bluuebunny/crossref_metadata_2025 huggingface dataset:
CertificateChain: decentralized healthcare training certificate management system using blockchain and smart contracts
Authors: Tellew Jeffrey , Kuo Tsung-Ting
Published: March 2022

Objective

Managing training certificates is an important issue in research that can lead to serious issues if not addressed properly. For institutions that currently do not have a dedicated management system for these training certificates, a central database is the most typical solution. However, such a system suffers from several risks, such as a single-point-of-failure.

Materials and Methods

To address this issue, we developed and evaluated CertificateChain, a decentralized training certificate management system by using peer-to-peer blockchain and automated smart contracts. We developed an efficient certificate dividing-and-merging algorithm to overcome the transaction size limit on blockchain.

Results

We performed experiments on the system to evaluate its performance, then created a web app and tested the system in a real-world scenario. CertificateChain scaled linearly in terms of time compared with the total number of certificates added and could be quickly queried for existing data stored on-chain.

Discussion

CertificateChain was able to store and retrieve the training certificates on the blockchain network, with limitations including a comparative analysis of other systems, evaluation of different consensus protocols, examining certificates off-chain, a thorough comparison with a centralized system, and the extension to the main public Ethereum network.

Conclusion

We believe that these results indicate that blockchain technology could be a viable decentralized alternative to traditional databases in this use case. Our software is publicly available at: https://doi.org/10.5281/zenodo.6257094.
Inorganic phosphate self-sufficient whole-cell biocatalysts containing two co-expressed phosphorylases facilitate cellobiose production
Authors: Wang Lei , Zheng Peng , Hu Meirong , Tao Yong
Published: March 2022

Cellobiose, a natural disaccharide, attracts extensive attention as a potential functional food/feed additive. In this study, we present an inorganic phosphate (Pi) self-sufficient biotransformation system to produce cellobiose by co-expressing sucrose phosphorylase (SP) and cellobiose phosphorylase (CBP). The Bifidobacterium adolescentis SP (BASP) and Cellvibrio gilvus CBP (CGCBP) were co-expressed in Escherichia coli. Escherichia coli cells containing BASP and CGCBP were used as whole-cell catalysts to convert sucrose and glucose to cellobiose. The effects of reaction pH, temperature, Pi concentration, and substrate concentration were investigated. In the optimum biotransformation conditions, 800 mM cellobiose was produced from 1.0 M sucrose, 1.0 M glucose, and 50 mM Pi, within 12 hr. The by-product fructose and residual substrate (sucrose and glucose) were efficiently removed by treatment with yeast, to help purify the product cellobiose. The wider applicability of this Pi self-sufficiency strategy was demonstrated in the production of laminaribiose by co-expressing SP and laminaribiose phosphorylase. This study suggests that the Pi self-sufficiency strategy through co-expressing two phosphorylases has the advantage of great flexibility for enhanced production of cellobiose (or laminaribiose).
A case of double appendix and cecum in an infant – case report
Authors: Habib Murad , Burki Sadia Asmat , Chaudhary Muhammad Amjad
Published: March 2022

The duplication of the cecum and appendix is a rare congenital anomaly found incidentally on exploration for another indication. We present here a case of a female child at 18 months of life, who was a diagnosed case of anorectal malformation with a persistent cloaca and at the time of the surgery, duplication of the appendix and cecum was found. Both the appendices were attached to the cecum with a separate base. Thus, appendectomies and a sigmoid divided colostomy were performed.
Early warning of precessing neutron-star black hole binary mergers with the near-future gravitational-wave detectors
Authors: Tsutsui T , Nishizawa A , Morisaki S
Published: March 2022

Since gravitational and electromagnetic waves from a compact binary coalescence carry independent information about the source, the joint observation is important for understanding the physical mechanisms of the emissions. Rapid detection and source localization of a gravitational wave signal are crucial for the joint observation to be successful. For a signal with a high signal-to-noise ratio, it is even possible to detect it before the merger, which is called early warning. In this article, we estimate the performances of the early warning for neutron-star black hole binaries, considering the precession effect of a binary orbit, with the near-future detectors such as A+, AdV+, KAGRA+ , and Voyager. We find that a gravitational wave source can be localized in $100 \, \rm {deg^2}$ on the sky before ∼10–$40 \, \rm {s}$ of time to merger once per year.
New LZ and PW(Z) relations of RR Lyrae stars calibrated withGaiaEDR3 parallaxes
Authors: Garofalo A , Delgado H E , Sarro L M , Clementini G , Muraveva T , Marconi M , Ripepi V
Published: March 2022

We present new luminosity–metallicity (LZ; $M_{V}\!-\!\rm [Fe/H]$ and $M_{G}\!-\!\rm [Fe/H]$) relations and, for the first time, empirical, Gaia three-band (G, GBP, GRP) period-Wesenheit-metallicity (PWZ) relations of RR Lyrae stars (RRLs) derived using a hierarchical Bayesian approach and new accurate parallaxes published for these variables in the Gaia Early Data Release 3 (EDR3). In a previous study, we obtained Bayesian hierarchically derived LZ relations from a sample of about four hundred Milky Way field RRLs with G-band light curves and trigonometric parallaxes published in the Gaia Data Release 2 (DR2), using V mean magnitudes, metallicities, absorptions, and pulsation periods available in the literature. We now extend that study in two directions. First, we update our previous results using trigonometric parallaxes from Gaia EDR3 and incorporate the Bayesian analysis of a first empirical PWZ relation derived using those field RRLs with G, GBP and GRP time-series photometry available in Gaia DR2. Secondly, we use Bayesian inference to derive LZ relations and empirical PW Gaia three-band relations from 385 RRLs belonging to 15 Milky Way globular clusters (GC) with literature-compiled spectroscopic metallicities ranging from −0.36 to −2.39 dex and prior distances extending from 2.2 to 41.2 kpc. From the samples of RRLs analysed in this paper we infer a mean Gaia EDR3 zero-point offset of −0.028 mas with median values ranging from −0.033 (LZ and PWZ models for field stars) to −0.024 mas (LZ model in the V band for GC RRLs).
Gemini NIFS survey of feeding and feedback processes in nearby active galaxies – VI. Stellar populations
Authors: Riffel Rogério , Dahmer-Hahn Luis G , Riffel Rogemar A , Storchi-Bergmann Thaisa , Dametto Natacha Z , Davies Richard , Burtscher Leonard , Bianchin Marina , Ruschel-Dutra Daniel , Ricci Claudio , Rosario David J
Published: March 2022

We use Gemini Near-Infrared Integral Field Spectrograph (NIFS) adaptive optics assisted data cubes to map the stellar population of the inner few hundred parsec of a sample of 18 nearby Seyfert galaxies. The near-infrared light is dominated by the contribution of young to intermediate-age stellar populations, with light-weighted mean ages ‹t›L ≲ 1.5 Gyr. Hot dust (HD) emission is centrally peaked (in the unresolved nucleus), but it is also needed to reproduce the continuum beyond the nucleus in nearly half of the sample. We have analysed the stellar population properties of the nuclear region and their relation with more global properties of the galaxies. We find a correlation between the X-ray luminosity and the contributions from the HD, featureless continuum (FC), and reddening AV. We attribute these correlations to the fact that all these properties are linked to the mass accretion rate to the active galactic nuclei (AGNs). We also find a correlation of the bolometric luminosity log($L_{\rm Bol_{\rm obs}}$) with the mass-weighted mean age of the stellar population, interpreted as due a delay between the formation of new stars and the triggering/feeding of the AGN. The gas reaching the supermassive black hole is probably originated from mass loss from the already somewhat evolved intermediate-age stellar population (‹t›L ≲ 1.5 Gyr). In summary, our results show that there is a significant fraction of young to intermediate-age stellar populations in the inner few 100 pc of active galaxies, suggesting that this region is facing a rejuvenation process in which the AGN, once triggered, precludes further star formation, in the sense that it can be associated with the lack of new star formation in the nuclear region.
Out of the blue: Phototropins of the leaf vascular bundle sheath mediate the regulation of leaf hydraulic conductance by blue light
Authors: Grunwald Yael , Gosa Sanbon Chaka , Torne-Srivastava Tanmayee , Moran Nava , Moshelion Menachem
Published: March 2022

The Arabidopsis (Arabidopsis thaliana) leaf veins bundle-sheath cells (BSCs)—a selective barrier to water and solutes entering the mesophyll—increase the leaf radial hydraulic conductance (Kleaf) by acidifying the xylem sap by their plasma membrane H+-ATPase,  AHA2. Based on this and on the BSCs’ expression of phototropins PHOT1 and PHOT2, and the known blue light (BL)-induced Kleaf increase, we hypothesized that, resembling the guard cells, BL perception by the BSCs’ phots activates its H+-ATPase, which, consequently, upregulates Kleaf. Indeed, under BL, the Kleaf of the knockout mutant lines phot1-5, phot2-1, phot1-5 phot2-1, and aha2-4 was lower than that of the wild-type (WT). BSC-only-directed complementation of phot1-5 or aha2-4 by PHOT1 or AHA2, respectively, restored the BL-induced Kleaf increase. BSC-specific silencing of PHOT1 or PHOT2 prevented such Kleaf increase. A xylem-fed kinase inhibitor (tyrphostin 9) replicated this also in WT plants. White light—ineffective in the phot1-5 mutant—acidified the xylem sap (relative to darkness) in WT and in the PHOT1-complemented phot1-5. These results, supported by BL increase of BSC protoplasts’ water permeability and cytosolic pH and their hyperpolarization by BL, identify the BSCs as a second phot-controlled water conductance element in leaves, in series with stomatal conductance. Through both, BL regulates the leaf water balance.
X-ray microcomputed and synchrotron tomographic analysis of the basicranial axis of emydopoid dicynodonts: implications for fossoriality and phylogeny
Authors: Macungo Zanildo , Benoit Julien , Fernandez Vincent , Araújo Ricardo M N
Published: March 2022

Emydopoidea is one of the major dicynodont subclades and includes some purported fossorial taxa. Various cranial and postcranial adaptations for fossoriality have long been recognized in cistecephalid emydopoids, but anatomical variation of their braincases remains poorly understood. Here, using laboratory and synchrotron X-ray tomography, we provide detailed anatomical descriptions of the basicranial axis of three emydopoids (Myosaurus, Kawingasaurus and a Malawian cistecephalid DMMM-PK-16-1) and compare them to the basal dicynodont Pristerodon. Cistecephalids show the presence of divergent crests on the posterior aspect of the opisthotic and a nuchal crest on their occipital plate, contrasting with the featureless occipital plate of other dicynodonts. These depressions and crests increase the attachment area of the atlanto-occipital muscles, suggesting that cistecephalids were capable of powerful movements of the head during digging. Additionally, Kawingasaurus has a pneumatized braincase and highly co-ossified basicranium, which is probably linked to the auditory system. We corroborate the hypothesis that cistecephalids, in addition to being forelimb diggers, were likely head-lift diggers, and we highlight some derived adaptations consistent with a quasi-obligate fossorial lifestyle. Furthermore, new basicranial phylogenetic characters and a re-evaluation of emydopoid relationships are proposed. We recovered Rastodon as a basal emydopoid, Thliptosaurus as a non-kingoriid emydopoid and novel interrelationships among cistecephalids.
Impact of Pratylenchus penetrans on Soybean Grown in Wisconsin, U.S.A.
Authors: Saikai Kanan , MacGuidwin Ann E.
Published: March 2022

Models were developed to quantify the impact of Pratylenchus penetrans to the early season growth and yield of soybean in field and greenhouse environments and to estimate yield loss because of P. penetrans in Wisconsin. There was a negative linear relationship between initial nematode population densities (Pi) and shoot and total plant weight at V2 and yield, pod number, seed number, and seed mass at harvest in the field. Relative yield loss, modeled for the second year of the field experiment, suggested a loss of 4.5% for yield and between 2.4 and 2.8% for yield components at the mean field Pi value. Negative linear relationships were demonstrated for the relative loss in those variables as well as for harvest index and shoot, root, and total plant weight at harvest in the greenhouse. Stress imposed by P. penetrans began within 2 weeks after planting and continued through harvest. Estimates of the percent loss attributed to each nematode Pi value were 0.020% for yield, 0.015% for pod number, and 0.017% for seed number. Pratylenchus spp. was the most widely prevalent pest nematode among samples submitted to a statewide nematode testing program. Molecular identification of a subset of 63 samples suggested 15% were infested with P. penetrans at a mean Pi value of 197 P. penetrans per 100 cm3 soil. Yield loss because of P. penetrans, estimated from prevalence data and our empirical greenhouse model, ranged from 0.23 to 2.76% among Wisconsin’s agricultural districts. The cumulative impact for all Pratylenchus spp. is likely much greater, given this loss estimate does not account for the monoecious species present in 79% of the samples.
The Future of Critical Care: Optimizing Technologies and a Learning Healthcare System to Potentiate a More Humanistic Approach to Critical Care
Authors: Meissen Heather , Gong Michelle Ng , Wong An-Kwok Ian , Zimmerman Jerry J. , Nadkarni Nalini , Kane-Gil Sandra L. , Amador-Castaneda Javier , Bailey Heatherlee , Brown Samuel M. , DePriest Ashley D. , Mary Eche Ifeoma , Narayan Mayur , Provencio Jose Javier , Sederstrom Nneka O. , Sevransky Jonathan , Tremper Jordan , Aslakson Rebecca A. ,   written on behalf of the Society of Critical Care Medicine’s Future of Critical Care Taskforce
Published: March 2022

While technological innovations are the invariable crux of speculation about the future of critical care, they cannot replace the clinician at the bedside. This article summarizes the work of the Society of Critical Care Medicine–appointed multiprofessional task for the Future of Critical Care. The Task Force notes that critical care practice will be transformed by novel technologies, integration of artificial intelligence decision support algorithms, and advances in seamless data operationalization across diverse healthcare systems and geographic regions and within federated datasets. Yet, new technologies will be relevant and meaningful only if they improve the very human endeavor of caring for someone who is critically ill.
Olive Oil Consumption and Cardiovascular Protection: Mechanism of Action
Authors: Chrysant Steven G. , Chrysant George S.
Published: March 2022

Cardiovascular diseases (CVDs) are still the leading cause of death and disability worldwide, and they could be prevented by a diet modification and a healthy lifestyle. Dietary modifications include a reduction in the consumption of saturated fatty acids and replacing them with mono or polyunsaturated fatty acids. Olive oil is a monounsaturated fatty acid and its increased consumption has been associated with a significant reduction of CVDs. Its significant cardiovascular benefits have been attributed to its high content of vitamin E, polyphenols, and other ingredients that possess significant anti-inflammatory and antioxidant properties. Several prospective and epidemiological studies have reported an inverse association between olive oil consumption and the incidence of CVD, hypertension, and type 2 diabetes mellitus. Also, a seminal study demonstrated that the use of a Mediterranean diet, which is rich in olive oil, fruits, vegetables, and fish, and low in red meat, was associated with significant reductions in CVD and mortality. However, despite its proven cardiovascular benefits, olive oil is scarcely used in the United States and other Western countries. To determine the current use of olive oil in the United States and other Western countries, a Medline search of the English literature between 2012 and January 2022 was conducted, and 36 pertinent articles were selected. The data from these articles, together with collateral literature, will be discussed in this concise review.
The Olfm4-defined human neutrophil subsets differ in proteomic profile in septic shock
Authors: Lundquist Hans , Andersson Henrik , Chew Michelle S. , Das Jyotirmoy , Turkina Maria V. , Welin Amanda
Published: March 2022

The specific granule glycoprotein olfactomedin-4 (Olfm4) marks a constitutive subset of neutrophils in humans, where 1-70% of peripheral blood neutrophils produce Olfm4. The proportion of Olfm4-high (Olfm4-H) neutrophils correlates with the severity of paediatric septic shock and could predict mortality in adult septic shock in previous studies, but it is not known whether and how the Olfm4-H neutrophils contribute to sepsis pathogenesis. The aim of this study was to decipher proteomic differences between the Olfm4-H and Olfm4-low (Olfm4-L) human neutrophil subsets at baseline and in the context of septic shock, hypothesizing that Olfm4 marks a neutrophil subset with a distinct proteomic profile, predisposing it for detrimental processes in sepsis. A novel protocol for the preparation of fixed, antibody-stained and sorted neutrophils for LC-MS/MS analysis of proteome was developed. In neutrophil subsets from healthy blood donors, 47 proteins had significantly higher abundance in the Olfm4-H population, and 62 proteins in the Olfm4-L population. Pathway enrichment analysis showed that the differences concerned proteins related to neutrophil degranulation, with e.g. Rab3d and a subunit of the vacuolar ATPase proton pump being more abundant in the Olfm4-H neutrophils, and the alarmin S100-A7, the major neutrophil chemotactic receptor CXCR1 and the antimicrobial peptide defensin alpha-4 being more abundant in the Olfm4-L neutrophils. The data suggest different preparedness to infection in the subsets. In the limited material analysed here, there was no significant correlation between the severity of sepsis and the proportion of Olfm4-H neutrophils, but an increased concentration of Olfm4 in plasma from septic shock patients as compared to healthy blood donors was observed. Furthermore, in neutrophil subsets isolated from septic shock patients, 28 proteins had significantly higher abundance in the Olfm4-H subset and 38 in the Olfm4-L subset, the latter including e.g. Fc receptor proteins and MHC class I molecules, suggesting distinct immunological responses. This is the first report pointing towards differential functions of the Olfm4-defined neutrophil subpopulations in humans and the data are consistent with the idea of distinct responses in the subsets during infection and inflammation.
Complex regulatory role of DNA methylation in caste- and age-specific expression of a termite
Authors: Harrison Mark C. , Dohmen Elias , George Simon , Sillam-Dussès David , Séité Sarah , Vasseur-Cognet Mireille
Published: March 2022

The reproductive castes of eusocial insects are often characterised by extreme lifespans and reproductive output, indicating an absence of the fecundity/longevity trade-off. The role of DNA methylation in the regulation of caste- and age-specific gene expression in eusocial insects is controversial. While some studies find a clear link to caste formation in honeybees and ants, others find no correlation when replication is increased across independent colonies. Although recent studies have identified transcription patterns involved in the maintenance of high reproduction throughout the long lives of queens, the role of DNA methylation in the regulation of these genes is unknown. We carried out a comparative analysis of DNA methylation in the regulation of caste-specific transcription and its importance for the regulation of fertility and longevity in queens of the higher termite, Macrotermes natalensis. We found evidence for significant, well-regulated changes in DNA methylation in mature compared to young queens, especially in several genes related to ageing and fecundity in mature queens. We also found a strong link between methylation and caste-specific alternative splicing. This study reveals a complex regulatory role of fat body DNA methylation both in the division of labour in termites, and during the reproductive maturation of queens.
G-matrix stability in clinally diverging populations of an annual weed
Authors: Henry Georgia Alexandria , Stinchcombe John R
Published: March 2022

How phenotypic and genetic divergence among populations is influenced by the genetic architecture of those traits, and how microevolutionary changes in turn affect the within-population patterns of genetic variation, are of major interest to evolutionary biology. Work on Ipomoea hederacea, an annual vine, has found genetic clines in the means of a suite of ecologically important traits, including flowering time, growth rate, seed mass, and corolla width. Here we investigate the genetic (co)variances of these clinally varying traits in two northern range-edge and two central populations of Ipomoea hederacea to evaluate the influence of the genetic architecture on divergence across the range. We find 1) limited evidence for clear differentiation between Northern and Southern populations in the structure of G, suggesting overall stability of G across the range despite mean trait divergence and 2) that the axes of greatest variation (gmax) were unaligned with the axis of greatest multivariate divergence. Together these results indicate the role of the quantitative genetic architecture in constraining evolutionary response and divergence among populations across the geographic range.
Do lanthanide-dependent microbial metabolisms drive the release of REEs from weathered granites?
Authors: Voutsinos Marcos Y. , West-Roberts Jacob A. , Sachdeva Rohan , Moreau John W. , Banfield Jillian F.
Published: March 2022

Prior to soil formation, phosphate liberated by rock weathering is often sequestered into highly insoluble lanthanide phosphate minerals. Dissolution of these minerals is critical for the release of phosphate to the biosphere, yet the microorganisms involved, and the genes required for lanthanide metabolism, are poorly understood. Here, we sampled weathered granite and associated soil to identify the zones of lanthanide phosphate mineral solubilization and genomically define the organisms implicated in lanthanide utilisation. We reconstructed 136 genomes from 11 bacterial phyla and found gene clusters implicated in lanthanide-based metabolism of methanol (primarily XoxF3 and XoxF5) are surprisingly common in microbial communities in moderately weathered granite where lanthanide phosphate minerals are dissolving. Notably, XoxF3 systems were found in Verrucomicrobia for the first time, and in Acidobacteria, Gemmatimonadetes, and Alphaproteobacteria. The XoxF-containing gene clusters are shared by diverse Acidobacteria and Gemmatimonadetes, and include conserved hypothetical proteins and transporters not associated with the few well studied XoxF systems. Given that siderophore-like molecules that strongly bind lanthanides may be required to solubilize lanthanide phosphates, it is notable that candidate siderophore biosynthesis systems were most prevalent in bacteria in moderately weathered rock, especially in Acidobacteria with lanthanide-based systems. We conclude that the confluence in the zone of moderate weathering of phosphate mineral dissolution, lanthanide utilisation, and methanol oxidation (thus carbonic acid production) may be important during the conversion of granitic rock to soil.
Modeling within-host and aerosol dynamics of SARS-CoV-2: the relationship with infectiousness
Authors: Heitzman-Breen Nora , Ciupe Stanca M.
Published: March 2022

The relationship between transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the amount of virus present in the proximity of a susceptible host is not understood. Here, we developed a within-host and aerosol mathematical model and used it to determine the relationship between viral kinetics in the upper respiratory track, viral kinetics in the aerosols, and new transmissions in golden hamsters challenged with SARS-CoV-2. We determined that infectious virus shedding early in infection correlates with transmission events, shedding of infectious virus diminishes late in the infection, and high viral RNA levels late in the infection is a poor indicator of transmission. We further showed that viral infectiousness increases in a density dependent manner with viral RNA and that their relative ratio is time-dependent. Such information is useful for designing interventions.

Author summary

Quantifying the relationship between SARS-CoV-2 dynamics in upper respiratory tract and in aerosols is key to understanding SARS-CoV-2 transmission and evaluating intervention strategies. Of particular interest is the link between the viral RNA measured by PCR and a subject’s infectiousness. Here, we developed a mechanistic model of viral transmission in golden hamsters and used data in upper respiratory tract and aerosols to evaluate key within-host and environment based viral parameters. The significance of our research is in identifying the timing and duration of viral shedding, how long it stays infectious, and the link between infectious virus and total viral RNA. Such knowledge enhances our understanding of the SARS-CoV-2 transmission window.
The therapeutic potential of D-Serine in reducing expression of the cytopathic genotoxin colibactin
Authors: Hallam Jennifer C , O’Boyle Nicky , Turner Natasha C A , Tang-Fichaux Min , Oswald Eric , Roe Andrew J
Published: March 2022

Some Escherichia coli strains belonging mainly to the B2 phylogroup harbour the pks island, a 54 kb genomic island encoding the biosynthesis genes for a genotoxic compound named colibactin. In eukaryotic cells, colibactin can induce DNA damage, cell cycle arrest and chromosomal instability. Moreover, production of colibactin has been implicated in the development of colorectal cancer. In this study, we demonstrate the inhibitory effect of D-Serine on the expression of the pks island in two colibactin-producing strains, CFT073 and Nissle 1917, and determine the implications for cytopathic effects on host cells. To investigate the specificity of the inhibitory effect of D-Serine, we also tested a comprehensive panel of proteinogenic L-amino acids and corresponding D-enantiomers for their ability to modulate clbB transcription using RT-qPCR. Several D-amino acids exhibited the ability to inhibit expression of clbB, with D-Serine exerting the strongest repressing activity (3.81-fold in CFT073; 3.80-fold in Nissle 1917) and thus, we focussed additional experiments on D-Serine. To investigate the cellular effect, we investigated if repression of colibactin by D-Serine could reduce the cytopathic responses normally observed during infection of HeLa cells with pks+ strains. Levels of γ-H2AX (a marker of DNA double strand breaks) were reduced 2.75-fold in cells infected with D-Serine treatment. Moreover, exposure of pks+E. coli to D-Serine during infection caused a reduction in cellular senescence that was observable at 72 h post infection. The recent finding of an association between pks-carrying commensal E. coli and CRC, highlights the necessity for the development of colibactin targeting therapeutics. Here we show that D-Serine can reduce expression of colibactin, and inhibit downstream cellular cytopathy, illuminating its therapeutic potential to prevent colibactin-associated disease.
Identification of a new Inovirus in the absence of bacterial infection in the human virome
Authors: Popgeorgiev Nikolay , Krupovic Mart , Hiblot Julien , Fancello Laura , Monteil-Bouchard Sonia , Desnues Christelle
Published: March 2022

Viruses infecting bacteria, known as bacteriophages, represent the most abundant viral particles in the human body. They participate in the control of the human associated bacterial communities and play an important role in the dissemination of virulence genes. Here we present the identification of a new genetic element, named RIP1, in the human virome. RIP1 shares conserved structural genes with the single-stranded DNA viruses of the Inoviridae family. Furthermore structure-function studies identified nuclear subcellular localization of the RIP1 DNA replication/recombination machinery. Additional metagenomics analysis and polymerase chain reaction detected RIP1 in multiple body sites including blood, cerebrospinal pericardial and amniotic fluids, nasal swabs and feces in the absence of concomitant bacterial infection, uncovering inovirus phage persistence in the human virome.
A web-based histology atlas for the freshwater sentinel speciesDaphnia magna
Authors: Ngu Mee S. , Vanselow Daniel J. , Zaino Carolyn R. , Lin Alex Y. , Copper Jean E. , Beaton Margaret J. , Orsini Luisa , Colbourne John K. , Cheng Keith C. , Ang Khai C.
Published: March 2022

Daphniaare keystone species of freshwater habitats used as model organisms in ecology and evolutionary biology. Their small size, wide geographic distribution, and sensitivity to chemicals make them useful as environmental sentinels in regulatory toxicology and chemical risk assessment. Biomolecular (-omic) assessments of responses to chemical toxicity, which reveal detailed molecular signatures, become more powerful when correlated with other phenotypic outcomes (such as behavioral, physiological, or histopathological) for comparative validation and regulatory relevance. However, the lack of histopathology or tissue phenotype characterization of this species presently limits our ability to access cellular mechanisms of toxicity. Here, we address the central concept that interpreting aberrant tissue phenotypes requires a basic understanding of species normal microanatomy. We introduce the female and maleDaphniaHistologyReferenceAtlas (DaHRA) for the baseline knowledge ofDaphnia magnamicroanatomy. Additionally, we also included developmental stages of femaleDaphniain this current atlas. This interactive web-based resource of adultDaphniafeatures overlaid vectorized demarcation of anatomical structures whose labels comply with an anatomical ontology created for this atlas. We demonstrate the potential utility of DaHRA for toxicological investigations by presenting aberrant phenotypes of acetaminophen-exposedD. magna. We envision DaHRA to facilitate the effort of integrating molecular and phenotypic data from the scientific community as we seek to understand how genes, chemicals, and environment interactions determine organismal phenotype.
Emergent periodicity in the collective synchronous flashing of fireflies
Authors: Sarfati Raphaël , Joshi Kunaal , Martin Owen , Hayes Julie C. , Iyer-Biswas Srividya , Peleg Orit
Published: March 2022

In isolation from their peers,Photinus carolinusfireflies flash with no intrinsic period between successive bursts. Yet, when congregating into large mating swarms, these fireflies transition into predictability, synchronizing with their neighbors with a rhythmic periodicity. Here we propose a mechanism for emergence of synchrony and periodicity, and formulate the principle in a mathematical framework. Remarkably, with no fitting parameters, analytic predictions from this simple principle and framework agree strikingly well with data. Next, we add further sophistication to the framework using a computational approach featuring groups of random oscillators via integrate-and-fire interactions controlled by a tunable parameter. This agent-based framework ofP. carolinusfireflies interacting in swarms of increasing density also shows quantitatively similar phenomenology and reduces to the analytic framework in the appropriate limit of the tunable coupling strength. We discuss our findings and note that the resulting dynamics follow the style of a decentralized follow-the-leader synchronization, where any of the randomly flashing individuals may take the role of the leader of any subsequent synchronized flash burst.
Direct measurement of the aerotactic response in a bacterial suspension
Authors: Bouvard J. , Douarche C. , Mergaert P. , Auradou H. , Moisy F.
Published: March 2022

Aerotaxis is the ability of motile cells to navigate towards oxygen. A key question is the dependence of the aerotactic velocity with the local oxygen concentration c. Here we combine simultaneous bacteria tracking and local oxygen concentration measurements using Ruthenium encapsulated in micelles to characterise the aerotactic response of Burkholderia contaminans, a motile bacterium ubiquitous in the environment and present in living organisms. In our experiments, an oxygen gradient is produced by the bacterial respiration in a sealed glass capillary permeable to oxygen at one end, producing a bacterial band travelling towards the oxygen source. We compute the aerotactic response χ(c) both at the population scale, from the drift velocity in the bacterial band, and at the bacterial scale, from the angular modulation of the run times. Both methods are consistent with a power-law χ ∝ c−2, in good agreement with existing models based on the biochemistry of bacterial membrane receptors.
Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery
Authors: Crooks Bethany A. , McKenzie Darrin , Cadd Luke C. , McCoy Ciaran J. , McVeigh Paul , Marks Nikki J. , Maule Aaron G. , Mousley Angela , Atkinson Louise E.
Published: March 2022

The endocannabinoid signalling (ECS) system is a complex lipid signalling pathway that modulates diverse physiological processes in both vertebrate and invertebrate systems. In nematodes, knowledge of endocannabinoid (EC) biology is derived primarily from the free-living model species Caenorhabditis elegans, where ECS has been linked to key aspects of nematode biology. The conservation and complexity of nematode ECS beyond C. elegans is largely uncharacterised, undermining the understanding of ECS biology in nematodes including species with key importance to human, veterinary and plant health. In this study we exploited publicly available omics datasets, in silico bioinformatics and phylogenetic analyses to examine the presence, conservation and life-stage expression profiles of EC-effectors across phylum Nematoda. Our data demonstrate that: (i) ECS is broadly conserved across phylum Nematoda, including in therapeutically and agriculturally relevant species; (ii) EC-effectors appear to display clade and lifestyle-specific conservation patterns; (iii) filarial species possess a reduced EC-effector complement; (iv) there are key differences between nematode and vertebrate EC-effectors; (v) life stage-, tissue- and sex-specific EC-effector expression profiles suggest a role for ECS in therapeutically relevant parasitic nematodes. These data also highlight putative novel targets for anthelmintic therapies. To our knowledge, this study represents the most comprehensive characterisation of ECS pathways in phylum Nematoda and inform our understanding of nematode ECS complexity. Fundamental knowledge of nematode ECS systems will seed follow-on functional studies in key nematode parasites to underpin novel drug target discovery efforts.

CONTRIBUTION TO THE FIELD

This manuscript reports the in silico characterisation of endocannabinoid (EC) signalling pathways across the nematode phylum. The physiological relevance and therapeutic potential of EC signalling in higher organisms has received significant attention. In contrast much of our knowledge on EC signalling in nematodes has been derived from the free-living nematode Caenorhabditis elegans where the EC signalling system appears to play key roles in nematode biology and features GPCRs distinct from vertebrate cannabinoid receptors. Unfortunately, the configuration and broader biological significance of EC signalling pathways across the nematode phylum, including in parasites of agricultural, veterinary and medical significance, remains unknown. The in silico exploration of the nematode EC signalling system reported here will provide baseline data on novel neuronal signalling pathways to seed future drug target discovery pipelines for parasites.
Enhancing bacteriophage therapeutics throughin situproduction and release of heterologous antimicrobial effectors
Authors: Du Jiemin , Meile Susanne , Baggenstos Jasmin , Jäggi Tobias , Piffaretti Pietro , Hunold Laura , Matter Cassandra I. , Leitner Lorenz , Kessler Thomas M. , Loessner Martin J. , Kilcher Samuel , Dunne Matthew
Published: March 2022

Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternatives. However, phage-mediated killing is often limited by bacterial resistance development (1,2). Here, we engineer phages for target-specific effector gene delivery and host-dependent production of colicin-like bacteriocins and cell wall hydrolases. Using urinary tract infection (UTI) as a model, we show how heterologous effector phage therapeutics (HEPTs) suppress resistance and improve uropathogen killing by dual phage- and effector-mediated targeting. Moreover, we designed HEPTs to control polymicrobial uropathogen communities through production of effectors with cross-genus activity. Using a phage-based companion diagnostic (3), we identified potential HEPT responder patients and treated their urineex vivo. Compared to wildtype phage, a colicin E7-producing HEPT demonstrated superior control of patientE. colibacteriuria. Arming phages with heterologous effectors paves the way for successful UTI treatment and represents a versatile tool to enhance and adapt phage-based precision antimicrobials.
BLMM: Parallelised Computing for Big Linear Mixed Models
Authors: Maullin-Sapey Thomas , Nichols Thomas E.
Published: March 2022

Within neuroimaging large-scale, shared datasets are becoming increasingly commonplace, challenging existing tools both in terms of overall scale and complexity of the study designs. As sample sizes grow, researchers are presented with new opportunities to detect and account for grouping factors and covariance structure present in large experimental designs. In particular, standard linear model methods cannot account for the covariance and grouping structures present in large datasets, and the existing linear mixed models (LMM) tools are neither scalable nor exploit the computational speed-ups afforded by vectorisation of computations over voxels. Further, nearly all existing tools for imaging (fixed or mixed effect) do not account for variability in the patterns of missing data near cortical boundaries and the edge of the brain, and instead omit any voxels with any missing data. Yet in the large-n setting, such a voxel-wise deletion missing data strategy leads to severe shrinkage of the final analysis mask. To counter these issues, we describe the “Big” Linear Mixed Models (BLMM) toolbox, an efficient Python package for large-scale fMRI LMM analyses. BLMM is designed for use on high performance computing clusters and utilizes a Fisher Scoring procedure made possible by derivations for the LMM Fisher information matrix and score vectors derived in our previous work, Maullin-Sapey and Nichols (2021).
Accurate in silico confirmation of rare copy number variant calls from exome sequencing data using transfer learning
Authors: Tan Renjie , Shen Yufeng
Published: March 2022

Exome sequencing has been widely used in genetic studies of human diseases and clinical genetic diagnosis. Accurate detection of copy number variants (CNVs) is important to fully utilize exome sequencing data. However, due to the nature of noisy data, none of the existing methods can achieve high precision and high recall rate at the same time. A common practice is to perform filtration with quality metrics followed by manual inspection of read depth of candidate CNV regions. This approach does not scale in large studies. To address this issue, we present a deep transfer learning method, CNV-espresso, for confirming rare CNVs from exome sequencing data in silico. CNV-espresso encodes candidate CNV regions from exome sequencing data as images and uses convolutional neural networks to classify the image into different copy numbers. We trained and evaluated CNV-espresso on a large-scale offspring-parents trio exome sequencing dataset, using inherited CNVs in probands as positives and CNVs with mendelian errors as negatives. We further tested the performance using samples that have both exome and whole genome sequencing (WGS) data. Assuming the CNVs detected from WGS data as proxy of ground truth, CNV-espresso significantly improves precision while keeping recall almost intact, especially for CNVs that span small number of exons in exome data. We conclude that CNV-espresso is an effective method to replace most of manual inspection of CNVs in large-scale exome sequencing studies.
Automated classification of estrous stage in rodents using deep learning
Authors: Wolcott Nora S. , Sit Kevin K. , Raimondi Gianna , Hodges Travis , Shansky Rebecca M. , Galea Liisa A. M. , Ostroff Linnaea E. , Goard Michael J.
Published: March 2022

The rodent estrous cycle modulates a range of biological functions, from gene expression to behavior. The cycle is typically divided into four stages, each characterized by distinct hormone concentration profiles. Given the difficulty of repeatedly sampling plasma steroid hormones from rodents, the primary method for classifying estrous stage is by identifying vaginal epithelial cell types. However, manual classification of epithelial cell samples is time-intensive and variable, even amongst expert investigators. Here, we use a deep learning approach to achieve classification accuracy at expert levels in a matter of seconds. Due to the heterogeneity and breadth of our input dataset, our deep learning approach (“EstrousNet”) is highly generalizable across rodent species, stains, and subjects. The EstrousNet algorithm exploits the temporal dimension of the hormonal cycle by fitting classifications to an archetypal estrous cycle, highlighting possible misclassifications and flagging anestrus phases (e.g., pseudopregnancy). EstrousNet allows for rapid estrous cycle staging, improving the ability of investigators to consider endocrine state in their rodent studies.
Cognitive penetrability of scene representations based on horizontal image disparities
Authors: Chen Yulan D. , Kaestner Milena , Norcia Anthony M.
Published: March 2022

The structure of natural scenes is signaled by many visual cues. Principal amongst them are the binocular disparities created by the laterally separated viewpoints of the two eyes. Disparity cues are believed to be processed hierarchically, first in terms of local measurements of absolute disparity and second in terms of more global measurements of relative disparity that allow extraction of the depth structure of a scene. Psychophysical and oculomotor studies have suggested that relative disparities are particularly relevant to perception, whilst absolute disparities are not. Here, we compare neural responses to stimuli that isolate the absolute disparity cue with stimuli that contain additional relative disparity cues, using the high temporal resolution of EEG to determine the temporal order of absolute and relative disparity processing. By varying the observers’ task, we assess the extent to which each cue is cognitively penetrable. We find that absolute disparity is extracted before relative disparity, and that task effects arise only at or after the extraction of relative disparity. Our results indicate a hierarchy of disparity processing stages leading to the formation of a proto-object representation upon which higher cognitive processes can act.
Estimating contemporary migration numbers of adults based on kinship relationships in iteroparous species
Authors: Akita Tetsuya
Published: March 2022

In this paper, we describe the development of estimators for the contemporary migration number and rate of adults between two populations in iteroparous species. The proposed estimators are based on known half-sibling (HS) and/or parent–offspring (PO) relationships observed between the populations across breeding seasons. The rationale is that the HS and PO pairs exhibit information about the occurrence frequency of parental movements during the breeding interval. The proposed method allows for variance in the average number of off-spring per parent both within and between populations. In addition, coupled with the PO pairs found within the population, the estimators can be obtained from only genetic data. Generally, a sample size representing the square root of the population size is required to obtain meaningful information regarding migration. We describe a detailed evaluation of the performance of the estimators by running an individual-based model, and the results provide guidance regarding sample sizes to ensure the required accuracy and precision. Furthermore, given that there are few effective methods to estimate adult movement (especially when populations cannot be genetically distinct), we discuss the usefulness of this proposed kinship assignment method in terms of conservation biology and wildlife management.
Polyploidy and plant-fungus symbiosis: evidence of cytotype-specific microbiomes in the halophyteSalicornia(Amaranthaceae)
Authors: Gonçalves Danilo Reis , Pena Rodica , Albach Dirk C.
Published: March 2022

Polyploidy is recognized as a mechanism of speciation in plants with cascading effects on biotic interactions. However, a limited number of studies have investigated the effects of polyploidy on the association of plants and microorganisms. Herein, we investigated whether twoSalicorniacytotypes (S. europaea– 2x andS. procumbens– 4x) show different root-associated fungal communities. Additionally, we explored the existence of cytotype-specific root anatomical traits, which could influence fungal recruitment and establishment.Salicorniaspp. were identified based on their ploidy level. The root-associated fungal microbiome ofSalicorniawas analyzed using high throughput amplicon sequencing (ITS1 of rDNA) in spring and summer. The following root anatomical traits were investigated: maximum root diameter, periderma thickness, parenchyma thickness, diameter of the vascular cylinder and maximum diameter of parenchyma cells. Our results showed that Shannon diversity and evenness indices were higher in samples ofSalicornia procumbens(4x) compared to those ofS. europaea(2x), and in summer the root-associated fungal community ofS. procumbens(4x) was significantly different from that ofS. europaea(2x). The ordersXylariales, MalassezialesandPleosporaleswere the most frequent root colonizers in both cytotypes and most of the taxa associated withSalicorniawere functionally classified as saprophytes or plant pathogens. Finally, we observed larger periderma and parenchyma layers inS. procumbens(4x) thanS. europaea(2x) that may contribute to the observed differences in community composition between the two cytotypes. Our results suggest that differences in ploidy may modulate plant interaction with fungi by affecting species recruitment and microbiome structure. In addition, cytotype-specific root traits may also have the potential to affect differently community assembly in the two cytotypes.