bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Multispecies Coalescent Model Outperforms Concatenation across Diverse Phylogenomic Data Sets
Authors: Jian Xiaodong , Edwards Scott V. , Liu Liang 
Published: December 2019

ABSTRACTA statistical framework of model comparison and model validation is essential to resolving the debates over concatenation and coalescent models in phylogenomic data analysis. A set of statistical tests are here applied and developed to evaluate and compare the adequacy of substitution, concatenation, and multispecies coalescent (MSC) models across 47 phylogenomic data sets collected across tree of life. Tests for substitution models and the concatenation assumption of topologically concordant gene trees suggest that a poor fit of substitution models (44% of loci rejecting the substitution model) and concatenation models (38% of loci rejecting the hypothesis of topologically congruent gene trees) is widespread. Logistic regression shows that the proportions of GC content and informative sites are both negatively correlated with the fit of substitution models across loci. Moreover, a substantial violation of the concatenation assumption of congruent gene trees is consistently observed across 6 major groups (birds, mammals, fish, insects, reptiles, and others, including other invertebrates). In contrast, among those loci adequately described by a given substitution model, the proportion of loci rejecting the MSC model is 11%, significantly lower than those rejecting the substitution and concatenation models, and Bayesian model comparison strongly favors the MSC over concatenation across all data sets. Species tree inference suggests that loci rejecting the MSC have little effect on species tree estimation. Due to computational constraints, the Bayesian model validation and comparison analyses were conducted on the reduced data sets. A complete analysis of phylogenomic data requires the development of efficient algorithms for phylogenetic inference. Nevertheless, the concatenation assumption of congruent gene trees rarely holds for phylogenomic data with more than 10 loci. Thus, for large phylogenomic data sets, model comparison analyses are expected to consistently and more strongly favor the coalescent model over the concatenation model. Our analysis reveals the value of model validation and comparison in phylogenomic data analysis, as well as the need for further improvements of multilocus models and computational tools for phylogenetic inference.
Structure-guided molecular grafting of a complex broadly neutralizing viral epitope
Authors: Bajic Goran , Maron Max J. , Tian Ming , Kelsoe Garnett , Kuraoka Masayuki , Schmidt Aaron G. 
Published: December 2019

ABSTRACTAntigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a “universal” influenza vaccine will come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use non-circulating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These “resurfaced” HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and H1/H3 cross-reactive bnAbs with high affinity. Subsequent serological analyses from murine prime-boost immunizations show that the rsHAs are both immunogenic and can enrich for RBS-directed antibodies. Our structure-guided, RBS grafting approach provides candidate immunogens for selectively presenting a conserved viral epitope.
Paralogs in the PKA regulon traveled different evolutionary routes to divergent expression in budding yeast
Authors: Heineike Benjamin Murray , El-Samad Hana 
Published: December 2019

AbstractFunctional divergence of duplicate genes, or paralogs, is an important driver of novelty in evolution. In the model yeast Saccharomyces cerevisiae, there are 547 paralog gene pairs that survive from an interspecies Whole Genome Hybridization (WGH) that occurred ∼100MYA. Many WGH paralogs (or ohnologs) are known to have differential expression during the yeast Environmental Stress Response (ESR), of which Protein Kinase A (PKA) is a major regulator. While investigating the transcriptional response to PKA inhibition in S. cerevisiae, we discovered that approximately 1/6th (91) of all ohnolog pairs were differentially expressed with a striking pattern. One member of each pair tended to have low basal expression that increased upon PKA inhibition, while the other tended to have high but unchanging expression. Examination of PKA inhibition data in the pre-WGH species K. lactis and PKA-related stresses in other budding yeasts indicated that unchanging expression in response to PKA inhibition is likely to be the ancestral phenotype prior to duplication. Analysis of promoter sequences of orthologs of gene pairs that are differentially expressed in S. cerevisiae further revealed that the emergence of PKA-dependence took different evolutionary routes. In some examples, regulation by PKA and differential expression appears to have arisen following the WGH, while in others, regulation by PKA appears to have arisen in one of the two parental lineages prior to the WGH. More broadly, our results illustrate the unique opportunities presented by a WGH event for generating functional divergence by bringing together two parental lineages with separately evolved regulation into one species. We propose that functional divergence of two ohnologs can be facilitated through such regulatory divergence, which can persist even when functional differences are erased by gene conversion.
Ex-situ cultivation of Isoetes cangae and Isoetes serracarajensis (Isoetaceae) two endemic species from Brazilian Amazon
Authors: Zandonadi Daniel Basílio , Martins Rodrigo Lemes , dos Santos Prado Luis Alfredo , Duarte Heitor Monteiro , Santos Mirella Pupo , Calderon Emiliano , Fernandes Ana Carolina Almeida , Santos Quézia Souza , Nunes Filipe Junior Gonçalves , Ribeiro Luis Carlos Felisberto , Fernandes Taís Nogueira , Castilho Alexandre , de Assis Esteves Francisco 
Published: December 2019

ABSTRACTIsoetes L. is a genus of lycophytes widely distributed around the world that has a large number of endemic species. Here we document the first successful large scale ex-situ cultivation of the new endemic species from Brazilian Amazon quillworts Isoetes cangae and Isoetes serracarajensis. These isoetids are endemic of an iron mining site and grow on a superficial iron crust that occurs over ferriferous rocks. This study aimed to develop the cultivation methods of the threatened species I. cangae and monitoring its unique physiology. Plants from both species brought from Amazon lagoons were cultivated through a year in a low-cost system at a different site during different seasons. The survival rate of plants was higher as 98% and both species developed well under cultivation but showed different patterns during linear growth: I. cangae showed faster leaf development but was slower on sprout production than I. serracarajensis. The mechanism of leaf expansion is related to plasma membrane H+-ATPase activation, near to 2-fold higher in I. cangae. On the other hand, the effective quantum yield of photosystem II was higher in I. serracarajensis than in I. cangae. During the cultivation, new sporophytes of I. cangae were produced, confirming its reproductive status. We have also tested elevated iron levels on the growth of plants, but no interference of iron concentration was observed. The results of this work have broad applicability, assisting other low-cost cultivation studies, which are very important in ecosystem recovery of mining areas and conservation strategies.
Design and analysis of CRISPR-based underdominance toxin-antidote gene drives
Authors: Champer Jackson , Champer Samuel E. , Kim Isabel , Clark Andrew G. , Messer Philipp W. 
Published: December 2019

ABSTRACTCRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we assess the performance of several CRISPR-based underdominance gene drive constructs employing toxin-antidote principles. These drives disrupt the wild-type version of an essential gene using a CRISPR nuclease (the toxin) while simultaneously carrying a recoded version of the gene (the antidote). Drives of this nature allow for releases that could be potentially confined to a desired geographic location. This is because such drives have a nonzero invasion threshold frequency, referring to the critical frequency required for the drive to spread through the population. We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters that have ubiquitous somatic expression. We also study several possible drive architectures, considering both “same-site” and “distant-site” systems, as well as several reciprocally targeting drives. Together, these drive variants provide a wide range of invasion threshold frequencies and options for both population modification and suppression. Our results suggest that CRISPR toxin-antidote underdominance drive systems could allow for the design of highly flexible and potentially confinable gene drive strategies.
Emergence of a novel immune-evasion strategy from an ancestral protein fold in bacteriophage Mu
Authors: Karambelkar Shweta , Udupa Shubha , Gowthami Vykuntham Naga , Ramachandra Sharmila Giliyaru , Swapna Ganduri , Nagaraja Valakunja 
Published: December 2019

AbstractThe broad host range bacteriophage Mu employs a novel ‘methylcarbamoyl’ modification to protect its DNA from diverse host restriction systems. Biosynthesis of the unusual modification is a longstanding mystery. Moreover, isolation of Mom, the phage protein involved in the modification has remained elusive to date. Here, we characterized the co-factor and metal binding properties of Mom and provide a molecular mechanism to explain ‘methylcarbamoyl’ation by Mom. Our computational analyses revealed a conserved GNAT (GCN5-related N-acetyltransferase) fold in Mom, predicting acetyl CoA as its co-factor. We demonstrate that Mom binds to acetyl CoA and identify the active site. Puzzlingly, none of the > 309,000 GNAT members identified so far catalyze Mom-like modification of their respective substrates. Besides, conventional acid-base catalysis deployed by typical acetyltransferases cannot support methylcarbamoylation of adenine seen in Mu phage. In contrast, free radical-chemistry, catalyzed by Fe-S cluster or transition metal ions can explain the seemingly challenging reaction between acetyl CoA and DNA. We discovered that Mom is an iron-binding protein, with the Fe2+/3+ion colocalized with acetyl CoA in the active site of Mom. Mutants defective for binding Fe2+/3+or acetyl CoA demonstrated compromised activity, indicating their importance in the DNA modification reaction. Iron-binding in the GNAT active site is unprecedented and represents a small step in the evolution of Mom from the ancestral acetyltransferase fold. Yet, the tiny step allows a giant chemical leap from usual acetylation to a novel methylcarbamoylation function, while conserving the overall protein architecture.SummaryStudying the arms race between bacteria and their viruses (bacteriophages or phages) is key to understanding microbial life and its complexity. An unprecedented DNA modification shields phage Mu from bacterial restriction endonucleases that destroy incoming phage DNA. Nothing is known of how the modification is brought about, except that a phage protein Mom is involved. Here, we discover acetyl CoA and iron as key requirements for the modification. We explain how by evolving the ability to bind iron - a transition metal capable of generating highly reactive free radicals, a well-studied scaffold like the acetyltransferase fold can gain novel catalytic prowess in Mom. These findings have broad implications for gene editing technologies and therapeutic application of phages.
Assessing the impacts of agriculture and its trade on Philippine biodiversity
Authors: Ortiz Andrea Monica D. , Torres Justine Nicole V. 
Published: December 2019

AbstractThe Philippines is home to a high number of unique species that can be found nowhere else in the world. However, its unique species and ecosystems are at high risk because of habitat loss and degradation. Agricultural land use and land use change are major drivers of biodiversity loss in the Philippines.In the Philippines, an important area that requires focus is plantation agriculture (monocropping) for high-value crops such as banana and pineapple, which are grown widely in the country, particularly in the island of Mindanao. The intensive nature of plantation agriculture means that it has many adverse effects on the environment while producing goods and commodities that are typically for trade and export with international partners. This means that local biodiversity losses may be driven by countries thousands of kilometers away.While many global studies have attempted to understand how biodiversity impacts are embodied within agricultural goods, there are few studies that have investigated the Philippines specifically. In this study, local and national-scale data are investigated to better characterize the nexus between agriculture, biodiversity, and trade in the Philippine context. Based on geographical data, many banana and pineapple plantations and their buffer zones interact and overlap with areas that are high in biodiversity, such as Protected Areas and Important Bird Areas. In this study, data shows that 82 threatened species, including the critically endangered Philippine eagle, are at risk of exposure to agricultural activities from high-value crops banana and pineapple. An additional and important political and legal analysis is also undertaken in the study to reveal key legislation and enabling environments relevant to the interactions between land use and biodiversity. More stringent definitions and protections for biodiversity are recommended to recognize the increasing role that agricultural production, and importantly, its global trade, has on threatened Philippine species and habitats.
Nature protection across countries: Do size and power matter?
Authors: Baldi Germán 
Published: December 2019

AbstractProtected areas are one of the most effective tools for nature conservation. Consequently, almost all countries have agreed to set increasingly demanding goals for the expansion of their protected area systems. However, there is a large disparity among countries, and research on the cultural drivers of differences remains quite unexplored. Here, we explore the relationship between protected extent and a limited spectrum of socio-economic characteristics, making focus on size and power features. Protected areas under strict conservation categories (I to IV, IUCN) were considered for 195 countries, and relationships were modeled by means of LOESS regressions, violin plots, and a random forest ensemble learning method. Larger and more powerful countries (in terms of land area, gross domestic product, or military expenditure) protect less and in relatively smaller units than smaller and less powerful countries. Out of the twenty most extensive countries of the world, only two exceed 10% of protection. This situation is problematic since an effective growth of the global protected area network depends on the willingness of larger and more powerful countries. We propose different hypothesesa posteriorithat explain the role of size and power driving protection. These hypotheses involve direct mechanisms (e.g., the persuasive capacity of large countries) or mechanisms that mediate the interactions of some others (e.g., tourism contribution to GDP and insularity). Independently of mechanisms, our results emphasize the conservation responsibilities of large and powerful countries and contribute to envision conservation scenarios in the face of changes in the number and size of countries.
Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination
Authors: Duru Adil Doganay , Sun Renhua , Allerbring Eva B. , Chadderton Jesseka , Kadri Nadir , Han Xiao , Uchtenhagen Hannes , Madhurantakam Chaithanya , Pellegrino Sara , Sandalova Tatyana , Nygren Per-Åke , Turner Stephen J. , Achour Adnane 
Published: December 2019

AbstractViral escape from CD8+cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8+T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape.Author SummaryViral escape mutagenesis correlates often with disease progression and represents a major hurdle for vaccination-based therapies. Here, we have designed and developed a novel generation of altered epitopes that re-establish and enhance significantly CD8+T cell recognition of a naturally occurring viral immune escape variant. Biophysical and structural analyses provide a clear understanding of the molecular mechanisms underlying this reestablished recognition. We believe that this approach can be implemented to currently available or novel vaccination approaches to efficiently restore T cell recognition of virus escape variants to control disease progression.
Assigning a role for chemosensory signal transduction inCampylobacter jejunibiofilms using a combined omics approach
Authors: Tram Greg , Klare William P. , Cain Joel A. , Mourad Basem , Cordwell Stuart J. , Korolik Victoria , Day Christopher J. 
Published: December 2019

AbstractBiofilms serve as a protective mechanism for bacteria to cope with environmental stress. Whilst ordinarily a fastidious organism, it has been long suggested thatC. jejuniis able to utilise this mode of growth as a way to transmit infection from the avian host to humans. Herein, we undertook a combinatorial approach to examine differential expression ofC. jejunigenes and protein abundance during biofilm formation. RNA sequencing and proteomicsviaquantitative liquid chromatography – tandem mass spectrometry (LC-MS/MS) revealed biofilm growth induced a substantial rearrangement of theC. jejunitranscriptome and proteome, with ∼600 genes differentially expressed in biofilms compared to planktonic cells. Biofilm-induced genes / proteins were those involved in iron metabolism and acquisition, cell division, glycan production and attachment, while those repressed were associated with metabolism, amino acid uptake and utilisation, and large tracts of the chemotaxis pathway.We further examined the role of chemotaxis inC. jejunibiofilm formation by assessing the behaviour of isogenic strains with deletions of thecheVandcheWgenes. Both ΔcheVand ΔcheWexhibited a significant decrease in directed motility when compared to wild-typeC. jejuni. Both mutants also demonstrated an increase in autoagglutination ability and increased biofilm formation. A subtle difference was also observed between the phenotypes of ΔcheVand ΔcheWmutants, both in motility and biofilm formation. This suggests roles for the CheV and CheW signal transduction proteins and may present signal transduction as a potential method for modulatingC. jejunibiofilm formation.Author summaryCampylobacter jejuniis a gastroenteric bacterium that is responsible for most cases of bacterial food poisoning in the developed world. The organism commonly resides in avian reservoirs and is passed to humans through contaminated poultry and animal products. Ordinarily,C. jejunirequires a strict set of conditions in order to survive and cause infections in humans. Biofilms are a method of bacterial growth that may provide shielding from harsh environments and provide an important link between reservoirs and human hosts. In this study, we have utilised a multi-platform approach to compare gene expression and protein abundance in planktonicC. jejunicells and those growing as a biofilm. We subsequently focused on the chemosensory system ofC. jejuniand demonstrated that signal transduction proteins play a role in biofilm formation. Our work has provided a broad profile of which genes are important toC. jejunibiofilms and that the chemosensory pathway has an influence on biofilm formation.
Prediction of fruit texture with training population optimization for efficient genomic selection in apple
Authors: Roth Morgane , Di Guardo Mario , Guerra Walter , Muranty Hélène , Patocchi Andrea , Costa Fabrizio 
Published: December 2019

AbstractTexture plays a major role in the determination of fruit quality in apple. Due to its physiological and economic relevance, this trait has been largely investigated, leading to the fixation of the major gene PG1 controlling firmness in elite cultivars. To further improve fruit texture, the targeting of an undisclosed reservoir of loci with minor effects is compelling. In this work, we aimed to unlock this potential with a genomic selection approach by predicting fruit acoustic and mechanical features as obtained with a TA.XTplus texture analyzer in 537 individuals genotyped with 8,294 SNP markers. The best prediction accuracies following cross-validations within the training set (TRS) of 259 individuals were obtained for the acoustic linear distance (0.64). Prediction accuracy was further improved through the optimization of TRS size and composition according to the test set. With this strategy, a maximal accuracy of 0.81 was obtained when predicting the synthetic trait PC1 in the family ‘Gala × Pink Lady’. We discuss the impact of genetic relatedness and clustering on trait variability and predictability. Moreover, we demonstrated the need for a comprehensive dissection of the complex texture phenotype and the potentiality of using genomic selection to improve fruit quality in apple.HighlightA genomic selection study, together with the optimization of the training set, demonstrated the possibility to accurately predict texture sub-traits valuable for the amelioration of fruit quality in apple.