bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural correlates of object-extracted relative clause processing across English and Chinese
Authors: Dunagan Donald , Stanojević Miloš , Coavoux Maximin , Zhang Shulin , Bhattasali Shohini , Li Jixing , Brennan Jonathan , Hale John 
Published: September 2022

AbstractAre the brain bases of language comprehension the same across all human languages, or do these bases vary in a way that corresponds to differences in linguistic typology? English and Mandarin Chinese attest such a typological difference in the domain of relative clauses. Using fMRI with English and Chinese participants, who listened to the same translation-equivalent story, we analyzed neuroimages time-aligned to object-extracted relative clauses in both languages. In a GLM analysis of these naturalistic data, comprehension was selectively associated with increased hemodynamic activity in left posterior temporal lobe, angular gyrus, inferior frontal gyrus, precuneus, and posterior cingulate cortex in both languages. This result suggests the processing of object-extracted relative clauses is subserved by a common collection of brain regions, regardless of typology. However, there were also regions that were activated uniquely in our Chinese participants albeit not to a significantly greater degree. These were in the temporal lobe. These Chinese-specific results could reflect structural ambiguity-resolution work that must be done in Chinese but not English ORCs.
A possible genomic footprint of polygenic adaptation on population divergence in seed beetles?
Authors: Arnqvist Göran , Sayadi Ahmed 
Published: September 2022

AbstractEfforts to unravel the genomic basis of incipient speciation are hampered by a mismatch between our toolkit and our understanding of the ecology and genetics of adaptation. While the former is focused on detecting selective sweeps involving few independently acting or linked speciation genes, the latter states that divergence typically occurs in polygenic traits under stabilizing selection. Here, we ask whether a role of stabilizing selection on polygenic traits in population divergence may be unveiled by using a phenotypically informed integrative approach, based on genome-wide variation segregating in divergent populations. We compare three divergent populations of seed beetles (Callosobruchus maculatus) where previous work has demonstrated a prominent role for stabilizing selection on, and population divergence in, key life history traits that reflect rate-dependent metabolic processes. We derive and assess predictions regarding the expected pattern of covariation between genetic variation segregating within populations and genetic differentiation between populations. Population differentiation was considerable (mean FST = 0.23 - 0.26) and was primarily built by genes showing high selective constraints and an imbalance in inferred selection in different populations (positive Tajima’s DNS in one and negative in one) and this set of genes was enriched with genes with a metabolic function. Repeatability of relative population differentiation was low at the level of individual genes but higher at the level of broad functional classes, again spotlighting metabolic genes. Absolute differentiation (dXY) showed a very different general pattern at this scale of divergence, more consistent with an important role for genetic drift. Although our exploration is consistent with stabilizing selection on polygenic metabolic phenotypes as an important engine of genome-wide relative population divergence and incipient speciation in our study system, we note that it is exceedingly difficult to firmly exclude other scenarios.
Intranasal oxytocin enhances social preference for parents over peers in male but not female peri-adolescent California mice (Peromyscus californicus)
Authors: Guoynes Caleigh D. , Marler Catherine A. 
Published: September 2022

ABSTRACTPeri-adolescence is a critical developmental stage marked by profound changes in the valence of social interactions with parents and peers. We hypothesized that the oxytocin (OXT) and vasopressin (AVP) systems, known for influencing social behavior, would be involved in the maintenance and breaking of bonding behavior expressed by peri-adolescent males and females. In rodents, OXT is associated with mother-pup bonding and may promote social attachment to members of the natal territory. AVP, on the other hand, can act in contrasting ways to OXT and has been associated with aggression and territoriality. Specifically, we predicted that in peri-adolescent male and female juveniles of the biparental and territorial California mouse (Peromyscus californicus), a) OXT would increase the social preferences for the parents over unfamiliar age-matched peers (one male and one female), and b) AVP would break the parent-offspring bond and either increase time in the neutral chamber and/or approach to their unfamiliar and novel peers. We examined anxiety and exploratory behavior using an elevated plus maze and a novel object task as a control. Peri-adolescent mice were administered an acute intranasal (IN) treatment of 0.5 IU/kg IN AVP, 0.5 IU/kg IN OXT, or saline control; five minutes later, the behavioral tests were conducted. As predicted, we found that IN OXT enhanced social preference for parents; however, this was only in male and not female peri-adolescent mice. IN AVP did not influence social preference in either sex. These effects appear specific to social behavior and not anxiety, as neither IN OXT nor AVP influenced behavior during the elevated plus maze or novel object tasks. To our knowledge, this is the first evidence indicating that OXT may play a role in promoting peri-adolescent social preferences for parents and delaying weaning in males.HIGHLIGHTSIn a 3-chambered choice test, peri-adolescent female and male California mice prefer their parents over peers or an empty chamberIntranasal oxytocin (IN OXT) enhances male but not female peri-adolescent social preference for their parentsIntranasal arginine vasopressin (IN AVP) did not influence social preference in either sexNeither IN OXT nor AVP alter peri-adolescent behavior in an elevated plus maze or novel object taskOXT may play a role in delaying weaning in males
Variation in mutation, recombination, and transposition rates inDrosophila melanogasterandDrosophila simulans
Authors: Wang Yiguan , McNeil Paul , Abdulazeez Rashidatu , Pascual Marta , Johnston Susan E. , Keightley Peter D. , Obbard Darren J. 
Published: September 2022

AbstractMutation, recombination, and transposition occurring during meiosis provide the variation on which natural selection can act and the rates at which they occur are important parameters in models of evolution. Thede novomutation rate determines levels of genetic diversity, responses to ongoing selection, and levels of genetic load. Recombination breaks up haplotypes and reduces the effects of linkage, helping to spread beneficial alleles and purge deleterious ones. Transposable elements (TE) selfishly replicate themselves through the genome, imposing fitness costs on the host and introducing complex mutations that can affect gene expression and give rise to new genes. However, even for key evolutionary models such asDrosophila melanogasterandD. simulansfew estimates of these parameters are available, and we have little idea of how rates vary between individuals, sexes, populations, or species. Here, we provide direct estimates of mutation, recombination, and transposition rates and their variation in a West African and a European population ofD. melanogasterand a European population ofD. simulans. Across 89 flies, we observe 58 single nucleotide mutations, 286 crossovers, and 89 TE insertions. Compared to the EuropeanD. melanogaster, we find the West African population has a lower mutation rate (1.67vs. 4.86 × 10−9site−1gen−1) and transposition rate (8.99vs. 23.36 × 10−5copy−1gen−1), but a higher recombination rate (3.44vs. 2.06 cM/Mb). The EuropeanD. simulanspopulation has a similar mutation rate to EuropeanD. melanogasterbut a significantly higher recombination rate and a lower but not significantly different transposition rate. Overall, we find paternal-derived mutations are more frequent than maternal ones in both species.HighlightsDe novomutation rates are 1.67 × 10−9site−1gen−1(95% HPD CI: 0.54 – 3.14 × 10−9), 4.86 × 10−9site−1gen−1(2.11 – 8.02 × 10−9), and 4.51 × 10−9site−1gen−1(1.94 – 7.75 × 10−9) for the West AfricanD. melanogaster, the EuropeanD. melanogasterand the EuropeanD. simulanspopulation, respectively.In females, recombination rates in the absence of large genomic inversions are 3.44 cM/Mb (2.72 – 4.18), 2.06 cM/Mb (1.57 - 2.57), and 3.04 cM/Mb (2.45 - 3.73) for the three populations, respectively. There was no strong evidence of recombination observed in males.Mutations (SNMs and indels) are male-biased.The West AfricanD. melanogasterpopulation has a lower TE activity than the other populations andCMC-Transibis the dominant active TE. The EuropeanD. melanogasterpopulation has multiple active TEs:Gypsy, CMC-Transib, Pao, JockeyandhAT-hobo; while in EuropeanD. simulans, they areGypsy, CMC-Transib, Pao, hAT-hobo, CopiaandTcMar-Mariner.
Robust residue-level error detection in cryo-electron microscopy models
Authors: Reggiano Gabriella , Farrell Daniel , DiMaio Frank 
Published: September 2022

ABSTRACTBuilding accurate protein models into moderate resolution (3-5Å) cryo-electron microscopy (cryo-EM) maps is challenging and error-prone. While the majority of solved cryo-EM structures are at these resolutions, there are few model validation metrics that can precisely evaluate the local quality of atomic models built into these maps. We have developed MEDIC (Model Error Detection in Cryo-EM), a robust statistical model to identify residue-level errors in protein structures built into cryo-EM maps. Trained on a set of errors from obsoleted protein structures, our model draws off two major sources of information to predict errors: the local agreement of model and map compared to expected, and how “native-like” the neighborhood around a residue looks, as predicted by a deep learning model. MEDIC is validated on a set of 28 structures that were subsequently solved to higher-resolutions, where our model identifies the differences between low- and high-resolution structures with 68% precision and 60% recall. We additionally use this model to rebuild 12 deposited structures, fixing 2 sequence registration errors, 51 areas with improper secondary structure, 51 incorrect loops, and 16 incorrect carbonyls, showing the value of this approach to guide model building.
The Respiratory Syncytial Virus G Protein Enhances the Immune Responses to the RSV F Protein in an Enveloped Virus-like Particle Vaccine Candidate
Authors: Cullen Lori McGinnes , Luo Bin , Wen Zhiyun , Zang Lan , Durr Eberhard , Morrison Trudy G. 
Published: September 2022

AbstractRespiratory syncytial virus (RSV) is a serious human respiratory pathogen, but no RSV vaccine has been licensed. Many of the vaccine candidates are focused on the viral F protein. However, it is the G protein that binds the likely receptor, CX3CR1, in human alveolar lung cells raising the question of the importance of the G protein in vaccine candidates. Using virus-like particle (VLP) vaccine candidates, we have directly compared VLPs containing only the pre-fusion F protein, only the G protein, or both glycoproteins. We report that VLPs containing both glycoproteins bind to anti-F protein specific monoclonal antibodies differently than VLPs containing only the pre-fusion F protein. Using RSV naïve cotton rats as an animal model, we have found that VLPs assembled only with the pre-F protein stimulated extremely weak neutralizing antibody (NAb) titers as did VLPs assembled with G protein. However, VLPs assembled with both glycoproteins stimulated quite robust neutralizing antibody titers, titers that were significantly higher than the combined titers induced by pre-F only or G only VLPs. VLPs assembled with both glycoproteins induced improved protection of the animals from RSV challenge compared to pre-F VLPs and induced significantly higher levels of antibodies specific for F protein antigenic sites 0, site III, and AM14 binding site compared with VLPs containing only the pre-F protein. These combined results indicate that assembly of pre-F protein with G protein in VLPs further stabilized the pre-fusion conformation or otherwise altered the conformation of the F protein increasing the induction of protective antibodies.ImportanceRSV causes significant disease in infants, young children, and the elderly. Thus, development of an effective vaccine for these populations is a priority. Most ongoing efforts in RSV vaccine development have focused on the viral fusion (F) protein, however, the importance of inclusion of G in vaccine candidates is unclear. Here, using VLPs assembled with only the F protein or only the G protein or both glycoproteins, we show that VLPs assembled with both glycoproteins are a far superior vaccine, in a cotton rat model, than VLPs containing only F protein or only G protein. The results show that the presence of G protein in the VLPs influences the conformation of the F protein and the immune responses to F protein resulting in significantly higher neutralizing antibody titers and better protection from RSV challenge. These results suggest that inclusion of G protein in a vaccine candidate may improve its effectiveness.
Trans-synaptic dwelling of SARS-CoV-2 particles perturbs neural synapse organization and function
Authors: Partiot Emma , Hirschler Aurélie , Colomb Sophie , Lutz Willy , Claeys Tine , Delalande François , Deffieu Maika S. , Roels Judith R.E. , Bons Joanna , Callon Domitille , Andreoletti Laurent , Labrousse Marc , Jacobs Frank M.J. , Rigau Valérie , Charlot Benoit , Martens Lennart , Carapito Christine , Ganesh Gowrishankar , Gaudin Raphael 
Published: September 2022

AbstractSARS-CoV-2 infection is associated with short- and long-term neurological and psychiatric complications, referred to as neuroCOVID. These symptoms are relatively heterogenous and fluctuating, hampering the discovery of molecular mechanisms underlying viro-induced brain perturbations. Here, we show that the human cerebral cortex poorly supports SARS-CoV-2 dissemination using post-mortem COVID-19 patient samples, ex vivo organotypic cultures of human brain explants and stem cell-derived cortical organoids. Despite restricted infection, the sole exposure of neural cells to SARS-CoV-2 particles is sufficient to induce significant perturbations on neural synapse organization associated to electrical activity dysfunction. Single-organoid proteomics revealed that exposure to SARS-CoV-2 is associated to trans-synaptic proteins upregulation and unveiled that incoming virions dwell at LPHN3/FLRT3-containing synapses. Our study provides new mechanistic insights on the origin of SARS-CoV-2-induced neurological disorders.One-Sentence SummarySARS-CoV-2 modulates neural plasticity and electrical activity as viral particles lodge at the trans-synaptic interface.
Reaction pathways for the enzymatic degradation of poly(ethylene terephthalate): What characterizes an efficient PET-hydrolase?
Authors: Schubert Sune , Schaller Kay , Bååth Jenny Arnling , Hunt Cameron , Borch Kim , Jensen Kenneth , Brask Jesper , Westh Peter 
Published: September 2022

AbstractBioprocessing of polyester waste has emerged as a promising tool in the quest for a cyclic plastic economy. One key step is the enzymatic breakdown of the polymer, and this entails a complicated pathway with substrates, intermediates, and products of variable size and solubility. We have elucidated this pathway for poly(ethylene terephthalate) (PET) and four enzymes. Specifically, we combined different kinetic measurements and a novel stochastic model, and found that the ability to hydrolyze internal bonds in the polymer (endo-lytic activity) was a key parameter for overall enzyme performance. Endo-lytic activity promoted the release of soluble PET fragments with two or three aromatic rings, which, in turn, were broken down with remarkable efficiency (kcat/KM-values of about 105M-1s-1) in the aqueous bulk. This meant that about 70% of the final, monoaromatic products was formed via soluble di-or tri-aromatic intermediates.
Role of UCP2 in the energy metabolism of the cancer cell line A549
Authors: Segalés Jessica , Sánchez-Martín Carlos , Pujol Aleida , Martín-Ruiz Marta , Rial Eduardo 
Published: September 2022

AbstractThe uncoupling protein UCP2 is a mitochondrial carrier whose transport activity remains controversial. The physiological contexts in which UCP2 is expressed have led to the assumption that, like UCP1, it uncouples oxidative phosphorylation and as a result it lowers the generation of reactive oxygen species. Other reports have involved UCP2 in the Warburg effect and results showing that UCP2 catalyzes the export of matrix C4 metabolites to facilitate glutamine utilization, suggests that the carrier could be involved in the metabolic adaptations required for cell proliferation. We have examined the role of UCP2 in the energy metabolism of the lung adenocarcinoma cell line A549 and show that UCP2 silencing decreased the basal rate of respiration although this inhibition was not compensated by an increase in glycolysis. Silencing did not lead to changes in proton leakage, as determined from the rate of respiration in the absence of ATP synthesis, or changes in the rate of formation of reactive oxygen species. The decrease in energy metabolism did not alter the cellular energy charge. The decreased cell proliferation observed in UCP2-silenced cells would explain the decreased cellular ATP demand. We conclude that UCP2 does not operate as an uncoupling protein while our results are consistent with its activity as a C4-metabolite carrier involved in the metabolic adaptations of proliferating cells.HighlightsUCP2 silencing decreases respiration without a compensatory increase in aerobic glycolysisATP levels remain unchanged despite the reduction in energy metabolismUCP2 silencing decreases cell proliferation that could explain the decrease in energy demandUCP2 silencing does not change the proton leakage rateData support the proposed involvement of UCP2 in the Warburg effect
Continuous millisecond conformational cycle of a DEAH box helicase reveals control of domain motions by atomic-scale transitions
Authors: Becker Robert A. , Hub Jochen S. 
Published: September 2022

AbstractHelicases are motor enzymes found in every living organism and viruses, where they maintain the stability of the genome and control against false recombination. The DEAH-box helicase Prp43 plays a crucial role in pre-mRNA splicing in unicellular organisms by translocating single-stranded RNA. The molecular mechanisms and conformational transitions of helicases are not understood at the atomic level. We present a complete conformational cycle of RNA translocation by Prp43 in atomic detail based on molecular dynamics simulations. To enable the sampling of such complex transition on the millisecond timescale, we combined two enhanced sampling techniques, namely simulated tempering and adaptive sampling guided by crystallographic data. During RNA translocation, the center-of-mass motions of the RecA-like domains followed the established inchworm model, whereas the domains crawled along the RNA in a caterpillar-like movement, suggesting an inchworm/caterpillar model. However, this crawling required a complex sequence of atomic-scale transitions involving the release of an arginine finger from the ATP pocket, stepping of the hook-loop and hook-turn motifs along the RNA backbone, and several others. These findings high-light that large-scale domain dynamics may be controlled by complex sequences of atomic-scale transitions.
Extensions of mean-field approximations for environmentally-transmitted pathogen networks
Authors: Davies Kale , Lenhart Suzanne , Day Judy , Lloyd Alun L. , Lanzas Cristina 
Published: September 2022

AbstractMany pathogens spread via environmental transmission, without requiring host- to-host direct contact. While models for environmental transmission exist, many are simply constructed intuitively with structures analogous to standard models for direct transmission. As model insights are generally sensitive to the underlying model assumptions, it is important that we are able understand the details and consequences of these assumptions. We construct a simple network model for an environmentally-transmitted pathogen and rigorously derive systems of ordinary differential equations (ODEs) based on different assumptions. We explore two key assumptions, namely homogeneity and independence, and demonstrate that relaxing these assumptions can lead to more accurate ODE approximations. We compare these ODE models to a stochastic implementation of the network model over a variety of parameters and network structures, demonstrating that with fewer restrictive assumptions we are able to achieve higher accuracy in our approximations and highlighting more precisely the errors produced by each assumption. We show that less restrictive assumptions lead to more complicated systems of ODEs and the potential for unstable solutions. Due to the rigour of our derivation, we are able to identify the reason behind these errors and propose potential resolutions.
Biosynthesis of iridoid sex pheromones in aphids
Authors: Köllner Tobias G. , David Anja , Luck Katrin , Beran Franziska , Kunert Grit , Zhou Jing-Jiang , Caputi Lorenzo , O’Connor Sarah E. 
Published: September 2022

AbstractIridoid monoterpenes, widely distributed in plants and insects, have many ecological functions. While the biosynthesis of iridoids has been extensively studied in plants, little is known about how insects synthesize these natural products. Here, we elucidated the biosynthesis of the iridoids cis-trans-nepetalactol and cis-trans-nepetalactone in the pea aphid Acyrthosiphon pisum [Harris], where they act as sex pheromones. The exclusive production of iridoids in hind legs of sexual female aphids allowed us to identify iridoid genes by searching for genes specifically expressed in this tissue. Biochemical characterization of candidate enzymes revealed that the iridoid pathway in aphids proceeds through the same sequence of intermediates as described for plants. The six identified aphid enzymes are unrelated to their counterparts in plants, conclusively demonstrating an independent evolution of the entire iridoid pathway in plants and insects. In contrast to the plant pathway, at least three of the aphid iridoid enzymes are likely membrane-bound. We demonstrated that a lipid environment facilitates the cyclization of a reactive enol intermediate to the iridoid cyclopentanoid-pyran scaffold in vitro, suggesting that membranes are an essential component of the aphid iridoid pathway. Altogether, our discovery of this complex insect metabolic pathway establishes the genetic and biochemical basis for the formation of iridoid sex pheromones in aphids and this discovery also serves as a foundation for understanding the convergent evolution of complex metabolic pathways between kingdoms.Significance StatementPlants, animals and microbes produce a plethora of natural products that are important for defense and communication. Most of these compounds show a phylogenetically restricted occurrence, but in rare instances, the same natural product is biosynthesized by organisms in two different kingdoms. The monoterpene-derived iridoids, for example, have been found in more than 50 plant families, but are also observed in several insect orders. The aphid iridoid pathway discovered in this study, one of the longest and most chemically complex insect-derived natural product biosynthetic pathways reported to date, is compared with iridoid biosynthetic pathways in plants and highlights the mechanisms underlying the convergent evolution of metabolic enzymes in insects and plants.