bluuebunny/crossref_metadata_2025 huggingface dataset:
Mating strategy predicts gene presence/absence patterns in a genus of simultaneously hermaphroditic flatworms
Authors: Wiberg R. Axel W. , Viktorin Gudrun , Schärer Lukas
Published: May 2022

Gene repertoire turnover is a characteristic of genome evolution. However, we lack well-replicated analyses of presence/absence patterns associated with different selection contexts. Here, we study ∼100 transcriptome assemblies across Macrostomum, a genus of simultaneously hermaphroditic flatworms exhibiting multiple convergent shifts in mating strategy and associated reproductive morphologies. Many species mate reciprocally, with partners donating and receiving sperm at the same time. Other species convergently evolved to mate by hypodermic injection of sperm into the partner. We find that for orthologous transcripts annotated as expressed in the body region containing the testes, sequences from hypodermically inseminating species diverge more rapidly from the model species, M. lignano, and have a lower probability of being observed in other species. For other annotation categories, simpler models with a constant rate of similarity decay with increasing genetic distance from M. lignano match the observed patterns well. Thus, faster rates of sequence evolution for hypodermically inseminating species in testis-region genes result in higher rates of homology detection failure, yielding a signal of rapid evolution in sequence presence/absence patterns. Our results highlight the utility of considering appropriate null models for unobserved genes, as well as associating patterns of gene presence/absence with replicated evolutionary events in a phylogenetic context.
A generic risk assessment model for animal disease entry through wildlife: The example of highly pathogenic avian influenza and African swine fever in The Netherlands
Authors: Counotte Michel J. , Petie Ronald , van Klink Ed G. M. , de Vos Clazien J.
Published: May 2022

Animal diseases can enter countries or regions through movements of infected wildlife. A generic risk model would allow to quantify the risk of entry via this introduction route for different diseases and wildlife species, despite the vast variety in both, and help policy-makers to make informed decisions. Here, we propose such a generic risk assessment model and illustrate its application by assessing the risk of entry of African swine fever (ASF) through wild boar and highly pathogenic avian influenza (HPAI) through wild birds for the Netherlands between 2014-2021. We used disease outbreak data and abstracted movement patterns to populate a stochastic risk model. We found that the entry risk of HPAI fluctuated between the years with a peak in 2021. In that year, we estimated the number of infected birds to reach the Dutch border by wild bird migration at 273 (95% uncertainty interval: 254-290). The probability that ASF outbreaks that occurred between 2014 and 2021, reached the Dutch border through wild boar movement was very low throughout the whole period; only the upper confidence bound indicated a small entry risk. On a yearly scale, the predicted entry risk for HPAI correlated well with the number of observed outbreaks. In conclusion, we present a generic and flexible framework to assess the entry risk of disease through wildlife. The model allows rapid and transparent estimation of the entry risk for diverse diseases and wildlife species. The modular structure of the model allows to add nuance and complexity, when required or when more data becomes available.
Advancing terrestrial biodiversity monitoring with satellite remote sensing in the context of the Kunming-Montreal global biodiversity framework
Authors: Timmermans Joris , Kissling W. Daniel
Published: May 2022

Satellite remote sensing (SRS) provides huge potential for tracking progress towards conservation targets and goals, but SRS products need to be tailored towards the requirements of ecological users and policymakers. In thisviewpointarticle, we propose to advance SRS products with a terrestrial biodiversity focus for tracking the goals and targets of the Kunming-Montreal global biodiversity framework (GBF). Of 371 GBF biodiversity indicators, we identified 58 unique indicators for tracking the state of terrestrial biodiversity, spanning 2 goals and 8 targets. Thirty-six shared enough information to analyse their underlying workflows and spatial information products. We used the concept of Essential Biodiversity Variables (EBV) to connect spatial information products to different dimensions of biodiversity (e.g. species populations, species traits, and ecosystem structure), and then counted EBV usage across GBF goals and targets. Combined with published scores on feasibility, accuracy, and immaturity of SRS products, we identified a priority list of terrestrial SRS products representing opportunities for scientific development in the next decade. From this list, we suggest two key directions for advancing SRS products and workflows in the GBF context using current instruments and technologies. First, existing terrestrial ecosystem distributions and live cover fraction SRS products (of above-ground biomass, ecosystem fragmentation, ecosystem structural variance, fraction of vegetation cover, plant area index profile, and land cover) need to be refined using a co-design approach to achieve harmonized ecosystem taxonomies, reference states and improved thematic detail. Second, new SRS products related to plant physiology and primary productivity (e.g. leaf area index, chlorophyll content & flux, foliar N/P/K content, and carbon cycle) need to be developed to better estimate plant functional traits, especially with deep learning techniques, radiative transfer models and multi-sensor frameworks. Advancements along these two routes could greatly improve the tracking of GBF target 2 (‘improve connectivity of priority terrestrial ecosystems), target 3 (‘ensure management of protected areas’), target 6 (‘control the introduction and impact of invasive alien species’), target 8 (‘minimize impact of climate change on biodiversity’), target 10 (‘increase sustainable productivity of agricultural and forested ecosystems’) and target 12 (‘increase public urban green/blue spaces’). Such improvements can have secondary benefits for other EBVs, e.g. as predictor variables for modelling species distributions and population abundances (i.e. data that are required in several GBF indicators). We hope that ourviewpointstimulates the advancement of biodiversity monitoring from space and a stronger collaboration among ecologists, SRS scientists and policy experts.
Hydroquinone, a cigarette smoke compound, affects cartilage homeostasis through activation of the aryl hydrocarbon receptor pathway
Authors: Heluany Cintia Scucuglia , de Palma Anna , Day Nicholas , Poliselli Farsky Sandra Helena , Nalesso Giovana
Published: May 2022

Exposure to cigarette smoke has a proven detrimental impact on different aspects of human health. Increasing evidences link smoking to degeneration of joint tissues. However, the toxic mechanisms elicited by the different components of cigarette smoke have not been fully elucidated yet. We have previously shown that exposure to hydroquinone (HQ), a pro-oxidant chemical present in cigarette smoke, can promote joint tissue degradation in murine models of rheumatoid arthritis through the activation of the aryl hydrocarbon receptor (AhR) pathway. Osteoarthritis (OA) is a chronic debilitating articular disease characterized by progressive degradation of the articular cartilage, whose onset and progression have also been associated with smoking. In this work we aimed to investigate the effect of HQ exposure on articular chondrocytes and how it affects cartilage homeostasis. Cell viability, gene expression, oxidative stress and inflammatory parameters were quantified in primary articular chondrocytes exposed to HQ in presence or absence of IL-1β pre-stimulation. HQ stimulation downregulated phenotypic markers genes such as SOX-9 and Col2a1, whereas upregulated the expression of the catabolic enzymes MMP-3 and ADAMTS5. HQ also promoted oxidative stress and reduced proteoglycan content. HQ exacerbated the pro-inflammatory effects mediated by the IL-1β co-stimulation. Finally, we showed that HQ-degenerative effects were mediated by the activation of AhR. Together, our findings address the harmful effects of HQ in the articular cartilage health, providing novel evidence surrounding the toxic mechanisms of environmental pollutants underlying the onset of articular diseases.
From retina to motoneurons: a substrate for visuomotor transformation in salamanders
Authors: Flaive Aurélie , Ryczko Dimitri
Published: May 2022

Abstract

The transformation of visual input into motor output is essential to approach a target or avoid a predator. In salamanders, visually-guided orientation behaviors have been extensively studied during prey capture. However, the neural circuitry involved is not resolved. Using salamander brain preparations, calcium imaging and tracing experiments, we describe a neural substrate through which retinal input is transformed into spinal motor output. We found that retina stimulation evoked responses in reticulospinal neurons of the middle reticular nucleus, known to control steering movements in salamanders. Microinjection of glutamatergic antagonists in the optic tectum (superior colliculus in mammals) decreased the reticulospinal responses. Using tracing we found that retina projected to the dorsal layers of the contralateral tectum, where the dendrites of neurons projecting to the middle reticular nucleus were located. In slices, stimulation of the tectal dorsal layers evoked glutamatergic responses in deep tectal neurons retrogradely labelled from the middle reticular nucleus. We then examined how tectum activation translated into spinal motor output. Tectum stimulation evoked motoneuronal responses, which were decreased by microinjections of glutamatergic antagonists in the contralateral middle reticular nucleus. Reticulospinal fibers anterogradely labelled from tracer injection in the middle reticular nucleus were preferentially distributed in proximity with the dendrites of ipsilateral motoneurons. Our work establishes a neural substrate linking visual and motor centers in salamanders. This retino-tecto-reticulo-spinal circuitry is well positioned to control orienting behaviors. Our study bridges the gap between the behavioral studies and the neural mechanisms involved in the transformation of visual input into motor output in salamanders.
Next-generation matrices for marine metapopulations: the case of sea lice on salmon farms*
Authors: Harrington Peter D. , Cantrell Danielle L. , Lewis Mark A.
Published: May 2022

Classifying habitat patches as sources or sinks and determining metapopulation persistence requires coupling connectivity between habitat patches with local demographic rates. In this paper we show how next-generation matrices, originally popularized in epidemiology to calculate new infections after one generation, can be used in an ecological context to couple connectivity with local demography to calculate sources and sinks as well as metapopulation persistence in marine metapopulations. To demonstrate the utility of the method, we construct a next-generation matrix for a network of sea lice populations on salmon farms in the Broughton Archipelago, BC, an intensive salmon farming region on the west coast of Canada where certain salmon farms are currently being removed under an agreement between local First Nations and the provincial government. We identify the salmon farms which are acting as the largest sources of sea lice and show that in this region the most productive sea lice populations are also the most connected. We find that the farms which are the largest sources of sea lice have not yet been removed from the Broughton Archipelago, and that warming temperatures could lead to increased sea louse growth.
Community review: a robust and scalable selection system for resource allocation within open science and innovation communities
Authors: Graham Chris L. B. , Landrain Thomas E. , Vjestica Amber , Masselot Camille , Lawton Elliot , Blondel Leo , Haenel Luca , Tzovoras Bastian Greshake , Santolini Marc
Published: May 2022

Resource allocation is essential to the selection and implementation of innovative projects in science and technology. With large stakes involved in concentrating large fundings over a few promising projects, current “winner-take-all” models for grant applications are time-intensive endeavours that mobilise significant researcher time in writing extensive project proposals, and rely on the availability of a few time-saturated volunteer experts. Such processes usually carry over several months, resulting in high effective costs compared to expected benefits. Faced with the need for a rapid response to the Covid19 pandemic in 2020, we devised an agile “community review” system to allocate micro-grants for the fast prototyping of innovative solutions. Here we describe and evaluate the implementation of this community review across 147 projects from the “Just One Giant Lab’s OpenCOVID19 initiative” and “Helpful Engineering” open research communities. The community review process uses granular review forms and requires the participation of grant applicants in the review process. Within a year, we organised 7 rounds of review, resulting in 614 reviews from 201 reviewers, and the attribution of 48 micro-grants of up to 4,000 euros. We show that this system is fast, with a median process duration of 10 days, scalable, with a median of 4 reviewers per project independent of the total number of projects, and fair, with project rankings highly preserved after the synthetic removal of reviewers. We investigate the potential bias introduced by involving applicants in the process, and find that review scores from both applicants and non-applicants have a similar correlation of r=0.28 with other reviews within a project, matching previous observations using traditional approaches. Finally, we find that the ability of projects to apply to several rounds allows to both foster the further implementation of successful early prototypes, as well as provide a pathway to constructively improve an initially failing proposal in an agile manner. Overall, this study quantitatively highlights the benefits of a frugal, community review system acting as a due diligence for rapid and agile resource allocation in open research and innovation programs, with particular implications for decentralised communities.
Genetic and peripheral visual system changes underlie evolving butterfly mate preference
Authors: VanKuren Nicholas W. , Buerkle Nathan P. , Westerman Erica L. , Im Alexandria K. , Massardo Darli , Southcott Laura M. , Lu Wei , Palmer Stephanie E. , Kronforst Marcus R.
Published: May 2022

Many studies have linked genetic variation to behavior, but less is known about how that variation alters the neural circuits that drive behavior. We investigated the genetic and neurobiological basis of courtship preference variation in Heliconius butterflies, which use vision to identify appropriate mates based on wing color patterns. We found that Heliconius cydno preference variation was strongly associated with genetic variation and differential expression of senseless-2, a gene predominantly expressed in the eye. Further measurements of photoreceptor sensitivities revealed differences in inter-photoreceptor inhibition of ultraviolet-sensitive cells corresponding to courtship preference variation. Our results reveal a genetic basis for preference/cue co-evolution, suggest a link between sens-2 and visual system variation, and support the idea that changing peripheral neural computations can significantly alter essential behaviors.

Genetic and expression variation of senseless-2 and inter-photoreceptor inhibition predict visual mate preference in a clade of diverse butterflies.
Localization of chemical synapses and modulatory release sites in the cardiac ganglion of the crab, Cancer borealis
Authors: Rue Mara C.P. , Baas-Thomas Natasha , Iyenger Priya , Scaria Lara , Marder Eve
Published: May 2022

The crustacean cardiac ganglion (CG) comprises nine neurons that provide rhythmic drive to the heart. The CG is the direct target of multiple modulators. Synapsin-like immunoreactivity was found clustered around the somata of the large cells (LC) and in a neuropil at the anterior branch of the CG trunk. This implicates the soma as a key site of synaptic integration, an unusual configuration in invertebrates. Proctolin is an excitatory neuromodulator of the CG and proctolin-like immunoreactivity exhibited partial overlap with putative chemical synapses near the LCs and at the neuropil. A proctolin-like projection was also found in a pair of excitatory nerves entering the CG. GABA-like immunoreactivity was nearly completely colocalized with chemical synapses near the LCs but absent at the anterior branch neuropil. GABA-like projections were found in a pair of inhibitory nerves entering the CG. Cancer borealis Allatostatin B1 (CbAST-B1), red pigment concentrating hormone (RPCH) and FLMRFamide-like immunoreactivity each had a unique pattern of staining and co-localization with putative chemical synapses. These results provide morphological evidence that synaptic input is integrated at LC somata in the CG. Our findings provide a topographical organization for some of the multiple inhibitory and excitatory modulators that alter the rhythmic output of this semi-autonomous motor circuit.
High precision magnetoencephalography reveals increased right-inferior frontal gyrus beta power during response conflict
Authors: Daniel Pria L. , Bonaiuto James J. , Bestmann Sven , Aron Adam R. , Little Simon
Published: May 2022

Flexibility of behavior and the ability to rapidly switch actions is critical for adaptive living in humans. It is well established that the right-inferior frontal gyrus (R-IFG) is recruited during outright action-stopping, relating to increased beta (12-30 Hz) power. Additionally, pre-supplementary motor area (pre-SMA) is plausibly recruited during response conflict/switching, relating to increased theta (4-8 Hz) power. It has been posited that inhibiting incorrect response tendencies is central to motor flexibility. However, it is not known if the commonly reported R-IFG beta signature of response inhibition in action-stopping is also recruited during response conflict, which would suggest overlapping networks for stopping and switching. In the current study, we analyzed high precision magnetoencephalography (hpMEG) data recorded with very high trial numbers (total n > 10,000) from 8 subjects during different levels of response conflict. We hypothesized that a R-IFG-triggered network for response inhibition is domain general and also involved in mediating response conflict. We therefore tested whether R-IFG showed increased beta power dependent on the level of response conflict. We also hypothesized that pre-SMA is an important node in response conflict processing, and tested whether pre-SMA theta power increased for response conflict trials. Using event-related spectral perturbations and linear mixed modeling, we found that both R-IFG beta and pre-SMA theta increased for response conflict trials, with the R-IFG beta increase specific to trials with strong response conflict. This result supports a more generalized role for R-IFG beta in response inhibition, beyond simple stopping behavior towards response switching.

Significance Statement

Response inhibition is a core component of cognitive control. Neural mechanisms of response inhibition are typically studied using stopping paradigms. However, there is an unresolved debate regarding whether the response inhibition network is specific to stopping or generalizes to switching between tasks and overcoming conflict between competing response tendencies. Increased beta (12-30 Hz) in R-IFG has historically been interpreted as a marker of successful response inhibition in the stop-signal task. Here, we investigated the presence of this electrophysiological marker of response inhibition specifically during response conflict (switching). We found R-IFG beta power increased for trials with strong response conflict, and not for weak or no response conflict, thereby supporting a generalized role for R-IFG beta in response inhibition and switching.
Salivary Proinflammatory Cytokines IL-1β, IL-6 and TNF Decrease With Age
Authors: Costantino Evangelina , Castell Sofía Daiana , Harman María Florencia , Pistoresi- Palencia María Cristina , Actis Adriana Beatriz
Published: May 2022

Objective

to analyze salivary concentrations interleukin-1β (IL-1β), 6 (IL-6) and tumor necrosis factor (TNF) according to age in healthy subjects to determine baseline inflammatory state of the oral mucosa in elderly subjects, who are at higher risk of developing inflammation-related diseases.

Materials and methods

sixty-four healthy volunteers were divided into groups according to age: 20-39 (G1; n=20); 40-59 (G2; n=24); 60-80 years (G3; n=20). Their stomatognathic system and periodontal status were assessed; consumption of food sources of fatty acids (FA) was evaluated using a validated food frequency questionnaire. IL-1β, IL-6, and TNF salivary levels were determined (ELISA) in mixed unstimulated saliva. Kruskal Wallis and Spearman’s correlation tests were applied (p<0.05).

Results

salivary IL-1β and TNF levels were lower in G2 (p=0.001) and G3 (p<0.001) than in G1; IL-6 levels were lower in G3 than in G2 and G1 (p= <0.001). IL-1β showed the highest concentration in all groups (p<0.001). No statistically significant differences in salivary cytokine levels were observed on sex in any of the groups. Associations were observed between salivary cytokines and consumption of some foods containing FA.

Conclusion

salivary concentration of proinflammatory cytokines decreased with age. It could be influenced by ageing-related changes. In addtition, the baseline inflammatory state of the oral mucosa would appear to be influenced by dietary intake of sources of anti-inflammatory FA.

Clinical relevance

the knowledge about inflammatory state of the oral mucosa, as determined by salivary cytokine concentrations, could be useful for understanding and prevention of developing inflammation-related diseases.
Boid Inclusion Body Disease (BIBD) Is Also a Disease of Wild Boa Constrictors
Authors: Alfaro-Alarcón Alejandro , Hetzel Udo , Smura Teemu , Baggio Francesca , Morales Juan Alberto , Kipar Anja , Hepojoki Jussi
Published: May 2022

Reptarenaviruses cause Boid Inclusion Body Disease (BIBD), a potentially fatal disease, occurring in captive constrictor snakes boas and pythons worldwide. Classical BIBD, characterized by the formation of pathognomonic cytoplasmic inclusion bodies (IBs), occurs mainly in boas, whereas in pythons, for example, reptarenavirus infection most often manifests as central nervous system signs with limited IB formation. The natural hosts of reptarenaviruses are unknown, although wild constrictor snakes are among the suspects. Here, we report BIBD with reptarenavirus infection in indigenous captive and wild boid snakes in Costa Rica using histology, immunohistology, transmission electron microscopy, next-generation sequencing (NGS), and RT-PCR. The snakes studied represented diagnostic post mortem cases of captive and wild caught snakes since 1989. The results from NGS on archival paraffin blocks confirm that reptarenaviruses have been present in wild boa constrictors in Costa Rica already in the 1980s. Continuous sequences de novo assembled from the low-quality RNA obtained from paraffin embedded tissue allowed the identification of a distinct pair of reptrarenavirus S and L segments in all studied animals; in most cases reference assembly could recover almost complete segments. Sampling of three prospective cases in 2018 allowed examination of fresh blood or tissues, and resulted in identification of additional reptarenavirus segments and hartmanivirus co-infection. Our results show that BIBD is not only a disease of captive snakes, but also occurs in indigenous wild constrictor snakes in Costa Rica, suggesting boa constrictors to play a role in natural reptarenavirus circulation.

IMPORTANCE

The literature describes cases of boid inclusion body disease (BIBD) in captive snakes since the 1970s, and in the 2010s, others and we identified reptarenaviruses as the causative agent. BIBD affects captive snakes globally, but the origin and the natural host of reptarenaviruses remains unknown. In this report, we show BIBD and reptarenavirus infections in two native Costa Rican constrictor snake species, and by studying archival samples, we show that both the viruses and the disease have been present in wild snakes in Costa Rica at least since the 1980s. The diagnosis of BIBD in wild boa constrictors suggests that this species plays a role in the circulation of reptarenaviruses. Additional sample collection and analysis would help to clarify this role further and the possibility of e.g. vector transmission from an arthropod host.
Pervasive transcription enhances the accessibility of H-NS-silenced promoters and generates bistability in Salmonella virulence gene expression
Authors: Figueroa-Bossi Nara , Sanchez-Romero María Antonia , Kerboriou Patricia , Naquin Delphine , Mendes Clara , Bouloc Philippe , Casadesús Josep , Bossi Lionello
Published: May 2022

In Escherichia coli and Salmonella, many genes silenced by the nucleoid structuring protein H-NS are activated upon inhibiting Rho-dependent transcription termination. This response is poorly understood and difficult to reconcile with the view that H-NS acts mainly by blocking transcription initiation. Here we have analysed the basis for the upregulation of H-NS-silenced Salmonella Pathogenicity Island 1 (SPI-1) in cells depleted of Rho-cofactor NusG. Evidence from genetic experiments, semi-quantitative 5’ RACE-Seq and ChiP-Seq shows that transcription originating from spurious antisense promoters, when not stopped by Rho, elongates into a H-NS-bound regulatory region of SPI-1, displacing H-NS and rendering the DNA accessible to the master regulator HilD. In turn, HilD’s ability to activate its own transcription triggers a positive feedback loop that results in transcriptional activation of the entire SPI-1. Significantly, single-cell analyses revealed that this mechanism is largely responsible for the coexistence of two subpopulations of cells that, although genetically identical, either express or don’t express SPI-1 genes. We propose that cell-to-cell differences produced by stochastic spurious transcription, combined with feedback loops that perpetuate the activated state, can generate bimodal gene expression patterns in bacterial populations.
Mobile Laser Scanner understory characterization: an exploratory study on hazel grouse in Italian Alps
Authors: Galluzzi Marta , Puletti Nicola , Armanini Marco , Chirichella Roberta , Mustoni Andrea
Published: May 2022

Forest vegetation structure assessment is a time expensive effort with traditional methods. The Mobile Laser Scanner (MLS) technology can greatly speed up field works, achieve detailed quantification of three-dimensional forest structure at detailed resolution and drive forest management to increase the conservation status of forests-specialist bird species. In this study, using Mobile hand-held Laser Scanner (MLS), we calculated a fine-scale vegetation density index (namely the Plant Density Index, PDI) to characterize the vertical structure of forest subcanopy (0-10 m). The collected MLS point clouds were used to estimate the abundance of Potential Hiding Refuges (PHR) for the hazel grouse (Tetrastes bonasia), a sedentary bird extremely sensitive to forest structure and composition. The study was carried out in 10 plots located in the Adamello Brenta Geopark (Southern Alps, Italy). The species was detected in 8 out of 18 transects in an uneven-aged spruce forest with a discontinuous tree cover. The PDI decreases as the height increases, showing greater value in the shrub and herbaceous layer while the upper values are represented by trees stems, and branches. Visibility analysis of lower understory, highlighted PHR mean value of 73.2% (sd = 9.2%). In our area, PDI and PHR revealed that the environmental factors for hazel grouse occurrence are forests with open habitats, understory vegetation, and good hiding opportunities. Our study is the first application that uses MLS derived parameters to describe the ecological niche of a grouse and we presented the surveyed area as “case report” of hazel grouse habitat.
Interpreting and de-noising genetically engineered barcodes in a DNA virus
Authors: Blois Sylvain , Goetz Benjamin M. , Bull James J. , Sullivan Christopher S.
Published: May 2022

The concept of a nucleic acid barcode applied to pathogen genomes is easy to grasp and the many possible uses are straightforward. But implementation may not be easy, especially when growing through multiple generations or assaying the pathogen long-term. The potential problems include: the barcode might alter fitness, the barcode may accumulate mutations, and construction of the marked pathogens may result in unintended barcodes that are not as designed. Here, we generate approximately 5000 randomized barcodes in the genome of the prototypic small DNA virus murine polyomavirus. We describe the challenges faced with interpreting the barcode sequences obtained from the library. Our Illumina NextSeq sequencing recalled much greater variation in barcode sequencing reads than the expected 5000 barcodes – necessarily stemming from the Illumina library processing and sequencing error. Using data from defined control virus genomes cloned into plasmid backbones we develop a vetted post-sequencing method to cluster the erroneous reads around the true virus genome barcodes. These findings may foreshadow problems with randomized barcodes in other microbial systems and provide a useful approach for future work utilizing nucleic acid barcoded pathogens.
Allosteric links between the hydrophilic N-terminus and transmembrane core of human Na+/H+ antiporter NHA2
Authors: Velázquez Diego , Průša Vojtěch , Masrati Gal , Sychrova Hana , Ben-Tal Nir , Zimmermannova Olga
Published: May 2022

The human Na+/H+ antiporter NHA2 (SLC9B2) transports Na+ or Li+ across the plasma membrane in exchange for protons, and is implicated in various pathologies. It is a 537 amino acids protein with an 82 residues long hydrophilic cytoplasmic N-terminus followed by a transmembrane part comprising 14 transmembrane helices. We optimized the functional expression of HsNHA2 in the plasma membrane of a salt-sensitive Saccharomyces cerevisiae strain and characterized a set of mutated or truncated versions of HsNHA2 in terms of their substrate specificity, transport activity, localization and protein stability. We identified a highly conserved proline 246, located in the core of the protein, as being crucial for ion selectivity. The replacement of P246 with serine or threonine resulted in antiporters with altered substrate specificity and increased resistance to the HsNHA2-specific inhibitor phloretin that were not only highly active at an acidic pH of 4.0 (like the native antiporter), but also at neutral pH. We also experimentally confirmed the importance of a putative salt bridge between E215 and R432 for antiporter function and structural integrity. Truncations of the first 50 - 70 residues of the N-terminus doubled the transport activity of HsNHA2, whilst changes in the charge at positions E47, E56, K57, or K58 decreased the antiporter’s transport activity. Thus, the hydrophilic N-terminal part of the protein appears to allosterically autoinhibit its cation transport. Our data also show this in vivo approach to be useful for a rapid screening of SNP’s effect on HsNHA2 activity.
LaeA-dependent production of small molecules ofAspergillus nigerthat compete with specific antibodies that bind to human immune receptors
Authors: Escobar N. , Keizer E. M. , van Neer J. F. , Arentshorst M. , van Strijp J. A. G. , Haas P. J. A. , Ram A. F. J. , Punt P. J. , Wösten H. A. B. , de Cock H.
Published: May 2022

Microorganisms secrete a variety of compounds into their environment such as proteins, carbohydrates, and secondary metabolites. These molecules play diverse roles in the interaction of microbes with their abiotic and biotic environment. Little is known about secreted fungal molecules mediating immune evasion. Here we screened culture media of three Aspergilli to assess whether these fungi secrete molecules that can compete with specific antibodies that bind to human immune receptors. Culture media ofAspergillus fumigatusAf293,Aspergillus tubingensisCBS 133792 and the non-acidifying mutant strainAspergillus nigerD15#26 contained components that showed competition for binding to a total of 13 receptors, of which PSGL-1, CXCR1, and CXCR2, were shared between the three species. Filtration experiments showed that most, if not all, interacting components were ≤ 3 kDa. Production of the components that competed with antibodies to bind to CD88 and CXCR2 was shown to be regulated by LaeA. The component(s) that competed for binding to CXCR1 was not only produced in the non-acidifying strainAspergillus nigerD15#26 but also in the non-acidifyingoahAdeletion strain ofAspergillus niger. Together, these data show thatAspergillusspecies might produce small molecules that interact with human immune receptors.
A critique of the hypothesis that CA repeats are primary targets of neuronal MeCP2
Authors: Chhatbar Kashyap , Connelly John , Webb Shaun , Kriaucionis Skirmantas , Bird Adrian
Published: May 2022

The DNA binding protein MeCP2 is reported to bind methylated cytosine in CG and CA motifs in genomic DNA, but it was recently proposed that arrays of tandemly repeated CA containing either methylated or hydroxymethylated cytosine are the primary targets for MeCP2 binding and function. Here we investigated the predictions of this hypothesis using a range of published datasets. We failed to detect enrichment of cytosine modification at genomic CA repeat arrays in mouse brain regions and found no evidence for preferential MeCP2 binding at CA repeats. Moreover, we did not observe a correlation between the CA repeat density near genes and their degree of transcriptional deregulation when MeCP2 was absent. Our results do not provide support for the hypothesis that CA repeats are key mediators of MeCP2 function. Instead, we found that CA repeats are subject to CAC methylation to a degree that is typical of the surrounding genome and contribute modestly to MeCP2-mediated modulation of gene expression in accordance with their content of this canonical target motif.
AA-amyloidosis in cats (Felis catus) housed in shelters
Authors: Ferri Filippo , Ferro Silvia , Porporato Federico , Callegari Carolina , Guglielmetti Chiara , Mazza Maria , Ferrero Marta , Crinò Chiara , Gallo Enrico , Drigo Michele , Coppola Luigi M. , Gerardi Gabriele , Schulte Tim Paul , Ricagno Stefano , Vogel Monique , Storni Federico , Bachmann Martin F. , Vogt Anne-Cathrine , Caminito Serena , Mazzini Giulia , Lavatelli Francesca , Palladini Giovanni , Merlini Giampaolo , Zini Eric
Published: May 2022

Systemic AA-amyloidosis is a protein-misfolding disease that is characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. In domestic short-hair cats, AA-amyloidosis has only been anecdotally reported and is considered a rare disease. Here we report that an astonishing 57-73% of early deceased short-hair cats kept in three independent shelters suffer from amyloid deposition in the liver, spleen, or kidney. Histopathology and mass spectrometry of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B=0.026, CI95%=0.007-0.046; p=0.010). Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease.
The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data
Authors: Leonard Hampton L. , Murtadha Ruqaya , Martinez-Carrasco Alejandro , Muller-Nedebock Amica , Gil-Martinez Ana-Luisa , Illarionova Anastasia , Moore Anni , Bustos Bernabe I. , Jadhav Bharati , Huxford Brook , Storm Catherine , Towns Clodagh , Vitale Dan , Chetty Devina , Yu Eric , Jama Fatumah , Grenn Francis P. , Salazar Gabriela , Rateau Geoffrey , Iwaki Hirotaka , Elsayed Inas , Foote Isabelle , van Rensburg Zuné Jansen , Kim Jonggeol Jeff , Yuan Jie , Lake Julie , Brolin Kajsa , Senkevich Konstantin , Wu Lesley , Tan Manuela M.X. , Periñán María Teresa , Makarious Mary B , Ta Michael , Pillay Nikita Simone , Betancor Oswaldo Lorenzo , Reyes-Pérez Paula R. , Jerez Pilar Alvarez , Saini Prabhjyot , al-Ouran Rami , Sivakumar Ramiya , Real Raquel , Reynolds Regina H. , Hu Ruifneg , Abrahams Shameemah , Rao Shilpa C. , Antar Tarek , Leal Thiago Peixoto , Iankova Vassilena , Scotton William J. , Song Yeajin , Singleton Andrew , Nalls Mike A. , Dey Sumit , Bandres-Ciga Sara , Blauwendraat Cornelis , Noyce Alastair J.
Published: May 2022

Background

Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities.

Objective

To coordinate a virtual hackathon to develop novel PD research tools.

Methods

49 early career scientists from 12 countries collaborated in a virtual 3-day hackathon event in May 2021, during which they built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools.

Results

Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools.

Conclusion

Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early career researchers. The resources generated can be used to accelerate research on the genetics of PD.
The trade-off function of photorespiration in a changing environment
Authors: Hernandez Jakob Sebastian , Nägele Thomas
Published: May 2022

The photorespiratory pathway in plants comprises metabolic reactions distributed across several cellular compartments. It emerges from the dual catalytic function of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) which either carboxylates or oxygenates ribulose-1,5-bisphosphate (RuBP). Carboxylation reactions produce 3-phospho-glycerate (3PGA) molecules which are substrate for central carbohydrate metabolism while oxygenation forms 2-phosphoglycolate (2PG) molecules which are substrate for the multicompartmental recovery process of photorespiration. Further, 2PG is a strong inhibitor of several enzymes involved in the Calvin-Benson-Bassham cycle which challenges the experimental and theoretical study of carbon assimilation, photorespiration and metabolic regulationin vivo. Here, an approach of structural kinetic modeling (SKM) is presented to investigate the extend of stabilization of CBC and carbohydrate metabolism by photorespiration. Further, our approach highlights the importance of feedback regulation by 2-PG for alleviation of environmental perturbation. Our findings indicate that oxygenation of RuBP by Rubisco significantly stabilizes CBC activity and, thus, carbohydrate metabolism. Based on our findings, we suggest a trade-off function of photorespiration which reduces carbon assimilation rates but simultaneously stabilizes metabolism by increasing plasticity of metabolic regulation within the chloroplast. Furthermore, our analysis suggests a stabilizing effect of increasing the partition of newly assimilated carbon going towards sucrose biosynthesis. With this, our analysis sheds light on the role of a multicompartmental metabolic pathway in stabilizing plant metabolism within a changing environment.
Spontaneously produced lysogenic phages are an important component of the soybean Bradyrhizobium mobilome
Authors: Joglekar Prasanna , Ferrell Barbra D. , Jarvis Tessa , Haramoto Kona , Place Nicole , Dums Jacob T , Polson Shawn W. , Wommack K. Eric , Fuhrmann Jeffry J.
Published: May 2022

The ability to nodulate and fix atmospheric nitrogen in soybean root nodules makes soybean Bradyrhizobium spp. (SB) critical in supplying humanity’s nutritional needs. The intricacies of SB-plant interactions have been studied extensively; however, bradyrhizobial ecology as influenced by phages has received somewhat less attention even though these interactions may significantly impact soybean yield. In batch culture four SB strains, S06B (B. japonicum, S06B-Bj), S10J (B. japonicum, S10J-Bj), USDA 122 (B. diazoefficiens, USDA 122-Bd), and USDA 76T (B. elkanii, USDA 76-Be), spontaneously (without apparent exogenous chemical or physical induction) produced phages throughout the growth cycle; for three strains, phage concentrations exceeded cell numbers by ca. 3-fold after 48 h incubation. Observed spontaneously produced phages (SPP) were tailed. Phage terminase large-subunit protein phylogeny revealed possible differences in phage packaging and replication mechanisms. Bioinformatic analyses predicted multiple prophage regions within each SB genome preventing accurate identification of SPP genomes. A DNA sequencing approach was developed that accurately delineated the boundaries of four SPP genomes within three of the SB chromosomes. Read mapping suggested that the SPP are capable of transduction. In addition to the phages, bacterial strains S06B-Bj and USDA 76-Be were rich in mobile elements consisting of insertion sequences (IS) and large, conjugable, broad host range plasmids. The prevalence of SPP along with IS and plasmids indicate that horizontal gene transfer likely plays an outsized role in SB ecology and may subsequently impact soybean productivity.

Importance

Previous studies have shown that IS and plasmids mediate horizontal gene transfer (HGT) of symbiotic nodulation (nod) genes in SB; however, these events require close cell to cell contact which could be limited in soil environments. Bacteriophage assisted gene transduction through spontaneously produced prophages could provide stable means of HGT not limited by the constraints of proximal cell to cell contact. Phage mediated HGT events could be important in SB population ecology with concomitant impacts on soybean agriculture.
A Standardized Ontology for Naming tRNA-derived RNAs Based on Molecular Origin
Authors: Holmes Andrew D. , Chan Patricia P. , Chen Qi , Ivanov Pavel , Drouard Laurence , Polacek Norbert , Kay Mark A. , Lowe Todd M.
Published: May 2022

Small RNAs processed from transfer RNA are recognized to have regulatory functions distinct from protein synthesis. This rapidly advancing field has led to a constellation of transcript nomenclatures. Building upon the accepted tRNA naming system and linking tRNA-derived small RNAs to their molecular sources, we propose an improved nomenclature. Facilitated by the tDRnamer system, it will promote inter-study comparisons leveraging a biologically-rooted nomenclature for this emerging class of intriguing regulators.
A comprehensive list of the replication promoters of Bunyavirales reveals a unique promoter structure in Nairoviridae differing from other virus families
Authors: Neriya Yutaro , Kojima Shohei , Sakiyama Arata , Kishimoto Mai , Iketani Takao , Watanabe Tadashi , Abe Yuichi , Shimoda Hiroshi , Nakagawa Keisuke , Koma Takaaki , Matsumoto Yusuke
Published: May 2022

Bunyaviruses belong to the order Bunyavirales, the largest group of RNA viruses. They infect a wide variety of host species around the world, including plants, animals and humans, and pose a major threat to public health. Major families in the order Bunyavirales have tri-segmented negative-sense RNA genomes, the 5’ and 3’ ends of which form complementary strands that serve as a replication promoter. Elucidation of the mechanisms by which viral RNA-dependent RNA polymerase recognizes the promoter to initiates RNA synthesis is important for understanding viral replication and pathogenesis, and for developing antivirals. A list of replication promoter configuration patterns may provide details on the differences in the replication mechanisms among bunyaviruses. Here, by using public sequence data of all known bunyavirus species, we constructed a comprehensive list of the replication promoters comprising 40 nucleotides in both the 5’ and 3’ ends of the genome that form a specific complementary strand. We showed that among tri-segmented bunyaviruses, viruses belonging to the family Nairoviridae, including the highly pathogenic Crimean-Congo hemorrhagic fever virus, have evolved a GC-rich promoter structure that differs from that of other bunyaviruses. The unique promoter structure might be related to the large genome size of the family Nairoviridae among bunyaviruses. It is possible that the large genome architecture confers a pathogenic advantage. The promoter list provided in this report is expected to be useful for predicting virus family-specific replication mechanisms of segmented negative-sense RNA viruses.
Splashed E-box and AP-1 motifs cooperatively drive regeneration-response and shape regeneration abilities
Authors: Tamaki Teruhisa , Yoshida Takafumi , Shibata Eri , Nishihara Hidenori , Ochi Haruki , Kawakami Atsushi
Published: May 2022

Injury triggers genetic program to induce gene expression for regeneration. Several studies have recently reported the identification of regeneration-response enhancers (RREs) in zebrafish; however, it remains unclear whether a common mechanism operates in RREs. Here, we show that E-box and activator protein 1 (AP-1) motifs cooperatively function as RREs. We identified three RREs from the fn1b promoter by a search of conserved sequences and an in vivo transgenic assay for regeneration-response in zebrafish. Two of them derived from transposons displayed RRE activity only when combined with the −0.7 kb fn1b promoter, while another non-transposable element functioned as a standalone enhancer. A search for transcription factor-binding motifs and validation by transgenic assay revealed that both of E-box and AP-1 motifs are necessary and sufficient for RREs. Such RREs responded to variety of tissue injuries including zebrafish heart and Xenopus limb bud regenerations. Our findings highlight that regeneration is regulated by merging two activating signals evoked by tissue injuries. It is speculated that a large pool of potential enhancers in the genome shaped regenerative capacities during evolution.

SUMMARY STATEMENT

The study revealed that regeneration-response enhancer is composed of two transcription factor-binding motifs. The fidelity of regeneration-dependent gene expression is ensured by merging two activating signals evoked by injuries.