bluuebunny/crossref_metadata_2025 huggingface dataset:
Reference nodule transcriptomes for Melilotus officinalis and Medicago sativa cv. Algonquin
Authors: Huang Rui , Snedden Wayne A , diCenzo George C
Published: February 2022

Host/symbiont compatibility is a hallmark of the symbiotic nitrogen-fixing interaction between rhizobia and legumes, mediated in part by plant produced nodule-specific cysteine-rich (NCR) peptides and the bacterial BacA membrane protein that can act as a NCR peptide transporter. In addition, the genetic and metabolic properties supporting symbiotic nitrogen fixation often differ between compatible partners, including those sharing a common partner, highlighting the need for multiple study systems. Here, we report high quality nodule transcriptome assemblies for Medicago sativa cv. Algonquin and Melilotus officinalis, two legumes able to form compatible symbioses with Sinorhizobium meliloti. The compressed M. sativa and M. officinalis assemblies consisted of 79,978 and 64,593 contigs, respectively, of which 33,341 and 28,278 were assigned putative annotations, respectively. As expected, the two transcriptomes showed broad similarity at a global level. We were particularly interested in the NCR peptide profiles of these plants, as these peptides drive bacterial differentiation during the symbiosis. A total of 412 and 308 NCR peptides were predicted from the M. sativa and M. officinalis transcriptomes, respectively, with approximately 9% of the transcriptome of both species consisting of NCR transcripts. Notably, transcripts encoding highly-cationic NCR peptides (isoelectric point > 9.5), which are known to have antimicrobial properties, were ~2-fold more abundant in M. sativa than in M. officinalis, and ~27-fold more abundant when considering only NCR peptides in the six-cysteine class. We hypothesize that the difference in abundance of highly-cationic NCR peptides explains our previous observation that some rhizobial bacA alleles which can support symbiosis with M. officinalis are unable to support symbiosis with M. sativa.
Effects of substrate on shrimp growth, water quality and bacterial community in the biofloc system nursing Penaeus vannamei postlarvae
Authors: Huang Hai-Hong , Li Chao-Yun , Lei Yan-Ju , Kuang Wei-Qi , Zhou Bo-Lan , Zou Wan-Sheng , Yang Pin-Hong
Published: February 2022

This study aimed to investigate the effects of substrate on water quality, shrimp growth and bacterial community in the biofloc system with a salinity of 5‰. Two treatments, biofloc system with (sB) or without (nB) addition of elastic solid packing filler (nylon) as substrate, were set up. Penaeus vannamei postlarvae (PL, ~ stage 15) were stocked at a density of 4000 PL m−3 in each treatment with triplicates for a 28-days culture experiment, taking glucose as carbon source (C:N 15:1). Results showed that the survival rate (96.3±3.6%), FCR (0.76±0.06) and productivity (1.54±0.12 kg m−3) in sB treatment were significantly better than those in nB treatment (81.0±7.1%, 0.98±0.08 and 1.14±0.09 kg m−3, P<0.05). All water parameters were in the recommended ranges. Substrate showed significant effect on TAN, TSS, turbidity, biofloc volume, pH and carbonate alkalinity (P < 0.05). Actinobacteria (4.0-22.7%), Bacteroidetes (10.4-33.5%), Firmicutes (0.2-11.2%), Planctomycetes (4.0-14.9%) and Proteobacteria (29.4-59.0%) were the most dominant phyla for both treatments. However, the bacterial community in sB treatment showed to be significantly different from that in nB treatment (Jaccard distance 0.94±0.01, P=0.001). Substrate showed significant effects on Shannon, Heip, Pielou and Simpson index, as well as relative abundances of Actinobacteria, Bacteroidetes and Planctomycetes (P < 0.05). The results suggested that addition of substrate affected the shrimp growth, water quality and bacterial community in the biofloc system nursing P. vannamei PL with a 5‰ salinity.
The efficacy of commercial decontamination agents differs between standardised test settings and real-world usage for a variety of bacterial species
Authors: Uy Benedict , Read Hannah , van de Pas Shara , Marnane Rebecca , Casu Francesca , Swift Simon , Wiles Siouxsie
Published: February 2022

Decontamination of surfaces and items plays an important role in reducing the spread of infectious microorganisms in many settings including hospitals and research institutes. Regardless of the location, appropriate decontamination procedures are required for maintaining biosafety and biosecurity. For example, effective decontamination of microbial cultures is essential to ensure proper biocontainment and safety within microbiological laboratories. To this end, many commercial decontamination agents are available which have been tested to a prescribed standard to substantiate their efficacy. However, these standardised tests are unlikely to accurately reflect all conditions encountered in medical and biomedical research. Despite this, laboratory workers and other users of decontamination agents may assume that all decontamination agents will work in all situations. We tested commonly used commercial decontamination agents against a range of bacterial species to determine their efficacy under real-world laboratory conditions. As each decontamination agent has a different recommended dilution for use, to compare their efficacy we calculated their ‘effective ratio’ which reflects the difference between the manufacturer-recommended dilution and the dilution needed to achieve decontamination under real-world laboratory conditions. Effective ratios above 1 indicate that the agent was active at a dilution more dilute than recommended whereas effective ratios lower than 1 indicate that the agent required a higher concentration than recommended. Our results show that the quaternary ammonium agents TriGene Advance and Chemgene HLD4L were the most active out of the agents tested, with biocidal activity measured at up to 64 times the recommended dilution. In contrast, hypochlorite (bleach) and Prevail™ (stabilised hydrogen peroxide) had the lowest effective ratios amongst the tested agents. In conclusion, our data suggest that not all decontamination agents will work at the recommended dilutions under real-world laboratory conditions. We recommend that the protocols for the use of decontamination agents are verified under the specific conditions required to ensure they are fit for purpose.
A Novel congenic Mouse Model to study Obesity, Diabetes and NAFLD
Authors: Kumar MJ Mahesh , Arindkar Shailendra , Nagarajan Perumal
Published: February 2022

The genetic background of the mutant mouse strain plays an important role in disease development. We investigated whetherLeprmutation on different genetic background (WSB/EiJ) influences the development of obesity, diabetes and non-alcoholic fatty liver diseases (NAFLD). For this study heterozygote (db/+) mice were backcrossed with WSB/EiJ strain (that is resistant to obesity and NAFLD) for more than 10 generations and intercrossed for five generations havingLeprmutated gene incorporated in WSB/EiJ background. The newly derived congenic strain was assessed and related with the B6.db strain and WSB/EiJ strain for the development of obesity, NAFLD. TheLeprmutated congenic strain on the WSB/EiJ background gained significant body weight and showed other characteristic features of obesity. However, the incidence of diabetes, NAFLD, and other kidney complications were not observed in this strain. The novel congenic mouse strain havingLeprgene on WSB/EiJ background would be a promising model for the study of obesity without NAFLD and will also help to understand the various mechanisms involved in the development of NAFLD.
N-acylethanolamine acid amide hydrolase is a novel target for drugs against SARS-CoV-2 and Zika virus
Authors: Lai Michele , La Rocca Veronica , Amato Rachele , Iacono Elena , Filipponi Carolina , Catelli Elisa , Bogani Lucia , Fonnesu Rossella , Lottini Giulia , De Carli Alessandro , Mengozzi Alessandro , Masi Stefano , Quaranta Paola , Spezia Pietro Giorgio , Freer Giulia , Lenzi Paola , Fornai Francesco , Piomelli Daniele , Pistello Mauro
Published: February 2022

Several compounds have been tested against SARS-CoV-2; at present, COVID-19 treatments decrease the deleterious inflammatory response and acute lung injury. However, the best therapeutic response would be expected by combining anti-inflammatory properties, while concomitantly blocking viral replication. These combined effects should drastically reduce both infection rate and severe complications induced by novel SARS-CoV-2 variants. Therefore, we explored the antiviral potency of a class of anti-inflammatory compounds that inhibit the N-Acylethanolamine acid amidase (NAAA). This enzyme catalyzes the hydrolysis of palmitoylethanolamide (PEA), a bioactive lipid that mediates anti-inflammatory and analgesic activity through the activation of peroxisome proliferator receptor-α (PPAR-α). Similarly, this pathway is likely to be a significant target to impede viral replication since PPAR-α activation leads to dismantling of lipid droplets, where viral replication of Flaviviruses and Coronaviruses occurs.

Here, we show that either genetic or pharmacological inhibition of the NAAA enzyme leads to five-fold reduction in the replication of both SARS-CoV-2 and ZIKV in various cell lines. Once NAAA enzyme is blocked, both ZIKV and SARS CoV-2 replication decrease, which parallels a sudden five-fold decrease in virion release. These effects induced by NAAA inhibition occurs concomitantly with stimulation of autophagy during infection. Remarkably, parallel antiviral and anti-inflammatory effects of NAAA antagonism were confirmed in ex-vivo experiments, within SARS-CoV-2 infected human PBMC cells, in which both viral genomes and TNF-α production drop by ~60%. It is known that macrophages contribute to viral spread, excessive inflammation and macrophage activation syndrome that NAAA inhibitors might prevent, reducing the macrophage-induced acute respiratory distress syndrome and subsequent death of COVID-19 patients.
SARS-CoV-2 ORF6 disrupts innate immune signalling by inhibiting cellular mRNA export
Authors: Hall Ross , Guedán Anabel , Yap Melvyn W. , Young George R. , Harvey Ruth , Stoye Jonathan P. , Bishop Kate N.
Published: February 2022

SARS-CoV-2 is a betacoronavirus and the etiological agent of COVID-19, a devastating infectious disease. Due to its far-reaching effect on human health, there is an urgent and growing need to understand the viral molecular biology of SARS-CoV-2 and its interaction with the host cell. SARS-CoV-2 encodes 9 predicted accessory proteins, which are presumed to be dispensable for in vitro replication, most likely having a role in modulating the host cell environment to aid viral replication. Here we show that the ORF6 accessory protein interacts with cellular Rae1 to inhibit cellular protein production by blocking mRNA export. We utilised cell fractionation coupled with mRNAseq to explore which cellular mRNA species are affected by ORF6 expression and show that ORF6 can inhibit the export of many mRNA including those encoding antiviral factors such as IRF1 and RIG-I. We also show that export of these mRNA is blocked in the context of SARS-CoV-2 infection. Together, our studies identify a novel mechanism by which SARS-CoV-2 can manipulate the host cell environment to supress antiviral responses, providing further understanding to the replication strategies of a virus that has caused an unprecedented global health crisis.

Author Summary

SARS-CoV-2 is the virus responsible for the current COVID-19 pandemic. Coronaviruses, like SARS-CoV-2, replicate their genome in the cytoplasm of the host cell by hijacking the cellular machinery. In addition to structural proteins and viral enzymes, SARS-CoV-2 encodes 9 accessory proteins. Although these are not required for in vitro replication, they are thought to modulate the host cell environment to favour viral replication. In this work, we show that the ORF6 accessory protein can supress cellular protein production by blocking mRNA nuclear export through interacting with the cellular protein Rae1, a known mRNA export factor. We also investigated which cellular mRNAs were retained in the nucleus when ORF6 was overexpressed. Interestingly, we found that ORF6 inhibited the export of many different mRNAs, including those encoding antiviral factors, like IRF1 and RIG-I, even in the absence of stimulation by interferon. Importantly, we found that the export of these mRNAs was similarly affected in the context of SARS-CoV-2 infection. Therefore, we believe we have identified a novel mechanism that SARS-CoV-2 uses to suppress antiviral responses in order to make the cell more permissive to infection.
Increasing viral transmission paradoxically reduces progression rates to severe COVID-19 during endemic transition
Authors: Hong Hyukpyo , Noh Ji Yun , Lee Hyojung , Choi Sunhwa , Choi Boseung , Kim Jae Kyoung , Shin Eui-Cheol
Published: February 2022

Natural infection with SARS-CoV-2 or vaccination induces virus-specific immunity protecting hosts from infection and severe disease. While the infection-preventing immunity gradually declines, the severity-reducing immunity is relatively well preserved. Here, based on the different longevity of these distinct immunities, we develop a mathematical model to estimate courses of endemic transition of COVID-19. Our analysis demonstrates that high viral transmission unexpectedly reduces the rates of progression to severe COVID-19 during the course of endemic transition despite increased numbers of infection cases. Our study also shows that high viral transmission amongst populations with high vaccination coverages paradoxically accelerates the endemic transition of COVID-19 with reduced numbers of severe cases. These results provide critical insights for driving public health policies in the era of ‘living with COVID-19’.
Does 2×2 airplane passenger contact tracing for infectious respiratory pathogens work? A systematic review of the evidence
Authors: Rafferty Anna C , Bofkin Kelly , Hughes Whitney , Souter Sara , Hosegood Ian , Hall Robyn N , Furuya-Kanamori Luis , Liu Bette , Drane Michael , Regan Toby , Halder Molly , Kelaher Catherine , Kirk Martyn D
Published: February 2022

We critically appraise the literature regarding in-flight transmission of a range of respiratory infections to provide an evidence base for public health policies for contact tracing passengers, given the limited pathogen-specific data for SARS-CoV-2 currently available. Using PubMed, Web of Science, and other databases including preprints, we systematically reviewed evidence of in-flight transmission of infectious respiratory illnesses. A meta-analysis was conducted where total numbers of persons on board a specific flight was known, to calculate a pooled Attack Rate (AR) for a range of pathogens. The quality of the evidence provided was assessed using a bias assessment tool developed for in-flight transmission investigations. We identified 103 publications detailing 165 flight investigations. Overall, 43.7% (72/165) of investigations provided evidence for in-flight transmission. H1N1 influenza A virus had the highest reported pooled attack rate per 100 persons (AR= 1.17), followed by SARS-CoV-2 (AR=0.54) and SARS-CoV (AR = 0.32), Mycobacterium tuberculosis (AR= 0.25), and measles virus (AR= 0.09). There was high heterogeneity in estimates between studies, except for TB. Of the 72 investigations that provided evidence for in-flight transmission, 27 investigations were assessed as having a high level of evidence, 23 as medium, and 22 as low. One third of the investigations that reported on proximity of cases showed transmission occurring beyond the 2×2 seating area. We suggest that for emerging pathogens, in the absence of pathogen-specific evidence, the 2×2 system should not be used for contact tracing. Instead, alternate contact tracing protocols and close contact definitions for enclosed areas, such as the same cabin on an aircraft or other forms of transport, should be considered as part of a whole of journey approach.
Sero-prevalence of anti-SARS-CoV-2 antibodies in Chattogram Metropolitan Area, Bangladesh
Authors: Ara Jahan , Islam Md. Sirazul , Quader Md. Tarek Ul , Das Anan , Hasib F. M. Yasir , Islam Mohammad Saiful , Rahman Tazrina , Das Seemanta , Chowdhury M.A. Hassan , Das Goutam Buddha , Chowdhury Sharmin
Published: February 2022

Background

Seroprevalence studies of coronavirus disease 2019 (COVID-19) assess the degree of undetected transmission in the community. Different groups, such as healthcare workers (HCWs), garment workers, and others, are deemed vulnerable due to their workplace hazards and immense responsibility.

Purpose

The present study was conducted to estimate the seroprevalence of anti-SARS-CoV-2 antibody (IgG) and its association with different explanatory variables. Further, the antibody was quantified to assess the increasing or decreasing trend over different intervention periods and according to other factors.

Methodology

This cross-sectional study observed health workers - doctor, nurse, hospital staff, etc. in and outpatients (non-COVID-19) and garments workers of Chattogram metropolitan area (CMA, N=748) from randomly selected six government and private hospitals and two garment factories. Study subjects were included upon written consent, fulfilling specific inclusion criteria. Venous blood was collected following standard aseptic methods. Qualitative and quantitative ELISA was used to identify and quantify antibodies (IgG) in serum samples. Descriptive, univariable, and multivariable statistical analysis was performed.

Results

Overall seroprevalence was estimated as 66.99% (95% CI: 63.40%-70.40%). Seroprevalence among HCWs, in and outpatients, and garments workers were 68.99 % (95% CI: 63.8%-73.7%), 81.37 % (95% CI: 74.7%-86.7%), and 50.56 % (95% CI: 43.5%-57.5%), respectively. Seroprevalence was 44.47 % (95% CI: 38.6%-50.4%) in the non-vaccinated population while it was significantly (p <0.001) higher in the population receiving the first dose (61.66 %, 95% CI: 54.8%-68.0%) and both (first and second) doses of vaccine (100%, 95% CI: 98.4%-100%). The mean titer of the antibody was estimated as 255.46 DU/ml and 159.08 DU/ml in the population with both doses and one dose of vaccine, respectively, compared to 53.71 DU/ml of the unvaccinated population. A decreasing trend in the titer of antibodies with increasing time after vaccination was observed.

Conclusions

Seroprevalence and mean antibody titer varied according to different factors in this study. The second dose of vaccine significantly increased the seroprevalence and titer, which decreased to a certain level over time. Although antibody was produced following natural infection, the mean titer was relatively low compared to antibody after vaccination. This study emphasizes the role of the vaccine in antibody production. Based on the findings, interventions like continuing extensive mass vaccination of the leftover unvaccinated population and bringing the mass population with a second dose under a third dose campaign might be planned.
Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study
Authors: Walmsley Sharon , Szadkowski Leah , Wouters Bradly , Clarke Rosemarie , Colwill Karen , Rochon Paula , Brudno Michael , Ravindran Rizani , Raboud Janet , McGeer Allison , Oza Amit , Graham Christopher , Silva Amanda , Manase Dorin , Parente Laura , Simpson Jacqueline , Dayam Roaya Monica , Pasculescu Adrian , Gingras Anne-Claude
Published: February 2022

Background

To partially immunize more persons against COVID-19 during a time of limited vaccine availability, Canadian public health officials recommended extending the vaccine dose interval and brand mixing. Impact on the antibody response among the older ambulatory population was unclear.

Methods

Decentralized prospective cohort study with self-report of adverse events and collection of dried blood spots. Data is presented for 1193 (93%) of the 911 older (aged >70 years) and 375 younger (30-50 years) recruits.

Findings

Local and systemic reactivity rates were high but short-lived, particularly in the younger cohort and with mRNA-1273 vaccine. After a single COVID-19 vaccine, 84% younger but only 46% older participants had positive IgG antibodies to both spike protein and receptor binding domain (RBD) antigens, increasing to 100/98% with the second dose respectively. In multivariable linear regression model, lower normalized IgG RBD antibody ratios two weeks after the second dose were statistically associated with older age, male gender, cancer diagnosis, lower body weight, BNT162b2 relative to mRNA-1273 and longer dose intervals. Antibody ratios in both cohorts declined 12 weeks post second vaccine dose.

Interpretation

We report success of a decentralized serology study. Antibody responses were higher in the younger than older cohort and were greater for those with at least one mRNA-1273 dose. The immunity threshold is unknown but correlations between binding and neutralizing antibodies are strongly positive. Trends with time and at breakthrough infection will inform vaccine booster strategies.

Funding

Supported by the Public Health Agency of Canada and the University Health Network Foundation.
Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission
Authors: Wenzel Dawn M. , Mackay Douglas R. , Skalicky Jack J. , Paine Elliott L. , Miller Matthew S. , Ullman Katharine S. , Sundquist Wesley I.
Published: February 2022

The 12 related human ESCRT-III proteins form filaments that constrict membranes and mediate fission, including during cytokinetic abscission. The C-terminal tails of polymerized ESCRT-III subunits also bind proteins that contain Microtubule-Interacting and Trafficking (MIT) domains. MIT domains can interact with ESCRT-III tails in many different ways to create a complex binding code that recruits essential cofactors to sites of ESCRT activity. Here, we have comprehensively and quantitatively mapped the interactions between all known ESCRT-III tails and 19 pure recombinant human MIT domains. We measured 228 pairwise interactions, quantified 58 positive interactions, and discovered 16 previously unreported interactions. We also report the crystal structure of the SPASTIN MIT domain in complex with the IST1 C-terminal tail. Three MIT enzymes were studied in detail and shown to: 1) localize to cytokinetic midbody membrane bridges through interactions with their specific ESCRT-III binding partners (SPASTIN-IST1, KATNA1-CHMP3, and CAPN7-IST1), 2) function in abscission (SPASTIN, KATNA1, and CAPN7), and 3) function in the “NoCut” abscission checkpoint (SPASTIN and CAPN7). Our studies define the human MIT-ESCRT-III interactome, identify new factors and activities required for cytokinetic abscission and its regulation, and provide a platform for analyzing ESCRT-III and MIT cofactor interactions in all ESCRT-mediated processes.
A catalytic mechanism for Renilla-type bioluminescence
Authors: Schenkmayerova Andrea , Toul Martin , Pluskal Daniel , Baatallah Racha , Gagnot Glwadys , Pinto Gaspar P. , Santana Vinicius T. , Stuchla Marketa , Neugebauer Petr , Chaiyen Pimchai , Damborsky Jiri , Bednar David , Janin Yves L. , Prokop Zbynek , Marek Martin
Published: February 2022

The widely used coelenterazine-powered Renilla luciferase was discovered over 40 years ago but the oxidative mechanism by which it generates blue photons remains unclear. Here we decipher Renilla-type bioluminescence through crystallographic, spectroscopic, and computational experiments. Structures of ancestral and extant luciferases complexed with the substrate-like analogue azacoelenterazine or a reaction product were obtained, providing unprecedented snapshots of coelenterazine-to-coelenteramide oxidation. Bound coelenterazine adopts a Y-shaped conformation, enabling the deprotonated imidazopyrazinone component to attack O2 via a radical charge-transfer mechanism. A high emission intensity is secured by an aspartate from a conserved proton-relay system, which protonates the excited coelenteramide product. Another aspartate on the rim of the catalytic pocket fine-tunes the electronic state of coelenteramide and promotes the formation of the blue light-emitting phenolate anion. The results obtained also reveal structural features distinguishing flash-type from glow-type bioluminescence, providing insights that will guide the engineering of next-generation luciferase–luciferin pairs for ultrasensitive optical bioassays.
The structure, binding, and function of a Notch transcription complex involving RBPJ and the epigenetic reader protein L3MBTL3
Authors: Hall Daniel , Giaimo Benedetto Daniele , Park Sung-Soo , Hemmer Wiebke , Friedrich Tobias , Ferrante Francesca , Bartkuhn Marek , Yuan Zhenyu , Oswald Franz , Borggrefe Tilman , Rual Jean-François , Kovall Rhett A.
Published: February 2022

The highly conserved Notch pathway transmits signals between neighboring cells to elicit distinct downstream transcriptional programs. In given contexts, Notch is a major regulator of cell fate specification, proliferation, and apoptosis, such that aberrant Notch signaling leads to a pleiotropy of human diseases, including developmental disorders and cancers. The canonical pathway signals through the transcription factor CSL (RBPJ in mammals), which forms a transcriptional activation complex with the intracellular domain of the Notch receptor and the coactivator Mastermind. CSL can also function as a transcriptional repressor by forming complexes with one of several different corepressor proteins, such as FHL1 or SHARP in mammals and Hairless in Drosophila. Recently, we identified the malignant brain tumor (MBT) family member L3MBTL3 as a bona fide RBPJ binding corepressor that recruits the repressive lysine demethylase LSD1/KDM1A to Notch target genes. Here we define the RBPJ-interacting domain (RBP-ID) of L3MBTL3 and report the 2.06 Å crystal structure of the complex formed between RBPJ, the RBP-ID of L3MBTL3 and DNA. The structure reveals the molecular interactions underlying L3MBTL3 complexation with RBPJ, which we comprehensively analyze with a series of L3MBTL3 and RBPJ mutations that span the binding interface. Compared to other RBPJ-binding proteins, we find that L3MBTL3 interacts with RBPJ via an unusual binding motif, which is sensitive to mutations throughout its RBPJ-interacting region. We also show that these disruptive mutations affect RBPJ and L3MBTL3 function in cells, providing further insights into Notch mediated transcriptional regulation.
A Multiscale study of phosphorylcholine driven cellular phenotypic targeting
Authors: Acosta-Gutiérrez Silvia , Matias Diana , Avila-Olias Milagros , Gouveia Virginia M. , Scarpa Edoardo , Forth Joe , Contini Claudia , Duro-Castano Aroa , Rizzello Loris , Battaglia Giuseppe
Published: February 2022

Phenotypic targeting requires the ability of the drug delivery system to discriminate over cell populations expressing a particular receptor combination. Such selectivity control can be achieved using multiplexed-multivalent carriers often decorated with multiple ligands. Here, we demonstrate that the promiscuity of a single ligand can be leveraged to create multiplexed-multivalent carriers achieving phenotypic targeting. We show how the cellular uptake of poly(2-methacryloyloxyethyl phosphorylcholine)-poly(2- (diisopropylamino)ethyl methacrylate) (PMPC-PDPA) polymersomes varies depending on the receptor expression among different cells. We investigate the PMPC-PDPA polymersome insertion at the single chain/receptor level using all-atom molecular modelling. We propose a theoretical statistical mechanics-based model for polymersome-cell association that explicitly considers the interaction of the polymersome with the cell glycocalyx shedding light on its effect on the polymersome binding. We validate our model experimentally and show that the binding energy is a non-linear function, allowing us to tune interaction by varying the radius and degrees of polymerisation. Finally, we show that PMPC-PDPA polymersomes can be used to target monocytes in vivo due to their promiscuous interaction with SRB1, CD36 and CD81.
Controversy over the decline of arthropods: a matter of temporal baseline?
Authors: Duchenne François , Porcher Emmanuelle , Mihoub Jean-Baptiste , Loïs Grégoire , Fontaine Colin
Published: February 2022

Abstract

Recently, a number of studies have reported somewhat contradictory patterns of temporal trends in arthropod abundance, from decline to increase. Arthropods often exhibit non-monotonous variation in abundance over time, making it important to account for temporal coverage in interpretation of abundance trends, which is often overlooked in statistical analysis. Combining four recently analysed datasets that led to contrasting outcomes, we first show that temporal abundance variations of arthropods are non-monotonous. Using simulations, we show non-monotony is likely to bias estimated linear abundance trends. Finally, analysing empirical data, we show that heterogeneity in estimated abundance trends is significantly related to the variation in temporal baseline of analysed time series. Once differences in baseline years, habitats and continents are accounted for, we do not find any statistical difference in estimated linear abundance trends among the four datasets. We also show that short time series produce more stochastic abundance trends than long series, making the dearth of old and long-term time series a strong limitation in the assessment of temporal trends in arthropod abundance. The lack of time series with a baseline year before global change acceleration is likely to lead to an underestimation of global change effects on biodiversity.
The genome of tropically adapted Brahman cattle (Bos taurus indicus) reveals novel genome variation in production animals
Authors: Ross Elizabeth M , Nguyen Loan T , Lamb Harrison J , Moore Stephen S , Hayes Ben J
Published: February 2022

Recent advances in sequencing technology have revolutionised access to large scale genomic data that can be assembled into a platinum quality genome. Here we present a high quality genome assembly with less than 300 gaps of a Brahman cow (B. taurus indicus). The assembly was generated using 195GB of PacBio and 169GB of Oxford Nanopore Technologies sequence data. The high quality genome assembly allows us to identify substantial GC content variation that is positively associated with gene rich islands, and negatively associated with genetic variation in the form of structural variants. In addition, 92371 structural variants that are segregating in the brahman population were identified. Gene ontology analysis revealed that genes with varying copy numbers were enriched for gene ontology terms related to immune function. This analysis has revealed the complex structure of the mammalian genome of an outbred species, and identifies the ability of long read data from diploid species can be used to not only assemble a high quality genome, but also discover novel genetic variation within that genome.
In-shoe plantar pressure depends on walking speed and type of weight-bearing activity in people with diabetes at high risk of ulceration
Authors: Hulshof Chantal M , van Netten Jaap J , Dekker Maartje G , Pijnappels Mirjam , Bus Sicco A
Published: February 2022

Background

In evaluating the biomechanical properties of therapeutic footwear, most often in-shoe plantar pressure is obtained during mid-gait steps at self-selected speed in a laboratory setting. However, this may not represent plantar pressures or indicate the cumulative stress experienced in daily life, where people adopt different walking speeds and weight-bearing activities.

Research question

In people with diabetes at high risk of ulceration, 1) what is the effect of walking speed on plantar pressure measures, and 2) what is the difference in plantar pressure measures between walking at self-selected speed and other weight-bearing activities?

Methods

In a cross-sectional study, we included 59 feet of 30 participants (5 females, mean age: 63.8 (SD 9.2) years). We assessed in-shoe plantar pressure with the Pedar-X system during three standardized walking speeds (0.8, 0.6 and 0.4 m/s) and eight types of activities versus walking at self-selected speed (3 components of the Timed Up and Go test (TUG), standing, accelerating, decelerating, stair ascending and descending and standing). Peak plantar pressure (PPP) and pressure-time integral (PTI) were determined for the hallux, metatarsal 1, metatarsal 2-3 and metatarsal 4-5. For statistical comparisons we used linear mixed models (α<0.05) with Holm-Bonferroni correction.

Results

With increasing walking speed, PPP increased and PTI decreased for all regions (p≤0.001). Standing, decelerating, stair ascending and TUG showed lower PPP than walking at self-selected speed for most regions (p≤0.004), whereas accelerating and stair descending showed similar PPP. Stair ascending and descending showed higher PTI than walking at self-selected speed (p≤0.002), standing showed lower PTI (p≤0.001), while the other activities showed similar PTI for most regions.

Significance

To best evaluate the biomechanical properties of therapeutic footwear, and to assess cumulative plantar tissue stress of people with diabetes at high risk of ulceration, plantar pressures during different walking speeds and activities of daily living should be considered.
Multiphase condensates from a kinetically arrested phase transition
Authors: Erkamp Nadia A. , Sneideris Tomas , Ausserwöger Hannes , Qian Daoyuan , Qamar Seema , Nixon-Abell Jonathon , George-Hyslop Peter St , Schmit Jeremy D. , Weitz David A. , Knowles Tuomas P.J.
Published: February 2022

The formation of biomolecular condensates through liquid-liquid phase separation from proteins and nucleic acids is emerging as a spatial organisational principle used by living cells. Many such biomolecular condensates are not, however, homogeneous fluids, but contain an internal structure consisting of distinct sub-compartments with different compositions. In many instances, such compartments inside the condensate are depleted in the biopolymers that make up the condensate. Here, we describe that this multiphase structure arises from a kinetically arrested phase transition. The combination of a change in composition coupled with a slow response to this change can lead to the spontaneous formation of multiple emulsions consisting of several inner cores within a polymer-rich middle phase. In the case of liquid-like biomolecular condensates, the slow diffusion of biopolymers causes nucleation of biopolymer-poor liquid inside of the condensate to achieve the new equilibrium composition. This framework shows that multiphase condensates can be a result of kinetic trapping, rather than thermodynamic stability, and provides and avenue to understand and control the internal structure of condensates in vitro and in vivo.
Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat
Authors: Hannon William W. , Roychoudhury Pavitra , Xie Hong , Shrestha Lasata , Addetia Amin , Jerome Keith R. , Greninger Alexander L. , Bloom Jesse D.
Published: February 2022

The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a SARS-CoV-2 outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.
Parallel Expansion and Divergence of an Adhesin Family in Pathogenic Yeasts IncludingCandida auris
Authors: Smoak Rachel A. , Snyder Lindsey F. , Fassler Jan S. , He Bin Z.
Published: February 2022

Opportunistic yeast pathogens evolved multiple times in the Saccharomycetes class, including the recently emerged, multidrug-resistantCandida auris. We show that homologs of a known yeast adhesin family inCandida albicans, the Hyr/Iff-like (Hil) family, are enriched in distinct clades ofCandidaspecies as a result of multiple, independent expansions. Following gene duplication, the tandem repeat-rich region in these proteins diverged extremely rapidly and generated large variations in length and β-aggregation potential, both of which were known to directly affect adhesion. The conserved N-terminal effector domain was predicted to adopt a β-helical fold followed by an α-crystallin domain, making it structurally similar to a group of unrelated bacterial adhesins. Nonsynonymous-to-synonymous substitution rate analysis of the effector domain inC. aurisrevealed relaxed selective constraint and signatures of positive selection, suggesting functional diversification after gene duplication. Lastly, we found the Hil family genes to be enriched at chromosomal ends, which likely contributed to their expansion via ectopic recombination and break-induced replication. We hypothesize that the expansion and diversification of adhesin families are a key step toward the emergence of fungal pathogens and also generate variation in adhesion and virulence within and between species.
Delayed puberty, gonadotropin abnormalities and subfertility in malePadi2/Padi4double knockout mice
Authors: Sams Kelly L. , Mukai Chinatsu , Marks Brooke A. , Mittal Chitvan , Demeter Elena Alina , Nelissen Sophie , Grenier Jennifer K. , Tate Ann E. , Ahmed Faraz , Coonrod Scott A.
Published: February 2022

Background

Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signalingin vitroand the goal of this study was to test for links between PAD2/PAD4 and hormone signalingin vivo.

Methods

Preliminary analysis ofPadi2andPadi4single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created aPadi2/Padi4double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects.

Results

Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO and WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis.

Conclusions

ThePadi2/Padi4DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the firstin vivoevidence linking PADs with hormone signaling.
Crowdsourced EEG Experiments: A proof of concept for remote EEG acquisition using EmotivPRO Builder and EmotivLABS
Authors: Williams Nikolas S , King William , Mackellar Geoffrey , Randeniya Roshini , McCormick Alicia , Badcock Nicholas A
Published: February 2022

Online research platforms have enabled mass data collection enabling representative samples for cognitive behavioural studies. However, the benefits of online data collection have not been available for cognitive neuroscience fields such as electroencephalography (EEG). In this study, we introduce an approach for remote EEG data collection. We demonstrate how an experiment can be built via the EmotivPRO Builder and deployed to the EmotivLABS website where it can be completed by participants who own EMOTIV EEG headsets. To demonstrate the data collection technique, we collected EEG while participants engaged in a resting state task where participants sat with their eyes open and then eyes closed for two minutes each. We observed a significant difference in alpha power between the two conditions thereby demonstrating the well-known alpha suppression effect. Thus, we demonstrate that EEG data collection, particularly for frequency domain analysis, can be successfully conducted online with remote users.
DNABERT-based explainable lncRNA identification in plant genome assemblies
Authors: Danilevicz Monica F. , Gill Mitchell , Tay Fernandez Cassandria G. , Petereit Jakob , Upadhyaya Shriprabha R. , Batley Jacqueline , Bennamoun Mohammed , Edwards David , Bayer Philipp E.
Published: February 2022

Long non-coding ribonucleic acids (lncRNAs) have been shown to play an important role in plant gene regulation, involving both epigenetic and transcript regulation. LncRNAs are transcripts longer than 200 nucleotides that are not translated into functional proteins but can be translated into small peptides. Machine learning models have predominantly used transcriptome data with manually defined features to detect lncRNAs, however, they often underrepresent the abundance of lncRNAs and can be biased in their detection. Here we present a study using Natural Language Processing (NLP) models to identify plant lncRNAs from genomic sequences rather than transcriptomic data. The NLP models were trained to predict lncRNAs for seven model and crop species (Zea mays,Arabidopsis thaliana,Brassica napus,Brassica oleracea,Brassica rapa,Glycine maxandOryza sativa) using publicly available genomic references. We demonstrated that lncRNAs can be accurately predicted from genomic sequences with the highest accuracy of 83.4% forZ. maysand the lowest accuracy of 57.9% forB. rapa, revealing that genome assembly quality might affect the accuracy of lncRNA identification. Furthermore, we demonstrated the potential of using NLP models for cross-species prediction with an average of 63.1% accuracy using target species not previously seen by the model. As more species are incorporated into the training datasets, we expect the accuracy to increase, becoming a more reliable tool for uncovering novel lncRNAs. Finally, we show that the models can be interpreted using explainable artificial intelligence to identify motifs important to lncRNA prediction and that these motifs frequently flanked the lncRNA sequence.

Highlights

We demonstrate for the first time the identification of lncRNAs from genomic sequences, instead of transcriptome sequences, allowing the identification of lowly expressed lncRNAs.

A deep learning model (natural language processing) was employed to predict lncRNAs in two monocot and five dicot plant species.

We used explainable machine learning to extract the genomic motifs associated with lncRNA identification and highlighted potentially conserved structures.
Single-cell analysis reveals a pathogenic cellular module associated with early allograft dysfunction after liver transplantation
Authors: Wang Zheng , Shao Xin , Wang Kai , Lu Xiaoyan , Zhuang Li , Yang Xinyu , Zhang Ping , Yang Penghui , Zheng Shusen , Xu Xiao , Fan Xiaohui
Published: February 2022

Liver transplantation (LT) is the standard therapy for patients with end-stage liver disease. Although LT technology has markedly progressed in recent decades, early allograft dysfunction (EAD) exacerbates the current organ shortage and impacts the prognosis of recipients. However, understanding of cellular characteristics and molecular events contributing to EAD is limited. Here, a large single-cell transcriptomic atlas of transplanted livers collected from four patients is constructed, including 58,243 cells, which are classified into 14 cell types and 29 corresponding subtypes with known markers, including liver parenchymal cells and non-parenchymal cells with different cell states. Compared to the pre-LT livers, graft remodeling is noted in the post-LT livers, with marked changes in several immune cells in either cell ratios or cell states. More importantly, an EAD-associated pathogenic cellular module is identified, consisting of mucosal-associated invariant T (MAIT) cells, granzyme B (GZMB)+granzyme K (GZMK)+natural killer (NK) cells, and S100A12+neutrophils, all of which are elevated in EAD patient after LT. This cellular module is also verified in two independent datasets. Collectively, these results reveal the cellular characteristics of transplanted livers and the EAD-associated pathogenic cellular module at the single-cell level, offering new insights into the EAD occurrence after LT.
Auto-Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System
Authors: Schmidt Frank , Abdesselem Houari B. , Suhre Karsten , Sohail Muhammad U. , Al-Nesf Maryam , Bensmail Ilham , Mashod Fathima , Sarwath Hina , Bernhardt Joerg , Tan Ti-Myen , Morris Priscilla E , Schenck Edward J. , Price David , Vaikath Nishant N. , Mohamed-Ali Vidya , Al-Maadheed Mohammed , Arredouani Abdelilah , Decock Julie , Blackburn Jonathan M. , Choi Augustine M.K. , El-Agnaf Omar M.
Published: February 2022

The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully understood. The current investigation screened two independent cohorts of 97 COVID-19 patients (Discovery (Disc) cohort from Qatar (n = 49) and Replication (Rep) cohort from New York (n = 48)) utilizing high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (P ≤ 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients that served as controls. Both cohorts showed substantial similarities (r2= 0.73) and exhibited higher autoantibodies responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. KREX analysis of the specific IgG autoantibody responses indicates that the targeted host proteins are supposedly increased in COVID-19 patients. The autoantigen-autoantibody response was cross-validated for SPANXN4 and STK25 proteins using Uniprot BLASTP and sequence alignment tools. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19 associated male reproductive tract complications and warrants further research.

Significance Statement

Coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, has emerged as a global pandemic with a high morbidity rate and multiorgan complications. It is observed that the host immune system contributes to the varied responses to COVID-19 pathogenesis. Autoantibodies, immune system proteins that mistakenly target the body’s own tissue, may underlie some of this variation. We screened total IgG autoantibody responses against 1,318 human proteins in two COVID-19 patient cohorts. We observed several novel markers in COVID-19 patients that are associated with male fertility, such as sperm protein SPANXN4, STK25, and the apoptotic factor ATF4. Particularly, elevated levels of autoantibodies against the testicular tissue-specific protein SPANXN4 offer significant evidence of anticipating the protein role in COVID-19 associated male reproductive complications.