bluuebunny/crossref_metadata_2025_split huggingface dataset:
How much doesNevary among species?
Authors: Galtier Nicolas , Rousselle Marjolaine 
Published: December 2019

AbstractGenetic drift is an important evolutionary force of strength inversely proportional toNe, the effective population size. The impact of drift on genome diversity and evolution is known to vary among species, but quantifying this effect is a difficult task. Here we assess the magnitude of variation in drift power among species of animals via its effect on the mutation load – which implies also inferring the distribution of fitness effects of deleterious mutations (DFE). To this aim, we analyze the non-synonymous (amino-acid changing) and synonymous (amino-acid conservative) allele frequency spectra in a large sample of metazoan species, with a focus on the primates vs. fruit flies contrast. We show that a Gamma model of the DFE is not suitable due to strong differences in estimated shape parameters among taxa, while adding a class of lethal mutations essentially solves the problem. Using the Gamma + lethal model and assuming that the mean deleterious effects of non-synonymous mutations is shared among species, we estimate that the power of drift varies by a factor of at least 500 between large-Neand small-Nespecies of animals,i.e., an order of magnitude more than the among-species variation in genetic diversity. Our results are relevant to Lewontin’s paradox while further questioning the meaning of theNeparameter in population genomics.
Unsupervised Clustering Reveals Spatially Varying Single Neuronal Firing Patterns in the Subthalamic Nucleus of Patients with Parkinson’s Disease
Authors: Kaku Heet , Ozturk Musa , Viswanathan Ashwin , Shahed Joohi , Sheth Sameer Anil , Kumar Suneel , Ince Nuri F. 
Published: December 2019

AbstractIntroductionSubthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson’s disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN.MethodsWe recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns.Results279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower (p<0.05) than the rest. Tonic firings were significantly ventral (p<0.05) while periodic (p<0.05) and non-periodic (p<0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores (r=0.51, p=0.04) and improvement in bradykinesia and rigidity (r=0.57, p=0.02) respectively.ConclusionStrengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.
Contacting domains that segregate lipid from solute transporters in malaria parasites
Authors: Garten Matthias , Beck Josh R. , Roth Robyn , Tenkova-Heuser Tatyana , Heuser John , Bleck Christopher K. E. , Goldberg Daniel E. , Zimmerberg Joshua 
Published: December 2019

ABSTRACTWhile membrane contact sites (MCS) between intracellular organelles are abundant1, and cell-cell junctions are classically defined2, very little is known about the contacts between membranes that delimit extracellular junctions within cells, such as those of chloroplasts and intracellular parasites. The malaria parasite replicates within a unique organelle, the parasitophorous vacuole (PV) but the mechanism(s) are obscure by which the limiting membrane of the PV, the parasitophorous vacuolar membrane (PVM), collaborates with the parasite plasma membrane (PPM) to support the transport of proteins, lipids, nutrients, and metabolites between the cytoplasm of the parasite and the cytoplasm of the host erythrocyte (RBC). Here, we demonstrate the existence of multiple micrometer-sized regions of especially close apposition between the PVM and the PPM. To determine if these contact sites are involved in any sort of transport, we localized the PVM nutrient-permeable and protein export channel EXP2, as well as the PPM lipid transporter PfNCR1. We found that EXP2 is excluded from, but PfNCR1 is included within these regions of close apposition. Thus, these two different transport systems handling hydrophilic and hydrophobic substances, respectively, assume complementary and exclusive distributions. This new structural and molecular data assigns a functional significance to a macroscopic membrane domain.
Does breeding season variation affect evolution of a sexual signaling trait in a tropical lizard clade?
Authors: Gray Levi N. , Barley Anthony J. , Hillis David M. , Pavón-Vázquez Carlos J. , Poe Steven , White Brittney A. 
Published: December 2019

AbstractSexually selected traits can be expected to increase in importance when the period of sexual behavior is constrained, such as in seasonally restricted breeders.Anolislizard male dewlaps are classic examples of multifaceted signaling traits, with demonstrated reproductive function reflected in courtship behavior. Fitch and Hillis found a correlation between dewlap size and seasonality in mainlandAnolisusing traditional statistical methods. Here, we present two tests of the Fitch-Hillis Hypothesis using new phylogenetic and morphological data sets for 44 species of MexicanAnolis. A significant relationship between dewlap size and seasonality is evident in phylogenetically uncorrected analyses but erodes once phylogeny is accounted for. This loss of statistical support for a relationship between a key aspect of dewlap morphology and seasonality also occurs within a species complex (A. sericeusgroup) that inhabits seasonal and aseasonal environments. Our results fail to support seasonality as a strong driver of evolution ofAnolisdewlap size. We discuss the implications of our results and the difficulty of disentangling the strength of single mechanisms on trait evolution when multiple selection pressures are likely at play.
α1A-adrenoceptor inverse agonists and agonists modulate receptor signalling through a conformational selection mechanism
Authors: Wu Feng-Jie , Williams Lisa M. , Abdul-Ridha Alaa , Gunatilaka Avanka , Vaid Tasneem M. , Kocan Martina , Whitehead Alice R. , Griffin Michael D.W. , Bathgate Ross A.D. , Scott Daniel J. , Gooley Paul R. 
Published: December 2019

AbstractG-Protein Coupled Receptors (GPCRs) transmit signals across the cell membrane via an allosteric network from the ligand-binding site to the G-protein binding site via a series of conserved microswitches. Crystal structures of GPCRs provide snapshots of inactive and active states, but poorly describe the conformational dynamics of the allosteric network that underlies GPCR activation. Here we analyse the correlation between ligand binding and receptor conformation of the α1A-adrenoceptor, known for stimulating smooth muscle contraction in response to binding noradrenaline. NMR of 13CεH3-methionine labelled α1A-adrenoreceptor mutants, each exhibiting differing signalling capacities, revealed how different classes of ligands modulate receptor conformational equilibria. 13CεH3-methionine residues near the microswitches revealed distinct states that correlated with ligand efficacies, supporting a conformational selection mechanism. We propose that allosteric coupling between the microswitches controls receptor conformation and underlies the mechanism of ligand modulation of GPCR signalling in cells.
Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes define survival threshold in erythroid progenitor cells
Authors: Adlung Lorenz , Stapor Paul , Tönsing Christian , Schmiester Leonard , Schwarzmüller Luisa E. , Wang Dantong , Timmer Jens , Klingmüller Ursula , Hasenauer Jan , Schilling Marcel 
Published: December 2019

SummarySurvival or apoptosis is a binary decision in individual cells. Yet, at the cell population level, a graded increase in survival of CFU-E cells is observed upon stimulation with Erythropoietin (Epo). To identify components of JAK2/STAT5 signal transduction that contribute to the graded population response, a cell population-level model calibrated with experimental data was extended to study the behavior in single cells. The single-cell model showed that the high cell-to-cell variability in nuclear phosphorylated STAT5 is caused by variability in the amount of EpoR:JAK2 complexes and of SHP1 as well as the extent of nuclear import due to the large variance in the cytoplasmic volume of CFU-E cells. 24 to 118 pSTAT5 molecules in the nucleus for 120 min are sufficient to ensure cell survival. Thus, variability in membrane-associated processes are responsible to convert a switch-like behavior at the single-cell level to a graded population level response.HighlightsMathematical modeling enables integration of heterogeneous dataSingle-cell modeling captures binary decision processMultiple sources of cell-to-cell variability in erythroid progenitor cellsMinimal amount of active STAT5 sufficient for survival of erythroid progenitor cells
One fly - one genome : Chromosome-scale genome assembly of a single outbred Drosophila melanogaster
Authors: Adams Matthew , McBroome Jakob , Maurer Nicholas , Pepper-Tunick Evan , Saremi Nedda , Green Richard E. , Vollmers Christopher , Corbett-Detig Russell B. 
Published: December 2019

AbstractA high quality genome assembly is a vital first step for the study of an organism. Recent advances in technology have made the creation of high quality chromosome scale assemblies feasible and low cost. However, the amount of input DNA needed for an assembly project can be a limiting factor for small organisms or precious samples. Here we demonstrate the feasibility of creating a chromosome scale assembly using a hybrid method for a low input sample, a single outbred Drosophila melanogaster. Our approach combines an Illumina shotgun library, Oxford nanopore long reads, and chromosome conformation capture for long range scaffolding. This single fly genome assembly has a N50 of 26 Mb, a length that encompasses entire chromosome arms, contains 95% of expected single copy orthologs, and a nearly complete assembly of this individual’s Wolbachia endosymbiont. The methods described here enable the accurate and complete assembly of genomes from small, field collected organisms as well as precious clinical samples.
Differential tolerance of Zymoseptoria tritici to altered optimal moisture conditions during the early stages of wheat infection
Authors: Boixel Anne-Lise , Gélisse Sandrine , Marcel Thierry C. , Suffert Frédéric 
Published: December 2019

AbstractFoliar plant pathogens require liquid or vapour water for at least part of their development, but their response and their adaptive tolerance to moisture conditions have been much less studied than other meteorological factors to date. We examined the impact on the wheat-Zymoseptoria tritici interaction of altering optimal moisture conditions conducive to infection. We assessed the responses in planta of 48 Z. tritici strains collected in two climatologically distinct locations (Ireland and Israel) to four high moisture regimes differing in the timing and the duration of uninterrupted exposure to saturated relative humidity (100% RH) during the first three days of infection. Individual- and population-level moisture reaction norms expressing how the sporulating area of a lesion change with the RH conditions were established based on visual assessments of lesion development at 14, 17 and 20 days post-inoculation (dpi). Our findings highlighted: (i) a critical time-dependent effect on lesion development of uninterrupted periods of exposure to 100% RH during these earliest infection stages; (ii) a marked interindividual variation in the sensitivity to RH conditions both in terms of strain average moisture response and plasticity; (iii) a higher tolerance – expressed at 14 dpi, not later – of the Israeli population to early interruption of optimal moisture conditions. By indicating that sensitivity to sub-optimal moisture conditions may vary greatly between Z. tritici individuals and populations, this study highlights the evidence of moisture adaptation signature in a plant pathogen. This suggests that understanding such variation will be critical to predict their response to changing climatic conditions.
The secreted acid phosphatase domain-containing GRA44 fromToxoplasma gondiiis required for C-myc induction in infected cells
Authors: Blakely William J , Holmes Michael J , Arrizabalaga Gustavo 
Published: December 2019

ABSTRACTDuring host cell invasion, the eukaryotic pathogenToxoplasma gondiiforms a parsitophorous vacuole to safely reside within, while partitioned from host cell defense mechanisms. From within this safe niche parasites sabotage multiple host cell systems including gene expression, apoptosis and intracellular immune recognition by secreting a large arsenal of effector proteins. Many parasite proteins studied for active host cell manipulative interactions have been kinases. Translocation of effectors from the parasitophorous vacuole into the host cell is mediated by a putative translocon complex, which includes proteins MYR1, MYR2, and MYR3. Whether other proteins are involved in the structure or regulation of this putative translocon is not known. We have discovered that the secreted protein GRA44, which contains a putative acid phosphatase domain, interacts with members of this complex and is required for host cell effects downstream of effector secretion. We have determined GRA44 is processed in a region with homology to sequences targeted by protozoan proteases of the secretory pathway and that both major cleavage fragments are secreted into the parasitophorous vacuole. Immunoprecipitation experiments showed that GRA44 interacts with a large number of secreted proteins included MYR1. Importantly, conditional knockdown of GRA44 resulted in a lack of host cell cMyc upregulation, which mimics the phenotype seen when members of the translocon complex are genetically disrupted. Thus, the putative acid phosphatase GRA44 is crucial for host cell alterations duringToxoplasmainfection and is associated with the translocon complex whichToxoplasmarelies upon for success as an intracellular pathogen.IMPORTANCEApproximately one third of humans are infected with the parasiteToxoplasma gondii.Toxoplasmainfections can lead to severe disease in those with a compromised or suppressed immune system. Additionally, infections during pregnancy present a significant health risk to the developing fetus. Drugs that target this parasite are limited, have significant side effects, and do not target all disease stages. Thus, a thorough understanding of how the parasite propagates within a host is critical in the discovery of novel therapeutic targets. To replicateToxoplasmarequires to enter the cells of the infected organism. In order to survive the environment inside a cell,Toxoplasmasecretes a large repertoire of proteins, which hijack a number of important cellular functions. How theseToxoplasmaproteins move from the parasite into the host cell is not well understood. Our work shows that the putative phosphatase GRA44 is part of a protein complex responsible for this process.
Mutations in disordered proteins as early indicators of nucleic acid changes triggering speciation
Authors: Forcelloni Sergio , Giansanti Andrea 
Published: December 2019

AbstractIntrinsically disordered proteins are characterized by unusual sequence composition, structural flexibility, and functional spectra. These properties play an essential role in fostering protein evolution and in the formation of complex cellular pathways, especially in multicellular organisms. In this study, we analyze the role of different structural variants of proteins in speciation processes. Firstly, we separate human and mouse proteomes (taken as a reference) in three variants of disorder: ordered proteins (ORDPs), structured proteins with intrinsically disordered protein regions (IDPRs), and intrinsically disordered proteins (IDPs). Secondly, we compare the DNA divergence with the corresponding protein divergence, by confronting human and mouse coding sequences (separated in ORDPs, IDPRs, and IDPs) with their homologs from 26 eukaryotes. As a general rule, we find that IDPs phenotypically diverge earlier than ORDPs and IDPRs. ORDPs diverge later but are phenotypically more reactive to nucleotide mutations than IDPRs and IDPs. We suggest that IDPs may be involved in the early stages of the speciation process, likely connected to their functional spectra, mainly related to nucleic acid binding and transcription factors. In contrast, ORDPs may be essential in accelerating further phenotypic divergence.
Genomic evidence for global ocean plankton biogeography shaped by large-scale current systems
Authors: Richter Daniel J. , Watteaux Romain , Vannier Thomas , Leconte Jade , Frémont Paul , Reygondeau Gabriel , Maillet Nicolas , Henry Nicolas , Benoit Gaëtan , Silva Ophélie Da , Delmont Tom O. , Fernàndez-Guerra Antonio , Suweis Samir , Narci Romain , Berney Cédric , Eveillard Damien , Gavory Frederick , Guidi Lionel , Labadie Karine , Mahieu Eric , Poulain Julie , Romac Sarah , Roux Simon , Dimier Céline , Kandels Stefanie , Picheral Marc , Searson Sarah ,   Tara Oceans Coordinators, Pesant Stéphane , Aury Jean-Marc , Brum Jennifer R. , Lemaitre Claire , Pelletier Eric , Bork Peer , Sunagawa Shinichi , Lombard Fabien , Karp-Boss Lee , Bowler Chris , Sullivan Matthew B. , Karsenti Eric , Mariadassou Mahendra , Probert Ian , Peterlongo Pierre , Wincker Patrick , de Vargas Colomban , d’Alcalà Maurizio Ribera , Iudicone Daniele , Jaillon Olivier 
Published: December 2019

AbstractBiogeographical studies have traditionally focused on readily visible organisms, but recent technological advances are enabling analyses of the large-scale distribution of microscopic organisms, whose biogeographical patterns have long been debated. Here we assessed the global structure of plankton geography and its relation to the biological, chemical and physical context of the ocean (the ‘seascape’) by analyzing metagenomes of plankton communities sampled across oceans during the Tara Oceans expedition, in light of environmental data and ocean current transport. Using a consistent approach across organismal sizes that provides unprecedented resolution to measure changes in genomic composition between communities, we report a pan-ocean, size-dependent plankton biogeography overlying regional heterogeneity. We found robust evidence for a basin-scale impact of transport by ocean currents on plankton biogeography, and on a characteristic timescale of community dynamics going beyond simple seasonality or life history transitions of plankton.
Population genetics of the coralAcropora millepora: Towards a genomic predictor of bleaching
Authors: Fuller Zachary L. , Mocellin Veronique J.L. , Morris Luke , Cantin Neal , Shepherd Jihanne , Sarre Luke , Peng Julie , Liao Yi , Pickrell Joseph , Andolfatto Peter , Matz Mikhail , Bay Line K. , Przeworski Molly 
Published: December 2019

AbstractAlthough reef-building corals are rapidly declining worldwide, responses to bleaching vary both within and among species. Because these inter-individual differences are partly heritable, they should in principle be predictable from genomic data. Towards that goal, we generated a chromosome-scale genome assembly for the coralAcropora millepora. We then obtained whole genome sequences for 237 phenotyped samples collected at 12 reefs distributed along the Great Barrier Reef, among which we inferred very little population structure. Scanning the genome for evidence of local adaptation, we detected signatures of long-term balancing selection in the heat-shock co-chaperonesacsin. We further used 213 of the samples to conduct a genome-wide association study of visual bleaching score, incorporating the polygenic score derived from it into a predictive model for bleaching in the wild. These results set the stage for the use of genomics-based approaches in conservation strategies.
Proteomics identifies signal peptide features determining the substrate specificity in human Sec62/Sec63-dependent ER protein import
Authors: Schorr Stefan , Nguyen Duy , Haßdenteufel Sarah , Nagaraj Nagarjuna , Cavalié Adolfo , Greiner Markus , Weissgerber Petra , Loi Marisa , Paton Adrienne W. , Paton James C. , Molinari Maurizio , Förster Friedrich , Dudek Johanna , Lang Sven , Helms Volkhard , Zimmermann Richard 
Published: December 2019

AbstractIn mammalian cells one-third of all polypeptides are integrated into the membrane or translocated into the lumen of the endoplasmic reticulum (ER) via the Sec61-channel. While the Sec61-complex facilitates ER-import of most precursor polypeptides, the Sec61-associated Sec62/Sec63-complex supports ER-import in a substrate-specific manner. So far, mainly posttranslationally imported precursors and the two cotranslationally imported precursors of ERj3 and prion protein were found to depend on the Sec62/Sec63-complexin vitro. Therefore, we determined the rules for engagement of Sec62/Sec63 in ER-import in intact human cells using a recently established unbiased proteomics approach. In addition to confirming ERj3, we identified twenty-two novel Sec62/Sec63-substrates under thesein vivo-like conditions. As a common feature, those previously unknown substrates share signal peptides with comparatively longer but less hydrophobic H-region and lower C-region polarity. Further analyses with four substrates, and ERj3 in particular, revealed the combination of a slowly-gating signal peptide and a downstream translocation-disruptive positively charged cluster of amino acid residues as decisive for the Sec62-/Sec63-requirement. In the case of ERj3, these features were found to be responsible for an additional BiP-requirement and to correlate with sensitivity towards the Sec61-channel inhibitor CAM741. Thus, the human Sec62/Sec63-complex may support Sec61-channel opening for precursor polypeptides with slowly-gating signal peptides by direct interaction with the cytosolic amino-terminal peptide of Sec61α or via recruitment of BiP and its interaction with the ER-lumenal loop 7 of Sec61α. These novel insights into the mechanism of human ER protein import contribute to our understanding of the etiology ofSEC63-linked Polycystic Liver Disease.DatabasesThe mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (http://www.ebi.ac.uk/pride/archive/projects/Identifiers) with the dataset identifiers: PXD008178, PXD011993, and PXD012078. Supplementary information was deposited at Mendeley Data under the DOI:10.17632/6s5hn73jcv.1 (http://dx.doi.or/10.17632/6s5hn73jcv.1).