bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probabilistically Weighted Multilayer Networks disclose the link between default mode network instability and psychosis-like experiences in healthy adults
Authors: Di Plinio Simone , Ebisch Sjoerd J H 
Published: May 2021

ABSTRACTThe brain is a complex system in which the functional interactions among its subunits vary over time. The trajectories of this dynamic variation contribute to inter-individual behavioral differences and psychopathologic phenotypes. Despite many methodological advancements, the study of dynamic brain networks still relies on biased assumptions in the temporal domain. The current paper has two goals. First, we present a novel method to study multilayer networks: by modelling intra-nodal connections in a probabilistic, biologically driven way, we introduce a temporal resolution of the multilayer network based on signal similarity across time series. This new method is tested on synthetic networks by varying the number of modules and the sources of noise in the simulation. Secondly, we implement these probabilistically weighted (PW) multilayer networks to study the association between network dynamics and subclinical, psychosis-relevant personality traits in healthy adults. We show that the PW method for multilayer networks outperforms the standard procedure in modular detection and is less affected by increasing noise levels. Additionally, the PW method highlighted associations between the temporal instability of default mode network connections and psychosis-like experiences in healthy adults. PW multilayer networks allow an unbiased study of dynamic brain functioning and its behavioral correlates.
Genomic contacts reveal the control of sister chromosome decatenation in E. coli
Authors: Conin Brenna , Billault-Chaumartin Ingrid , Sayyed Hafez El , Cockram Charlotte , Koszul Romain , Espéli Olivier 
Published: May 2021

AbstractIn bacteria, chromosome segregation occurs progressively, from the origin to the terminus, a few minutes after the replication of each locus. In-between replication and segregation, sister loci are maintained in an apparent cohesive state by topological links. Whereas topoisomerase IV (Topo IV), the main bacteria decatenase, controls segregation, little is known regarding the influence of the cohesion step on chromosome folding. In this work, we investigated chromosome folding in cells with altered decatenation activities. Within minutes after Topo IV inactivation, a massive chromosome reorganization takes place, associated with increases in trans-contacts between catenated sister chromatids and in long-range cis-contacts between the terminus and distant loci on the genome. A genetic analysis of these signals allowed us to decipher specific roles for Topo IV and Topo III, an accessory decatenase. Moreover we revealed the role of MatP, the terminus macrodomain organizing system and MukB, the E. coli SMC in organizing sister chromatids tied by persistent catenation links. We propose that large-scale conformation changes observed in these conditions reveal a defective decatenation hub located in the terminus area. Altogether, our findings support a model of spatial and temporal partition of the tasks required for sister chromosome segregation.
The Medaka Inbred Kiyosu-Karlsruhe (MIKK) Panel
Authors: Fitzgerald Tomas , Brettell Ian , Leger Adrien , Wolf Nadeshda , Kusminski Natalja , Monahan Jack , Barton Carl , Herder Cathrin , Aadepu Narendar , Gierten Jakob , Becker Clara , Hammouda Omar T. , Hasel Eva , Lischik Colin , Lust Katharina , Suzuki Risa , Tsingos Erika , Tavhelidse Tinatini , Thumberger Thomas , Watson Philip , Welz Bettina , Khouja Nadia , Naruse Kiyoshi , Birney Ewan , Wittbrodt Joachim , Loosli Felix 
Published: May 2021

AbstractUnraveling the relationship between genetic variation and phenotypic traits remains a fundamental challenge in biology. Mapping variants underlying complex traits while controlling for confounding environmental factors is often problematic. To address this, we have established a vertebrate genetic resource specifically to allow for robust genotype-to-phenotype investigations. The teleost medaka (Oryzias latipes) is an established genetic model system with a long history of genetic research and a high tolerance to inbreeding from the wild. Here we present the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel: the first near-isogenic panel of 80 inbred lines in a vertebrate model derived from a wild founder population. Inbred lines provide fixed genomes that are a prerequisite for the replication of studies, studies which vary both the genetics and environment in a controlled manner and functional testing. The MIKK panel will therefore enable phenotype-to-genotype association studies of complex genetic traits while allowing for careful control of interacting factors, with numerous applications in genetic research, human health, and drug development and fundamental biology. Here we present a detailed characterisation of the genetic variation across the MIKK panel, which provides a rich and unique genetic resource to the community by enabling large-scale experiments for mapping complex traits.
Lactate is a major energy substrate for cortical neurons and enhances their firing activity
Authors: Karagiannis Anastassios , Gallopin Thierry , Lacroix Alexandre , Plaisier Fabrice , Piquet Juliette , Geoffroy Hélène , Hepp Régine , Naudé Jérémie , Le Gac Benjamin , Egger Richard , Lambolez Bertrand , Li Dongdong , Rossier Jean , Staiger Jochen F. , Imamura Hiromi , Seino Susumu , Roeper Jochen , Cauli Bruno 
Published: May 2021

SummaryGlucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with Kir6.2 and SUR1 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.HighlightsMost cortical neurons subtypes express pancreatic beta-cell like KATP channels.Lactate enhances spiking activity via its uptake and closure of KATP channels.Cortical neurons take up and oxidize lactate.Cortical neurons produce ATP mainly by oxidative phosphorylation.
Comparative analyses and phylogenetic relationships of 15Trapa(Trapaceae) species based on Complete Chloroplast Genomes
Authors: Fan Xiangrong , Wang Wuchao , Wagutu Godfrey K. , Li Wei , Li Xiuling , Chen Yuanyuan 
Published: May 2021

AbstractTrapaL. is floating-leaved aquatic plants with important economic and ecological values. However, species identification and phylogenetic relationship are still unresolved forTrapa. In this study, complete chloroplast genomes of 13Trapaspecies/taxa were sequenced and annotated. Combined with released sequences of the other two species, comparative analysis of cp genomes was first performed on the 15Trapaspecies/taxa. The 15 cp genomes exhibited quadripartite structures with medium size of 155, 453-155, 559 bp. IR/SC junctions were conservative with no obvious change found. Long repetitive repeats and SSRs were mostly detected in the intergenic and LSC regions, providing useful plastid markers for species and relationship identification. Three phylogenetic analyses (MP, ML and BI) consistently showed two clusters withinTrapa, including large- and small-seed species/taxa, respectively. This study provided the baseline information for phylogeography ofTrapa, which would facilitate the management and utilization of genetic resources of the genus.
Loricarioid catfish evolved skin denticles that recapitulate teeth at the structural, developmental, and genetic levels
Authors: Rivera-Rivera Carlos J. , Guevara-Delgadillo Nadezhda I. , Bahechar Ilham A. , Shea Claire A. , Montoya-Burgos Juan I. 
Published: May 2021

AbstractThe first vertebrate mineralized skeleton was an external bony armor coated with dental structures. The subsequent emergence of a mineralized endoskeleton and of teeth are considered key innovations in the diversification of vertebrates. Although time clouds our understanding of the initial evolution of these mineralized structures, recent re-emergences may shed light on the underlying processes. Loricarioid catfishes are a lineage that, much like the ancestral vertebrates, bear denticle-clad bony armor from head to tail. Loricarioid denticles (LDs) and oral teeth are very similar in superstructure. We show here that other extra-oral dental structures are found as ancestral characters only in lineages that are distantly related to loricarioids such as sharks or coelacanth, indicating that LDs have independently re-emerged in loricarioid catfishes. We investigate whether the similarities between LDs and teeth extend to their developmental and genetic context, and how their development compares to that of other vertebrate integument structures. Our detailed study of the development of LDs, and gene expression analyses through in situ hybridization confirm that all 12 genes from the tooth-forming gene regulatory network (oGRN) are expressed in developing LDs in a similar way as they are expressed in developing teeth. We then compare the developmental, structural, and genetic aspects of LD and teeth with that of other integument appendages such as fish scales, shark dermal denticles, feathers and hairs. We find that LDs share all developmental cues with teeth and, to a lesser extent, with the other vertebrate integument structures. Taken together, our results indicate that denticles have re-emerged on the trunk of loricarioid catfishes through the ectopic co-option of the oGRN rather than the resurrection of an ancestral trunk-specific denticle genetic pathway.
Towards risk-based surveillance of African Swine Fever in Switzerland
Authors: Amado Maria Elena Vargas , Carmo Luís Pedro , Berezowski John , Fischer Claude , Santos Maria João , Grütter Rolf 
Published: May 2021

AbstractAfrican Swine Fever (ASF) has emerged as a disease of great concern to swine producers and government disease control agencies because of its severe consequences to animal health and the pig industry. Early detection of an ASF introduction is considered essential for reducing the harm caused by the disease. Risk-based surveillance approaches have been used as enhancements to early disease epidemic detection systems in livestock populations. Such approaches may consider the role wildlife plays in hosting and transmitting a disease. In this study, a novel method is presented to estimate and map the risk of introducing ASF into the domestic pig population through wild boar intermediate hosts. It makes use of data about hunted wild boar, rest areas along motorways connecting ASF affected countries to Switzerland, outdoor piggeries, and forest cover. These data were used to compute relative wild boar abundance as well as to estimate the risk of both disease introduction into the wild boar population and disease transmission to domestic pigs. The way relative wild boar abundance was calculated adds to the current state of the art by considering the effect of beech mast on hunting success and the probability of wild boar occurrence when distributing relative abundance values among individual grid cells. The risk of ASF introduction into the domestic pig population by wild boar was highest near the borders of France, Germany, and Italy. On the north side of the Alps, areas of high risk were located on the unshielded side of the main motorway crossing the Central Plateau, which acts as a barrier for wild boar. The results of this study can be used to focus surveillance efforts for early disease detection on high risk areas. The developed method may also inform policies to control other diseases that are transmitted by direct contact from wild boar to domestic pigs.
Genomic variations and epigenomic landscape of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel
Authors: Leger Adrien , Brettell Ian , Monahan Jack , Barton Carl , Wolf Nadeshda , Kusminski Natalja , Herder Cathrin , Aadepu Narendar , Becker Clara , Gierten Jakob , Hammouda Omar T. , Hasel Eva , Lischik Colin , Lust Katharina , Suzuki Risa , Tavhelidse Tinatini , Thumberger Thomas , Tsingos Erika , Watson Philip , Welz Bettina , Naruse Kiyoshi , Loosli Felix , Wittbrodt Joachim , Birney Ewan , Fitzgerald Tomas 
Published: May 2021

AbstractThe teleost medaka (Oryzias latipes) is a well-established vertebrate model system, with a long history of genetic research, and multiple high-quality reference genomes available for several inbred strains (HdrR, HNI and HSOK). Medaka has a high tolerance to inbreeding from the wild, thus allowing one to establish inbred lines from wild founder individuals. We have exploited this feature to create an inbred panel resource: the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel. This panel of 80 near-isogenic inbred lines contains a large amount of genetic variation inherited from the original wild population. We used Oxford Nanopore Technologies (ONT) long read data to further investigate the genomic and epigenomic landscapes of a subset of the MIKK panel. Nanopore sequencing allowed us to identify a much greater variety of high-quality structural variants compared with Illumina sequencing. We also present results and methods using a pan-genome graph representation of 12 individual medaka lines from the MIKK panel. This graph-based reference MIKK panel genome revealed novel differences between the MIKK panel lines compared to standard linear reference genomes. We found additional MIKK panel-specific genomic content that would be missing from linear reference alignment approaches. We were also able to identify and quantify the presence of repeat elements in each of the lines. Finally, we investigated line-specific CpG methylation and performed differential DNA methylation analysis across the 12 lines. We thus present a detailed analysis of the MIKK panel genomes using long and short read sequence technologies, creating a MIKK panel specific pan genome reference dataset allowing for the investigation of novel variation types that would be elusive using standard approaches.
Functional or vestigial? The genomics of the pineal gland in Xenarthra
Authors: Valente Raul , Alves Filipe , Pinto Isabel Sousa , Ruivo Raquel , Castro L. Filipe C. 
Published: May 2021

AbstractVestigial organs are historical echoes of past phenotypes. Determining whether a specific organ constitutes a functional or vestigial structure can be a challenging task, given that distinct levels of atrophy may arise between and within lineages. The mammalian pineal gland, an endocrine organ involved in melatonin biorhythmicity, represents a classic example, often yielding contradicting anatomical observations. In Xenarthra (sloths, anteaters and armadillos), a peculiar mammalian order, the presence of a distinct pineal organ was clearly observed in some species (i.e. Linnaeus’s two-toed sloth) but undetected in other closely related species (i.e. brown-throated sloth). In the nine-banded armadillo, contradicting evidence supports either functional or vestigial scenarios. Thus, to untangle the physiological status of the pineal gland in Xenarthra, we used a genomic approach to investigate the evolution of the gene hub responsible for melatonin synthesis and signaling. We show that both synthesis and signaling compartments are eroded and were lost independently. Additionally, by expanding our analysis to 157 mammal genomes we offer a comprehensive view showing that species with very distinctive habitats and lifestyles have convergently evolved a similar phenotype: Cetacea, Pholidota, Dermoptera, Sirenia and Xenarthra. Our findings suggest that the recurrent inactivation of melatonin genes correlates with pineal atrophy, and endorse the use of genomic analyses to ascertain the physiological status of suspected vestigial structures.
Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit
Authors: Gilbert Alice , Elorza-Vidal Xabier , Rancillac Armelle , Chagnot Audrey , Yetim Mervé , Hingot Vincent , Deffieux Thomas , Boulay Anne-Cécile , Alvear-Perez Rodrigo , Cisternino Salvatore , Martin Sabrina , Taib Sonia , Gelot Antoinette , Mignon Virginie , Favier Maryline , Brunet Isabelle , Declèves Xavier , Tanter Mickael , Estevez Raul , Vivien Denis , Saubaméa Bruno , Cohen-Salmon Martine 
Published: May 2021

AbstractAbsence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC); this rare type of leukodystrophy is characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes (PvAPs, which along with blood vessels form the gliovascular unit (GVU)). We analyzed the GVU in the Mlc1 knock-out mouse model of MLC. The absence of MLC1 led to an accumulation of fluid in the brain but did not modify the endothelial organization or the integrity of the blood-brain barrier. From P10 onward, the postnatal acquisition of vascular smooth muscle cell contractility was altered, resulting in a marked reduction in arterial perfusion and neurovascular coupling. These anomalies were correlated with alterations in astrocyte morphology, astrocyte polarity and the structural organization of the PvAP’s perivascular coverage, and poor intraparenchymal circulation of the cerebrospinal fluid (CSF). Hence, MLC1 is required for the postnatal development and organization of PvAPs and controls vessel contractility and intraparenchymal interstitial fluid clearance. Our data suggest that (i) MLC is a developmental disorder of the GVU, and (ii) PvAP and VSMC maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease.
Decoding Angiotensin II Type 1 Receptor Allosteric Communication to Gq and β-arrestin
Authors: Nivedha Anita K. , Cao Yubo , Lee Sangbae , Bhattacharya Supriyo , Laporte Stéphane A. , Vaidehi Nagarajan 
Published: May 2021

AbstractThe allosteric communication between the agonist binding site and the G protein or β-arrestin coupling sites in G protein-coupled receptors (GPCRs) play an important role in determining ligand efficacy towards these two signaling pathways and hence the ligand bias. Knowledge of the amino acid residue networks involved in the allosteric communication will aid understanding GPCR signaling and the design of biased ligands. Angiotensin II type I receptor (AT1R) is an ideal model GPCR to study the molecular basis of ligand bias as it has multiple β-arrestin2 and Gq protein biased agonists as well as three-dimensional structures. Using Molecular Dynamics simulations, dynamic allostery analysis, and functional BRET assays, we identified a network of residues involved in allosteric communication from the angiotensin II binding site to the putative Gq coupling sites and another network to the β-arrestin2 coupling sites, with 6 residues common to both pathways located in TM3, TM5 and TM6. Our findings unveil unique and common allosteric communication residue hubs for Gq and β-arr2 coupling by AngII ligands and suggests that some of these residues can be targeted to design biased AT1R ligands. Finally, we show through analysis of the inter-residue distance distributions of the activation microswitches involved in class A GPCR activation for ten different agonists, that these microswitches behave like rheostats with different relative strengths of activation, which we speculate could modulate the relative efficacy of these agonists toward the two signaling pathways.Significance StatementKnowledge of the residues involved in allosteric communication from the ligand binding site to the G protein or β-arrestin (β-arr) coupling sites in GPCRs will aid in understanding their role in mediating ligand bias. Using a combination of molecular dynamics simulations and functional signaling assays we have identified a network of residues involved in allosteric communication from the Angiotensin II (Ang II) binding site to the Gq and β-arr2 coupling sites in the Ang II type I receptor (AT1R). The residues in the allosteric network for β-arr2 coupling are distributed across multiple structural regions of AT1R compared to Gq coupling. The residues in the two networks show conserved chemical properties across class A GPCRs, demonstrating the importance of allosteric communication in modulating ligand bias.
Heritability and phenotypic plasticity of biting time behaviors in the major African malaria vectorAnopheles arabiensis
Authors: Govella Nicodem J. , Johnson Paul C. D. , Killeen Gerry F. , Ferguson Heather M. 
Published: May 2021

AbstractUse of Insecticide Treated Nets for malaria control has been associated with shifts in mosquito vector feeding behavior including earlier and outdoor biting on humans. The relative contribution of phenotypic plasticity and heritability to these behavioural shifts is unknown. Elucidation of the mechanisms behind these shifts is crucial for anticipating impacts on vector control. We used a novel portable semi-field system (PSFS) to experimentally measure heritability of biting time in the malaria vectorAnopheles arabiensisin Tanzania. In PSFS assays, the biting time of F2 offspring (early: 18:00-21:00, mid: 22:00-04:00 or late: 05:00-07:00) was significantly associated with that of their wild-caught F0 grandmothers, corresponding to an estimated heritability of 0.30 (95% CI: 0.20, 0.41). F2 from early-biting F0 were more likely to bite early than F2 from mid or late late-biting F0. Similarly, the probability of biting late was higher in F2 derived from mid and late-biting F0 than from early-biting F0. Our results indicate that variation in biting time is attributable to additive genetic variation. Selection can therefore act efficiently on mosquito biting times, highlighting the need for control methods that target early and outdoor biting mosquitoes.
Pathogen clonal expansion underlies multiorgan dissemination and organ-specific outcomes during systemic infection
Authors: Hullahalli Karthik , Waldor Matthew K. 
Published: May 2021

AbstractThe dissemination of pathogens through blood and their establishment within organs lead to severe clinical outcomes. However, the within-host dynamics that underly pathogen spread to and clearance from systemic organs remain largely uncharacterized. Here, we investigate the population dynamics of extraintestinal pathogenic E. coli, a common cause of bacteremia, during systemic infection. We show that while bacteria are largely cleared by most organs, organ-specific clearance failures are pervasive and result from dramatic expansions of clones representing less than 0.0001% of the inoculum. Clonal expansion underlies the variability in bacterial burden between animals, and stochastic dissemination of clones profoundly alters the pathogen population structure within organs. Despite variable pathogen expansion events, host bottlenecks are consistent yet highly sensitive to infection variables, including inoculum size and macrophage depletion. Finally, we identify organ-specific bacterial genetic factors that distinguish between establishment of within-organ pathogen populations and subsequent survival or expansion.