bluuebunny/crossref_metadata_2025 huggingface dataset:
The Deep(er) Roots of Eukaryotes and Akaryotes
Authors: Harish Ajith , Morrison David A.
Published: January 2020

Locating the root-node of the “tree of life” (ToL) is one of the hardest problems in phylogenetics1. The root-node or the universal common ancestor (UCA) divides the descendants into organismal domains2. Two notable variants of the two-domains ToL (2D-ToL) have gained support recently3,4, though, Williams and colleagues (W&C)4claim that one is better supported than the other. Here, we argue that important aspects of estimating evolutionary relatedness and assessing phylogenetic signal in empirical data were overlooked4. We focus on phylogenetic character reconstructions necessary to describe the UCA or its closest descendants in the absence of reliable fossils. It is well-known that different character-types present different perspectives on evolutionary history that relate to different phylogenetic depths5–7. Which of the 2D-ToL2,4hypotheses is better supported depends on which kind of molecular features – protein-domains or their component amino-acids – are better for resolving the common ancestors (CA) at the roots of clades. In practice, this involves reconstructing character compositions of the ancestral nodes all the way back to the UCA2,3.
The fungal collaboration gradient dominates the root economics space in plants
Authors: Bergmann Joana , Weigelt Alexandra , van der Plas Fons , Laughlin Daniel C. , Kuyper Thom W. , Guerrero-Ramirez Nathaly , Valverde-Barrantes Oscar J. , Bruelheide Helge , Freschet Grégoire T. , Iversen Colleen M. , Kattge Jens , McCormack M. Luke , Meier Ina C. , Rillig Matthias C. , Roumet Catherine , Semchenko Marina , Sweeney Christopher J. , van Ruijven Jasper , York Larry M. , Mommer Liesje
Published: January 2020

Plant economics run on carbon and nutrients instead of money. Leaf strategies aboveground span an economic spectrum from ‘live fast and die young’ to ‘slow and steady’, but the economy defined by root strategies belowground remains unclear. Here we take a holistic view of the belowground economy, and show that root-mycorrhizal collaboration can short circuit a one-dimensional economic spectrum, providing an entire space of economic possibilities. Root trait data from 1,781 species across the globe confirm a classical fast-slow ‘conservation’ gradient but show that most variation is explained by an orthogonal ‘collaboration’ gradient, ranging from ‘do-it-yourself’ resource uptake to ‘outsourcing’ of resource uptake to mycorrhizal fungi. This broadened ‘root economics space’ provides a solid foundation for predictive understanding of belowground responses to changing environmental conditions.

One Sentence Summary

Collaboration broadens the ‘root economics space’ ranging from ‘do-it-yourself’ resource acquisition to ‘outsourcing’ to mycorrhizal partners.
Genetic population structure constrains local adaptation in sticklebacks
Authors: Kemppainen Petri , Li Zitong , Rastas Pasi , Löytynoja Ari , Fang Bohao , Yang Jing , Guo Baocheng , Shikano Takahito , Merilä Juha
Published: January 2020

Repeated and independent adaptation to specific environmental conditions from standing genetic variation is common. However, if genetic variation is limited, the evolution of similar locally adapted traits may be restricted to genetically different and potentially less optimal solutions or prevented from happening altogether. Using a quantitative trait locus (QTL) mapping approach, we identified the genomic regions responsible for the repeated pelvic reduction (PR) in three crosses between nine-spined stickleback populations expressing full and reduced pelvic structures. In one cross, PR mapped to linkage group 7 (LG7) containing the genePitx1, known to control pelvic reduction also in the three-spined stickleback. In the two other crosses, PR was polygenic and attributed to ten novel QTL, of which 90% were unique to specific crosses. When screening the genomes from 27 different populations for deletions in thePitx1regulatory element, these were only found in the population in which PR mapped to LG7, even though the morphological data indicated large effect QTL for PR in several other populations as well. Consistent with the available theory and simulations parameterised on empirical data, we hypothesise that the observed variability in genetic architecture of PR is due to heterogeneity in the spatial distribution of standing genetic variation caused by >2x stronger population structuring among freshwater populations and >10x stronger genetic isolation by distance in the sea in nine-spined sticklebacks as compared to three-spined sticklebacks.
Invertebrate Community Associated with the Asexual Generation ofBassettia pallidaAshmead (Hymenoptera: Cynipidae)
Authors: Weinersmith Kelly L. , Forbes Andrew A. , Ward Anna K.G. , Brandão-Dias Pedro F. P. , Zhang Y. Miles , Egan Scott P.
Published: January 2020

Cynipid gall wasps play an important role in structuring oak invertebrate communities. Wasps in the Cynipini tribe typically lay their eggs in oaks (QuercusL.), and induce the formation of a “gall”, which is a tumor-like growth of plant material that surrounds the developing wasp. As the wasp develops, the cynipid and its gall are attacked by a diverse community of natural enemies, including parasitoids, hyperparasitoids, and inquilines. Determining what structures these species-rich natural enemy communities across cynipid gall wasp species is a major question in gall wasp biology. Additionally, gall wasps are ecosystem engineers, as the abandoned gall is used by other invertebrates. The gall-associated insect communities residing on live oaks (Quercus geminataSmall andQ. virginianaMill.) are emerging as a model system for answering ecological and evolutionary questions ranging from community ecology to the evolution of new species. Documenting the invertebrates associated with cynipids in this system will expand our understanding of the mechanisms influencing eco-evolutionary processes, record underexplored axes of biodiversity, and facilitate future work. Here, we present the community of natural enemies and other associates of the asexual generation of the crypt gall wasp,Bassettia pallidaAshmead. We compare the composition of this community to communities recently documented from two other cynipid gall wasps specializing on live oaks along the U.S. Gulf coast,Disholcaspis quercusvirensAshmead andBelonocnema treataeMayr.B. pallidaand their crypts support a diverse arthropod community, including over 25 parasitoids, inquilines, and other associated invertebrates spanning 5 orders and 16 families.
Late Holocene land vertebrate fauna from Cueva de los Nesofontes, Western Cuba: stratigraphy, last appearance dates, diversity and paleoecology
Authors: Orihuela Johanset , Pérez Orozco Leonel , Álvarez Licourt Jorge L. , Viera Muñoz Ricardo A. , Santana Barani Candido
Published: January 2020

Here we report a Late Holocene fossil-rich cave deposit from Cueva de los Nesofontes, Mayabeque Province, Cuba. The deposit’s formation and its fauna were studied through a multidisciplinary approach that included stable isotope analyses, radiocarbon chronology, stratigraphy, sedimentology, and taphonomy. Thousands of microvertebrate skeletal remains were recovered, representing a diverse land vertebrate fauna that included threatened and extinct species. The deposit is characterized by profuseNesophontesremains due to raptor predation. Previously unreported last appearance dates are provided for the extinct island-shrewNesophontes major, the batsArtibeus anthonyiandPhyllops vetus. Radiocarbon (14C AMS) age estimates between ∼1960 rcyr BP and the present were recovered. The presence of locally extinct species, including the endemic parakeetPsittacara eups, the flickerColaptescf.auratus/fernandinae, and the lipotyphlanSolenodon cubanussuggests that these species had broader distributions in the near past. Isotope analyses and faunal composition indicate the previous presence of diverse habitats, including palm grove savannas and mixed woodlands. Isotopes also provide insight into the habitat and coexistence of the extinct batArtibeus anthonyiand extantA. jamaicensis, the diet ofNesophontes major, and local paleoenvironmental conditions. Oxygen isotopes reveal an excursion suggestive of drier/colder local conditions between 660 and 770 AD. Our research further expands the understanding of Cuban Quaternary extinction episodes and provides data on the distribution and paleoecology of extinct taxa. It supports the conclusion that many Cuban extinct species survived well into the pre-Columbian late Holocene and retained wide distribution ranges until human colonization.
Multiplexed Single-cell Metabolic Profiles Organize the Spectrum of Cytotoxic Human T Cells
Authors: Hartmann Felix J. , Mrdjen Dunja , McCaffrey Erin , Glass David R. , Greenwald Noah F. , Bharadwaj Anusha , Khair Zumana , Baranski Alex , Baskar Reema , Angelo Michael , Bendall Sean C.
Published: January 2020

Cellular metabolism regulates immune cell activation, differentiation and effector functions to the extent that its perturbation can augment immune responses. However, the analytical technologies available to study cellular metabolism lack single-cell resolution, obscuring metabolic heterogeneity and its connection to immune phenotype and function. To that end, we utilized high-dimensional, antibody-based technologies to simultaneously quantify the single-cell metabolic regulome in combination with phenotypic identity. Mass cytometry (CyTOF)-based application of this approach to early human T cell activation enabled the comprehensive reconstruction of the coordinated metabolic remodeling of naïve CD8+T cells and aligned with conventional bulk assays for glycolysis and oxidative phosphorylation. Extending this analysis to a variety of tissue-resident immune cells revealed tissue-restricted metabolic states of human cytotoxic T cells, including metabolically repressed subsets that expressed CD39 and PD1 and that were enriched in colorectal carcinoma versus healthy adjacent tissue. Finally, combining this approach with multiplexed ion beam imaging by time-of-flight (MIBI-TOF) demonstrated the existence of spatially enriched metabolic neighborhoods, independent of cell identity and additionally revealed exclusion of metabolically repressed cytotoxic T cell states from the tumor-immune boundary in human colorectal carcinoma. Overall, we provide an approach that permits the robust approximation of metabolic states in individual cells along with multimodal analysis of cell identity and functional characteristics that can be applied to human clinical samples to study cellular metabolism how it may be perturbed to affect immunological outcomes.
Standardized and reproducible measurement of decision-making in mice
Authors:   The International Brain Laboratory, Aguillon-Rodriguez Valeria , Angelaki Dora E. , Bayer Hannah M. , Bonacchi Niccolò , Carandini Matteo , Cazettes Fanny , Chapuis Gaelle A. , Churchland Anne K. , Dan Yang , Dewitt Eric E. J. , Faulkner Mayo , Forrest Hamish , Haetzel Laura M. , Hausser Michael , Hofer Sonja B. , Hu Fei , Khanal Anup , Krasniak Christopher S. , Laranjeira Inês , Mainen Zachary F. , Meijer Guido T. , Miska Nathaniel J. , Mrsic-Flogel Thomas D. , Murakami Masayoshi , Noel Jean-Paul , Pan-Vazquez Alejandro , Rossant Cyrille , Sanders Joshua I. , Socha Karolina Z. , Terry Rebecca , Urai Anne E. , Vergara Hernando M. , Wells Miles J. , Wilson Christian J. , Witten Ilana B. , Wool Lauren E. , Zador Anthony
Published: January 2020

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We designed a task for head-fixed mice that combines established assays of perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be successfully reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path towards achieving reproducibility in neuroscience through collaborative open-science approaches.
Stability and dynamics of the human gut microbiome and its association with systemic immune traits
Authors: Byrd Allyson L. , Liu Menghan , Fujimura Kei E. , Lyalina Svetlana , Nagarkar Deepti R. , Charbit Bruno , Bergstedt Jacob , Patin Etienne , Harrison Oliver J. , Quintana-Murci Lluís , Duffy Darragh , Albert Matthew L. ,   The Milieu Intérieur Consortium
Published: January 2020

Analysis of 1,363 deeply sequenced gut microbiome samples from 946 healthy donors of the Milieu Intérieur cohort provides new opportunities to discover how the gut microbiome is associated with host factors and lifestyle parameters. Using a genome-based taxonomy to achieve higher resolution analysis, we found an enrichment of Prevotella species in males, and that bacterial profiles are dynamic across five decades of life (20-69), with Bacteroidota species consistently increased with age while Actinobacteriota species, including Bifidobacterium, decreased. Longitudinal sampling revealed short-term stability exceeds inter-individual differences; however, the degree of stability was variable between donors and influenced by their baseline community composition. We then integrated the microbiome results with systemic immunophenotypes to show that host/microbe associations discovered in animal models, such as T regulatory cells and short chain fatty acids, could be validated in human data. These results will enable personalized medicine approaches for microbial therapeutics and biomarkers.
Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting
Authors: Lohmueller Jason , Butchy Adam A. , Tivon Yaniv , Kvorjak Michael , Miskov-Zivanov Natasa , Deiters Alexander , Finn Olivera J.
Published: January 2020

Chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors are engineered cell-surface receptors that sense a target antigen and respond by activating T cell receptor signaling or a customized gene program, respectively. To expand the targeting capabilities of these receptors, we have developed switchable adaptor receptor systems for which receptor specificity can be directed post-translationally via covalent attachment of a co-administered antibody. Instead of directly targeting an antigen, our receptors contain the SNAPtag self-labeling enzyme, which reacts with benzylguanine (BG)-conjugated antibodies to assemble covalently-associated antigen receptors. We demonstrate that activation of SNAP-CAR and SNAP-synNotch receptors and their downstream effector functions can be successfully targeted by several clinically-relevant BG-conjugated antibodies in an antigen-specific and antibody dose-dependent manner. To better define parameters affecting receptor signaling, we developed a mathematical model of switchable receptor systems. SNAP receptors provide a powerful new strategy to post-translationally reprogram the targeting specificity of engineered cells.
Mechanical Instability of Adherens Junctions Overrides Intrinsic Quiescence of Hair Follicle Stem Cells
Authors: Biswas Ritusree , Banerjee Avinanda , Lembo Sergio , Zhao Zhihai , Lakshmanan Vairavan , Nakasaki Manando , Kutyavin Vassily , Wright Graham , Palakodeti Dasaradhi , Ross Robert , Jamora Colin , Vasioukhin Valeri , Jie Yan , Raghavan Srikala
Published: January 2020

Vinculin, a mechanotransducer associated with both adherens junctions (AJ) and focal adhesions (FA) plays a central role in force transmission through these cell-cell and cell-substratum contacts. Here we describe the conditional knock out (KO) of vinculin in murine skin. Remarkably, we find that the loss of vinculin function results in the loss of bulge stem cell (BuSC) quiescence. We demonstrate that vinculin KO cells are impaired in force generation resulting in mechanically weak AJs. Mechanistically, vinculin functions by keeping α-catenin in a stretched conformation, which in turn regulates the retention of YAP1, another potent mechanotransducer and regulator of cell proliferation, to the junctions. Conditional KO of α-catenin specifically in the BuSCs further corroborates the importance of stable AJs in the maintenance of quiescence and stemness. Altogether, our data provides definitive mechanistic insights into the hitherto unexplored regulatory link between the mechanical stability of cell-junctions and the maintenance of BuSC quiescence.
Gene expression in isolated cowpea (Vigna unguiculata L. Walp) cells from meiosis to seed initiation
Authors: Gursanscky Nial , Mazurkiewicz Danielle , Juranić Martina , Johnson Susan D. , León Gloria , Escobar-Guzmán Rocio , Salinas-Gamboa Rigel , Amasende-Morales Itzel , Riboni Matteo , Hand Melanie , Spriggs Andrew , Vielle-Calzada Jean-Philippe , Koltunow Anna M.G.
Published: January 2020

Molecular knowledge of pathways regulating seed formation in legumes, remains scarce. Thirteen isolated cell-type transcriptomes were developed, spanning temporal events of male and female gametogenesis and seed initiation, to examine pathways involved in cowpea seed formation.In situhybridization confirmed localization ofin silicoidentified cell-specific genes, verifying transcriptome utility. Cowpea andArabidopsisreproductive cells showed some conservation in regulators enabling cell-type expression as some cowpea cell-specific genes promoters and theirArabidopsishomologs directed expression to identical reproductive cell-types in transgenic plants.In silicoanalyses revealed gene expression similarities and differences with genes in pathways regulating reproductive events in other plants. Meiosis-related genes were expressed at mitotic stages of gametogenesis and during sporophytic development in cowpea. Plant hormone pathways showing preferential expression at particular reproductive stages were identified. Expression of epigenetic pathways, resembling those found inArabidopsis,including microRNA mediated gene silencing, RNA directed DNA methylation and histone modification were associated with particular stages of male and female gametophyte development, suggesting roles in gametogenic cell specification and elaboration. Analyses of cell-cycle related gene expression in mature cowpea female gametophytes, indicated that the egg and central cell were arrested at the G1/S and G2/M cell cycle phases, respectively, prior to fertilization. Pre-fertilization female gametophyte arrest was characterized by barely detectable auxin biosynthesis gene expression levels, and elevated expression of genes involved in RNA-mediated gene silencing and histone modification. These transcriptomes provide a useful resource for additional interrogation to support functional analyses for development of higher yielding cowpea and syntenic legume crops.

One sentence summary

Analyses of laser capture derived cell-type transcriptomes spanning meiosis to seed initiation revealed gene expression profiles during cell specification and reproductive development in cowpea.
Developing an endogenous quorum-sensing based CRISPRi circuit for autonomous and tunable dynamic regulation of multiple targets in industrialStreptomyces
Authors: Tian Jinzhong , Yang Gaohua , Gu Yang , Sun Xinqiang , Lu Yinhua , Jiang Weihong
Published: January 2020

Dynamic regulation has emerged as an effective strategy to improve product titers by balancing metabolic networks, which can be implemented by coupling gene expression to pathway-independent regulatory elements, such as quorum-sensing (QS) systems. However, these QS-based circuits are often created on heterologous systems and must be carefully tuned through tedious testing and optimization process to make them work well, which hampers their application in industrial microbes including streptomycetes. In this study, we design a pathway-independent QS circuit by directly integrating an endogenous QS system with CRISPRi (named EQCi) in the industrial rapamycin-producing strainStreptomyces rapamycinicus. EQCi has the advantages of both the QS system and CRISPRi, which enables tunable, fully autonomous and dynamic regulation of multiple targets simultaneously. To demonstrate its effectiveness, we downregulate three key nodes in essential pathways separately to divert metabolic flux toward rapamycin biosynthesis. In each case, significant increases in rapamycin titers are achieved. We further apply EQCi to simultaneously control these three key nodes with proper repression strength by changing sgRNA targeting positions. The final rapamycin titer reaches to 1836±191 mg/L, which is the highest reported titer. Notably, compared to traditional static engineering strategy, which result in growth arrest and suboptimal rapamycin titers, EQCi regulation substantially promote rapamycin titers without affecting cell growth, which indicates that it can achieve the trade-off between essential pathways and product synthesis. Collectively, this study provides a simple and effective strategy for optimizing product titers and may have the potential to apply to other industrial microorganisms.
Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels
Authors: Sharmin Nazlee , Lamothe Shawn M. , Baronas Victoria A. , Silver Grace , Hao Yubin , Kurata Harley T.
Published: January 2020

Many voltage-dependent ion channels are regulated by accessory proteins, although the underlying mechanisms and consequences are often poorly understood. We recently reported a novel function of the amino acid transporter Slc7a5 as a powerful regulator of Kv1.2 voltage-dependent activation. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement (‘disinhibition’) with holding potentials more negative than −120 mV. Disinhibition of Kv1.1 is strongly attenuated by shRNA knockdown of endogenous Slc7a5. We investigated a variety of chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5. Overall, our study highlights additional Slc7a5-sensitive Kv1 subunits, and demonstrates that features of Slc7a5 sensitivity can be swapped by exchanging voltage-sensing domains.

IMPACT STATEMENT

The voltage-sensing mechanism of a subfamily of potassium channels can be powerfully modulated in unconventional ways, by poorly understood regulatory partners.
Novel ratio-metric features enable the identification of new driver genes across cancer types
Authors: Sudhakar Malvika , Rengaswamy Raghunathan , Raman Karthik
Published: January 2020

An emergent area of cancer genomics has been the identification of driver genes. Driver genes confer a selective growth advantage to the cell and push it towards tumorigenesis. Functionally, driver genes can be divided into two categories, tumour suppressor genes (TSGs) and oncogenes (OGs), which have distinct mutation type profiles. While several driver genes have been discovered, many remain undiscovered, especially those that are mutated at a low frequency across samples. The current methods are not sufficient to predict all driver genes because the underlying characteristics of these genes are not yet well understood. Thus, to predict novel genes, we need to define new features and models that are not biased and identify genes that might otherwise be overshadowed by mutation profiles of recurrent driver genes. In this study, we define new features and build a model to identify novel driver genes. We overcome overfitting and show that certain mutation types such as nonsense mutations are more important for classification. Some known cancer driver genes, which are predicted by the model as TSGs with high probability are ARID1A, TP53, and RB1. In addition to these known genes, potential driver genes predicted are CD36, ZNF750 and ARHGAP35 as TSGs and TAB3 as an oncogene. Overall, our approach surmounts the issue of low recall and bias towards genes with high mutation rates and predicts potential novel driver genes for further experimental screening.
Morphological profiling of human T and NK lymphocytes identifies actin-mediated control of the immunological synapse
Authors: German Yolla , Vulliard Loan , Rubio Aude , Boztug Kaan , Ferrand Audrey , Menche Jörg , Dupré Loïc
Published: January 2020

The detection and neutralization of infected cells and tumors by cytotoxic lymphocytes is a vital immune defense mechanism. The immunological synapse orchestrates the target recognition process and the subsequent cytotoxic activity. Here, we present an integrated experimental and computational strategy to systematically characterize the morphological properties of the immunological synapse of human cytotoxic lymphocytes. Our approach combines high-content imaging with an unbiased, data-driven identification of high-resolution morphological profiles. Such profiling discriminates with high accuracy immunological synapse perturbations induced by an array of actin drugs in both model cell lines and primary lymphocytes. It reveals inter-individual heterogeneity in lymphocyte morphological traits. Furthermore, it uncovers immunological synapse alterations in functionally defective CD8+T cells from immunodeficient patients carryingARPC1Bmutations. Our study thus provides a foundation for the application of morphological profiling as a powerful and scalable approach to monitor lymphocyte activation status in experimental and disease settings.
Mixed Logistic Regression in Genome-Wide Association Studies
Authors: Milet Jacqueline , Perdry Hervé
Published: January 2020

Motivation

Mixed linear models (MLM) have been widely used to account for population structure in case-control genome-wide association studies, the status being analyzed as a quantitative phenotype. Chenet al.proved that this method is inappropriate and proposed a score test for the mixed logistic regression (MLR). However this test does not allow an estimation of the variants’ effects.

Results

We propose two computationally efficient methods to estimate the variants’ effects. Their properties are evaluated on two simulations sets, and compared with other methods (MLM, logistic regression). MLR performs the best in all circumstances. The variants’ effects are well evaluated by our methods, with a moderate bias when the effect sizes are large. Additionally, we propose a stratified QQ-plot, enhancing the diagnosis ofp-values inflation or deflation, when population strata are not clearly identified in the sample.

Availability

All methods are implemented in the R packagemilorGWASavailable athttps://github.com/genostats/milorGWAS.

Contact

herve.perdry@u-psud.fr

Supplementary information

Supplementary data are available atBioinformaticsonline.
Retromer retrieves the Wilson Disease protein, ATP7B from lysosomes in a copper-dependent mode
Authors: Das Santanu , Maji Saptarshi , Ruturaj  , Bhattacharya Indira , Saha Tanusree , Gupta Arnab
Published: January 2020

ATP7B utilizes lysosomal exocytosis to export copper from hepatocytes. We investigated the fate of ATP7B, post-copper export. At high copper ATP7B traffics to lysosomes and upon subsequent copper chelation, returns to Trans Golgi Network. At high copper, ATP7B co-localizes with lysosomal marker, Lamp1 and the core member of retromer complex, Vps35. Knocking down VPS35 did not alter copper-responsive vesicularization of ATP7B; rather upon subsequent copper chelation, ATP7B failed to relocalize to TGN that could be rescued by overexpressing wtVPS35. Using super-resolution microscopy and proximity ligation assays we demonstrate that VPS35 and ATP7B are juxtaposed on the same lysosomal compartment and their interaction is indirect. Utilizing in-cell photoamino acid-based UV-crosslinking and subsequent immunoprecipitation, we detected ATP7B and retromer subunits, VPS35 and VPS26 in a large complex in high copper conditions, hence confirming their interaction. We demonstrate that retromer regulates lysosome to TGN trafficking of the copper transporter ATP7B and it is dependent upon cellular copper level.
Wege: A New Metric for Ranking Locations for Biodiversity Conservation
Authors: Farooq Harith , Anderson Josue , Belluardo Francesco , Nanvonamuquitxo Cristovao , Bennett Dominic , Moat Justin , Soares Amadeu , Faurby Soren , Antonelli Alexandre
Published: January 2020

Aim

In order to implement effective conservation policies, it is crucial to know how biodiversity is distributed and one of the most widely used systems is the Key Biodiversity Areas (hereafter KBA) criteria, developed by the International Union for Conservation of Nature (IUCN). Here we develop a tool to rank Key Biodiversity Areas in a continuous scale to allow the ranking between KBAs and test this tool on a simulated dataset of 10 000 scenarios of species compositions of reptiles and mammals in eight locations in Mozambique.

Location

Mozambique, Africa

Methods

We compare the KBA criteria with four priorisation metrics (weighted endemism, extinction risk, evolutionary distinctiveness and EDGE score) to rank the biodiversity importance of eight sites with a randomly generated species composition of reptiles and mammals in Mozambique.

Results

We find that none of these metrics is able to provide a suitable ranking of the sites surveyed that would ultimately allow prioritization. We therefore develop and validate the “WEGE index” (Weighted Endemism including Global Endangerment index), which is an adaptation of the EDGE score (Evolutionarily Distinct and Globally Endangered) and allows the ranking of sites according to the KBA criteria but on a continuous scale.

Main conclusions

For our study system, the WEGE index scores areas that trigger KBA status higher and is able to rank their importance in terms of biodiversity by using the range and threat status of species present at the site. Prioritization may be crucial for policy making and real-life conservation, allowing the choice between otherwise equally qualified sites according to the KBA categories. WEGE is intended to support a transparent decision-making process in conservation.
Non-essential function of KRAB zinc finger gene clusters in retrotransposon suppression
Authors: Wolf Gernot , de Iaco Alberto , Sun Ming-An , Bruno Melania , Tinkham Matthew , Hoang Don , Mitra Apratim , Ralls Sherry , Trono Didier , Macfarlan Todd S.
Published: January 2020

The Krüppel-associated box zinc finger protein (KRAB-ZFP) family amplified and diversified in mammals by segmental duplications, but the function of the majority of this gene family remains largely unexplored due to the inaccessibility of the gene clusters to conventional gene targeting. We determined the genomic binding sites of 61 murine KRAB-ZFPs and genetically deleted in mouse embryonic stem (ES) cells five large KRAB-ZFP gene clusters encoding nearly one tenth of the more than 700 mouse KRAB-ZFPs. We demonstrate that clustered KRAB-ZFPs directly bind and silence retrotransposons and block retrotransposon-borne enhancers from gene activation in ES cells. Homozygous knockout mice generated from ES cells deleted in one of two KRAB-ZFP clusters were born at sub-mendelian frequencies in some matings, but heterozygous intercrosses could also yield knockout progeny with no overt phenotype. We further developed a retrotransposon capture-sequencing approach to assess mobility of the MMETn family of endogenous retrovirus like elements, which are transcriptionally activated in KRAB-ZFP cluster KOs, in a pedigree of KRAB-ZFP cluster KO and WT mice. We identified numerous somatic and several germ-line MMETn insertions, and found a modest increase in activity in mutant animals, but these events were detected in both wild-type and KO mice in stochastic and highly variable patterns. Our data suggests that the majority of young KRAB-ZFPs play a non-essential role in transposon silencing, likely due to the large redundancy with other KRAB-ZFPs and other transposon restriction pathways in mice.

One Sentence Summary

Megabase-scale deletions of KRAB-ZFP gene clusters in mice leads to retrotransposon activation.
A comparison of gene expression and DNA methylation patterns across tissues and species
Authors: Blake Lauren E. , Roux Julien , Hernando-Herraez Irene , Banovich Nicholas E. , Perez Raquel Garcia , Hsiao Chiaowen Joyce , Eres Ittai , Cuevas Claudia , Marques-Bonet Tomas , Gilad Yoav
Published: January 2020

Previously published comparative functional genomic data sets from primates using frozen tissue samples, including many data sets from our own group, were often collected and analyzed using nonoptimal study designs and analysis approaches. In addition, when samples from multiple tissues were studied in a comparative framework, individuals and tissues were confounded. We designed a multitissue comparative study of gene expression and DNA methylation in primates that minimizes confounding effects by using a balanced design with respect to species, tissues, and individuals. We also developed a comparative analysis pipeline that minimizes biases attributable to sequence divergence. Thus, we present the most comprehensive catalog of similarities and differences in gene expression and DNA methylation levels between livers, kidneys, hearts, and lungs, in humans, chimpanzees, and rhesus macaques. We estimate that overall, interspecies and inter-tissue differences in gene expression levels can only modestly be accounted for by corresponding differences in promoter DNA methylation. However, the expression pattern of genes with conserved inter-tissue expression differences can be explained by corresponding interspecies methylation changes more often. Finally, we show that genes whose tissue-specific regulatory patterns are consistent with the action of natural selection are highly connected in both gene regulatory and protein–protein interaction networks.
Changing the fallow paradigm: A win–win strategy for the post‐2020 Common Agricultural Policy to halt farmland bird declines
Authors: Tarjuelo Rocío , Margalida Antoni , Mougeot François
Published: January 2020

Farmland bird populations have declined sharply due to agricultural intensification. In Europe, these negative population trends have been linked to the loss of semi‐natural vegetation types, particularly fallow land. The work of Sanz‐Pérez et al. (2019) has far‐reaching implications for the conservation of farmland biodiversity. We argue that it supports a new paradigm for the understanding and management of fallows that should be integrated into the forthcoming post‐2020 Common Agricultural Policy (CAP).

Following the abolition of mandatory set‐aside by the European Union in 2008, fallows declined steadily in Europe until 2015, when the CAP implemented greening measures. These restored the requirement to leave 5% of arable land as ecological focus areas (EFAs) to enhance biodiversity. While fallows are one of the most beneficial forms of EFA for farmland birds, farmers prefer the less conservation effective planting of nitrogen‐fixing and catch crops (currently more than 70% of EFAs). CAP incentives have been insufficient to make unproductive EFAs such as fallows more attractive to farmers.

Sanz‐Pérez et al. (2019) evaluated the impact of different fallow land management practices on the abundance of specialist farmland birds. They concluded that extensive practices – such as tilling or shredding once or twice per year before the breeding season – were more beneficial to these declining species than leaving fallows unmanaged and recommended their incorporation into agri‐environment schemes. But such schemes have had low uptake, and thus a limited potential to drive the widespread recovery of farmland birds at either national or European levels. The post‐2020 CAP, currently under development, should integrate simple fallow management practices within new conditionalities or eco‐schemes to address this problem.

Synthesis and applications. The loss of fallow land underlies the decline of farmland birds. The post‐2020 CAP must overcome past mismatches between incentives to farmers and biodiversity benefits and increase farmers’ uptake of the most beneficial options for biodiversity, including fallows. Promoting light management of fallow land within the new CAP eco‐schemes is a win–win strategy because it would simultaneously allow farmers to continue extensive weed control and enhance habitat quality for farmland birds.
Long inter‐fire intervals do not guarantee a large seed bank in a serotinous shrub (Banksia spinulosa Sm.)
Authors: Whelan Robert J. , Ayre David J.
Published: January 2020

It is often assumed that long‐lived woody perennials with canopy‐stored seed banks steadily accumulate seeds over time since fire. Trends in flowering and fruiting have usually been inferred from synchronic studies of sites of different post‐fire ages or counting stored seeds in apparent age classes, and mostly in obligate‐seeder species. Long‐term longitudinal studies on a broader range of species are needed to fully understand the dynamics of flower and fruit production and accumulation of viable seeds. Key questions are as follows: What is the annual trend in flowering and cone production? Is this matched by accumulation of cones and seeds? How is seed germinability related to cone age at the time of a fire?

We counted inflorescences and tagged cones produced annually by the resprouting shrub Banksia spinulosa in 315 plants over 13 years at one site and in 46 plants over 20 years at another. At the end of the study, we harvested all accumulated cones, burned them and assessed seed viability using germination trials.

We detected enormous inter‐plant variation in reproductive effort and output. 50% of inflorescences was produced by only 10%–15% of plants. There was a potential for accumulation of massive seed banks. However, (a) only 8%–10% of inflorescences became cones; (b) only 44%–50% of these were retained until harvest; (c) many retained cones suffered seed predation; and (d) viability of retained seeds declined with cone age. The result of these processes meant that the accumulated seed bank was only two to four seeds per plant, 82%–94% of the viable seeds had been produced in 6 years prior to harvest and only 12%–26% of plants contributed to this viable seed bank.

Synthesis: Cone and seed losses and declining seed viability in B. spinulosa mean that almost all viable seeds come from the past few years of flowering even though apparently intact cones may be retained for decades. If this is typical for resprouting serotinous shrubs, it is important to understand trends in flowering and fruit set over time because the magnitude of recruitment will depend on fecundity in the few years prior to a fire.
An integrated RNA‐Seq and network study reveals the effect of nicotinamide on adrenal androgen synthesis
Authors: Gao Xueying , Yu Zhiheng , Yang Jie , Gao Yutong , Li Shumin , Zhang Wei
Published: January 2020

Acne vulgaris is a chronic inflammatory disease of the skin resulting from androgen‐induced increased sebum production and altered keratinization. Nicotinamide (NAM), an amide form of vitamin B3 with a well‐established safety profile, has shown good therapeutic potential in treating acne and its complications. NAM has anti‐inflammatory effects and reduces sebum but its function in androgen biosynthesis remains unknown. In this study, we used a widely used cell model, starved human adrenal NCI‐H295R cells, to examine the effects of NAM in androgen production and its mediated network changes. By treating NCI‐H295R cells with 1‐25 mmol/L of NAM, we found that cell viability was only slightly inhibited at the highest dose (25 mmol/L). NAM reduced testosterone production in a dose‐dependent manner. Transcriptomic analysis demonstrated that key enzymes of androgen biosynthesis were significantly decreased under NAM treatment. In addition, gene set enrichment analysis (GSEA) showed that gene sets of cell cycle, steroid biosynthesis, TGFβ signalling, and targets of IGF1 or IGF2 were enriched in NAM‐treated cells. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway and Gene ontology (GO) analysis of the differentially expressed genes also suggested that steroidogenesis and SMAD signalling were affected by NAM. Overall, these crucial genes and pathways might form a complex network in NAM‐treated NCI‐H295R cells and result in androgen reduction. These findings help explain the potential molecular actions of NAM in acne vulgaris, and position NAM as a candidate for the treatment of other hyperandrogenic disorders.
Host permissiveness to baculovirus influences time‐dependent immune responses and fitness costs
Authors: Pan Qinjian , Shikano Ikkei , Felton Gary W. , Liu Tong-Xian , Hoover Kelli
Published: January 2020

Insects possess specific immune responses to protect themselves from different types of pathogens. Activation of immune cascades can inflict significant developmental costs on the surviving host. To characterize infection kinetics in a surviving host that experiences baculovirus inoculation, it is crucial to determine the timing of immune responses. Here, we investigated time‐dependent immune responses and developmental costs elicited by inoculations from each of two wild‐type baculoviruses, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Helicoverpa zea single nucleopolyhedrovirus (HzSNPV), in their common host H. zea. As H. zea is a semi‐permissive host of AcMNPV and fully permissive to HzSNPV, we hypothesized there are differential immune responses and fitness costs associated with resisting infection by each virus species. Newly molted 4th‐instar larvae that were inoculated with a low dose (LD15) of either virus showed significantly higher hemolymph FAD‐glucose dehydrogenase (GLD) activities compared to the corresponding control larvae. Hemolymph phenoloxidase (PO) activity, protein concentration and total hemocyte numbers were not increased, but instead were lower than in control larvae at some time points post‐inoculation. Larvae that survived either virus inoculation exhibited reduced pupal weight; survivors inoculated with AcMNPV grew slower than the control larvae, while survivors of HzSNPV pupated earlier than control larvae. Our results highlight the complexity of immune responses and fitness costs associated with combating different baculoviruses.
Early Cretaceous A‐type Granites in the Dandong Area, NE China and its Geodynamical Implications
Authors: SONG Yunhong , HAO Libo , YANG Fengchao , ZHAO Dongfang , ZHANG Zhehuan
Published: January 2020

A‐type granites, as an important petrologic sign to build up environmental recognition, were mainly formed in extensional tectonic settings. A biotite syenogranite from the Fenghuangshan pluton in Dandong, Liaoning Province gave SHRIMP zircon U‐Pb ages of 122.5 ± 1.6 Ma, 124.9 ± 1.7 Ma and 126.9 ± 1.1 Ma. The monzogranites have SHRIMP zircon U‐Pb ages of 118.2 ± 1.6 Ma, 128.1 ± 1.7 Ma and 131.6 ± 1.9 Ma, giving an emplacement age for the pluton in the Early Cretaceous. SiO2 is 65.48–74.49 wt%, whereas that of K2O is 4.16–6.44 wt%, and that of Na2O is 2.99–4.70 wt%. They also contain 13.24–15.76 wt% of Al2O3, with an A/CNK ratio of 0.92–1.10, averaging 1.02. The alkalinity rate (AR) ranges from 2.68 to 5.12, and this range is within the AR of peraluminous type rocks. The granites of Fenghuangshan pluton are characterized by high contents of Na and K and low contents of Ca (thermophile element) and Mg, which are features of A‐type granites. The (Na2O + K2O) – Fe2O3∗ × 5 – (CaO + MgO) × 5 discrimination diagram also shows that Fenghuangshan pluton is an A2‐type granite. The above granite has zircon ∊Hf(t) values ranging from –17.06 to –9.09, with single‐stage Hf model ages (TDM) of 1141 Ma to 1498 Ma and two‐stage Hf crustal model ages (TDMC) of 1762 Ma to 2263 Ma. A comprehensive analysis suggests that the Fenghuangshan pluton might have been formed from the lithospheric‐plate sliding during the late stages of evolution of hot rift structures and might have been closely associated with the tectonic settings of Mesozoic Eurasia and the ancient Pacific Plate.
The r toolbox grainscape for modelling and visualizing landscape connectivity using spatially explicit networks
Authors: Chubaty Alex M. , Galpern Paul , Doctolero Sam C.
Published: January 2020

Networks are widely used for modelling landscape connectivity and have many ecological and conservation applications. The nodes in these models describe geographic locations (such as habitat patches or protected areas) and links describe the potential for organisms (or their propagules) to move among nodes.

We present the r package grainscape which facilitates working with these networks within a spatially explicit framework. Package analyses are based on the minimum planar graph, a class of network where links among nodes are influenced by the spatial characteristics of features across the entire landscape.

Modelling outputs are compatible with downstream packages including igraph for network analysis and ggplot2 for visualization. Tools for analysis (e.g. finding corridors) and scaling networks (e.g. grains of connectivity) are also provided. Models can be exported for visualization and analysis in Geographic Information System (GIS) or network software.

This package provides a computationally‐efficient programmatic toolbox for many landscape connectivity research questions, enabling researchers to easily customize models, work at large geographic extents, generate their own network metrics, conduct sensitivity analyses and seamlessly employ r statistical functions to test models using biological data. A detailed guide, provided as an Appendix, illustrates common analysis and model variants with accompanying r code.