexed biomarker detection at concentrations < 10pg/mL with a sample volume < 10 μL, including all processes from sampling to analyzed data delivery within 30 min, while only requiring a 5-min assay incubation. The assay procedure applied both a spatial-spectral microfluidic encoding scheme and an image data analysis algorithm based on machine learning with a convolutional neural network (CNN) for pre-equilibrated single-molecule protein digital counting. This unique approach remarkably reduced errors facing the high-capacity multiplexing of digital immunoassay at low protein concentrations. Longitudinal data obtained for a panel of 14 serum cytokines in human patients receiving chimeric antigen receptor-T (CAR-T) cell therapy manifested the powerful biomarker profiling capability and great potential of the assay for its translation to near-real-time bedside immune status monitoring.
Exploring lesson study in postsecondary education through self-study
Authors: Moghaddam Alireza , Arnold Christine , Azam Saiqa , Goodnough Karen , Maich Kimberly , Penney Sharon , Young Gabrielle 
Published: August 2020

PurposeThe purpose of this collaborative self-study inquiry was to enhance the professional practice of faculty members through the adoption of lesson study. A seven-member faculty of education self-study group engaged in lesson study in a computer and learning resources for primary/elementary teachers’ course with teacher candidates.Design/methodology/approachThis study focused on providing teacher candidates with increased opportunities for action and expression during in-class instruction. This collaborative lesson study inquiry (Fernandezet al., 2003; Fernandez and Yoshida, 2004; Murata, 2011) involved the four-step process of planning, doing, checking and acting (PDCA) (Cheng, 2019). Several data collection methods were adopted and data sources analyzed.FindingsChallenges the group encountered during the study included ascertaining the goals of lesson study and offering critical feedback to each other. While this made decision-making more intricate and intentional, there was exceptional value in participating in the lesson study process. The results revealed three overarching themes: 1) challenges in classroom observations; 2) hesitation in providing supportive feedback to colleagues and 3) deliberations regarding what constitutes expertise within subject-specific preservice teacher education.Originality/valueWhile lesson study has been adopted fairly extensively in K-12 settings, its adoption in postsecondary education is limited (Chenault, 2017). Considering the merits of lesson study for K-12 practitioners, this research investigated the similar advantages that lesson study might have for postsecondary education faculty, students and programs.
Determinants of Islamic social reporting in Islamic banks of Pakistan
Authors: Hussain Arif , Khan Muhammad , Rehman Alam , Sahib Zada Shehnaz , Malik Shumaila , Khattak Asiya , Khan Hassan 
Published: August 2020

Purpose
This study aims to spotlight and explore various determinants of Islamic social reporting (ISR) in Islamic banks of Pakistan.

Design/methodology/approach
The authors have used firm size, firm profitability, firm age, board size and board independence as determinants of ISR. The authors collected data from Islamic banks listed on Pakistan Stock Exchange for the period 2012–2019. Multiple estimation techniques, i.e. fixed effect model, random effect model and one-step difference generalized method of moment (GMM), have been applied.

Findings
Random effect model was found to be more robust as compared to fixed effect model and one-step difference GMM. The results reported by the random effect model, preferred among the three, show that firm size, firm profitability, firm age and board size are important determinants of ISR in Islamic banks of Pakistan, while board independence does not determine social reporting for Islamic banks in Pakistan. Although social reporting in annual reports of Islamic banks in Pakistan is increasing, further improvement and compliance is required to ensure accountability and transparency in financial reporting as recommended by Islamic teachings. The study has certain managerial implications, especially for top management of Islamic banks.

Originality/value
To the best of the authors’ knowledge, this study is the first to discuss determinants of ISR in Islamic banks of Pakistan. The developed framework herein provides a precise guideline for Islamic banking to enhance their performance, which has never been discussed before.
In defence of digital contact-tracing: human rights, South Korea and Covid-19
Authors: Ryan Mark 
Published: August 2020

Purpose
The media has even been very critical of some East Asian countries’ use of digital contact-tracing to control Covid-19. For example, South Korea has been criticised for its use of privacy-infringing digital contact-tracing. However, whether their type of digital contact-tracing was unnecessarily harmful to the human rights of Korean citizens is open for debate. The purpose of this paper is to examine this criticism to see if Korea’s digital contact-tracing is ethically justifiable.

Design/methodology/approach
This paper will evaluate Korea’s digital contact-tracing through the lens of the four human rights principles to determine if their response is ethically justifiable. These four principles were originally outlined in the European Court of Human Rights, namely, necessary, proportional, scientifically valid and time-bounded (European Court of Human Rights 1950).

Findings
The paper will propose that while the use of Korea’s digital contact-tracing was scientifically valid and proportionate (albeit, in need for improvements), it meets the necessity requirement, but is too vague to meet the time-boundedness requirement.

Originality/value
The Covid-19 pandemic has proven to be one of the worst threats to human health and the global economy in the past century. There have been many different strategies to tackle the pandemic, from somewhat laissez-faire approaches, herd immunity, to strict draconian measures. Analysis of the approaches taken in the response to the pandemic is of high scientific value and this paper is one of the first to critically engage with one of these methods – digital contact-tracing in South Korea.