bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifestyle physical activity intensity and rapid-rate non-sustained ventricular tachycardia in arrhythmogenic cardiomyopathy
Authors: Ramos-Maqueda Javier , Migueles Jairo H. , Molina-Jiménez María , Ruiz-González David , Cabrera-Borrego Eva , Ruiz-Salas Amalio , Soriano-Maldonado Alberto , Jiménez-Jáimez Juan
Published: July 2022

Objectives

This study aimed to investigate the association of accelerometer-measured lifestyle physical activity with the incidence of rapid-rate non-sustained ventricular tachycardias (RR-NSVT) during a 30-day recording period in AC patients.

Methods

This multicenter, observational study enrolled 72 AC patients, including right, left-, and biventricular forms of the disease, with underlying desmosomal and non desmosomal mutations. Lifestyle physical activity was objectively monitored with accelerometers (i.e., movement sensors), and RR-NSVT were identified from a textile Holter electrocardiogram (ECG) for 30 days as those faster than 188 bpm and longer than 18 beats.

Results

Sixty-three AC patients (38±17.6 years, 57% men) provided data on physical activity and ventricular tachycardias. A total of 17 patients experienced 1 ≥ RR-NSVTs, and a total of 35 events were recorded. Participants presenting RR-NSVTs during the 30-day measurement (n=17) did not perform more lifestyle physical activity (P=0.734), neither more activities of moderate-to-vigorous intensity (P=0.245) than their peers without RR-NSVTs in this period. Likewise, participants with RR-NSVTs did not increase their activity level, neither the activities of any intensity (−5 min/day on average) nor those of moderate-to-vigorous intensity (+2 min/day on average) in the days of RR-NSVTs occurrence. Finally, we observed that around half of the RR-NSVTs recorded in the 30 days occurred at rest (i.e., 19 RR-NSVTs), and the other half occurred after or during physical activity (i.e.,16 RR-NSVTs).

Conclusion

These findings suggest that lifestyle physical activity, mainly of light and moderate intensity, does not increase the risk for RR-NSVTs in AC patients.

Summary box

What is already known

Arrhythmogenic cardiomyopathy (AC) is associated to sport-triggered sudden cardiac death

Competitive sports and high-intensity exercise are contraindicated in AC patients

Rapid-rate non-sustained ventricular arrhythmias (RR-NSVT) are a surrogate of sudden cardiac death in this population

What this study adds

Conscious investigation on the relationship between lifestyle physical activity of different intensities with ventricular arrhythmias in AC patients

Accelerometer-measured lifestyle physical activity, mainly of light and moderate intensity, seem not to be associated with the occurrence of RR-NSVTs

How this study might affect clinical practice in the future

This study provides strong evidence for the promotion of lifestyle physical activity among AC patients to ensure they obtain the multiple benefits and risk reductions associated with physical activity
SpatialSort: A Bayesian Model for Clustering and Cell Population Annotation of Spatial Proteomics Data
Authors: Lee Eric , Chern Kevin , Nissen Michael , Wang Xuehai ,   IMAXT Consortium, Huang Chris , Gandhi Anita K. , Bouchard-Côté Alexandre , Weng Andrew P. , Roth Andrew
Published: July 2022

Emerging spatial proteomics technologies have created new opportunities to move beyond quantifying the composition of cell types in tissue and begin probing spatial structure. However, current methods for analysing such data are designed for non-spatial data and ignore spatial information. We present SpatialSort, a spatially aware Bayesian clustering approach that allows for the incorporation of prior biological knowledge. SpatialSort clusters cells by accounting for affinities of cells of different types to neighbours in space. Additionally, by incorporating prior information about cell types, SpatialSort outperforms current methods and can perform automated annotation of clusters.
dRFEtools: Dynamic recursive feature elimination for omics
Authors: Benjamin Kynon JM , Katipalli Tarun , Paquola Apuã CM
Published: July 2022

Technology advances have generated larger omics datasets with applications for machine learning. Even so, in many datasets, the number of measured features greatly exceeds the number of observations or experimental samples. Dynamic recursive feature elimination (RFE) provides a flexible feature elimination framework to tackle this problem and to gain biological insight by selecting feature sets that are relevant for prediction. Here, we developed dRFEtools that implements dynamic RFE, and show that it reduces computational time with high accuracy compared to RFE. Given a prediction task on a dataset, dRFEtools identifies a minimal, non-redundant, set of features and a functionally redundant set of features leading to higher prediction accuracy compared to RFE. We demonstrate dRFEtools’ ability to identify biologically relevant information from genomic data using RNA-Seq and genotype data from the BrainSeq Consortium. dRFEtools provides an interpretable and flexible tool to gain biological insights from omics data using machine learning.
A learning experience elicits sex-dependent neurogenomic responses in Bicyclus anynana butterflies
Authors: Ernst David A. , Agcaoili Gabrielle A. , Merrill Abbigail N. , Westerman Erica L.
Published: July 2022

Sexually dimorphic behavior is pervasive across animals, with males and females exhibiting different mate selection, parental care, foraging, dispersal, and territorial strategies. However, the genetic underpinnings of sexually dimorphic behaviors are poorly understood. Here we investigate gene networks and expression patterns associated with sexually dimorphic imprinting-like learning in the butterfly Bicyclus anynana. In this species, both males and females learn visual preferences, but learn preferences for different traits and use different signals as salient, unconditioned cues. To identify genes and gene networks associated with this behavior, we examined gene expression profiles of the brains and eyes of male and female butterflies immediately post training and compared them to the same tissues of naïve individuals. We found more differentially expressed genes and a greater number of significant gene networks in the eye, indicating a role of the peripheral nervous system in visual imprinting-like learning. Females had higher chemoreceptor expression levels than males, supporting the hypothesized sexual dimorphic use of chemical cues during the learning process. In addition, genes that influence B. anynana wing patterns (sexual ornaments), such as invected, spalt, and apterous, were also differentially expressed in the brain and eye, suggesting that these genes may influence both sexual ornaments and the preferences for these ornaments. Our results indicate dynamic and sex-specific responses to social scenario in both the peripheral and central nervous systems and highlight the potential role of wing patterning genes in mate preference and learning across the Lepidoptera.
First experimental evidence for active farming in ambrosia beetles and strong heredity of garden microbiomes
Authors: Diehl Janina M.C. , Kowallik Vienna , Keller Alexander , Biedermann Peter H. W.
Published: July 2022

Fungal cultivation is a defining feature for advanced agriculture in attine ants and fungus-farming termites. In a third supposedly fungus-farming group, wood-colonizing ambrosia beetles (Curculionidae: Scolytinae and Platypodinae), an experimental proof for the effectiveness of beetle activity for selective promotion of their food fungi over others is lacking and farming has only been assumed based on observations of social and hygienic behaviors.

Here, we experimentally removed mothers and their offspring from young nests of the fruit-tree pinhole borer,Xyleborinus saxesenii(Scolytinae). By amplicon sequencing of bacterial and fungal communities of nests with and without beetles we could show that beetles are indeed able to actively shift symbiont communities. Although being consumed, theRaffaeleafood fungi were more abundant when beetles were present while a weed fungus (Chaetomium sp.) as well as overall bacterial diversity were reduced in comparison to nests without beetles. Core symbiont communities were generally low diverse and there were strong signs for vertical transmission not only for the cultivars, but also for secondary symbionts. Our findings verify the existence of active farming, even though the exact mechanisms underlying the selective promotion and/or suppression of symbionts need further investigation.
BRAFV600E expression in thyrocytes causes recruitment of immunosuppressive STABILIN-1 macrophages
Authors: Spourquet C , Delcorte O , Lemoine P , Dauguet N , Loriot A , Achouri Y , Hollmén M , Jalkanen S , Huaux F , Lucas S , Van Meerbeeck P , Knauf JA , Fagin JA , Dessy C , Mourad M , Henriet P , Tyteca D , Marbaix E , Pierreux CE
Published: July 2022

Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancers (TC), and BRAFV600E genetic alteration is found in 60% of this endocrine cancer. This oncogene is associated with poor prognosis, resistance to radioiodine therapy and tumor progression. Histological follow-up by anatomo-pathologists reveals that 2/3 of surgically-removed thyroids do not present malignant lesions. Continued fundamental research into the molecular mechanisms of TC downstream of BRAFV600E remains thus central to better understand the clinical behavior of these tumors.

To study PTC, we used a mouse model in which expression of BRAFV600E is specifically switched on in thyrocytes by doxycycline administration. Upon daily intraperitoneal doxycycline injection, thyroid tissue rapidly acquired histological features mimicking human PTC. Transcriptomic analysis revealed major changes in immune signaling pathways upon BRAFV600E induction. Multiplex immunofluorescence confirmed the abundant recruitment of macrophages, among which a population of LYVE-1+/CD206+/STABILIN-1+ was dramatically increased. By genetically inactivating the gene coding for the scavenger receptor STABILIN-1, we showed an increase of CD8+ T cells in this in situ BRAFV600E dependent TC. Finally, we demonstrated the presence of CD206+/STABILIN-1+ macrophages in human thyroid pathologies. Altogether, we revealed the recruitment of immunosuppressive STABILIN-1 macrophages a PTC mouse model and the relevance of these observations in human thyroid tissues.
Cardiolipin coordinates inflammatory metabolic reprogramming through regulation of Complex II assembly and stability
Authors: Reynolds Mack B. , Hong Hanna S. , Michmerhuizen Britton C , Lawrence Anna-Lisa E. , Zhang Li , Knight Jason S. , Lyssiotis Costas A. , Abuaita Basel H. , O’Riordan Mary X.
Published: July 2022

Macrophage metabolic plasticity enables repurposing of electron transport from energy generation to inflammation and host defense. Altered Respiratory Complex II function has been implicated in cancer, diabetes and inflammation but regulatory mechanisms are incompletely understood. Here we show that macrophage inflammatory activation triggers Complex II disassembly and succinate dehydrogenase-B subunit loss through sequestration and mitophagy. Mitochondrial fission was required for lipopolysaccharide-stimulated succinate dehydrogenase-B degradation but not sequestration. We hypothesized that this Complex II regulatory mechanism might be coordinated by the mitochondrial phospholipid cardiolipin. Cardiolipin synthase knockdown prevented lipopolysaccharide-induced metabolic remodeling and Complex II disassembly, sequestration and degradation. Cardiolipin-depleted macrophages were defective in lipopolysaccharide-induced pro-inflammatory cytokine production, a phenotype partially rescued by Complex II inhibition. Thus, cardiolipin acts as a critical organizer of inflammatory metabolic remodeling.
The nervous system leverages the non-linear properties of the Achilles tendon to regulate ankle impedance during postural control
Authors: Jakubowski Kristen L. , Ludvig Daniel , Perrault Eric J. , Lee Sabrina S.M.
Published: July 2022

Regulating ankle impedance is essential for controlled interactions with the environment and rejecting unexpected disturbances. Ankle impedance in the sagittal plane depends strongly on the triceps surae and Achilles tendon, but their relative contributions remain unknown. It is commonly assumed that ankle impedance is controlled by changing muscle activation and, thereby, muscle impedance, but this ignores the fact that tendon impedance also changes with loading caused by increases in muscle activation. Thus, we sought to determine the relative contributions from the triceps surae and Achilles tendon during conditions relevant to postural control. We used a novel technique that combines B-mode ultrasound imaging with joint-level perturbations to quantify ankle, muscle, and tendon impedance simultaneously across activation levels from 0 – 30% of maximum voluntary contraction. We found that muscle and tendon stiffness, the static component of impedance, increased with voluntary plantarflexion contractions, but that muscle stiffness exceeded tendon stiffness at very low loads (21 ± 7 N). Above these loads, corresponding to 1.3% of maximal strength for an average participant in our study, ankle stiffness was determined predominately by Achilles tendon stiffness. Hence, the nervous system leverages the non-linear properties of the Achilles tendon to increase ankle stiffness during postural conditions.
Spatial frequency representation in V2 and V4 of macaque monkey
Authors: Zhang Ying , Schriver Kenneth E. , Hu Jia Ming , Roe Anna Wang
Published: July 2022

Spatial frequency (SF) is an important attribute in the visual scene and is a defining feature of visual processing channels. However there remains many unsolved questions about how primate visual cortex, in particular extrastriate areas V2 and V4, codes this fundamental information. Here, using intrinsic signal optical imaging in visual cortex of Macaque monkeys, we quantify the relationship between spatial frequency maps and (1) visual topography, (2) color and orientation maps, and (3) across visual areas V1, V2, and V4. We find that in orientation regions, low to high spatial frequency is mapped orthogonally to orientation; however, in color regions, which is reported to contain orthogonal axes of color and lightness, only low spatial frequencies are represented without a gradient of SF representation. This produces the first observation of a population spatial frequency fluctuation related to the repeating color/orientation organizations. These findings support a generalized hypercolumn model across cortical areas, comprised of two orthogonal parameters with additional parameters.
High intraspecific growth variability despite strong evolutionary heritage in a neotropical forest
Authors: Schmitt Sylvain , Hérault Bruno , Derroire Géraldine
Published: July 2022

Individual tree growth is a key determinant of species performance and a driver of forest dynamics and composition. Previous studies on tree growth unravelled the variation in species growth as a function of demographic trade-offs that are partially predicted using functional traits. They have explored the environmental determinants of species growth potential and the variation of intraspecific growth over space and time due to environment and biotic factors. However, variation in individual growth within species remains underexplored for a whole community and the relative role of species’ evolutionary heritage and of local environments remains unquantified. Here, based on 36 years of diameter records for thousands of mapped individuals belonging to 138 species, we assessed individual tree growth potential in a local neotropical forest community in the Amazon basin. We further related variation in individual growth potential with taxonomic levels, local topography, and neighbourhood crowding, before exploring species growth potential link to functional traits and distribution along the phylogeny. We found that most of the variation in growth potential was individual, and that taxonomic structure explained a third of the observed variation. Species growth potential was phylogenetically conserved with positive conservatism up to the genus level in the vast majority of species. Functional traits of roots, wood and leaves together predicted species growth potential. Phylogeny suggested joint selection of species’ growth strategies and associated functional traits during convergent evolutions. Finally, neighbourhood crowding had a significant effect on individual growth potential, although much of this inter-individual variation remains largely unexplained and the underlying ecological and evolutionary factors are still little explored. The high intraspecific variation observed could allow individuals in these hyperdiverse ecosystems to respond to the variable light and competitive conditions offered by successional niches during forest gap dynamics.
Strong positive selection in Aedes aegypti and the rapid evolution of insecticide resistance
Authors: Love R. Rebecca , Sikder Josh R. , Vivero Rafael J. , Matute Daniel R. , Schrider Daniel R.
Published: July 2022

Aedes aegypti vectors the pathogens that cause dengue, yellow fever, Zika virus, and chikungunya, and is a serious threat to public health in tropical regions. Decades of work has illuminated many aspects of Ae. aegypti’s biology and global population structure, and has identified insecticide resistance genes; however, the size and repetitive nature of the Ae. aegypti genome have limited our ability to detect positive selection in this mosquito. Combining new whole genome sequences from Colombia with publicly available data from Africa and the Americas, we identify multiple strong candidate selective sweeps in Ae. aegypti, many of which overlap genes linked to or implicated in insecticide resistance. We examine the voltage-gated sodium channel gene in three American cohorts, and find evidence for successive selective sweeps in Colombia. The most recent sweep encompasses an intermediate-frequency haplotype containing four candidate insecticide resistance mutations that are in near-perfect linkage disequilibrium with one another in the Colombian sample. We hypothesize that this haplotype may continue to rapidly increase in frequency and perhaps spread geographically in the coming years. These results extend our knowledge of how insecticide resistance has evolved in this species, and add to a growing body of evidence suggesting Ae. aegypti has an extensive genomic capacity to rapidly adapt to insecticide-based vector control.
Specification of the endocrine primordia controlling insect moulting and metamorphosis by the JAK/STAT signalling pathway
Authors: García-Ferrés Mar , Sánchez-Higueras Carlos , Espinosa-Vázquez Jose Manuel , Hombría James C-G
Published: July 2022

The corpora allata and the prothoracic glands control moulting and metamorphosis in insects. These endocrine glands are specified in the maxillary and labial segments at positions homologous to those forming the trachea in more posterior segments. Glands and trachea can be homeotically transformed into each other suggesting that all three evolved from a metamerically repeated organ that diverged to form glands in the head and respiratory organs in the trunk. While much is known about tracheal specification, there is limited information about corpora allata and prothorathic gland specification. Here we show that the expression of a key regulator of early gland development, the snail gene, is controlled by the Dfd and Scr Hox genes and by the Hedgehog and Wnt signalling pathways that induce localised transcription of upd, the ligand of the JAK/STAT signalling pathway, which lies at the heart of gland specification. Our results show that the same upstream regulators are required for the early gland and tracheal primordia specification, reinforcing the hypothesis that they originated from a segmentally repeated organ present in an ancient arthropod.

Summary statement

By analysing snail regulation in the CA and PG we describe their specification network, which converges on JAK/STAT pathway activation and reveals shared upstream regulators with the trachea.
Revisiting the significance of keratin expression in complex epithelia
Authors: Cohen Erez , Johnson Craig , Redmond Catherine J. , Nair Raji R. , Coulombe Pierre A.
Published: July 2022

A large group of keratin genes (n=54 in the human genome) code for intermediate filament (IF)-forming proteins and show differential regulation in epithelial cells and tissues. Keratin expression can be highly informative about the type of epithelial tissue, differentiation status of constituent cells, and biological context (e.g., normal vs. diseased settings). The foundational principles underlying the use of keratin expression to gain insight about epithelial cells and tissues primarily originated in pioneering studies conducted in the 1980s. The recent emergence of single cell transcriptomics provides an opportunity to revisit these principles and gain new insight into epithelial biology. Re-analysis of single cell RNAseq data collected from human and mouse skin has confirmed long-held views regarding the quantitative importance and pairwise regulation of specific keratin genes in keratinocytes of surface epithelia. Further, such analyses confirm and extend the notion that changes in keratin gene expression occur gradually as progenitor keratinocytes commit to and undergo differentiation, and challenge the prevailing assumption that specific keratin combinations reflect a mitotic vs. a post-mitotic, differentiating state. Our findings provide a blueprint for similar analyses in other tissues, and warrant a more nuanced approach in the use of keratin genes as biomarkers in epithelia.
Message in a Bottle: Archived DNA Reveals Marine Heatwave-Associated Shifts in Fish Assemblages
Authors: Gold Zachary , Kelly Ryan P. , Shelton Andrew Olaf , Thompson Andrew R. , Goodwin Kelly D. , Gallego Ramón , Parsons Kim M. , Thompson Luke R. , Kacev Dovi , Barber Paul H.
Published: July 2022

Marine heatwaves can drive large-scale shifts in marine ecosystems but studying their impacts on whole species assemblages can be difficult. Here, we leverage the taxonomic breadth and resolution of DNA sequences derived from environmental DNA (eDNA) in the ethanol of a set of 23-year longitudinal ichthyoplankton samples, combining these with microscopy-derived ichthyoplankton identification to yield higher-resolution, species-specific quantitative abundance estimates of fish assemblages in the California Current Large Marine Ecosystem during and after the 2014–16 Pacific marine heatwave. This integrated dataset reveals patterns of tropicalization with increases in southern, mesopelagic species and associated declines in important temperate fisheries targets (e.g., North Pacific Hake (Merluccius productus) and Pacific Sardine (Sardinops sagax)). We observed novel assemblages of southern, mesopelagic fishes and temperate species (e.g., Northern Anchovy, Engraulis mordax) even after the return to average water temperatures. Our innovative preservative derived eDNA metabarcoding and quantitative modeling approaches open the door to reconstructing the historical dynamics of assemblages from modern and archived samples worldwide.

Novel quantitative abundance estimates from archived DNA reveals marine heatwave-associated shifts in fish assemblages.
Data-driven discovery of canonical large-scale brain dynamics
Authors: Piccinini Juan , Deco Gustavo , Kringelbach Morten , Laufs Helmut , Perl Yonatan Sanz , Tagliazucchi Enzo
Published: July 2022

Human behavior and cognitive function correlate with complex patterns of spatio-temporal brain dynamics, which can be simulated using computational models with different degrees of biophysical realism. We used a data-driven optimization algorithm to determine and classify the types of local dynamics that enable the reproduction of different observables derived from functional magnetic resonance recordings. The phase space analysis of the resulting equations revealed a predominance of stable spiral attractors, which optimized the similarity with the empirical data in terms of the synchronization, metastability, and functional connectivity dynamics. For stable limit cycles, departures from harmonic oscillations improved the fit in terms of functional connectivity dynamics. Eigenvalue analyses showed that the proximity to Hopf bifurcations improved the accuracy of the simulation for wakefulness, while deep sleep was associated with increased stability. Our results provide testable predictions that constrain the landscape of suitable biophysical models, while supporting noise-driven dynamics close to a bifurcation as a canonical mechanism underlying the complex fluctuations that characterize endogenous brain activity.
Computationally efficient framework for diagnosing, understanding, and predicting biphasic population growth
Authors: Murphy Ryan J. , Maclaren Oliver J. , Calabrese Alivia R. , Thomas Patrick B. , Warne David J. , Williams Elizabeth D. , Simpson Matthew J.
Published: July 2022

Throughout the life sciences, biological populations undergo multiple phases of growth, often referred to asbiphasic growthfor the commonly-encountered situation involving two phases. Biphasic population growth occurs over a massive range of spatial and temporal scales, ranging from microscopic growth of tumours over several days, to decades-long re-growth of corals in coral reefs that can extend for hundreds of kilometres. Different mathematical models and statistical methods are used to diagnose, understand, and predict biphasic growth. Common approaches can lead to inaccurate predictions of future growth that may result in inappropriate management and intervention strategies being implemented. Here we develop a very general computationally efficient framework, based on profile likelihood analysis, for diagnosing, understanding, and predicting biphasic population growth. The two key components of the framework are: (i) an efficient method to form approximate confidence intervals for the change point of the growth dynamics and model parameters; and, (ii) parameter-wise profile predictions that systematically reveal the influence of individual model parameters on predictions. To illustrate our framework we explore real-world case studies across the life sciences.
An agent-based modelling framework for assessing SARS-CoV-2 indoor airborne transmission risk
Authors: Knapp Simon , Dunne Robert , Tabor Bruce , Hickson Roslyn I. , Dunstall Simon
Published: July 2022

We develop a framework for modelling the risk of infection from airborne Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in well-mixed environments in the presence of interventions designed to reduce infection risk. Our framework allows development of models that are highly tailored to the specifics of complex indoor environments, including layout, people movements, and ventilation. We explore its utility through case studies, two of which are based on actual sites.

Our results reflect previously quantified benefits of masks and vaccinations. We also produce quantitative estimates of the effects of air filters, and reduced indoor occupancy for which we cannot find quantitative estimates but for which positive benefits have been postulated.

We find that increased airflow reduces risk due to dilution, even if that airflow is via recirculation in a large space. Our case studies have identified interventions which seem to generalise, and others which seem to be dependent on site-specific factors, such as occupant density.
Amis Pacilo and Yami Cipoho are not the same as the Pacific breadfruit starch crop—Target enrichment phylogenomics of a long-misidentified Artocarpus species sheds light on the northward Austronesian migration from the Philippines to Taiwan
Authors: Chuang Chia-Rong , Hsieh Chia-Lun , Chang Chi-Shan , Wang Chiu-Mei , Tandang Danilo N. , Gardner Elliot M. , Audi Lauren , Zerega Nyree J. C. , Chung Kuo-Fang
Published: July 2022

‘Breadfruit’ is a common tree species in Taiwan. In the indigenous Austronesian Amis culture of eastern Taiwan, ‘breadfruit’ is known as Pacilo, and its fruits are consumed as food. On Lanyu (Botel Tobago) where the indigenous Yami people live, ‘breadfruit’ is called Cipoho and used for constructing houses and plank-boats. Elsewhere in Taiwan, ‘breadfruit’ is also a common ornamental tree. As an essential component of traditional Yami culture, Cipoho has long been assumed to have been transported from the Batanes Island of the Philippines to Lanyu. As such, it represents a commensal species that potentially can be used to test the hypothesis of the northward Austronesian migration ‘into’ Taiwan. However, recent phylogenomic studies using target enrichment show that Taiwanese ‘breadfruit’ might not be the same as the Pacific breadfruit (Artocarpus altilis) that was domesticated in Oceania and widely cultivated throughout the tropics. To resolve persistent misidentification of this culturally and economically important tree species of Taiwan, we sampled 36 trees of Taiwanese Artocarpus and used the Moraceae probe set to enrich 529 nuclear genes. Along with 28 archived Artocarpus sequence datasets (representing a dozen taxa from all subgenera), phylogenomic analyses showed that all Taiwanese ‘breadfruit’ samples, together with a cultivated ornamental tree from Hawaii, form a fully supported clade within the A. treculianus complex, which is composed only of endemic Philippine species. Morphologically, the Taiwanese ‘breadfruit’ matches the characters of A. treculianus. Within the Taiwanese samples of A. treculianus, Amis samples form a fully supported clade derived from within the paraphyletic grade composed of Yami samples, suggesting a Lanyu origin. Results of our target enrichment phylogenomics are consistent with the scenario that Cipoho was transported northward from the Philippines to Lanyu by Yami ancestors, though the possibility that A. treculianus is native to Lanyu cannot be ruled out completely.
An Sfi1-like centrin-interacting centriolar plaque protein affects nuclear microtubule homeostasis
Authors: Wenz Christoph , Simon Caroline S. , Romão Tatiany Patricia , Stürmer Vanessa , Machado Marta , Klages Natacha , Klemmer Anja , Voß Yannik , Ganter Markus , Brochet Mathieu , Guizetti Julien
Published: July 2022

Malaria-causing parasites achieve rapid proliferation in human blood through multiple rounds of asynchronous nuclear division followed by daughter cell formation. Nuclear divisions critically depend on the centriolar plaque, which organizes intranuclear spindle microtubules. The centriolar plaque consists of an extranuclear compartment, which is connected via a nuclear pore-like structure to a chromatin-free intranuclear compartment. Composition and function of this non-canonical centrosome remain largely elusive. Centrins, which reside in the extranuclear part, are among the very few centrosomal proteins conserved in Plasmodium falciparum. Here we identify a novel centrin-interacting centriolar plaque protein. Conditional knock down of this Sfi1-like protein (PfSlp) caused a growth delay in blood stages, which correlated with a reduced number of daughter cells. Surprisingly, intranuclear tubulin abundance was significantly increased, which raises the hypothesis that the centriolar plaque might be implicated in regulating tubulin levels. Disruption of microtubule homeostasis caused polymerization of excess microtubules and aberrant mitotic spindles. Time-lapse microscopy revealed that this prevented or delayed spindle extension. Our study thereby identifies a novel extranuclear centriolar plaque factor and establishes a functional link to the intranuclear compartment of this divergent eukaryotic centrosome.
Electricity-free nucleic acid extraction method from dried blood spots on filter paper for point-of-care diagnostics
Authors: Malpartida-Cardenas Kenny , Baum Jake , Cunnington Aubrey , Georgiou Pantelis , Rodriguez-Manzano Jesus
Published: July 2022

Background

Nucleic acid extraction is a crucial step for molecular biology applications, being a determinant for any diagnostic test procedure. Dried blood spots (DBS) have been used for decades for serology, drug monitoring, environmental investigations, and molecular studies. Nevertheless, nucleic acid extraction from DBS remains one of the main challenges to translate them to the point-of-care (POC).

Method

We have developed a fast nucleic acid extraction (NAE) method from DBS which is electricity-free and relies on cellulose filter papers (DBSFP). The performance of NAE was assessed with loop-mediated isothermal amplification (LAMP), targeting the human reference gene beta-actin. The developed method was evaluated against FTA cards and magnetic bead-based purification, using time-to-positive (min) for comparative analysis. We optimised and validated the developed method for elution (eluted disk) and disk directly in the reaction (in-situ disk), RNA and DNA detection, and whole blood stored in anticoagulants (K2EDTA and lithium heparin). Furthermore, the compatibility of DBSFP with colourimetric detection was studied to show the transferability to the POC.

Results

The proposed DBSFP is based on grade 3 filter paper pre-treated with 8% (v/v) igepal surfactant, 1 min washing step with PBS 1X and elution in TE 1X buffer after 5 min incubation at room temperature, enabling NAE under 7 min. Obtained results were comparable to gold standard methods across tested matrices, targets and experimental conditions, demonstrating the versatility of the methodology. Lastly, eluted disk colourimetric detection was achieved with a sample-to-result turnaround time under 35 min.

Conclusions

The developed method is a fast, electricity-free, and low-cost solution for NAE from DBSFP enabling molecular testing in virtually any POC setting.
The intracellular and plasma membrane pools of PI4P control megakaryocyte maturation and proplatelet formation
Authors: Bura Ana , Begonja Antonija Jurak
Published: July 2022

Megakaryocytes (MKs) develop from hematopoietic stem cells (HSCs) after stimulation by the cytokine thrombopoietin (TPO). During megakaryopoiesis, MKs enlarge, undergo the process of endomitosis and develop intracellular membranes (the demarcation membrane system, DMS) which serve as a source for future platelets (PLTs). During DMS formation, there is an active transport from the Golgi apparatus to the DMS for the delivery of proteins, lipids, and membranes. The most important phosphoinositide that controls anterograde transport from the Golgi apparatus to the PM is phosphatidylinositol-4-monophosphate (PI4P) controlled by the SACM1L phosphatase at the Golgi and the endoplasmic reticulum (ER). The role of SACM1L and PI4P in megakaryopoiesis has not been investigated so far. Here we show that in primary mouse MKs, SACM1L is mostly localized and condensed perinuclearly in immature MKs, while at later stages it is mostly dispersed and confines to the ER. At the same time, PI4P is mostly found at the Golgi apparatus and the plasma membrane (PM) in immature MKs while in mature MKs it is in the periphery of the cell and at the PM. The exogenous expression of wild-type, but not C389S mutant (catalytically dead) SACM1L, results in the retention of the Golgi apparatus leading to the increased number of immature MKs, as well as a decreased number of MKs that form proplatelets. The inhibition of the production of PI4P specifically at the PM (inhibiting PI4-kinase IIIα) resulted also in a significant decrease of MKs that form proplatelets. These results indicate that both Golgi and PM pools of PI4P mediate MK maturation and proplatelet formation.
Computer Simulation of the interaction between SARS-CoV-2 Spike Protein and the Surface of Coinage Metals
Authors: Sahihi Mehdi , Faraudo Jordi
Published: July 2022

A prominent feature of the SARS-CoV-2 virus is the presence of a large glycoprotein spike protruding from the virus envelope. The spike determines the interaction of the virus with the environment and the host. Here, we used an all-atom molecular dynamics simulation method to investigate the interaction of up and down conformations of the S1 subunit of the SARS-CoV-2 spike with the (100) surface of Au, Ag and Cu. Our results revealed that the spike protein is adsorbed onto the surface of these metals, being Cu the metal with the highest interaction with the spike. In our simulations, we considered the spike protein in both its up conformation Sup(one receptor binding domain exposed) and down conformation Sdown(no exposed receptor binding domain). We found that the affinity of the metals for the up conformation was higher than their affinity for the down conformation. The structural changes in the Spike in the up conformation were also larger than the changes in the down conformation. Comparing the present results for metals with those obtained in our previous MD simulations of Supwith other materials (celulose, graphite, and human skin models), we see that Au induces the highest structural change in Sup, larger than those obtained in our previous studies.

GRAPHICAL ABSTRACT
Discovery of an AIM2 inflammasome inhibitor for the treatment of DNA-driven inflammatory disease
Authors: Green Jack P. , El-Sharkawy Lina Y. , Roth Stefan , Zhu Jie , Cao Jiayu , Leach Andrew G. , Liesz Arthur , Freeman Sally , Brough David
Published: July 2022

Inflammation driven by DNA sensors is now understood to be central to disease pathogenesis. Here we describe new inhibitors of pathogenic DNA sensing, primarily of the inflammasome forming sensor AIM2. Molecular modelling and biochemistry has revealed potent inhibitors of AIM2 that work by binding competitively to the DNA binding site. Though less potent, these AIM2 inhibitors, 4-sulfonic calixarenes, also inhibit DNA sensors cGAS and TLR9 demonstrating a broad utility against pathogenic DNA-driven inflammatory responses. The 4-sulfonic calixarenes inhibited AIM2 dependent post-stroke T cell death, highlighting a proof of concept that the 4-sulfonic calixarenes could be effective at combatting post-stroke immunosuppression. By extension, we propose a broad utility against DNA driven inflammation in disease. Finally, we reveal that the ancient drug suramin, by virtue of its structural similarities, is an excellent inhibitor of DNA-dependent inflammation and propose that suramin could be rapidly repurposed to meet an ever increasing clinical need.
Extensive plant use of exometabolites
Authors: Hu Yuntao , Andeer Peter F. , Zheng Qing , Kosina Suzanne M. , Jardine Kolby J. , Ding Yezhang , Han La Zhen , Gao Yu , Zengler Karsten , Bowen Benjamin P. , Mortimer Jenny C. , Vogel John P. , Northen Trent R.
Published: July 2022

Root exudation has been extensively studied due to its importance in soil carbon cycling and in supporting growth of soil microbes. However, the extent and dynamics of plant uptake of exogenous metabolites is poorly understood. To gain new insights into these processes we used13C-tracing to characterize plant uptake of exometabolites across a panel of diverse plant species (Arabidopsis thaliana, Brachypodium distachyon, Lotus japonicus, Panicum virgatum, andKalanchoe fedtschenkoi) grown in sterile hydroponic cultures. The uptake of exometabolites accounted for 23% of the overallB. distachyoncarbon budget, and we identified 33 metabolites that were taken up by plants. Counterintuitively, many metabolites had higher uptake rates during the day vs. night. Thirteen of the metabolites from root exudates were found to promote root growth inA. thaliana, including hydroxybenzoate, threonate,N-acetyl-glucosamine, and uracil. Together these results indicate that the root uptake of organics can account for a significant portion of the plant carbon budget and that exogenous small molecules used by plants alter root growth with implications for plant nutrition, organic farming, soil nutrient cycling, and rhizosphere community dynamics.
Bipartite viral RNA genome heterodimerization influences genome packaging and virion thermostability
Authors: Zhou Yiyang , Routh Andrew L.
Published: July 2022

Diverse RNA-RNA interactions occur throughout the lifecycle of RNA viruses, including genome dimerization or multimerization through non-covalent association of two or more genomic segments. Both homo-dimerization of retrovirus genomic RNA and hetero-multimerization of genomic segments of multipartite viruses are recognized as important factors that govern genome packaging. The heterodimer of the bipartite alphanodaviruses represents a unique case as its formation is conserved among different virus species but is only observed within the context of fully assembled virus particles. In spite of this, the RNA sequences involved in heterodimerization are unknown. It also remains unclear whether the formation of this heterodimer might impact any stage of the virus lifecycle. In this study, we used Flock House virus (FHV) as a model system to uncover the nucleotide composition of the heterodimer and dissected the impact of heterodimer formation upon numerous stages of the virus lifecycle. We developed a novel Next-Generation Sequencing (NGS) approach called “XL-ClickSeq” to probe candidate heterodimer sequences. We found that the heterodimer is formed via intermolecular base-pairing and its formation is retained in defective virus particles. One heterodimer site was identified by thermodynamic prediction that, upon mutagenic disruption, exhibited significant deficiencies in genome packaging and encapsidation specificity to viral genomic RNA. Furthermore, we demonstrate that disruption of this RNA secondary structure directly impacts the thermostability of mature virus particles. These results demonstrated that the intermolecular RNA-RNA interactions within the encapsidated genome of an RNA virus can have an important impact on virus particle integrity and stability and thus its transmission to a new host.
The kinase Rio1 and a ribosome collision-dependent decay pathway survey the integrity of 18S rRNA cleavage
Authors: Parker Melissa D. , Getzler Adam J. , Karbstein Katrin
Published: July 2022

The 18S rRNA sequence is highly conserved, particularly at its 3’-end. In contrast, the sequence around the 3’-end is degenerate with similar sites nearby. How RNA is correctly processed by the endonuclease Nob1 is not known, especially because in vitro experiments have shown it to be error-prone. Here we used yeast genetics, biochemistry, and next generation sequencing to investigate a role for Rio1 in monitoring the 3’-end of 18S rRNA. We demonstrate that Nob1 can miscleave its rRNA substrate and that miscleaved rRNA accumulates upon bypassing the Rio1-mediated quality control step, but not in healthy cells with intact quality control mechanisms. Mechanistically, we show that Rio1 binding to miscleaved rRNA is weakened. Accordingly, excess Pno1 results in accumulation of miscleaved rRNA. Ribosomes containing miscleaved rRNA enter the polysomes and produce dominant negative growth defects, suggesting that they cause defects during translation. Our data strongly suggest that ribosome collisions identify these miscleaved 18S rRNA-containing ribosomes as partially functional and target them for degradation. Altogether, the data support a model in which Rio1 inspects the 3’-end of the nascent 18S rRNA, only removing Nob1 and Pno1 from the ribosomes with precisely cleaved 18S rRNA to prevent miscleaved 18S rRNA-containing ribosomes from erroneously engaging in translation, where they induce ribosome collisions. The data also demonstrate how ribosome collisions “purify” the cells of altered ribosomes with different functionalities, with important implications for the concept of ribosome heterogeneity.
TNF licenses macrophages to undergo rapid caspase-1, -11, and -8-mediated cell death that restricts Legionella pneumophila infection
Authors: Pollock Tzvi , R. Vázquez Marrero Víctor , Brodsky Igor E. , Shin Sunny
Published: July 2022

The inflammatory cytokine tumor necrosis factor (TNF) is associated with host defense against many intracellular pathogens, including Legionella pneumophila. Legionella causes the severe pneumonia Legionnaires’ Disease and predominantly affects individuals with a suppressed immune system, such as those receiving therapeutic TNF blockade to treat autoinflammatory disorders. TNF induces pro-inflammatory gene expression, cellular proliferation, and survival signals in certain contexts, but can also trigger programmed cell death in others. It remains unclear, however, which of the many downstream activities of TNF contribute to control of intracellular bacterial pathogens like Legionella. In this study, we demonstrate that TNF signaling licenses macrophages to die rapidly in response to Legionella infection. We find that TNF-licensed cells undergo rapid gasdermin-dependent, pyroptotic death downstream of inflammasome activation. We also find that TNF signaling upregulates components of the inflammasome response, and that the caspase-11 mediated non-canonical inflammasome is the first inflammasome to be activated, with caspase-1 and caspase-8 mediating delayed pyroptotic death. We find that all three caspases are collectively required for optimal TNF-mediated restriction of bacterial replication in macrophages. Furthermore, caspase-8 is required for control of pulmonary Legionella infection. These findings reveal a TNF-dependent mechanism in macrophages for the activation of rapid cell death that is collectively mediated by caspases-1, -8, and -11 and subsequent restriction of Legionella infection.
Unexpected higher convergence of human-great ape enteric viromes in central African forest than in a European zoo: A One Health analysis
Authors: Narat Victor , Salmona Maud , Kampo Mamadou , Heyer Thibaut , Mercier-Delarue Severine , Ranger Noémie , Rupp Stephanie , Ambata Philippe , Njouom Richard , Simon François , Le Goff Jérôme , Giles-Vernick Tamara
Published: July 2022

Human-animal pathogenic transmissions threaten both human and animal health, and the processes catalyzing zoonotic spillover and spillback are complex. Prior field studies offer partial insight into these processes but overlook animal ecologies and human perceptions and practices facilitating human-animal contact. Conducted in Cameroon and a European zoo, this holistic study elucidates these processes, integrating metagenomic, historical, anthropological and great ape ecological analyses, and real-time evaluation of human-great ape contact types and frequencies. Surprisingly, we find more enteric virome sharing between Cameroonian humans and great apes than in the zoo, a virome convergence between Cameroonian humans and gorillas, and adenovirus and enterovirus taxa as most frequently shared between Cameroonian humans and great apes. In addition to physical contact from hunting, meat handling and fecal exposure, overlapping human cultivation and gorilla pillaging in forest gardens explain these unexpected findings. Our multidisciplinary study identifies environmental co-use as a complementary mechanism for viral sharing.