bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution Metatranscriptomic Characterization of the Pulmonary RNA Virome After Lung Transplantation
Authors: Mitchell Alicia B. , Li Ci-Xiu , Oliver Brian G.G. , Holmes Edward C. , Glanville Allan R.
Published: March 2021

Background.

Lung transplantation provides a unique opportunity to investigate the constituents and temporal dynamics of the human pulmonary microbiome after lung transplantation. For methodological reasons, prior studies using metagenomics have detected DNA viruses but not demonstrated the presence of RNA viruses, including those that are common community acquired. In this proof-of-concept study, we aimed to further characterize the pulmonary microbiome after lung transplantation by using metagenomic next-generation sequencing (mNGS), with a particular focus on the RNA virome.

Methods.

We performed a single-center longitudinal study of lower respiratory tract RNA viruses and bacteria using bronchoalveolar lavage at postoperative day 1 and week 6 analyzed with total RNA sequencing (metatranscriptomics). Five primary and 5 repeat transplant recipients were recruited.

Results.

mNGS identified 5 RNA viruses (nil in the normal saline control), including 4 species of human rhinovirus not previously reported in Australia: A7 (HRV-A7), C22 (HRV-C22), B52 (HRV-B52), and B72 (HRV-B72). Overall, 12/20 specimens were virus positive in 7/10 cases. Human parainfluenza virus 3 was the most frequent virus in 7/20 specimens in 5/10 cases. In this small study, we did not detect a significant difference in abundance and diversity of RNA viruses and bacteria at postoperative day 1 and 6 wk, nor differences between retransplant recipients and primary lung transplant recipients.

Conclusions.

Our study demonstrates how mNGS can also identify RNA viruses within the human pulmonary virome, including novel RNA viruses, and paves the way for a greater understanding of the complex relationships among the constituents of the pulmonary infectome.
Analysis of functional MRI signal complexity based on permutation fuzzy entropy in bipolar disorder
Authors: Xiang Jie , Tan Yuan , Niu Yan , Sun Jie , Zhang Nan , Li Dandan , Wang Bin
Published: March 2021

Bipolar disorder is a manifestation of an emotional disease and is associated with emotional and cognitive dysfunction. The entropy-based method has been widely used to study the complexity of resting-state functional MRI (rs-fMRI) signals in mental diseases; however, alterations in the brain rs-fMRI signal complexities in bipolar disorder patients remain unclear, and previously used entropy methods are sensitive to noise. Here, we performed a work using permutation fuzzy entropy (PFEN), which has better performance than previously used methods, to analyze the brain complexity of bipolar disorder patients. Based on PFEN research, we obtained brain entropy maps of 49 bipolar disorder patients and 49 normal control, extracted the regions of interest to analyze the complexity of abnormal brain regions and further analyzed the correlation between the PFEN values of abnormal brain regions and the clinical measurement scores. Compared with the values in the normal control group, we found that significantly increased PFEN values mainly appeared in the middle temporal gyrus, angular gyrus, superior occipital gyrus and medial superior frontal gyrus, and the decreased PFEN values were found in the inferior temporal gyrus in bipolar disorder patients. In addition, the PFEN values of the angular gyrus was significantly negatively correlated with clinical scores. These findings improve our understanding of the pathophysiology of bipolar disorder patients.
Sparsity induced by covariance transformation: some deterministic and probabilistic results
Authors: Rybak Jakub , Battey Heather S.
Published: March 2021

Motivated by statistical challenges arising in modern scientific fields, notably genomics, this paper seeks embeddings in which relevant covariance models are sparse. The work exploits a bijective mapping between a strictly positive definite matrix and its orthonormal eigen-decomposition, and between an orthonormal eigenvector matrix and its principle matrix logarithm. This leads to a representation of covariance matrices in terms of skew-symmetric matrices, for which there is a natural basis representation, and through which sparsity is conveniently explored. This theoretical work establishes the possibility of exploiting sparsity in the new parametrization and converting the conclusion back to the one of interest, a prospect of high relevance in statistics. The statistical aspects associated with this operation, while not a focus of the present work, are briefly discussed.
Multi-spike solutions of a hybrid reaction–transport model
Authors: Bressloff P. C.
Published: March 2021

Simulations of classical pattern-forming reaction–diffusion systems indicate that they often operate in the strongly nonlinear regime, with the final steady state consisting of a spatially repeating pattern of localized spikes. In activator–inhibitor systems such as the two-component Gierer–Meinhardt (GM) model, one can consider the singular limit
D

a

 ≪ 
D

h

, where
D

a

and
D

h

are the diffusivities of the activator and inhibitor, respectively. Asymptotic analysis can then be used to analyse the existence and linear stability of multi-spike solutions. In this paper, we analyse multi-spike solutions in a hybrid reaction–transport model, consisting of a slowly diffusing activator and an actively transported inhibitor that switches at a rate
α
between right-moving and left-moving velocity states. Such a model was recently introduced to account for the formation and homeostatic regulation of synaptic puncta during larval development in
Caenorhabditis elegans
. We exploit the fact that the hybrid model can be mapped onto the classical GM model in the fast switching limit
α
 → ∞, which establishes the existence of multi-spike solutions. Linearization about the multi-spike solution yields a non-local eigenvalue problem that is used to investigate stability of the multi-spike solution by combining analytical results for
α
 → ∞ with a graphical construction for finite
α
.
Wildlife disturbances as a source of conspecific negative density-dependent mortality in tropical trees
Authors: Luskin Matthew Scott , Johnson Daniel J. , Ickes Kalan , Yao Tze Leong , Davies Stuart J.
Published: March 2021

Large vertebrates are rarely considered important drivers of conspecific negative density-dependent mortality (CNDD) in plants because they are generalist consumers. However, disturbances like trampling and nesting also cause plant mortality, and their impact on plant diversity depends on the spatial overlap between wildlife habitat preferences and plant species composition. We studied the impact of native wildlife on a hyperdiverse tree community in Malaysia. Pigs (
Sus scrofa
) are abnormally abundant at the site due to food subsidies in nearby farmland and they construct birthing nests using hundreds of tree saplings. We tagged 34 950 tree saplings in a 25 ha plot during an initial census and assessed the source mortality by recovering tree tags from pig nests (
n
= 1672 pig-induced deaths). At the stand scale, pigs nested in flat dry habitats, and at the local neighbourhood scale, they nested within clumps of saplings, both of which are intuitive for safe and efficient nest building. At the stand scale, flat dry habitats contained higher sapling densities and higher proportions of common species, so pig nesting increased the weighted average species evenness across habitats. At the neighbourhood scale, pig-induced sapling mortality was associated with higher heterospecific and especially conspecific sapling densities. Tree species have clumped distributions due to dispersal limitation and habitat filtering, so pig disturbances in sapling clumps indirectly caused CNDD. As a result, Pielou species evenness in 400 m
2
quadrats increased 105% more in areas with pig-induced deaths than areas without disturbances. Wildlife induced CNDD and this supported tree species evenness, but they also drove a 62% decline in sapling densities from 1996 to 2010, which is unsustainable. We suspect pig nesting is an important feature shaping tree composition throughout the region.
Evidence of economical territory selection in a cooperative carnivore
Authors: Sells Sarah N. , Mitchell Michael S. , Podruzny Kevin M. , Gude Justin A. , Keever Allison C. , Boyd Diane K. , Smucker Ty D. , Nelson Abigail A. , Parks Tyler W. , Lance Nathan J. , Ross Michael S. , Inman Robert M.
Published: March 2021

As an outcome of natural selection, animals are probably adapted to select territories economically by maximizing benefits and minimizing costs of territory ownership. Theory and empirical precedent indicate that a primary benefit of many territories is exclusive access to food resources, and primary costs of defending and using space are associated with competition, travel and mortality risk. A recently developed mechanistic model for economical territory selection provided numerous empirically testable predictions. We tested these predictions using location data from grey wolves (Canis lupus) in Montana, USA. As predicted, territories were smaller in areas with greater densities of prey, competitors and low-use roads, and for groups of greater size. Territory size increased before decreasing curvilinearly with greater terrain ruggedness and harvest mortalities. Our study provides evidence for the economical selection of territories as a causal mechanism underlying ecological patterns observed in a cooperative carnivore. Results demonstrate how a wide range of environmental and social conditions will influence economical behaviour and resulting space use. We expect similar responses would be observed in numerous territorial species. A mechanistic approach enables understanding how and why animals select particular territories. This knowledge can be used to enhance conservation efforts and more successfully predict effects of conservation actions.
Validation strategy of a bioinformatics whole genome sequencing workflow for Shiga toxin-producing Escherichia coli using a reference collection extensively characterized with conventional methods
Authors: Bogaerts Bert , Nouws Stéphanie , Verhaegen Bavo , Denayer Sarah , Van Braekel Julien , Winand Raf , Fu Qiang , Crombé Florence , Piérard Denis , Marchal Kathleen , Roosens Nancy H. C. , De Keersmaecker Sigrid C. J. , Vanneste Kevin
Published: March 2021

Whole genome sequencing (WGS) enables complete characterization of bacterial pathogenic isolates at single nucleotide resolution, making it the ultimate tool for routine surveillance and outbreak investigation. The lack of standardization, and the variation regarding bioinformatics workflows and parameters, however, complicates interoperability among (inter)national laboratories. We present a validation strategy applied to a bioinformatics workflow for Illumina data that performs complete characterization of Shiga toxin-producing

Escherichia coli

(STEC) isolates including antimicrobial resistance prediction, virulence gene detection, serotype prediction, plasmid replicon detection and sequence typing. The workflow supports three commonly used bioinformatics approaches for the detection of genes and alleles: alignment with blast+, kmer-based read mapping with KMA, and direct read mapping with SRST2. A collection of 131 STEC isolates collected from food and human sources, extensively characterized with conventional molecular methods, was used as a validation dataset. Using a validation strategy specifically adopted to WGS, we demonstrated high performance with repeatability, reproducibility, accuracy, precision, sensitivity and specificity above 95 % for the majority of all assays. The WGS workflow is publicly available as a ‘push-button’ pipeline at https://galaxy.sciensano.be. Our validation strategy and accompanying reference dataset consisting of both conventional and WGS data can be used for characterizing the performance of various bioinformatics workflows and assays, facilitating interoperability between laboratories with different WGS and bioinformatics set-ups.
Deprivation and Early Involuntary Retirement: Area-Level Analysis across English Local Authorities
Authors: Giri Prosenjit , Basu Subhashis , Giri Abrahjit
Published: March 2021

Introduction

Retirement is a major transition point in life. Falling economic support ratios in many countries have led to a rise in the state retirement age and impending changes to eligibility for state and occupational benefit schemes such as pensions as Governments seek to curb expenditure. Permanently incapacitated individuals from work may face increasing challenges in accessing financial support. Such difficulties may impact those most deprived differentially with potentially significant consequences for morbidity and mortality. Few studies thus far have examined early retirement from a societal perspective. This study explores involuntary retirement in this regard.

Methods

A retrospective analysis of the association between deprivation with IHR success rates for Local Authorities (LA) in England between 2015-18 was conducted. Deprivation status was assigned according to the proportion of Lower-Layer Super Output Areas in the most deprived 10% nationally using data from the National Statistics SocioEconomic Classification 2015. Freedom of Information Requests were sent to all 326 LAs in England to obtain data on successful IHR applications, number of active members of respective pensions schemes and numbers of applications.

Results

131 LAs provided complete data for IHR applications, numbers of approved applications and eligible members. Several others provided data on application numbers but not those awarded. he national IHR approval rate was 2.16 per 1000 members, with a range of 0.16 to 8.96. There was a trend towards a greater proportion of approved application per 1000 eligible members in more affluent LAs.

Conclusion

The results from this brief analysis suggest that there is an association between increasing rates of ill-health retirement and higher area-level deprivation. Policy should note that those in more deprived areas face a quadruple whammy; a greater risk of becoming incapacitated from public health and occupational exposures, more limited access to medical support, less opportunities for alternative work and potentially disproportionate disadvantage from stringent pension eligibility criteria.
Cytoplasmic domain and enzymatic activity of ACE2 is not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells
Authors: Yang Hang , Zhao Xiaohui , Xun Meng , Xu Lingjie , Liu Bing , Wang Hongliang
Published: March 2021

The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor- human angiotensin converting enzyme 2 (ACE2). Here, we used lentivirus based pseudotypes bearing spike protein to demonstrate that entry of SARS-CoV-2 into host cells is dependent on clathrin-mediated endocytosis, and phosphoinositides play essential role during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 is not required for efficient virus entry. These results provide new insights into SARS-CoV-2 cellular entry and present potential targets for drug development.
Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome: a randomized, controlled trial
Authors: Pickering Harry , Hart John D. , Burr Sarah , Stabler Richard , Maleta Ken , Kalua Khumbo , Bailey Robin L. , Holland Martin J.
Published: March 2021

Background

Mass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities.

Methods

This study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.

Findings

The proportion of bacteria carrying macrolide resistance increased after azithromycin treatment; the effect was enhanced in children treated within six months of sampling. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.

Interpretation

The impacts of MDA with azithromycin, including increased carriage of macrolide-resistant bacteria, were enhanced in children treated more recently, suggesting effects may be transient. Increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage.

Funding

Bill and Melinda Gates Foundation
Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay
Authors: Riester Elena , Findeisen Peter , Hegel J. Kolja , Kabesch Michael , Ambrosch Andreas , Rank Christopher M , Langen Florina , Laengin Tina , Niederhauser Christoph
Published: March 2021

Background

The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the in vitro quantitative detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the performance of this assay using samples from seven sites in Germany, Austria, and Switzerland.

Methods

Anonymized frozen, residual serum, or plasma samples from blood donation centers or routine diagnostic testing were used for this study. For specificity and sensitivity analyses, presumed negative samples collected before October 2019 and SARS-CoV-2 PCR-confirmed single or sequential samples were tested, respectively. The performance of the Elecsys Anti-SARS-CoV-2 S immunoassay was also compared with other commercial immunoassays.

Results

The overall specificity (n=7880 pre-pandemic samples) and sensitivity (n=240 PCR-positive samples [≥14 days post-PCR]) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87–99.99) and 97.92% (95% CI: 95.21– 99.32), respectively. Compared with seven other immunoassays, the Elecsys Anti-SARS-CoV-2 S assay had comparable or greater specificity and sensitivity. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG, ADVIA Centaur® SARS-CoV-2 Total, ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG and IgA assays, and significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgG and IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG assays.

Conclusion

The Elecsys Anti-SARS-CoV-2 S assay demonstrated a robust and favorable performance across samples from multiple European sites, with a very high specificity and sensitivity for the detection of anti-S antibodies.
Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients
Authors: Antar Annukka A. R. , Yu Tong , Pisanic Nora , Azamfirei Razvan , Tornheim Jeffrey A. , Brown Diane M. , Kruczynski Kate , Hardick Justin P. , Sewell Thelio , Jang Minyoung , Church Taylor , Walch Samantha N. , Reuland Carolyn , Bachu Vismaya S. , Littlefield Kirsten , Park Han-Sol , Ursin Rebecca L. , Ganesan Abhinaya , Kusemiju Oyinkansola , Barnaba Brittany , Charles Curtisha , Prizzi Michelle , Johnstone Jaylynn R. , Payton Christine , Dai Weiwei , Fuchs Joelle , Massaccesi Guido , Armstrong Derek T. , Townsend Jennifer L. , Keller Sara C. , Demko Zoe O , Hu Chen , Wang Mei-Cheng , Sauer Lauren M. , Mostafa Heba H. , Keruly Jeanne C. , Mehta Shruti H. , Klein Sabra L. , Cox Andrea L. , Pekosz Andrew , Heaney Christopher D. , Thomas David L. , Blair Paul W. , Manabe Yukari C.
Published: March 2021

Background

Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.

Methods

Ninety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.

Results

Viral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044).

Conclusions

We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.
Years of Life Lost Associated with COVID-19 Deaths in the United States During the First Year of the Pandemic
Authors: Quast Troy , Andel Ross , Gregory Sean , Storch Eric A.
Published: March 2021

Background

Years of Life Lost (YLL) measure the shortfall in life expectancy due to a medical condition and have been used in multiple contexts. Previously it was estimated that there were 1.2 million YLLs associated with COVID-19 deaths in the United States through July 11, 2020. The aim of this study is to update YLL estimates for the first full year of the pandemic.

Methods

We employed data regarding COVID-19 deaths in the United States through January 31, 2021 by jurisdiction, gender, and age group. We used actuarial life expectancy tables by gender and age to estimate YLLs.

Results

We estimated roughly 3.9 million YLLs due to COVID-19 deaths, which corresponds to roughly 9.2 YLLs per death. We observed a large range across states in YLLs per 10,000 capita, with New York City at 298 and Vermont at 12. Nationally, males had a higher number of YLLs per death than females (9.5 versus 8.8), but there was significant variation in gender differences across states.

Conclusions

Our estimates provide further insight into the mortality effects of COVID-19. The observed differences across states and genders demonstrate the need for disaggregated analyses of the pandemic’s effects.
SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection
Authors: Choudhary Manish C. , Crain Charles R. , Qiu Xueting , Hanage William , Li Jonathan Z.
Published: March 2021

Background

Both SARS-CoV-2 reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection.

Methods

A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent SARS-CoV-2 to community-driven evolution.

Results

Twenty reinfection and nine persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment.

Conclusions

Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

Funding

This study was funded in part by the NIH grant 106701.

Disclosures

Dr. Li has consulted for Abbvie.
Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates
Authors: Francica Joseph R. , Flynn Barbara J. , Foulds Kathryn E. , Noe Amy T. , Werner Anne P. , Moore Ian N. , Gagne Matthew , Johnston Timothy S. , Tucker Courtney , Davis Rachel L. , Flach Britta , O’Connell Sarah , Andrew Shayne F. , Lamb Evan , Flebbe Dillon R. , Nurmukhambetova Saule T. , Donaldson Mitzi M. , Todd John-Paul M. , Zhu Alex Lee , Atyeo Caroline , Fischinger Stephanie , Gorman Matthew J , Shin Sally , Edara Venkata Viswanadh , Floyd Katharine , Lai Lilin , Tylor Alida , McCarthy Elizabeth , Lecouturier Valerie , Ruiz Sophie , Berry Catherine , Tibbitts Timothy , Andersen Hanne , Cook Anthony , Dodson Alan , Pessaint Laurent , Ry Alex Van , Koutsoukos Marguerite , Gutzeit Cindy , Teng I-Ting , Zhou Tongqing , Li Dapeng , Haynes Barton F. , Kwong Peter D. , McDermott Adrian , Lewis Mark G. , Fu Tong Ming , Chicz Roman , van der Most Robbert , Corbett Kizzmekia S. , Suthar Mehul S. , Alter Galit , Roederer Mario , Sullivan Nancy J. , Douek Daniel C. , Graham Barney S. , Casimiro Danilo , Seder Robert A.
Published: March 2021

Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody FCreceptors mediating effector functionsin vitro. Pseudovirus and live virus neutralizing IC50titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3×106PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials.
Somatic piRNAs and Transposons are Differentially Regulated During Skeletal Muscle Atrophy and Programmed Cell Death
Authors: Tsuji Junko , Thomson Travis , Brown Christine , Ghosh Subhanita , Theurkauf William E. , Weng Zhiping , Schwartz Lawrence M.
Published: March 2021

PiWi-interacting RNAs (piRNAs) are small single-stranded RNAs that can repress transposon expression via epigenetic silencing and transcript degradation. They have been identified predominantly in the ovary and testis, where they serve essential roles in transposon silencing in order to protect the integrity of the genome in the germline. The potential expression of piRNAs in somatic cells has been controversial. In the present study we demonstrate the expression of piRNAs derived from both genic and transposon RNAs in the intersegmental muscles (ISMs) from the tobacco hawkmothManduca sexta.These piRNAs are abundantly expressed, are ~27 nt long, map antisense to transposons, are oxidation resistant, exhibit a uridine bias at their first nucleotide, and amplify via the canonical ping-pong pathway. An RNA-seq analysis demonstrated that 20 piRNA pathway genes are expressed in the ISMs and are developmentally regulated. The abundance of piRNAs does not change when the muscles initiate developmentally-regulated atrophy, but are repressed when cells become committed to undergo programmed cell death at the end of metamorphosis. This change in piRNA expression is associated with the targeted repression of several retrotransposons and the induction of specific DNA transposons. The developmental changes in the expression of piRNAs, piRNA pathway genes, and transposons are all regulated by 20-hydroxyecdysone, the steroid hormone that controls the timing of ISM death. Taken together, these data provide compelling evidence for the existence of piRNA in somatic tissues and suggest that they may play roles in developmental processes such as programmed cell death.

Author Summary

piRNAs are a class of small non-coding RNAs that suppress the expression of transposable elements, parasitic DNA that if reintegrated, can harm the integrity of the host genome. The expression of piRNAs and their associated regulatory proteins has been studied predominantly in germ cells and some stem cells. We have found that they are also expressed in skeletal muscles in the mothManduca sextathat undergo developmentally-regulated atrophy and programmed cell death at the end of metamorphosis. The expression of transposons becomes deregulated when the muscles become committed to die, which may play a functional role in the demise of the cell by inducing genome damage. piRNA-mediated control of transposons may represent a novel mechanism that contributes to the regulated death of highly differentiated somatic cells.
The anti-immune dengue subgenomic flaviviral RNA is found in vesicles in mosquito saliva and associated with increased infectivity
Authors: Yeh Shih-Chia , Tan Wei-Lian , Chowdhury Avisha , Chuo Vanessa , Kini R. Manjunatha , Pompon Julien , Garcia-Blanco Mariano A.
Published: March 2021

Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We show that salivary sfRNA is protected in detergent-sensitive, protease-resistant compartments. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in human cells. Since sfRNA potently inhibits innate immunity in human cells, we posit that sfRNA in mosquito saliva is present in extracellular vesicles that deliver it to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission.
The Hob proteins are novel and conserved lipid binding proteins at ER-PM contact sites
Authors: Neuman Sarah D. , Jorgensen Jeff R. , Cavanagh Amy T. , Smyth Jeremy T. , Selegue Jane E. , Emr Scott D. , Bashirullah Arash
Published: March 2021

Membrane contact sites are critical junctures for organelle signaling and communication. Endoplasmic reticulum-plasma membrane (ER-PM) contact sites were the first membrane contact sites to be described; however, the protein composition and molecular function of these sites is still emerging. Here, we leverage yeast andDrosophilamodel systems to uncover a novel role for the Hobbit/Hob proteins at ER-PM contact sites. We find that Hobbit localizes to ER-PM contact sites in both yeast cells and theDrosophilalarval salivary glands, and this localization is mediated by an N-terminal ER membrane anchor and conserved C-terminal sequences. The C-terminus of Hobbit binds to plasma membrane phosphatidylinositols, and the distribution of these lipids is altered inhobbitmutant cells. Notably, the Hobbit protein is essential for viability in higher animals, providing one of the first examples of a membrane contact site-localized lipid binding protein that is required for development.
Functional interdependence of the actin nucleator Cobl and Cobl-like in dendritic arbor development
Authors: Izadi Maryam , Seemann Eric , Schlobinski Dirk , Schwintzer Lukas , Qualmann Britta , Kessels Michael M.
Published: March 2021

Local actin filament formation is indispensable for development of the dendritic arbor of neurons. We show that, surprisingly, the action of single actin filament-promoting factors was insufficient for powering dendritogenesis. Instead, this process required the actin nucleator Cobl and its only evolutionary distant ancestor Cobl-like acting interdependently. This coordination between Cobl-like and Cobl was achieved by physical linkage by syndapin I. Syndapin I formed nanodomains at convex plasma membrane areas at the base of protrusive structures and interacted with three motifs in Cobl-like, one of which was Ca2+/calmodulin-regulated. Consistently, syndapin I, Cobl-like’s newly identified N terminal calmodulin-binding site and the single Ca2+/calmodulin-responsive syndapin-binding motif all were critical for Cobl-like’s functions. In dendritic arbor development, local Ca2+/CaM-controlled actin dynamics thus relies on regulated and physically coordinated interactions of different F-actin formation-promoting factors and only together they have the power to bring about the sophisticated neuronal morphologies required for neuronal network formation.
Development of spin-contrast-variation neutron powder diffractometry for extracting the structure factor of hydrogen atoms
Authors: Miura Daisuke , Kumada Takayuki , Sekine Yurina , Motokawa Ryuhei , Nakagawa Hiroshi , Oba Yojiro , Ohhara Takashi , Takata Shin-ichi , Hiroi Kosuke , Morikawa Toshiaki , Kawamura Yukihiko , Ohishi Kazuki , Suzuki Jun-ichi , Miyachi Yoshiyuki , Iwata Takahiro
Published: March 2021

A spin-contrast-variation neutron powder diffractometry technique that extracts the structure factor of hydrogen atoms, i.e. the contribution of hydrogen atoms to a crystal's structure factor, has been developed. Crystals of L-glutamic acid were dispersed in a D-polystyrene matrix containing 4-methacryloyloxy-2,2,6,6,-tetramethyl-1-piperidinyloxy to polarize their proton spins dynamically. The intensities of the diffraction peaks of the sample changed according to the proton polarization, and the structure factor of the hydrogen atoms was extracted from the proton-polarization-dependent intensities. This technique is expected to enable analyses of the structures of hydrogen-containing materials that are difficult to determine with conventional powder diffractometry.
Tomographic X-ray scattering based on invariant reconstruction: analysis of the 3D nanostructure of bovine bone
Authors: De Falco Paolino , Weinkamer Richard , Wagermaier Wolfgang , Li Chenghao , Snow Tim , Terrill Nicholas J. , Gupta Himadri S. , Goyal Pawan , Stoll Martin , Benner Peter , Fratzl Peter
Published: March 2021

Small-angle X-ray scattering (SAXS) is an effective characterization technique for multi-phase nanocomposites. The structural complexity and heterogeneity of biological materials require the development of new techniques for the 3D characterization of their hierarchical structures. Emerging SAXS tomographic methods allow reconstruction of the 3D scattering pattern in each voxel but are costly in terms of synchrotron measurement time and computer time. To address this problem, an approach has been developed based on the reconstruction of SAXS invariants to allow for fast 3D characterization of nanostructured inhomogeneous materials. SAXS invariants are scalars replacing the 3D scattering patterns in each voxel, thus simplifying the 6D reconstruction problem to several 3D ones. Standard procedures for tomographic reconstruction can be directly adapted for this problem. The procedure is demonstrated by determining the distribution of the nanometric bone mineral particle thickness (T parameter) throughout a macroscopic 3D volume of bovine cortical bone. The T parameter maps display spatial patterns of particle thickness in fibrolamellar bone units. Spatial correlation between the mineral nanostructure and microscopic features reveals that the mineral particles are particularly thin in the vicinity of vascular channels.
Mitigating background caused by extraneous scattering in small-angle neutron scattering instrument design
Authors: Barker John George , Cook Jeremy C. , Chabot Jean Philippe , Kline Steven R. , Zhang Zhenhuan , Gagnon Cedric
Published: March 2021

Measurements, calculations and design ideas to mitigate background caused by extraneous scattering in small-angle neutron scattering (SANS) instruments are presented. Scattering includes processes such as incoherent scattering, inelastic scattering and Bragg diffraction. Three primary sources of this type of background are investigated: the beam stop located in front of the detector, the inside lining of the detector vessel and the environment surrounding the sample. SANS measurements were made where materials with different albedos were placed in all three locations. Additional measurements of the angle-dependent scattering over the angular range of 0.7π–0.95π rad were completed on 16 different shielding materials at five wavelengths. The data were extrapolated to cover scattering angles from π/2 to π rad in order to estimate the materials' albedos. Modifications to existing SANS instruments and sample environments to mitigate extraneous scattering from surfaces are discussed.
Do audit committee characteristics improve financial reporting quality in emerging markets? Evidence from Iran
Authors: Safari Gerayli Mehdi , Rezaei Pitenoei Yasser , Abdollahi Ahmad
Published: March 2021

Purpose

The purpose of this study is to investigate the association between certain audit committee characteristics like independence and financial expertise with financial reporting quality (FRQ) of the firms listed on the Tehran Stock Exchange (TSE).

Design/methodology/approach

The sample includes the 558 firm-year observations from companies listed on the TSE during the years 2012–2017, and the study’s hypotheses were tested using multivariate regression model based on panel data.

Findings

The authors find that audit committee independence has no significant effect on corporate FRQ, whereas audit committee's financial expertise significantly improves firms' FRQ. In other words, higher financial expertise of an audit committee can lead to an increase in its FRQ. The findings of the study are robust to alternate measures of FRQ, individual analysis of the research hypotheses for each year and endogeneity problem.

Originality/value

To the best of the authors’ knowledge, this is the first study to analyze the association between audit committee characteristics and FRQ in emerging capital markets, and so, the findings of the study not only extend the extant theoretical literature concerning the audit committee in developing countries including emerging capital market of Iran but also help investors, managers, capital market regulators, policymakers and audit profession regulators to make informed decisions.
Assessment of nutritional quality of snacks and beverages sold in university vending machines: a qualitative assessment
Authors: Faris MoezAlIslam E. , Al-Bakheit Ala'a , Hasan Hayder , Cheikh Ismail Leila , Jahrami Haitham , Rajab Dina , Afra Almashgouni Afra , Alshehhi Alanood , Aljabry Asma , Aljarwan Mariam , Alnaqbi Moza , Obaid Reyad Shaker
Published: March 2021

Purpose

Vending machines (VMs) provide quick access for snack foods and beverages for students during their study days. These vended foods have been reported to affect the student's nutritional status and contributing to obesity by increasing the caloric intake. This study aimed to evaluate the nutritional value of snacks and beverages provided by VM at the university campuses.

Design/methodology/approach

A cross-sectional observational study in one large urban university with four campuses was conducted. In total, 55 VMs were found distributed over 50 buildings of the four university campuses. Of the vending slots surveyed, only 57 snacks and beverage food items were found repeated. These items were vended and analyzed using nutrient databases, and their nutritional quality was assessed using nutrient adequacy ratio and nutritional quality score.

Findings

Most vended snacks were salty (77%) and sweet (23%). Neither snacks nor beverages were nutrient-dense, and the majority (65%) of snacks and beverages were calorie-dense, with high contents of sugar, sodium and saturated fat; while they were low in vitamins C and A, calcium, iron, sodium, protein and dietary fibers. None of the vended beverages met the low calorie, low sugars and high-fiber criteria.

Research limitations/implications

One limitation of the current work is represented in the fact that VM snacks and beverages are not fixed throughout the year days, and exposed to continuous changes, depending on the customers' attitudes and economic and financial considerations related to the operating contractor company and the customer students. Thus, a continuous, long-term evaluation is suggested to be conducted for a more representative and reflective evaluation of the nutritional quality of vended snacks and beverages.

Practical implications

Poor nutritional quality has been found for vended foods. Healthier food options should be provided to improve students' dietary intake.

Social implications

Attention has to be directed toward the nutritional quality of VM foods, and how to provide adolescents and young adults with healthy options.

Originality/value

This is the first study conducted in the United Arab Emirates (UAE) and Gulf Cooperation Council countries (GCC) assessing the nutritional value of vending machine foods in university settings.
Effects of internal marketing on strategic orientations in the banking sector
Authors: Mazzarolo Aloisio Henrique , Mainardes Emerson Wagner , Montemor Danilo Soares
Published: March 2021

Purpose

The purpose of this study was to assess whether internal marketing tends to influence the perception of bank employees regarding the strategic orientations of banks toward the market, brand and value. The authors also aimed to determine whether employees' organizational commitment mediates the relationship between internal marketing and the three strategic orientations and whether they influence bank employees' perception of obtaining a competitive advantage.

Design/methodology/approach

The authors conducted a survey with 832 bank employees using an online questionnaire. The authors performed data analysis by modeling structural equations with data estimation using the PLS-SEM.

Findings

The results showed that internal marketing positively influences bank employees' perception of banks' strategic marketing orientations and through that their perception of a competitive advantage. The authors also note that organizational commitment can partially mediate the relationship between internal marketing and the strategic orientations tested in this study.

Research limitations/implications

The findings indicate that banks' investment in employee valuation tends to generate positive results in relation to their adherence to marketing strategies, with the potential to result in a competitive advantage.

Originality/value

The results demonstrate the strength of internal marketing in the strategic orientations of banks, indicating that having employees who are committed to their bank contributes to the delivery of a high-quality service focused on the external customers, generating a competitive advantage.
How can universities improve student loyalty? The roles of university social responsibility, service quality, and “customer” satisfaction and trust
Authors: Latif Khawaja Fawad , Bunce Louise , Ahmad Muhammad Shakil
Published: March 2021

Purpose

Student loyalty is important if universities are to stay in business by recruiting and retaining satisfied students who provide positive evaluations of their university to others. The current study employed a theoretical framework established by consumer researchers to test the hypothesis that university social responsibility (USR) would predict student loyalty, but that this relation would be mediated by perceived service quality, student satisfaction, and student trust in their university.

Design/methodology/approach

Fee-paying university students in Pakistan (n = 608) completed a questionnaire to assess their perception of USR and service quality, their satisfaction with and trust in their university, and loyalty toward their university.

Findings

Structural equation modelling with partial least squares software supported the hypotheses that higher perceived USR would be related to higher student loyalty, and that this relation would be mediated by perceived service quality, student satisfaction, and student trust.

Originality/value

This study provides a novel contribution to the limited literature on USR and its relations with student loyalty. Several models have previously examined the relation between corporate social responsibility and general consumer loyalty, but these have limited applicability to the education sector. The data in this study support a model showing that USR supports student loyalty through its positive impact on perceptions of service quality, student satisfaction, and student trust. The findings suggest that USR could be a marketing tool that supports student loyalty, as long as USR initiatives increase students' perceptions of service quality, satisfaction and trust in their university.