bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTAedes 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

AbstractThe 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 statementBy 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

SummaryA 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

AbstractMarine 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.SummaryNovel 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

AbstractHuman 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

AbstractThroughout 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

Abstract‘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

AbstractMalaria-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

AbstractBackgroundNucleic 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).MethodWe 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.ResultsThe 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.ConclusionsThe 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

AbstractMegakaryocytes (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

ABSTRACTA 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

AbstractInflammation 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

SummaryRoot 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.