bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychedelics and schizophrenia: Distinct alterations to Bayesian inference
Authors: Rajpal Hardik , Mediano Pedro A.M. , Rosas Fernando E. , Timmermann Christopher B. , Brugger Stefan , Muthukumaraswamy Suresh , Seth Anil K. , Bor Daniel , Carhart-Harris Robin L. , Jensen Henrik J.
Published: February 2022

Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways: one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different alterations of normal consciousness, here we compare the changes in neural dynamics induced by LSD and ketamine (in healthy volunteers) against those associated with schizophrenia, as observed in resting-state M/EEG recordings. While both conditions exhibit increased neural signal diversity, our findings reveal that this is accompanied by an increased transfer entropy from the front to the back of the brain in schizophrenia, versus an overall reduction under the two drugs. Furthermore, we show that these effects can be reproduced via different alterations of standard Bayesian inference applied on a computational model based on the predictive processing framework. In particular, the effects observed under the drugs are modelled as a reduction of the precision of the priors, while the effects of schizophrenia correspond to an increased precision of sensory information. These findings shed new light on the similarities and differences between schizophrenia and two psychotomimetic drug states, and have potential implications for the study of consciousness and future mental health treatments.
Stable Potassium Isotopes (41K/39K) Track Transcellular and Paracellular Potassium Transport in Biological Systems
Authors: Higgins John A. , Ramos Danielle Santiago , Gili Stefania , Spetea Cornelia , Kanoski Scott , Ha Darren , McDonough Alicia A. , Youn Jang H.
Published: February 2022

As the most abundant cation in archaeal, bacterial, and eukaryotic cells, potassium (K+) is an essential element for life. While much is known about the machinery of transcellular and paracellular K transport – channels, pumps, co-transporters, and tight-junction proteins - many quantitative aspects of K homeostasis in biological systems remain poorly constrained. Here we present measurements of the stable isotope ratios of potassium (41K/39K) in three biological systems (algae, fish, and mammals). When considered in the context of our current understanding of potential mechanisms of K isotope fractionation and K+transport in these biological systems, our results provide evidence that the fractionation of K isotopes depends on transport pathway and transmembrane transport machinery. Specifically, we find that passive transport of K+down its electrochemical potential through channels and pores in tight-junctions at favors39K, a result which we attribute to a kinetic isotope effect associated with dehydration and/or size selectivity at the channel/pore entrance. In contrast, we find that transport of K+against its electrochemical gradient via pumps and co-transporters is associated with less/no isotopic fractionation, a result that we attribute to small equilibrium isotope effects that are expressed in pumps/co-transporters due to their slower turnover rate and the relatively long residence time of K+in the ion pocket. These results indicate that stable K isotopes may be able to provide quantitative constraints on transporter-specific K+fluxes (e.g. the fraction of K efflux from a tissue by channels vs. co-transporters) and how these fluxes change under different physiological states. In addition, precise determination of K isotope effects associated with K+transport through channels, pumps, and co-transporters may provide unique constraints on the mechanisms of K transport that could be tested with steered molecular dynamic simulations.
Detection and Interspecies Comparison of SARS-CoV-2 Delta Variant (AY.3) in Feces from a Domestic Cat and Human Samples
Authors: Lenz Olivia C. , Marques Andrew D. , Kelly Brendan J. , Rodino Kyle G. , Cole Stephen D. , Perera Ranawaka A.P.M. , Weiss Susan R. , Bushman Frederic D. , Lennon Elizabeth M.
Published: February 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of the global COVID-19 pandemic. However, whole genome sequencing data of the viral genomes that infect non-human animal species has been scant. Here, we detected and sequenced a SARS-CoV-2 delta variant (AY.3) in fecal samples from an 11-year-old domestic house cat previously exposed to an owner who tested positive for SARS-CoV-2. Molecular testing of two fecal samples collected 7 days apart yielded relatively high levels of viral RNA. Sequencing of the feline-derived viral genomes showed the two to be identical, and differing by between 4 and 14 single nucleotide polymorphisms in pairwise comparisons to human-derived lineage AY.3 sequences collected in the same geographic area and time period. However, several mutations unique to the feline samples reveal their divergence from this cohort on phylogenetic analysis. These results demonstrate continued spillover infections of emerging SARS-CoV-2 variants that threaten human and animal health, as well as highlight the importance of collecting fecal samples when testing for SARS-CoV-2 in animals. To the authors’ knowledge, this is the first published case of a SARS-CoV-2 delta variant in a domestic cat in the United States.
Rapid Carbon Dioxide Capture and Short-Term Biocompatible Sequestration in Aquatic Environments by Monoethanolamine Scrubbing within Calcium Alginate Gel
Authors: Ogundare Simon
Published: February 2022

Alginate is a biopolymer extracted from the cell walls of algae, and can crosslink with divalent cations to form an insoluble hydrogel. In this paper, we develop a method to immobilize monoethanolamine, an amine CO2 scrubber, within calcium alginate gel. By mixing monoethanolamine into an alginate solution as the gel was formed, we suspended the compound in the gel, facilitating a means to capture carbon dioxide directly from aquatic environments into the gel, while tethering monoethanolamine and the products formed from CO2 capture to the gel. To delay the eventual diffusion of monoethanolamine out of the gel, we investigated (1) the effect of increasing alginate concentration and (2) the effect of additional alginate layers on the outward diffusion of dye placed in the center of the bead. Using ultraviolet-visible spectroscopy to quantify diffusion rates over time, we determined that increased alginate concentration paired with increased layering significantly decreased the rate of outward diffusion. Finally, we prepared beads using North Atlantic seawater as a solvent and compared the rate of dye leakage in seawater and distilled water to that in beads prepared in distilled water. Expectedly, we concluded that beads prepared with solvents isotonic to their environments would exhibit less leakage as well as greater mechanical stability, resisting swelling, bursting, or splitting behaviors.
The Human “Contaminome”: Bacterial, Viral, and Computational Contamination in Whole Genome Sequences from 1,000 Families
Authors: Chrisman Brianna , He Chloe , Jung Jae-Yoon , Stockham Nate , Paskov Kelley , Washington Peter , Wall Dennis P.
Published: February 2022

Background

The unmapped readspace of whole genome sequencing data tends to be large but is often ignored. We posit that it contains valuable signals of both human infection and contamination. Using unmapped and poorly aligned reads from whole genome sequences (WGS) of over 1,000 families and 5,000 individuals, we present insights into common viral, bacterial, and computational contamination that plague whole genome sequencing studies.

Results

We present several notable results: (1) In addition to known contaminants such as Epstein-Barr virus and phiX, sequences from whole blood and lymphocyte cell lines contain many other contaminants, likely originating from storage, prep, and sequencing pipelines. (2) Sequencing plate and biological sample source of a sample strongly influence contamination profile. And, (3) Y-chromosome fragments not on the human reference genome commonly mismap to bacterial reference genomes.

Conclusion

Both experiment-derived and computational contamination is prominent in next-generation sequencing data. Such contamination can compromise results from WGS as well as metagenomics studies, and standard protocols for identifying and removing contamination should be developed to ensure the fidelity of sequencing-based studies.

genomics WGS contamination
Transmission Dynamics of Human Herpesviruses and Other Blood DNA Viruses from Whole Genome Sequences of Families
Authors: Chrisman Brianna , He Chloe , Jung Jae-Yoon , Stockham Nate , Paskov Kelley , Washington Peter , Wall Dennis P.
Published: February 2022

1

While hundreds of thousands of human whole genome sequences (WGS) have been collected in the effort to better understand genetic determinants of disease, these whole genome sequences have rarely been used to study another major determinant of human health: the human virome. Using the unmapped reads from WGS of 1,000 families, we present insights into the human blood DNA virome. In addition to extensively cataloguing the viruses detected in WGS of human whole blood and lymphoblastoid cell lines, we use the family structure of our dataset to show that household drives transmission of many microbes. We also identify several cases of inherited chromosomally integrated herpes 6A and 6B and locate candidate integration sequences for these cases. We document genetic diversity within exogenous and integrated HHV species and within integration sites of HHV-6. Finally, in the first observation of its kind, we present evidence that suggests widespreadde novoHHV-6B integration and HHV-7 episome replication in lymphoblastoid cell lines. These findings show that the unmapped read space of WGS may be a promising avenue for virology research.
NetMix2: Unifying network propagation and altered subnetworks
Authors: Chitra Uthsav , Park Tae Yoon , Raphael Benjamin J.
Published: February 2022

A standard paradigm in computational biology is to use interaction networks to analyze high-throughput biological data. Two common approaches for leveraging interaction networks are: (1)network ranking, where one ranks vertices in the network according to both vertex scores and network topology; (2)altered subnetworkidentification, where one identifies one or more subnetworks in an interaction network using both vertex scores and network topology. The dominant approach in network ranking is network propagation which smooths vertex scores over the network using a random walk or diffusion process, thus utilizing the global structure of the network. For altered subnetwork identification, existing algorithms either restrict solutions to subnetworks insubnetwork familieswith simple topological constraints, such as connected subnetworks, or utilize ad hoc heuristics that lack a rigorous statistical foundation. In this work, we unify the network propagation and altered subnetwork approaches. We derive a subnetwork family which we call thepropagation familythat approximates the subnetworks ranked highly by network propagation. We introduce NetMix2, a principled algorithm for identifying altered subnetworks from a wide range of subnetwork families, including the propagation family, thus combining the advantages of the network propagation and altered subnetwork approaches. We show that NetMix2 outperforms network propagation on data simulated using the propagation family. Furthermore, NetMix2 outperforms other methods at recovering known disease genes in pan-cancer somatic mutation data and in genome-wide association data from multiple human diseases. NetMix2 is publicly available athttps://github.com/raphael-group/netmix2.
Pancreatic Tumor Eradication via Selective PIN1 Inhibition in Cancer Associated Fibroblasts and T Lymphocytes Engagement
Authors: Liu Jiaye , Li Meng , Li Kewei , Wang Yang , Li Shan , Wu Wenshuang , Du Lingyao , Mu Chunyang , Zhang Xiaoyun , Li Chuan , Peng Wei , Shen Junyi , Liu Yang , Yang Dujiang , Zhang Kaixiang , Ning Qingyang , Fu Xiaoying , Zeng Yu , Ni Yinyun , Pan Qiuwei , Zhou Zongguang , Liu Yi , Hu Yiguo , Wen Tianfu , Li Zhihui , Liu Yong
Published: February 2022

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase PIN1, whose overexpression in CAFs hasn’t been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective PIN1 inhibition in CAFs on pancreatic cancer, we formulate DNA-barcoded micellular systems (DMS) encapsulating PIN1 inhibitor. DMS functionalized with CAFs-targeting antibodies (antiCAFs-DMS) can selectively inhibit PIN1 in CAFs of the tumor, leading to efficacious but temporal tumor inhibitions. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to antiCAFs-DMS and thus prepare the bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT shows its potent capacity to eradicate pre-established subcutaneous and orthotopic pancreatic cancer on mice.
Generative pretraining from large-scale transcriptomes: Implications for single-cell deciphering and clinical translation
Authors: Shen Hongru , Shen Xilin , Hu Jiani , Liu Jilei , Zhang Chao , Wu Dan , Feng Mengyao , Yang Meng , Li Yang , Yang Yichen , Wang Wei , Zhang Qiang , Yang Jilong , Chen Kexin , Li Xiangchun
Published: February 2022

Exponential accumulation of single-cell transcriptomes poses great challenge for efficient assimilation. Here, we present an approach entitledtGPTtowards integration of 22.3 million single-cell transcriptomes by modeling gene expression rankings as generative pretraining task.tGPTis conceptually simple in that it autoregressively models the ranking of a gene in the context of its preceding neighbors. We demonstrated the high performance oftGPTon a range of fundamental single-cell analysis tasks and novel applications on bulk tissues. The single-cell clusters and cell lineage trajectories derived fromtGPTare highly aligned with known cell labels and states. The feature patterns of tumor bulk tissues learned bytGPTare associated with a wide range of genomic alteration events, prognosis and treatment outcome of immunotherapy.tGPTrepresents a new analytical paradigm for integrating and deciphering massive amount of transcriptome data and it will facilitate the interpretation and clinical translation of single-cell transcriptomes.
The clinical impact of maternal COVID-19 on mothers, their infants, and placentas with an analysis of vertical transfer of maternal SARS-CoV-2-specific IgG antibodies
Authors: Ward JD , Cornaby C , Kato T , Gilmore RC , Bunch D , Miller MB , Boucher RC , Schmitz JL , Askin FA , Scanga LR
Published: February 2022

Introduction

The effect of SARS-CoV-2 infection on pregnant mothers, the placenta, and infants is not fully understood and sufficiently characterized.

Methods

We performed a retrospective, observational cohort study in Chapel Hill, NC of 115 mothers with SARS-CoV-2 and singleton pregnancies from December 1, 2019 to May 31, 2021. We performed a chart review to document the infants’ weight, length, head circumference, survival, congenital abnormalities, and hearing loss, maternal complications, and placental pathology classified by the Amsterdam criteria.

Results

The average infant weight, length, and head circumference were all within the normal range for gestational age, the infants had no identifiable congenital abnormalities, and all infants and mothers survived. Only one infant (0.870%) became infected with SARS-CoV-2. Moderate and severe maternal COVID-19 were associated with increased caesarean section, premature delivery, infant NICU admission, and maternal respiratory failure, and were more likely in Type 1 (p=0.0055) and Type 2 (p=0.0285) diabetic mothers. Most placentas (n=63, 54.8%) showed normal or non-specific findings, while a subset had mild maternal vascular malperfusion (n=26, 22.6%) and/or mild microscopic ascending intrauterine infection (n=28, 24.3%).

Discussion

Most mothers with SARS-CoV-2 and their infants had a routine clinical course. Maternal SARS-CoV-2 infection was not associated with intrauterine fetal demise, infant death, congenital abnormalities, or hearing loss. Infant infection with SARS-CoV-2 was rare and not via the placenta. Most placentas had non-specific findings and a subset showed mild maternal vascular malperfusion and/or mild microscopic ascending intrauterine infection, which were not associated with maternal COVID-19 severity.
Unravelling the population structure and transmission patterns of Mycobacterium tuberculosis in Mozambique, a high TB/HIV burden country
Authors: Saavedra B. , López M.G. , Chiner-Oms Á. , García A.M. , Cancino I , Torres-Puente M. , Villamayor L. , Madrazo C. , Mambuque E. , Sequera VG. , Respeito D. , Blanco S. , Augusto O. , López-Varela E. , García-Basteiro AL. , Comas I.
Published: February 2022

Genomic studies of Mycobacterium tuberculosis complex (MTBC) might shed light on the dynamics of its transmission, especially in high-burden settings, where recent outbreaks are embedded in the complex natural history of the disease. We applied Whole-genome sequencing (WGS) to characterize the local population of MTBC, unravel potential transmission links and evaluate associations with host and pathogen factors.

Methods

A one-year prospective study was conducted in Mozambique, a high HIV/TB burden country. WGS was applied to 295 positive cultures. We combined phylogenetic, geographical and clustering analysis, and investigated associations between risk factors of transmission.

Findings

A significant high proportion of strains were in recent transmission (45.5%). We fully characterized MTBC isolates by using phylogenetic approaches and dating evaluation. We found two likely endemic clades, comprised of 67 strains, belonging to L1.2, dating from the late XIX century and associated with recent spread among PLHIV.

Interpretation

Our results unveil the population structure of MTBC in our setting. The clustering analysis revealed an unexpected pattern of spread and high rates of progression, suggesting the failure of control measures. The long-term presence of local strains in Mozambique, which were responsible for large transmission among HIV/TB coinfected patients, hint at possible coevolution with sympatric host populations and challenge the role of HIV in TB transmission.

Funding

Ministry of Enterprise and Knowledge (Government of Catalonia & European Social Fund, AGAUR fellowship); European Research Council (ERC) European Union’s Horizon 2020.
Variation in English Covid booster uptake
Authors: Dropkin Greg
Published: February 2022

Introduction

Variable and low takeup of the Covid booster is a recognised problem, associated with age, gender, ethnicity, and deprivation. Are there other relevant predictors?

Methods

Data was downloaded from the UK Government Coronavirus Dashboard for Middle Super Output Areas in England, along with demographic, employment, and health data from public sources. Mixed models with a random factor for Upper Tier Local Authority were analysed as quasibinomial Generalized Additive Models, and the estimated random factors were then fitted with Bayesian linear mixed models using flu vaccination uptake, change in public health budgets, vaccination centres, and Region.

Results

Models for the MSOA Covid 1st and 2nd vaccinations and the 3rd injection (including the booster), fit the data well. Index of Multiple Deprivation, proportion Aged 15-24 and 25-44, and ethnicity groupings Other White, Indian-Pakistani-Bangladeshi, and African-Caribbean-Other, are highly significant predictors of lower uptake. The estimated random factors vary widely amongst local authorities, and can be predicted by flu vaccine uptake, rise in public health budgets, and regional effects which are positive for London and South East, and negative for North West and North East. Vaccination centres did not reach 90% significance.

Discussion

Covid vaccination rates at each stage are very well modelled if local authority random effects are included along with non-linear terms for demographic, employment and health data. Deprivation, younger age, and Other White, South Asian, and Afro-Caribbean ethnicities are associated with lower uptake. Modelling the local effects indicates that increasing public health budgets would improve vaccination uptake.
The role of CYP2C19 gene polymorphisms on antiplatelet activity of clopidogrel among Arabs: systematic review and meta-analysis
Authors: Alkattan Abdullah N. , Radwan Nashwa M. , Mahmoud Nagla E. , Alfaleh Amjad F. , Alfaifi Amal , Alabdulkareem Khaled I.
Published: February 2022

This study aimed to predict the preventive effect of clopidogrel against recurrent cardiovascular events (CVEs) among the Arab population carrying different CYP2C19 mutations and to determine the frequency of polymorphic alleles and genotypes of CYP2C19 among them. The review included all the studies that reported data related to the CYP2C19 polymorphisms among Arab populations. The review included Arab CVDs patients who are categorized into carriers (cases) and non-carriers (controls) of CYP2C19 alleles and used clopidogrel as secondary prophylaxis. The patients who had recurrent CVEs or had high on-treatment platelet reactivity (HTPR) while using clopidogrel treatment were described as (events). The results showed a significantly increased risk of recurrent CVDs events by about three folds was associated with carriers of CYP2C19*2 and CYP2C19*3 mutations compared to non-carriers (OR= 3.32, CI=1.94-5.67, and OR=3.53, CI=1.17-10.63 respectively). However, no significant difference was recorded between both studied groups regarding the presence of CYP2C19*17 mutation (OR=0.80, (CI=0.44-1.44). The results also revealed that 59 (4.16%) of Arabs carrying two CYP2C19*2 alleles (homozygous), and 356 (25.12%) have one CYP2C19*2 allele and one CYP2C19*1 allele (heterozygous). Moreover, 42 (2.96%) were carrying two CYP2C19*17 alleles (homozygous), and 262 (18.49%) were carrying one CYP2C19*17 allele and one wild-type allele of CYP2C19 (heterozygous). The most common CYP2C19 genotypes reported among Arabs was the wild-type *1/*1, of which 49.26% of them had the homozygous form of the CYP2C19*1 allele. The frequency of the CYP2C19*1 allele was 71.07%, followed by the CYP2C19*2 allele (16.73%) and CYP2C19*17 (12.21%), respectively. The CYP2C19*3 allele was detected rarely among Arabs (<1%) compared to CYP2C19*1, *2, and *17 alleles. The present study revealed that Arabs carrying CYP2C19*2 and CYP2C19*3 alleles may not respond to clopidogrel and may put those patients at risk of recurrent CVEs. Carriers of the CYP2C19*17 allele, on the other hand, did not show a significant role either in increasing or decreasing the antiplatelet efficacy of clopidogrel. The CYP2C19 genotypes including *1/*1, *1/*2, *1/*17, *2/*2, and *17/*17 are commonly distributed among the Arabs.
The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis
Authors: Almulla Abbas F. , Supasitthumrong Thitiporn , Tunvirachaisakul Chavit , Algon Ali Abbas Abo , Al-Hakeim Hussein K. , Maes Michael
Published: February 2022

Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both may induce indoleamine-2,3- dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of the current study was to systematically review and meta-analyze the TRYCAT pathway status including levels of TRP and kynurenine (KYN) and IDO activity, as assessed using the KYN/TRP ratio. This systematic review was performed in December 2021 and searched data in PubMed, Google Scholar, and Web of sciences. In our meta-analysis we included 14 articles which examine TRP and TRYCATs in COVID-19 patients versus non-COVID-19 controls, and severe/critical versus mild/moderate COVID-19. Overall, the analysis was performed on 1269 individuals, namely 794 COVID-19 patients and 475 controls. The results show a significant (p <0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD=1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD= 1.123, 95% CI: 0.730;1.516) and significantly lower TRP ((SMD= - 1.002, 95%CI: -1.738; -0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD= 0.945, 95%CI: 0.629; 1.262) and KYN (SMD= 0.806, 95%CI: 0.462; 1.149) were also significantly (p <0.001) higher and TRP lower (SMD= -0.909, 95% CI: -1.569; -0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in the kynurenic acid (KA)/KYN ratio and KA between COVID-19 patients and controls. Our results indicate increased activity of the IDO enzyme in COVID-19 and in severe/critical patients. The TRYCAT pathway is probably implicated in the pathophysiology and progression of COVID-19 and may signal a worse outcome of the disease.

One-sentence summary

The current meta-analysis study revealed a significant increase in peripheral blood IDO activity and kynurenine levels and a significant reduction in tryptophan in COVID-19 versus controls and in severe/critical COVID-19 versus mild/moderate COVID-19.
Rare and population-specific functional variation across pig lines
Authors: Ros-Freixedes Roger , Valente Bruno D. , Chen Ching-Yi , Herring William O. , Gorjanc Gregor , Hickey John M , Johnsson Martin
Published: February 2022

Background

It is expected that functional, mainly missense and loss-of-function (LOF), and regulatory variants are responsible for phenotypic differences among breeds, genetic lines, and varieties of livestock and crop species that have undergone diverse selection histories. However, there is still limited knowledge about the existing missense and LOF variation in livestock commercial populations, in particular regarding population-specific variation and how it can affect applications such as across-breed genomic prediction.

Methods

We re-sequenced the whole genome of 7,848 individuals from nine commercial pig breeding lines (average sequencing coverage: 4.1x) and imputed whole-genome genotypes for 440,610 pedigree-related individuals. The called variants were categorized according to predicted functional annotation (from LOF to intergenic) and prevalence level (number of lines in which the variant segregated; from private to widespread). Variants in each category were examined in terms of distribution along the genome, minor allele frequency, Wright’s fixation index (FST), individual load, and association to production traits.

Results

Of the 46 million called variants, 28% were private (called in only one line) and 21% were widespread (called in all nine lines). Genomic regions with low recombination rate were enriched with private variants. Low-prevalence variants (called in one or a few lines only) were enriched for lower allele frequencies, lower FST, and putatively functional and regulatory roles (including loss-of-function and deleterious missense variants). Only a small subset of low-prevalence variants was found at intermediate allele frequencies and had large estimated effects on production traits. Individuals on average carried less private deleterious missense alleles than expected compared to other predicted consequence types. A small subset of low-prevalence variants with intermediate allele frequencies and higher FST were detected as significantly associated to the production traits and explained small fractions of phenotypic variance (up to 3.2%). These associations were tagged by other more widespread variants, including intergenic variants.

Conclusions

Most low-prevalence variants are kept at very low allele frequency and only a small subset contributed detectable fractions of phenotypic variance. Not accounting for low-prevalence variants is therefore unlikely to hinder across-breed analyses, in particular for genomic prediction of breeding values using reference populations of a different genetic background.
Influenza virus-like particle-based hybrid vaccine containing RBD induces immunity against influenza and SARS-CoV-2 viruses
Authors: Bommireddy Ramireddy , Stone Shannon , Bhatnagar Noopur , Kumari Pratima , Munoz Luis E. , Oh Judy , Kim Ki-Hye , Berry Jameson T. L. , Jacobsen Kristen M. , Jaafar Lahcen , Naing Swe-Htet , Blackerby Allison N. , Gaag Tori Van der , Wright Chloe N. , Lai Lilin , Pack Christopher D. , Ramachandiran Sampath , Suthar Mehul S. , Kang Sang-Moo , Kumar Mukesh , Reddy Shaker J. C. , Selvaraj Periasamy
Published: February 2022

Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the influence of immune responses induced by other vaccinations on the durability and efficacy of the immune response to SARS-CoV-2 vaccine is still unknown. We have developed a hybrid vaccine for SARS-CoV-2 and influenza viruses using influenza virus-like particles (VLP) incorporated by protein transfer with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 S1 RBD fused to GM-CSF as an adjuvant. GPI-RBD-GM-CSF fusion protein was expressed in CHO-S cells, purified and incorporated onto influenza VLPs to develop the hybrid vaccine. Our results show that the hybrid vaccine induced a strong antibody response and protected mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having significantly lower lung viral titers compared to naive mice. These results suggest that the hybrid vaccine strategy is a promising approach for developing multivalent vaccines to prevent influenza A and SARS-CoV-2 infections.
Epithelial uptake ofAspergillus fumigatusdrives efficient fungal clearancein vivoand is aberrant in Chronic Obstructive Pulmonary Disease (COPD)
Authors: Bertuzzi M. , Howell G.J. , Thomson D.D. , Fortune-Grant R. , Möslinger A. , Dancer P. , Van Rhijn N. , Motsi N. , Du X. , Codling A. , Sash R. , Demirbag M. , Bignell E.M.
Published: February 2022

Hundreds of spores of the common mouldAspergillusfumigatus (Af)are inhaled daily by human beings, representing a constant, often fatal, threat to our respiratory health. The small size ofAfspores suggest that interactions withAirwayEpithelialCells (AECs) are frequent and we and others have previously demonstrated that AECs are able to internaliseAfspores. We thus hypothesised thatAfspore uptake and killing by AECs is important for driving efficient fungal clearancein vivoand that defective spore uptake and killing would represent major risk factors forAspergillus-related diseases. In order to test this, we utilised single-cell approaches based onImagingFlowCytometry (IFC) and live-cell microfluidic imaging to measure spore uptake and outcomesin vitro,in vivoand using primary human AECs.In vitro, viability of immortalised AECs was largely unaffected byAfuptake and AECs were able to significantly curtail the growth of internalised spores. Applying our approach directly to infected mouse lungs we demonstrated, for the first time, thatAfspores are internalised and killed by AECs during whole animal infection, whereby only ~3% of internalised spores remained viable after 8 hours of co-incubation with murine AECs. Finally,in vitroanalysis of primary human AECs from healthy and at-risk donors revealed significant alterations in the uptake and consequent outcomes in Chronic Obstructive Pulmonary Disease (COPD), whereby gorging COPD-derived AECs were unable to quell intracellularAfas efficiently as healthy primary AECs. We have thus demonstrated that AECs efficiently killAfspores upon uptakein vivoand that this process is altered in COPD, a well-known risk factor for debilitating fungal lung disease, thereby suggesting that AECs critically contribute to the efficient clearance of inhaledAfspores and that dysregulation of curative AEC responses represents a potent driver ofAspergillus-related diseases.
Activation of a bacterial flow sensor by hypochlorous acid from stimulated neutrophils
Authors: Foik Ilona P. , Urban Lauren A. , Huang Andy P. , Downing Timothy L. , Siryaporn Albert
Published: February 2022

Bacteria sense environmental stressors and activate responses to improve their survival in harsh growth conditions. Neutrophils respond to the presence of bacteria by producing oxidative antibacterial species including hypochlorous acid (HOCl). However, the extent that bacteria detect activated neutrophils or HOCl has not been known. Here, we report that the opportunistic bacterial pathogen Pseudomonas aeruginosa responds to activated neutrophils by activating the fro system, which regulates the expression of antioxidative factors. We show that this response is specific to HOCl and that other oxidative factors including H2O2, do not trigger a fro response. The fro system has been previously shown to detect flow that is present in host vasculature, such as in animal circulatory systems. Our data thus suggest a model in which fro serves as an early host detection system in P. aeruginosa that improves its survival against neutrophil-mediated defenses, which could promote colonization in human tissue and increase pathogenicity.

One Sentence Summary

P. aeruginosa primes its defenses against neutrophils by sensing flow and hypochlorous acid via the fro system.
Conserved Neutralizing Epitopes on the N-Terminal Domain of Variant SARS-CoV-2 Spike Proteins
Authors: Wang Zijun , Muecksch Frauke , Cho Alice , Gaebler Christian , Hoffmann Hans-Heinrich , Ramos Victor , Zong Shuai , Cipolla Melissa , Johnson Briana , Schmidt Fabian , DaSilva Justin , Bednarski Eva , Tanfous Tarek Ben , Raspe Raphael , Yao Kaihui , Lee Yu E. , Chen Teresia , Turroja Martina , Milard Katrina G. , Dizon Juan , Kaczynska Anna , Gazumyan Anna , Oliveira Thiago Y. , Rice Charles M. , Caskey Marina , Bieniasz Paul D. , Hatziioannou Theodora , Barnes Christopher O. , Nussenzweig Michel C.
Published: February 2022

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for the antibody system. Neutralizing antibodies targeting the RBD bind to several different sites on this domain. In contrast, most neutralizing antibodies to NTD characterized to date bind to a single supersite, however these antibodies were obtained by methods that were not NTD specific. Here we use NTD specific probes to focus on anti-NTD memory B cells in a cohort of pre-omicron infected individuals some of which were also vaccinated. Of 275 NTD binding antibodies tested 103 neutralized at least one of three tested strains: Wuhan-Hu-1, Gamma, or PMS20, a synthetic variant which is extensively mutated in the NTD supersite. Among the 43 neutralizing antibodies that were further characterized, we found 6 complementation groups based on competition binding experiments. 58% targeted epitopes outside the NTD supersite, and 58% neutralized either Gamma or Omicron, but only 14% were broad neutralizers. Three of the broad neutralizers were characterized structurally. C1520 and C1791 recognize epitopes on opposite faces of the NTD with a distinct binding pose relative to previously described antibodies allowing for greater potency and cross-reactivity with 7 different variants including Beta, Delta, Gamma and Omicron. Antibody C1717 represents a previously uncharacterized class of NTD-directed antibodies that recognizes the viral membrane proximal side of the NTD and SD2 domain, leading to cross-neutralization of Beta, Gamma and Omicron. We conclude SARS-CoV-2 infection and/or Wuhan-Hu-1 mRNA vaccination produces a diverse collection of memory B cells that produce anti-NTD antibodies some of which can neutralize variants of concern. Rapid recruitment of these cells into the antibody secreting plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants including omicron.
Spatial Growth Rate of Emerging SARS-CoV-2 Lineages in England, September 2020–December 2021
Authors: Smallman-Raynor M.R. , Cliff A.D. ,   The COVID-19 Genomics UK (COG-UK) Consortium
Published: February 2022

This paper uses a robust method of spatial epidemiological analysis to assess the spatial growth rate of multiple lineages of SARS-CoV-2 in the local authority areas of England, September 2020–December 2021. Using the genomic surveillance records of the COVID-19 Genomics UK (COG-UK) Consortium, the analysis identifies a substantial (7.6-fold) difference in the average rate of spatial growth of 37 sample lineages, from the slowest (Delta AY.4.3) to the fastest (Omicron BA.1). Spatial growth of the Omicron (B.1.1.529 and BA) variant was found to be 2.81× faster than the Delta (B.1.617.2 and AY) variant and 3.76× faster than the Alpha (B.1.1.7 and Q) variant. In addition to AY.4.2 (a designated variant under investigation, VUI-21OCT-01), three Delta sublineages (AY.43, AY.98 and AY.120) were found to display a statistically faster rate of spatial growth than the parent lineage and would seem to merit further investigation. We suggest that the monitoring of spatial growth rates is a potentially valuable adjunct to routine assessments of the growth of emerging SARS-CoV-2 lineages in a defined population.
Autism in a dish: ES cell models of autism with copy number variations reveal cell-type-specific vulnerability
Authors: Nomura Jun , Zuko Amila , Kishimoto Keiko , Mutsumine Hiroaki , Fukatsu Kazumi , Nomura Yoshiko , Liu Xiaoxi , Nakai Nobuhiro ,   ES library team, Takahashi Eiki , Kouno Tsukasa , Shin Jay W. , Takumi Toru
Published: February 2022

Human genetics has identified numerous single nucleotide variations (SNVs) and copy number variations (CNVs) associated with autism spectrum disorders (ASD) and other psychiatric disorders. However, the lack of standardized biological resources impedes understanding of the common pathophysiology of ASD. Here, using next-generation chromosome engineering based on the CRISPR/Cas9 system, we established a biological resource including 65 genetically modified mouse embryonic stem cell (mESC) lines as genetic models of human SNVs and CNVs. To illustrate cell-type and CNV specific molecular features of ASD, we performed single-cell RNA sequencing (37,397 cells in total), morphological, and physiological analyses using 12 representative cell lines with CNVs highly associated with ASD. These results uncover gene ontology (GO) terms, canonical pathways, upstream regulators, and related neuropsychiatric disorders in a cell-type and CNV specific manner.
Research on flexible skin technique for adaptive bump inlet structure
Authors: Zhao Chang , Zhou Li , Qiu Tao
Published: February 2022

Purpose

Adaptive bump inlet can adaptively change the shape of inlet bump surface according to the flight speed of aircraft, ensuring that the inlet has good inlet-engine match performance in a wide speed range. This paper aims to use a composite flexible skin reinforced by shape memory alloy (SMA) fiber as the deformable structure at bump surface to realize the adjustable bump surface of adaptive bump inlet.

Design/methodology/approach

According to the deformation and load-bearing requirements of adaptive bump, SMA is applied to the design of adaptive bump inlet due to its characteristic of super-elasticity. A kind of SMA fiber is studied. A composite flexible skin reinforced by SMA is proposed, and its mechanical properties are analyzed. On this basis, an adaptive bump inlet is designed in which the composite flexible skin reinforced by SMA is used as bump surface, and the shape of the bump surface is adjusted by way of pressuring. The design scheme and specific parameters of the adaptive bump are given.

Findings

An adaptive bump surface that meets the design requirements of the inlet is designed, which can effectively adjust the inlet throat area with a throat area change rate of 20%.

Originality/value

An adaptive bump inlet with composite flexible skin as a deformable structure at bump surface is designed, and SMA is applied as the reinforcing fiber.
Port logistic issues and challenges in the Industry 4.0 era for emerging economies: an India perspective
Authors: Sarkar Bishal Dey , Shankar Ravi , Kar Arpan Kumar
Published: February 2022

Purpose

In Industry 4.0 era, many existing port logistics systems are inconsistent, old and ineffective and it restricts the effective operations of port logistics. The study aims to understand the issues faced by the players/actors of port logistics in the Industry 4.0 era for emerging economies and to develop a conceptual framework for managing the port logistics issues associated with it and by providing their possible solutions.

Design/methodology/approach

The study is divided into two parts, first part deals with identifying the major port logistics issues in Industry 4.0 era for emerging economies. It is achieved by conducting a semi-structured interview during the field visit to one of the major container handling ports in India. Second, the study adopts Soft System Methodology (SSM) to understand the issues and challenges faced by various actors of port logistics in the Industry 4.0 era and uses CATWOE analysis to identify the root causes.

Findings

Issues related to loading/unloading, transit, storage (warehouse), customs clearance, regulatory authorities, port management unit and inland transport connection providers are considered in the study and using SSM a final implementable model has been developed. This study focuses on analyzing and understanding the complete communication and organization structure of the port logistics system. The study identifies the major issues, various inefficiencies and root causes faced by various actors of port logistics during information sharing, cargo movement, the arrangement of the cargo shipments, etc. Further, the study develops a final implementable model by combining the delivery system, criteria system and Industry 4.0-enabled system.

Research limitations/implications

The study enables concerned authorities like state government, central government and policymakers to have a profound understanding of the issues faced by the actors of the port logistics system. The study brings out valuable insights that help managers and stakeholders to make informed decisions for managing the port logistics issues and develop necessary policies aimed to deliver the cargoes in right place at right time. The current study also has some limitations because of sensitivity associated with concerned areas, due to its confidentiality, lack of availability of complete data and the nonsharing attitude of respondents. Further, the study was conducted only for private container shipping terminals and public container terminals were not included.

Originality/value

This research analyzes the port logistics sector as a whole system through SSM to identify issues and challenges faced by various actors of port logistics for emerging economies in the Industry 4.0 era. The study develops a comprehensive and integrated framework for reducing the unpredictability of costs and time for key processes. Further, the framework creates a transparent platform and helps in bringing standardization to ports.
Impact of ESG disclosure and financial reporting quality on investment efficiency
Authors: Ellili Nejla Ould Daoud
Published: February 2022

Purpose

This study aims to examine the impacts of environmental, social and governance (ESG) disclosure and financial reporting quality (FRQ) on investment efficiency.

Design/methodology/approach

Several econometric models have been applied to estimate the impacts of ESG disclosure and FRQ on investment efficiency, using the United Arab Emirates (UAE) as a sample in 2010–2019. Estimations considered subsamples of underinvestment, overinvestment and low and high FRQ values.

Findings

Empirical results show a positive relationship between ESG disclosure, FRQ and investment efficiency, and that this relationship is more important in the underinvestment and high FRQ sub-samples. Results suggest that ESG disclosure improves transparency, mitigates information asymmetry and enhances investment efficiency.

Research limitations/implications

The findings could help UAE regulators incorporate ESG information into reporting and implement effective mechanisms to increase the extent of ESG information to improve investment efficiency. This study only examined UAE traded companies. Future research should investigate other factors influencing investment efficiency and conduct comparative studies across Gulf Cooperation Council countries.

Social implications

This study reveals the significant positive impact of ESG disclosure and FRQ on investment efficiency. These findings will help companies optimize their ESG information disclosure, improve the quality of their financial reports and comply with ESG standards. The study aims to develop knowledge that will not only benefit companies regarding the potential impact of ESG disclosure but also help national and international society create a better social environment and reduce climate change.

Originality/value

To the best of the authors’ knowledge, this study is the first to examine the relationship between ESG disclosure, FRQ and corporate investment efficiency. The research contributes to understanding the financial impacts of ESG disclosure and FRQ and supports regulators’ efforts to enforce ESG disclosure and improve FRQ.
The gold standard: developing a maturity model to assess collaborative scheduling
Authors: Scala Natalie M. , Liu Min , Alves Thais da Costa Lago , Schiavone Vincent , Hawkins Dominique
Published: February 2022

Purpose

The overall contribution of this work is to provide a usable maturity model for collaborative scheduling (CS) that extends the literature, identifies inconsistencies in schedule development, and improves collaboration in the construction industry.

Design/methodology/approach

Via subject matter expert elicitation and focus groups, the maturity model establishes five pillars of collaboration—scheduling significance, planners and schedulers, scheduling representation, goal alignment with owner, and communication. The maturity model is then validated through iterative feedback and chi-squared statistical analysis of data obtained from a survey. The five pillars are tied to the literature and previous work in CS.

Findings

The analysis shows that current industry projects are not consistent in collaboration practice implementation, and the maturity model identifies areas for collaboration improvement. The study's contributions to the body of knowledge are (1) developing a maturity model-based approach to define and measure the current level of collaboration and (2) discovering the level of consistency in scheduling collaboration practice implementation.

Practical implications

The findings provide a benchmark for self-evaluation and peer-to-peer comparison for project managers. The model is also useful for project managers to develop effective strategies for improvement on targeted dimensions and metrics.

Originality/value

The construction engineering and management (CEM) literature does not contain targeted models for scheduling collaboration in the context of maturity and, broadly speaking, neither does the literature at large. The literature also lacks actionable items as presented for the maturity model for collaborative scheduling (MMCS).