bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of sharing full versus averaged social information on social influence and estimation accuracy
Authors: Jayles Bertrand , Sire Clément , Kurvers Ralf H. J. M.
Published: July 2021

The recent developments of social networks and recommender systems have dramatically increased the amount of social information shared in human communities, challenging the human ability to process it. As a result, sharing aggregated forms of social information is becoming increasingly popular. However, it is unknown whether sharing aggregated information improves people’s judgments more than sharing the full available information. Here, we compare the performance of groups in estimation tasks when social information is fully shared versus when it is first averaged and then shared. We find that improvements in estimation accuracy are comparable in both cases. However, our results reveal important differences in subjects’ behaviour: (i) subjects follow the social information more when receiving an average than when receiving all estimates, and this effect increases with the number of estimates underlying the average; (ii) subjects follow the social information more when it is higher than their personal estimate than when it is lower. This effect is stronger when receiving all estimates than when receiving an average. We introduce a model that sheds light on these effects, and confirms their importance for explaining improvements in estimation accuracy in all treatments.
Dental biofilm and its ecological interrelationships in ovine periodontitis
Authors: Borsanelli Ana Carolina , Athayde Flávia R. F. , Agostinho Sabrina D. , Riggio Marcello P. , Dutra Iveraldo S.
Published: July 2021

Introduction. Periodontitis, one of the most common oral disorders in sheep, is caused by a mixed and opportunistic microbiota that severely affects the health and welfare of animals. However, little is known about the ecological processes involved and the composition of the microbiota associated with the development of the disease.

Hypothesis/Gap Statement. Using high-throughput sequencing of the 16S ribosomal RNA gene and network analysis it would be possible to discriminate the microbiomes of clinically healthy sheep and those with periodontitis and possibly identify the key microorganisms associated with the disease.

Aim. The present study aimed to characterise the composition of dental microbiomes and bacterial co-occurrence networks in clinically healthy sheep and animals with periodontitis.

Methodology. Dental biofilm samples were collected from ten sheep with periodontitis and ten clinically healthy animals. Bacteria were identified using high-throughput sequencing of the 16S ribosomal RNA gene.

Results. The most prevalent genera in the dental microbiota of sheep with periodontitis were

Petrimonas

,

Acinetobacter

,

Porphyromonas

and

Aerococcus

. In clinically healthy animals, the most significant genera were unclassified Pasteurellaceae, Pseudomonas, and Neisseria. Fusobacterium was found at high prevalence in the microbiomes of both groups. The dental microbiota of sheep in the two clinical conditions presented different profiles and the diversity and richness of bacteria was greater in the diseased animals. Network analyses showed the presence of a large number of antagonistic interactions between bacteria in the dental microbiota of animals with periodontitis, indicating the occurrence of a dysbiotic community. Through the interrelationships, members of the

Prevotella

genus are likely to be key pathogens, both in the dental microbiota of healthy animals and those with periodontitis.

Porphyromonas

stood out among the top three nodes with more centrality and the largest number of hubs in the networks of animals with periodontitis.

Conclusion. The dental biofilm microbiota associated with ovine periodontitis is dysbiotic and with significant antagonistic interactions, which discriminates healthy animals from diseased animals and highlights the importance of key bacteria, such as

Petrimonas

,

Porphyromonas

,

Prevotella

and

Fusobacterium

species.
Socioeconomic status effects on health vary between rural and urban Turkana
Authors: Lea Amanda J. , Waigwa Charles , Muhoya Benjamin , Lotukoi Francis , Peng Julie , Henry Lucas P. , Abhyankar Varada , Kamau Joseph , Martins Dino , Gurven Michael , Ayroles Julien F.
Published: July 2021

Background and objectives

Understanding the social determinants of health is a major goal in evolutionary biology and human health research. Low socioeconomic status (often operationalized as absolute material wealth) is consistently associated with chronic stress, poor health, and premature death in high income countries. However, the degree to which wealth gradients in health are universal—or are instead made even steeper under contemporary, post-industrial conditions—remains poorly understood.

Methodology

We quantified absolute material wealth and several health outcomes among a population of traditional pastoralists, the Turkana of northwest Kenya, who are currently transitioning toward a more urban, market-integrated lifestyle. We assessed whether wealth associations with health differed in subsistence-level versus urban contexts. We also explored the causes and consequences of wealth-health associations by measuring serum cortisol, potential sociobehavioral mediators in early life and adulthood, and adult reproductive success (number of surviving offspring).

Results

Higher socioeconomic status and greater material wealth predicts better self-reported health and more offspring in traditional pastoralist Turkana, but worse cardiometabolic health and fewer offspring in urban Turkana. We do not find robust evidence for either direct biological mediators (i.e., cortisol) or indirect sociobehavioral mediators (e.g., adult diet or health behaviors, early life experiences) of wealth-health relationships in either context.

Conclusions and implications

While social gradients in health are well-established in humans and animals across a variety of socioecological contexts, we show that the relationship between wealth and health can vary within a single population. Our findings emphasize that changes in economic and societal circumstances may directly alter how, why, and under what conditions socioeconomic status predicts health.

Lay summary

High socioeconomic status predicts better health and more offspring in traditional Turkana pastoralists, but worse health and fewer offspring in individuals of the same group living in urban centers. Together, our work shows that under different economic and societal circumstances, wealth effects on health may manifest in very different ways.
Effectiveness, acceptability and potential harms of peer support for self-harm in non-clinical settings: A systematic review
Authors: Seif Nada Abou , Bastien Rayanne John-Baptiste , Wang Belinda , Davies Jessica , Isaken Mette , Ball Ellie , Pitman Alexandra , Rowe Sarah
Published: July 2021

Background

Many people who have self-harmed prefer informal sources of support, or support from those with lived experience. However, little is known about whether peer support improves outcomes for people who have self-harmed, and what might be the risks of peer support interventions in non-clinical settings.

Objectives

The aims of this review are to examine the effectiveness, acceptability and potential risks of peer support for self-harm, and how these risks might be mitigated.

Methods

We searched two bibliographic databases and grey literature for papers published since 2000. We included peer support for self-harm that occurred in voluntary sector organisations, providing one-to-one or group support, or via moderated online peer support forums. We excluded peer support within clinical settings, peer support provided by relatives or friends who self-harm, or peer support from unmoderated online forums. Quality appraisal was conducted on included papers, and study findings were summarised using a narrative synthesis.

Results

Ten papers met the inclusion criteria for this review, and most (n=8) were conducted in the United Kingdom. Eight of the papers focused on peer support that was delivered through online mediums and two examined face-to-face self-harm recovery/support groups. Limited conclusions about the effectiveness of peer support interventions for self-harm can be made, as we found no studies comparing this to other treatments or a control group. Peer support for self-harm was found to be acceptable and was viewed as having a range of benefits including a reduction of loneliness, a sense of community and empowerment, improvements in interpersonal skills, and access to information and support. The most commonly perceived risk associated with peer support for self-harm was the potential for triggering self-harm. Other potential risks identified were being re-traumatised by listening to other people’s stories, not having the knowledge or skills to help others, and misunderstandings or disagreements with other peers/group members.

Conclusions

Our findings highlighted a range of benefits of being part of a group with very specific shared experiences. This justifies investment in the provision of such resources, supported by safeguards to mitigate the potential risks from peer support interventions. Suggestions include organisations using professional facilitators for groups, including trigger warnings for online forums, and providing regular supervision and training so that peers are prepared and feel confident to support vulnerable people whilst maintaining their own emotional health.
Vaccines against Covid-19, venous thromboembolism, and thrombocytopenia. A population-based retrospective cohort study
Authors: Laporte Joan-Ramon , Coma Ermengol , Fina Francesc , García-Eroles Luís , Vidal Xavier , Medina Manuel
Published: July 2021

Background

We aimed at estimating the risk of venous thromboembolism (VTE), thrombocytopenia (TCP), and VTE associated with TCP, by age and sex, after the first dose of both adenovirus vector-based and mRNA-based Covid-19 vaccines, and after the second dose of m-RNA vaccines.

Methods

In this population-based retrospective cohort study in the national health care databases in Catalonia, we examined three groups: 1 662 719 people 10 years of age and over vaccinated with the first dose of a Covid-19 vaccine, 622 778 with the second dose, and 190 616 diagnosed of Covid-19 in the same period (between1 January 2021 and 18 April 2021). The rates of various clinical presentations of VTE and TCP were compared with those in the reference population (7 013 040 people served by the health care system in 2019). The two primary outcomes were the observed 21 day rate of a composite variable of cerebral venous sinus thrombosis, mesenteric thrombosis, portal vein thrombosis, or any venous thromboembolism (VTE) associated with thrombocytopenia (TCP), and the rate of any VTE associated with TCP (VTE+TCP). Analyses were standardised by age and sex.

Results

The 21 day rate per 100 000 of the primary composite variable was 2.15 in the reference population, 5.65 following the first vaccine dose (standardised difference, 2.53 (95% CI [CI], 1.04 to 4.00), and 7.23 following the second dose (standardised difference, 4.07 (95% CI, 1.43 to 6.70). The event rates of VTE+TCP and of all the secondary variables showed the same patterns.

Excess event rates were higher in men than in women, and they were not especially increased in any particular age group. All Covid-19 vaccines were associated with increased rates of the outcome variables.

Excess event rates were much higher in the Covid-19 cohort (35.60 per 100 000 (95% CI, 26.15 to 45.06).

Conclusions

We observed increases of rates of venous thromboembolism in usual and unusual anatomical sites and of thrombocytopenia in recipients of both adenovirus vector and mRNA vaccines against Covid-19. Excess rates were higher in men than in women and they were not particularly elevated in any specific age group.
Bayesian Inference of Joint Coalescence Times for Sampled Sequences
Authors: Simon Helmut , Huttley Gavin
Published: July 2021

The site frequency spectrum (SFS) is a commonly used statistic to summarize genetic variation in a sample of genomic sequences from a population. Such a genomic sample is associated with an imputed genealogical history with attributes such as branch lengths, coalescence times and the time to the most recent common ancestor (TMRCA) as well as topological and combinatorial properties. We present a Bayesian model for sampling from the joint posterior distribution of coalescence times conditional on the SFS associated with a sample of sequences in the absence of selection. In this model, the combinatorial properties of a genealogy, which is represented as a coalescent tree, are expressed as matrices. This facilitates the calculation of likelihoods and the effective sampling of the entire space of tree structures according to the Equal Rates Markov (or Yule-type) measure. Unlike previous methods, assumptions as to the type of stochastic process that generated the genealogical tree are not required. Novel approaches to defining both uninformative and informative prior distributions are employed. The uncertainty in inference due to the stochastic nature of mutation and the unknown tree structure is expressed by the shape of the posterior distributions. The method is implemented using the general purpose Markov Chain Monte Carlo software PyMC3. From the sampled posterior distribution of coalescence times, one can also infer related quantities such as the number of ancestors of a sample at a given time in the past (ancestral distribution) and the probability of specific relationships between branch lengths (for example, that the most recent branch is longer than all the others). The performance of the method is evaluated against simulated data and is also applied to historic mitochondrial data from the Nuu-Chah-Nulth people of North America. The method can be used to obtain estimates of the TMRCA of the sample. The relationship of these estimates to those given by “Thomson’s estimator” is explored.
ETAS®50 Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages
Authors: Shirato Ken , Takanari Jun , Kizaki Takako
Published: July 2021

Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. ETAS®50, a standardized extract ofAsparagus officinalisstem, is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide- and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of ETAS®50 on pro-inflammatory responses in S1-stimulated murine peritoneal exudate macrophages. Co-treatment of the cells with ETAS®50 significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. ETAS®50 also markedly suppressed the S1-induced transcription of IL-6 and IL-1β. However, among the TLR4 signaling proteins, ETAS®50 did not affect the degradation of inhibitor κBα, nuclear translocation of nuclear factor-κB p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, ETAS®50 significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1β by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that ETAS®50 attenuates S1-induced IL-6 and IL-1β production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, ETAS®50 may be beneficial in regulating excessive inflammation in patients with COVID-19.
Plasmid supercoiling decreases during the dark phase in cyanobacteria: a clarification of the interpretation of chloroquine-agarose gels
Authors: Rüdiger Salima , Rediger Anne , Kölsch Adrian , Dienst Dennis , Axmann Ilka M. , Machné Rainer
Published: July 2021

In cyanobacteria DNA supercoiling varies over the diurnal light/dark cycle and is integrated with the circadian transcription program and (Woelfle et al. [2007], Vijayan et al. [2009], PNAS). Specifically, Woelfle et al. have reported that DNA supercoiling of an endogenous plasmid became progressively higher during prolonged dark phases in Synechococcus elongatus PCC 7942. This is counterintuitive, since higher levels of negative DNA supercoiling are commonly associated with exponential growth and high metabolic flux. Vijayan et al. then have reverted the interpretation of plasmid mobility on agarose gels supplemented with chloroquine diphosphate (CQ), but not further discussed the differences. Here, we set out to clarify this open issue in cyanobacterial DNA supercoiling dynamics. We first re-capitulate Keller’s band counting method (1975, PNAS) using CQ instead of ethidium bromide as the intercalating agent. A 500x–1000x higher CQ concentration is required in the DNA relaxation reaction (topoisomerase I) than in the agarose gel buffer to quench all negative supercoiling of pUC19 extracted from Escherichia coli. This is likely due to the dependence of both, the DNA binding affinity of CQ and the induced DNA unwinding angle, on the ionic strength of the buffer. Lower levels of CQ were required to fully relax in vivo pUC19 supercoiling than were used by Woelfle et al. Next, we analyzed the in vivo supercoiling of endogenous plasmids of Synechocystis sp. PCC 6803, at two different CQ concentrations. These experiments indicate that negative supercoiling of plasmids does not increase but decreases in the dark phase, and progressively decreases further in prolonged darkness.
The structural role of bacterial eDNA in the formation of biofilm streamers
Authors: Secchi Eleonora , Savorana Giovanni , Vitale Alessandra , Eberl Leo , Stocker Roman , Rusconi Roberto
Published: July 2021

Across diverse habitats, bacteria are mainly found as biofilms, surface-attached communities embedded in a self-secreted matrix of extracellular polymeric substances (EPS), which enhances bacterial resistance to antimicrobial treatment and mechanical stresses. In the presence of flow and geometric constraints such as corners or constrictions, biofilms take the form of long, suspended threads known as streamers, which bear important consequences in industrial and clinical settings by causing clogging and fouling. The formation of streamers is thought to be driven by the viscoelastic nature of the biofilm matrix. Yet, little is known about the structural composition of streamers and how it affects their mechanical properties. Here, using a microfluidic platform that allows growing and precisely examining biofilm streamers, we show that extracellular DNA (eDNA) constitutes the backbone and is essential for the mechanical stability ofPseudomonas aeruginosa’ s streamers. This finding is supported by the observations that DNA-degrading enzymes prevent the formation of streamers and clear already formed ones, and that the antibiotic ciprofloxacin promotes their formation by increasing the release of eDNA. Furthermore, using mutants for production of the exopolysaccharide Pel, an important component ofP. aeruginosa’ s EPS, we reveal a new, although indirect role of Pel, in tuning the mechanical properties of the streamers. Taken together, these results highlight the importance of eDNA and of its interplay with Pel in determining the mechanical properties ofP. aeruginosastreamers, and suggest that targeting the composition of streamers can be an effective approach to control the formation of these biofilm structures.
A bacterial dynamin-like protein confers a novel phage resistance strategy on the population level in Bacillus subtilis
Authors: Guo Lijun , Sattler Laura , Graumann Peter , Bramkamp Marc
Published: July 2021

Bacillus subtilis DynA is a member of the dynamin superfamily, involved in membrane remodeling processes. DynA was shown to catalyze full membrane fusion and it plays a role in membrane surveillance against antibiotics. We show here that DynA also provides a novel resistance mechanism against phage infection. Cells lacking DynA are efficiently lysed after phage infection and virus replication. DynA does not prevent phage infection and replication in individual cells, but significantly delays host cell lysis, thereby slowing down the release of phage progeny from the host cells. During the process, DynA forms large, almost immobile clusters on the cell membrane that seem to support membrane integrity. Single molecule tracking revealed a shift of freely diffusive molecules within the cytosol towards extended, confined motion at the cell membrane following phage induction. Thus, the bacterial dynamins are the first anti-phage system reported to delay host cell lysis and the last line of defense of a multilayered antiviral defense. DynA is therefore providing protective effects on the population, but not on single cell level.
FH loss in RPE cells causes retinal degeneration in a human RPE-porcine retinal explant co-culture model
Authors: Armento Angela , Murali Aparna , Marzi Julia , Arrango-Gonzalez Blanca , Kilger Ellen , Clark Simon J , Schenke-Layland Katja , Ramlogan-Steel Charmaine A , Steel Jason C , Ueffing Marius
Published: July 2021

Age-related Macular degeneration (AMD) is a degenerative disease of the macula affecting the elderly population. Treatment options are limited, partly due to the lack of understanding of AMD pathology and the sparse availability of research models, that replicate the complexity of the human macula and the intricate interplay of the genetic, aging and life-style risk factors contributing to AMD. One of the main genetic risks associated with AMD is located on Complement Factor H (CFH) gene, leading to an amino acid substitution in the FH protein (Y402H). However, the mechanism of how this FH variant promotes the onset of AMD remains unclear. Previously, we have shown that FH deprivation in RPE cells, via CFH silencing, leads to increased inflammation, metabolic impairment and vulnerability towards oxidative stress. In this study, we established a novel co-culture model comprised of CFH silenced RPE cells and porcine retinal explants derived from the visual streak of the porcine eyes, closely resembling the human macula. We show that retinae exposed to FH-deprived RPE cells show signs of retinal degeneration, with rod cells being the first cells to undergo degeneration. Moreover, via Raman analyses, we observe that the main changes involve the mitochondria and lipid composition of the co-cultured retinae upon FH loss. Interestingly, the detrimental effects of FH loss in RPE cells on the neuroretina were independent of glial cell activation and external complement sources. Moreover, we show that the co-culture model is also suitable for human retinal explants, and we observed a similar trend when RPE cells deprived of FH were co-cultured with human retinal explants from a single donor eye. Our findings highlight the importance of RPE derived FH for retinal homeostasis and provide a valuable model for AMD research.
N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry
Authors: Wang Dongxia , Zhou Bin , Keppel Theodore , Solano Maria , Baudys Jakub , Goldstein Jason , Finn M.G. , Fan Xiaoyu , Chapman Asheley P. , Bundy Jonathan L. , Woolfitt Adrian R. , Osman Sarah , Pirkle James L. , Wentworth David E. , Barr John R.
Published: July 2021

N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.
African Swine Fever Virus and host response - transcriptome profiling of the Georgia 2007/1 strain and porcine macrophages
Authors: Cackett Gwenny , Portugal Raquel , Matelska Dorota , Dixon Linda , Werner Finn
Published: July 2021

African swine fever virus (ASFV) has a major global economic impact. With a case fatality in domestic pigs approaching 100%, it currently presents the largest threat to animal farming. Although genomic differences between attenuated and highly virulent ASFV strains have been identified, the molecular determinants for virulence at the level of gene expression have remained opaque. Here we characterise the transcriptome of ASFV genotype II Georgia 2007/1 (GRG) during infection of the physiologically relevant host cells, porcine macrophages. In this study we applied Cap Analysis Gene Expression sequencing (CAGE-seq) to map the 5’ ends of viral mRNAs at 5 and 16 hours post-infection. A bioinformatics analysis of the sequence context surrounding the transcription start sites (TSSs) enabled us to characterise the global early and late promoter landscape of GRG. We compared transcriptome maps of the GRG isolate and the lab-attenuated BA71V strain that highlighted GRG virulent-specific transcripts belonging to multigene families, including two predicted MGF 100 genes I7L and I8L. In parallel, we monitored transcriptome changes in the infected host macrophage cells. Of the 9,384 macrophage genes studied, transcripts for 652 host genes were differentially regulated between 5 and 16 hours-post-infection compared with only 25 between uninfected cells and 5 hours post-infection. NF-kB activated genes and lysosome components like S100 were upregulated, and chemokines such as CCL24, CXCL2, CXCL5 and CXCL8 downregulated.

Importance

African swine fever virus (ASFV) causes haemorrhagic fever in domestic pigs with case fatality rates approaching 100%, and no approved vaccines or antivirals. The highly-virulent ASFV Georgia 2007/1 strain (GRG) was the first isolated when ASFV spread from Africa to the Caucasus region in 2007. Then spreading through Eastern Europe, and more recently across Asia. We used an RNA-based next generation sequencing technique called CAGE-seq to map the starts of viral genes across the GRG DNA genome. This has allowed us to investigate which viral genes are expressed during early or late stages of infection and how this is controlled, comparing their expression to the non-virulent ASFV-BA71V strain to identify key genes that play a role in virulence. In parallel we investigated how host cells respond to infection, which revealed how the ASFV suppresses components of the host immune response to ultimately win the arms race against its porcine host.
The benefits of merging passive and active tracking approaches: new insights into riverine migration by salmonid smolts
Authors: Chavarie Louise , Honkanen Hannele M. , Newton Matthew , Lilly Jessie M. , Greetham Hannah R. , Adams Colin E.
Published: July 2021

The process of smolting is a critical phase in the life-cycle of anadromous salmonids and it has been associated with substantial rates of mortality. Survival during freshwater and marine migration is known to have population level effects, thus an understanding of the patterns of mortality has the potential to yield important insights into population bottlenecks. Despite important advancements in tracking techniques, the specifics of mortality events in anadromous salmonids during their initial migration to sea remains somewhat elusive. Here, we develop a framework combining spatial and temporal detections of smolt riverine migration from two tracking techniques, which enable inferences to be made about mortality locations, causes, and rates. In this study, we demonstrate that during their initial riverine transitional phase, smolts were particularly vulnerable to predators. Specifically, avian predation appeared to be the main cause of mortality (42%), although piscine predation events were not trivial (14%). Our results suggested some direct and indirect tagging-induced mortality (e.g., through increased predation vulnerability), which highlights the importance of determining tagging mortality in a telemetry study to ensure adequate interpretation of migration success. Overall, by estimating migration loss and its variability, our study framework should help to guide management actions to mitigate the widespread population declines these species are currently facing.
A dual barcoding approach to bacterial strain nomenclature: Genomic taxonomy ofKlebsiella pneumoniaestrains
Authors: Hennart Melanie , Guglielmini Julien , Maiden Martin C.J. , Jolley Keith A. , Criscuolo Alexis , Brisse Sylvain
Published: July 2021

Sublineages within microbial species can differ widely in their ecology and pathogenicity, and their precise definition is important in basic research and industrial or public health applications. Whereas the classification and naming of prokaryotes is unified at the species level and higher taxonomic ranks, universally accepted definitions of sublineages within species are largely missing, which introduces confusion in population biology and epidemiological surveillance.

Here we propose a broadly applicable genomic classification and nomenclature approach for bacterial strains, using the prominent public health threatKlebsiella pneumoniaeas a model. Based on a 629-gene core genome multilocus sequence typing (cgMLST) scheme, we devised a dual barcoding system that combines multilevel single linkage (MLSL) clustering and life identification numbers (LIN). Phylogenetic and clustering analyses of >7,000 genome sequences captured population structure discontinuities, which were used to guide the definition of 10 infra-specific genetic dissimilarity thresholds. The widely used 7-gene multilocus sequence typing (MLST) nomenclature was mapped onto MLSL sublineages (threshold: 190 allelic mismatches) and clonal group (threshold: 43) identifiers for backwards nomenclature compatibility. The taxonomy is publicly accessible through a community-curated platform (https://bigsdb.pasteur.fr/klebsiella), which also enables external users’ genomic sequences identification.

The proposed strain taxonomy combines two phylogenetically informative barcodes systems that provide full stability (LIN codes) and nomenclatural continuity with previous nomenclature (MLSL). This species-specific dual barcoding strategy for the genomic taxonomy of microbial strains is broadly applicable and should contribute to unify global and cross-sector collaborative knowledge on the emergence and microevolution of bacterial pathogens.
A machine learning based analysis to probe the relationship between odorant structure and olfactory behaviour inC. elegans
Authors: Vishnoi Aayushi , Sharma Rati
Published: July 2021

The chemical basis of smell remains an unsolved problem, with ongoing studies mapping perceptual descriptor data from human participants to the chemical structures using computational methods. These approaches are, however, limited by linguistic capabilities and inter-individual differences in participants. We use olfactory behaviour data from the nematodeC. elegans, which has isogenic populations in a laboratory setting, and employ machine learning approaches for a binary classification task predicting whether or not the worm will be attracted to a given monomolecular odorant. Among others, we use architectures based on Natural Language Processing methods on the SMILES representation of chemicals for molecular descriptor generation and show that machine learning algorithms trained on the descriptors give robust prediction results. We further show, by data augmentation, that increasing the number of samples increases the accuracy of the models. From this detailed analysis, we are able to achieve accuracies comparable to that in human studies and infer that there exists a non trivial relationship between the features of chemical structures and the nematode’s behaviour.
Correcting machine learning models using calibrated ensembles with ‘mlensemble’
Authors: Konopka Tomasz
Published: July 2021

Machine learning models in bioinformatics are often trained and used within the scope of a single project, but some models are also reused across projects and deployed in translational settings. Over time, trained models may turn out to be maladjusted to the properties of new data. This creates the need to improve their performance under various constraints. This work explores correcting models without retraining from scratch and without accessing the original training data. It uses a taxonomy of strategies to guide the development of a software package, ‘mlensemble’. Key features include joining heterogeneous models into ensembles and calibrating ensembles to the properties of new data. These are well-established techniques but are often hidden within more complex tools. By exposing them to the application level, the package enables analysts to use expert knowledge to adjust models whenever needed. Calculations with imaging data show benefits when the noise characteristics of the training and the application datasets differ. An example using genomic single-cell data demonstrates model portability despite batch effects. The generality of the framework makes it applicable also in other subject domains.
Counting actin in contractile rings reveals novel contributions of cofilin and type II myosins to fission yeast cytokinesis
Authors: Malla Mamata , Pollard Thomas D. , Chen Qian
Published: July 2021

Cytokinesis by animals, fungi and amoebas depends on actomyosin contractile rings, which are stabilized by continuous turnover of actin filaments. Remarkably little is known about the amount of polymerized actin in contractile rings, so we used low concentration of GFP-Lifeact to count total polymerized actin molecules in the contractile rings of live fission yeast cells. Contractile rings of wild-type cells accumulated polymerized actin molecules at 4,900/min to a peak number of ∼198,000 followed by a loss of actin at 5,400/min throughout ring constriction. In adf1-M3 mutant cells with cofilin that severs actin filaments poorly, contractile rings accumulated polymerized actin at twice the normal rate and eventually had almost two-fold more actin along with a proportional increase in type II myosins Myo2, Myp2 and formin Cdc12. Although 30% of adf1-M3 mutant cells failed to constrict their rings fully, the rest lost actin from the rings at the wild-type rates. Mutations of type II myosins Myo2 and Myp2 reduced contractile ring actin filaments by half and slowed the rate of actin loss from the rings.
Effects of theta transcranial alternating current stimulation (tACS) on exploration and exploitation during uncertain decision-making
Authors: Wischnewski Miles , Compen Boukje
Published: July 2021

Exploring ones surroundings may yield unexpected rewards, but is associated with uncertainty and risk. Alternatively, exploitation of certain outcomes is related to low risk, yet potentially better outcomes remain unexamined. As such, risk-taking behavior depends on perceived uncertainty and a trade-off between exploration-exploitation. Previously, it has been suggested that risk-taking may relate to theta activity in the prefrontal cortex. Furthermore, previous studies hinted at a relationship between a right-hemispheric bias in frontal theta asymmetry and risky behavior. In the present double-blind sham-controlled within-subject study, we applied bifrontal transcranial alternating current stimulation (tACS) at the theta frequency (5 Hz) on eighteen healthy volunteers during a gambling task. Two tACS montages with either left-right or posterior-anterior current flow were employed at an intensity of 1 mA. Results showed that, compared to sham, theta tACS increased perceived uncertainty irrespective of current flow direction. Despite this observation, no direct effect of tACS on exploration behavior and general risk-taking was observed. Furthermore, frontal theta asymmetry was more right-hemispherically biased after posterior-anterior tACS, compared to sham. Finally, we used electric field simulation to identify which regions were targeted by the tACS montages as an overlap in regions may explain why the two montages resulted in comparable outcomes. Our findings provide a first step towards understanding the relationship between frontal theta oscillations and different features of risk-taking.

Highlights

–

Risk taking is related to uncertainty, exploration and exploitation

–

Frontal theta tACS was applied to modulate aspects of risk taking

–

tACS did increase perceived uncertainty, but not exploration behavior

–

tACS induced a right hemispheric shift in frontal theta asymmetry
The Alzheimer’s gene SORL1 is a regulator of endosomal traffic and recycling in human neurons
Authors: Mishra Swati , Knupp Allison , Szabo Marcell P. , Williams Charles A. , Kinoshita Chizuru , Hailey Dale W. , Wang Yuliang , Young Jessica E.
Published: July 2021

Background

Loss of the Sortilin-related receptor 1 (SORL1) gene seems to act as a causal event for Alzheimer’s disease (AD). Recent studies have established that loss of SORL1, as well as mutations in autosomal dominant AD genes APP and PSEN1/2, pathogenically converge by swelling early endosomes, AD’s cytopathological hallmark. Acting together with the retromer trafficking complex, SORL1 has been shown to regulate the recycling of the amyloid precursor protein (APP) out of the endosome, contributing to endosomal swelling and to APP misprocessing. We hypothesized that SORL1 plays a broader role in neuronal endosomal recycling and used human induced pluripotent stem cell derived neurons (hiPSC-Ns) to test this hypothesis. We examined endosomal recycling of three transmembrane proteins linked to AD pathophysiology: APP, the BDNF receptor Tropomyosin-related kinase B (TRKB), and the glutamate receptor subunit AMPA1 (GLUA1).

Methods

We used isogenic hiPSCs engineered to have SORL1 depleted or to have enhanced SORL1 expression. We differentiated neurons from these cell lines and mapped the trafficking of APP, TRKB and GLUA1 within the endosomal network using confocal microscopy. We also performed cell surface recycling and lysosomal degradation assays to assess the functionality of the endosomal network in both SORL1 depleted and overexpressing neurons. Finally, we analyzed alterations in gene expression in SORL1 depleted neurons using RNA-sequencing.

Results

We find that as with APP, endosomal trafficking of GLUA1 and TRKB is impaired by loss of SORL1. We show that trafficking of all three cargo to late endosomes and lysosomes is affected by manipulating SORL1 expression. We also show that depletion of SORL1 significantly impacts the endosomal recycling pathway for APP and GLUA1 at the level of the recycling endosome and trafficking to the cell surface. This has a functional effect on neuronal activity as shown by multi-electrode array (MEA). Conversely, increased SORL1 expression enhances endosomal recycling for APP and GLUA1. Our unbiased transcriptomic data further support SORL1’s role in endosomal recycling. We observe altered expression networks that regulate cell surface trafficking and neurotrophic signaling in SORL1 depleted neurons.

Conclusion

Collectively, and together with other recent observations, these findings suggest that SORL1 is a broad regulator of retromer-dependent endosomal recycling in neurons, a conclusion that has both pathogenic and therapeutic implications for Alzheimer’s disease.
Alzheimer’s Disease Classification Accuracy is Improved by MRI Harmonization based on Attention-Guided Generative Adversarial Networks
Authors: Sinha Surabhi , Thomopoulos Sophia I. , Lam Pradeep , Muir Alexandra , Thompson Paul M.
Published: July 2021

Alzheimer’s disease (AD) accounts for 60% of dementia cases worldwide; patients with the disease typically suffer from irreversible memory loss and progressive decline in multiple cognitive domains. With brain imaging techniques such as magnetic resonance imaging (MRI), microscopic brain changes are detectable even before abnormal memory loss is detected clinically. Patterns of brain atrophy can be measured using MRI, which gives us an opportunity to facilitate AD detection using image classification techniques. Even so, MRI scanning protocols and scanners differ across studies. The resulting differences in image contrast and signal to noise make it important to train and test classification models on multiple datasets, and to handle shifts in image characteristics across protocols (also known asdomain transferordomain adaptation). Here, we examined whether adversarial domain adaptation can boost the performance of a Convolutional Neural Network (CNN) model designed to classify AD. To test this, we used an Attention-Guided Generative Adversarial Network (GAN) to harmonize images from three publicly available brain MRI datasets - ADNI, AIBL and OASIS - adjusting for scanner-dependent effects. Our AG-GAN optimized a joint objective function that included attention loss, pixel loss, cycle-consistency loss and adversarial loss; the model was trained bidirectionally in an end-to-end fashion. For AD classification, we adapted the popular 2D AlexNet CNN to handle 3D images. Classification based on harmonized MR images significantly outperformed classification based on the three datasets in non-harmonized form, motivating further work on image harmonization using adversarial techniques.
AJILE12: Long-term naturalistic human intracranial neural recordings and pose
Authors: Peterson Steven M. , Singh Satpreet H. , Dichter Benjamin , Scheid Michael , Rao Rajesh P. N. , Brunton Bingni W.
Published: July 2021

Understanding the neural basis of human movement in naturalistic scenarios is critical for expanding neuroscience research beyond constrained laboratory paradigms. Here, we describe ourAnnotated Joints in Long-term Electrocorticography for 12 human participants(AJILE12) dataset, the largest human neurobehavioral dataset that is publicly available; the dataset was recorded opportunistically during passive clinical epilepsy monitoring. AJILE12 includes synchronized intracranial neural recordings and upper body pose trajectories across 55 semi-continuous days of naturalistic movements, along with relevant metadata, including thousands of wrist movement events and annotated behavioral states. Neural recordings are available at 500 Hz from at least 64 electrodes per participant, for a total of 1280 hours. Pose trajectories at 9 upper-body keypoints were estimated from 118 million video frames. To facilitate data exploration and reuse, we have shared AJILE12 on The DANDI Archive in the Neurodata Without Borders (NWB) data standard and developed a browser-based dashboard.
Determination of best Raman spectroscopy spatial offsets for transcutaneous bone quality assessments in human hands
Authors: Chen Keren , Massie Christine , Awad Hani A. , Berger Andrew J.
Published: July 2021

Spatially offset Raman spectroscopy (SORS) is able to detect bone signal transcutaneously and could assist in predicting bone fracture risk. Criteria for optimal source-detector offsets for transcutaneous human measurements, however, are not well-established. Although larger offsets yield a higher percentage of bone signal, the absolute amount of bone signal decreases. Spectral unmixing into bone, adipose, and non-adipose components was employed to quantify changes in bone signal to noise ratio across a range of offsets, and optimal offsets for phalanx and metacarpal measurements were determined. The bone signal to noise ratio was maximized at offsets ranging from 4-6 mm.
Interactive effects of herbivory and the level and fluctuations of nutrient availability on dominance of alien plants in synthetic native communities
Authors: Li Yanjun , Gao Yingzhi , van Kleunen Mark , Liu Yanjie
Published: July 2021

Numerous studies have highlighted the role of nutrient availability and fluctuations therein for invasion success of alien plants. Others also highlighted the role of herbivores in invasion success. However, how herbivory and the level and fluctuations in nutrient availability interact in driving alien plant invasion into resident communities remains largely unexplored.

We grew eight invasive alien species as target species in pot□mesocosms with five different synthetic native communities in a three-factorial design with two levels of nutrient availability (low vs high), two levels of nutrient fluctuations (constant vs pulsed) and two levels of herbivory (with vs without).

The relative biomass production of the alien target plants decreased in response to an increase in nutrient availability, and increased in response to the presence of herbivores. Furthermore, herbivory could interact with changes in nutrient availability and nutrient fluctuations to affect the dominance of the alien target species (a marginally significant interaction; 90% CIs: [0.125, 2.712]).

Our multispecies experiment indicates that herbivory could mediate the interactive effect of nutrient enrichment and variability in nutrient supply on invasion of alien plants into native communities. Therefore, we recommend that studies testing the fluctuating resources hypothesis should also consider interactive effect of other trophic levels.