bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre- and post-target cortical processes predict speech-in-noise performance
Authors: Kim Subong , Schwalje Adam T. , Liu Andrew S. , Gander Phillip E. , McMurray Bob , Griffiths Timothy D. , Choi Inyong 
Published: October 2019

AbstractUnderstanding speech in noise (SiN) is a complex task that recruits multiple cortical subsystems. There is a variance in individuals’ ability to understand SiN that cannot be explained by simple hearing profiles, which suggests that central factors may underlie the variance in SiN ability. Here, we elucidated a few cortical functions involved during a SiN task and their contributions to individual variance using both within- and across-subject approaches. Through our within-subject analysis of source-localized electroencephalography, we investigated how acoustic signal-to-noise ratio (SNR) alters cortical evoked responses to a target word across the speech recognition areas, finding stronger responses in left supramarginal gyrus (SMG, BA40 thedorsal lexiconarea) with quieter noise. Through an individual differences approach, we found that listeners show different neural sensitivity to the background noise and target speech, reflected in the amplitude ratio of earlier auditory-cortical responses to speech and noise, named as aninternal SNR. Listeners with betterinternal SNRshowed better SiN performance. Further, we found that the post-speech time SMG activity explains a further amount of variance in SiN performance that is not accounted for byinternal SNR. This result demonstrates that at least two cortical processes contribute to SiN performance independently: pre-target time processing to attenuate neural representation of background noise and post-target time processing to extract information from speech sounds.
Transcriptomic responses associated with carbon and energy flows under high salinity stress suggest the overflow of acetyl-CoA from glycolysis and NADPH co-factor induces high lipid accumulation and halotolerance inChlorellasp. HS2
Authors: Yun Jin-Ho , Pierrelée Michaël , Cho Dae-Hyun , Kim Urim , Heo Jina , Choi Dong-Yun , Lee Yong Jae , Lee Bongsoo , Kim HyeRan , Habermann Bianca , Chang Yong Keun , Kim Hee-Sik 
Published: October 2019

AbstractPreviously, we isolatedChlorellasp. HS2 (referred hereupon HS2) from a local tidal rock pool and demonstrated its halotolerance and relatively high biomass productivity under different salinity conditions. To further understand acclimation responses of this alga against high salinity stress, we performed transcriptome analysis of triplicated culture samples grown in freshwater and marine conditions at both exponential and stationary growth phases.De novoassembly followed by differential expression analysis identified 5907 and 6783 differentially expressed genes (DEGs) respectively at exponential and stationary phases from a total of 52770 transcripts, and the functional enrichment of DEGs with KEGG database resulted in 1445 KEGG Orthology (KO) groups with a defined differential expression. Specifically, the transcripts involved in photosynthesis, TCA and Calvin cycles were downregulated, whereas the upregulation of DNA repair mechanisms and an ABCB subfamily of eukaryotic type ABC transporter was observed at high salinity condition. In addition, while key enzymes associated with glycolysis pathway and triacylglycerol (TAG) synthesis were determined to be upregulated from early growth phase, salinity stress seemed to reduce the carbohydrate content of harvested biomass from 45.6 dw% to 14.7 dw% and nearly triple the total lipid content from 26.0 dw% to 62.0 dw%. These results suggest that the reallocation of storage carbon toward lipids played a significant role in conferring the viability of this alga under high salinity stress, most notably by remediating high level of cellular stress partially caused by ROS generated in oxygen-evolving thylakoids.Summary StatementRedirection of storage carbon towards the synthesis of lipids played a critical role in conferring the halotolerance of aChlorellaisolate by remediating excess oxidative stress experienced in photosystems.
Multi-region exome sequencing of ovarian teratomas reveals 2N near-diploid genomes, paucity of somatic mutations, and extensive allelic imbalances shared across mature, immature, and disseminated components
Authors: Heskett Michael B. , Sanborn John Z. , Boniface Christopher , Goode Benjamin , Chapman Jocelyn , Garg Karuna , Rabban Joseph T. , Zaloudek Charles , Benz Stephen C. , Spellman Paul T. , Solomon David A. , Cho Raymond J. 
Published: October 2019

AbstractImmature teratoma is a subtype of malignant germ cell tumor of the ovary that occurs most commonly in the first three decades of life, frequently with bilateral ovarian disease. Despite being the second most common malignant germ cell tumor of the ovary, little is known about its genetic underpinnings. Here we performed multi-region whole exome sequencing to interrogate the genetic zygosity, clonal relationship, DNA copy number, and mutational status of 52 pathologically distinct tumor components from 10 females with ovarian immature teratomas, with bilateral tumors present in 5 cases and peritoneal dissemination in 7 cases. We found that ovarian immature teratomas are genetically characterized by 2N near-diploid genomes with extensive loss of heterozygosity and an absence of genes harboring recurrent somatic mutations or known oncogenic variants. All components within a single ovarian tumor (immature teratoma, mature teratoma with different histologic patterns of differentiation, and yolk sac tumor) were found to harbor an identical pattern of loss of heterozygosity across the genome, indicating a shared clonal origin. In contrast, the 4 analyzed bilateral teratomas showed distinct patterns of zygosity changes in the right versus left sided tumors, indicating independent clonal origins. All disseminated teratoma components within the peritoneum (including gliomatosis peritonei) shared a clonal pattern of loss of heterozygosity with either the right or left primary ovarian tumor. The observed genomic loss of heterozygosity patterns indicate that diverse meiotic errors contribute to the formation of ovarian immature teratomas, with 11 out of the 15 genetically distinct clones determined to result from the failure of meiosis I or II. Overall, these findings suggest that copy-neutral loss of heterozygosity resulting from meiotic abnormalities may be sufficient to generate ovarian immature teratomas from germ cells.
Disruption of Redox Balance Enhances the Effects of BRAF-inhibition in Melanoma Cells
Authors: Paudel B. Bishal , Lewis Joshua E. , Hardeman Keisha N. , Hayford Corey E. , Robbins Charles J. , Codreanu Simona G. , Sherrod Stacy D. , McLean John A. , Kemp Melissa L. , Quaranta Vito 
Published: October 2019

SummaryMelanomas harboringBRAFmutations can be treated with BRAF inhibitors (BRAFi), but responses are varied and tumor recurrence is inevitable. Here, using an integrative approach of experimentation and mathematical flux balance analyses inBRAF-mutated melanoma cells, we report that elevated antioxidant capacity is linked to BRAFi sensitivity in melanoma cells. High levels of antioxidant metabolites in cells with reduced BRAFi sensitivity confirm this conclusion. By extending our analyses to other melanoma subtypes in TCGA, we predict that elevated redox capacity is a general feature of melanomas, not previously observed. We propose that redox vulnerabilities could be exploited for therapeutic benefits and identify unsuspected combination targets to enhance the effects of BRAFi in any melanoma, regardless of mutational status.
Coordination through inhibition: control of stabilizing and updating circuits in spatial orientation working memory
Authors: Han Rui , Huang Hsuan-Pei , Chuang Chia-Lung , Yen Hung-Hsiu , Kao Wei-Tse , Chang Hui-Yun , Lo Chung-Chuan 
Published: October 2019

AbstractSpatial orientation memory plays a crucial role in animal navigation. Recent studies of tethered Drosophila melanogaster (fruit fly) in a virtual reality setting showed that the head direction is encoded in the form of an activity bump, i.e. localized neural activity, in the torus-shaped ellipsoid body (EB). However, how this system is involved in orientation working memory is not well understood. We investigated this question using free moving flies (Drosophila melanogaster) in a spatial orientation memory task by manipulating two EB subsystems, C and P circuits, which are hypothesized for stabilizing and updating the activity bump, respectively. To this end, we suppressed or activated two types of inhibitory ring neurons (EIP and P) which innervate EB, and we discovered that manipulating the two inhibitory neuron types produced distinct behavioral deficits, suggesting specific roles of the inhibitory neurons in coordinating the stabilization and updating functions of the EB circuits. We further elucidate the neural mechanisms underlying such control circuits using a connectome-constrained spiking neural network model.Significance statementHead-direction (HD) system has been discovered in rodents for decades. But the detailed neural circuit mechanisms underlying the HD system were only described recently by studies of fruit flies on the similar HD system. However, how this fruit fly HD system involves in orientation memory was not well investigated. The present study addresses this question by investigating free moving flies in a spatial orientation working memory task. By combining neural functional experiments and neural circuit modelling, the study shows how disrupting either of the two subcircuits, one stabilizing and the other updating the neural activity, in the HD system leads to different behavioral impairments. The result suggests specific roles of the HD subcircuits in the spatial orientation working memory.Visual Abstract
Carbon metabolism, transcriptome and RNA editome in developmental paths differentiation ofCoprinopsis cinerea
Authors: Xie Yichun , Chang Jinhui , Kwan Hoi Shan 
Published: October 2019

AbstractThe balance and interplay between sexual and asexual reproduction is one of the most attractive mysteries in fungi. The choice of developmental strategy reflects the ability of fungi to adapt to the changing environment. However, the evolution of developmental paths and the metabolic regulation during differentiation and morphogenesis are poorly understood. Here, we monitor the carbohydrate metabolism and gene expression regulation during the early differentiation process from the “fungal stem cell”, vegetative mycelium, to the highly differentiated tissue/cells, fruiting body, oidia or sclerotia, of a homokaryotic fruitingCoprinopsis cinereastrain A43mut B43mut pab1-1 #326, uncovering the systematic changes during morphogenesis and the evolutionary process of developmental strategies. Conversion between glucose and glycogen and conversion between glucose and beta-glucan are the main carbon flows in the differentiation processes. Genes related to carbohydrate transport and metabolism are significantly differentially expressed among paths. RNA editing, a novel layer of gene expression regulation, occurs in all four developmental paths and enriched in cytoskeleton and carbohydrate metabolic genes. It is developmentally regulated and evolutionarily conserved in basidiomycetes. Evolutionary transcriptomic analysis on four developmental paths showed that all transcriptomes are under purifying selection, and the more stressful the environment, the younger the transcriptome age. Oidiation has the lowest value of transcriptome age index (TAI) and transcriptome divergence index (TDI), while fruiting process has the highest of both indexes. These findings provide new insight to the regulations of carbon metabolism and gene expressions during fungal developmental paths differentiation.ImportanceFungi is a group of species with high diversity and plays essential roles to the ecosystem. The life cycle of fungi is complex in structure and delicate in function. Choice of developmental strategies and internal changes within the organism are both important for the fungus to fulfill their ecological functions, reflecting the relationship between environment and the population. This study put the developmental process of vegetative growth, sexual and asexual reproduction, resistant structure formation of a classical model basidiomycetes fungus,C. cinerea, together for the first time to view the developmental paths differentiation process with physiology, transcriptomics and evolutionary prospects. Carbohydrate assays and RNA-seq showed the changes of the fungus. Our results fill the gaps on gene expression regulation during the early stage of developmental paths differentiation, and expand our understanding of the evolutionary process of life history and reproductive strategy in fungi.
Accelerated clearing and molecular labeling of large tissue samples using magnetohydrodynamic force
Authors: Dwyer Joseph , Ramirez M. Desmond , Katz Paul S. , Karlstrom Rolf O. , Bergan Joseph 
Published: October 2019

AbstractHere we report a strategy to efficiently render opaque biological tissues transparent and demonstrate that this approach can be modified to rapidly label intact samples with antibodies for large volume fluorescence microscopy. This strategy applies a magnetohydrodynamic (MHD) force to accelerate the removal of lipids from and the introduction of antibodies into tissue samples as large as an intact adult mouse brain. This strategy complements a growing array of tools that enable high-resolution 3-dimensional anatomical analyses in intact tissues using fluorescence microscopy. MHD-accelerated clearing and MHD-accelerated antibody labeling are fast, reliable, inexpensive, and compatible with existing strategies for high-quality fluorescence microscopy of intact tissues.
Mating changes the genital microbiome in both sexes of the common bedbugCimex lectulariusacross populations
Authors: Bellinvia Sara , Johnston Paul R. , Mbedi Susan , Otti Oliver 
Published: October 2019

ABSTRACTMany bacteria live on host surfaces, in cells, and specific organ systems. Although gut microbiomes of many organisms are well-documented, the bacterial communities of reproductive organs, i.e. genital microbiomes, have received little attention. During mating, male and female genitalia interact and copulatory wounds can occur, providing an entrance for sexually transmitted microbes. Besides being potentially harmful to the host, invading microbes might interact with resident genital microbes and affect immunity. While sexual transmission of individual symbiont species is relatively well-understood, few studies have addressed how mating changes genital microbiomes. Here, we characterize male and female genital microbiomes in four different populations of the common bedbugCimex lectulariusand investigate mating-induced changes. We dissected reproductive organs from virgin and mated individuals to sequence their genital microbiomes. We show that mating changes genital microbiomes, suggesting bacteria are sexually transmitted. This raises the question how the host’s physiological and immunological mechanisms control mating-induced changes in their genital microbiomes. Also, genital microbiomes varied between populations and the sexes. This provides evidence for local and sex-specific adaptation of bacteria and hosts, again suggesting that bacteria might play an important role in shaping the evolution of reproductive traits. Coadaptation of genital microbiomes and reproductive traits might further lead to reproductive isolation between populations, giving reproductive ecology an important role in speciation. Future studies should investigate the transmission dynamics between the sexes and populations to uncover potential reproductive barriers.
Inference with selection, varying population size and evolving population structure: Application of ABC to a forward-backward coalescent process with interactions
Authors: Lepers Clotilde , Billiard Sylvain , Porte Matthieu , Méléard Sylvie , Tran Viet Chi 
Published: October 2019

AbstractGenetic data are often used to infer history, demographic changes or detect genes under selection. Inferential methods are commonly based on models making various strong assumptions: demography and population structures are supposeda prioriknown, the evolution of the genetic composition of a population does not affect demography nor population structure, and there is no selection nor interaction between and within genetic strains. In this paper, we present a stochastic birth-death model with competitive interaction to describe an asexual population, and we develop an inferential procedure for ecological, demographic and genetic parameters. We first show how genetic diversity and genealogies are related to birth and death rates, and to how individuals compete within and between strains. This leads us to propose an original model of phylogenies, with trait structure and interactions, that allows multiple merging. Second, we develop an Approximate Bayesian Computation framework to use our model for analyzing genetic data. We apply our procedure to simulated and real data. We show that the procedure give accurate estimate of the parameters of the model. We finally carry an illustration on real data and analyze the genetic diversity of microsatellites on Y-chromosomes sampled from Central Asia populations in order to test whether different social organizations show significantly different fertility.
Capacitive coupling increases the accuracy of cell-specific tumour ablation by electric fields
Authors: Wimberger Terje , Köhler Verena K. , Ehmoser Eva K. , Wassermann Klemens J. 
Published: October 2019

AbstractIrreversible electroporation holds great potential for cell-specific lysis due to the size-dependent susceptibility of cells to externally imposed electric fields. Previous attempts at selective cell lysis lead to significant overlap between affected populations and struggle with inconsistent biological outcome. We propose that charge transfer at the electrode-liquid interface is responsible by inducing multifactorial effects originating from both the electric field and electrochemical reactions. A promising remedy is the coating of electrodes with a high-k dielectric layer. The resulting capacitive coupling restores the selective potential of electric field mediated lysis in a microfluidic setup. Initial experiments show the consistent depletion of erythrocytes from whole blood while leaving leukocytes intact. The same is true for the reproducible and selective depletion of Jurkat and MCF-7 cells in a mixture with leukocytes. Unexpectedly, the observed order of lysis cannot be correlated with cell size. This implies that the cellular response to capacitive coupling features a selective characteristic that is different from conventional lysis configurations.
TET1-mediated DNA hydroxy-methylation regulates adult remyelination
Authors: Moyon Sarah , Frawley Rebecca , Marshall-Phelps Katy LH , Kegel Linde , Bøstrand Sunniva MK , Sadowski Boguslawa , Huang Dennis , Jiang Yong-Hui , Lyons David , Möbius Wiebke , Casaccia Patrizia 
Published: October 2019

AbstractAdult myelination is essential for brain function and response to injury, but the molecular mechanisms remain elusive. Here we identify DNA hydroxy-methylation, an epigenetic mark catalyzed by Ten-Eleven translocation (TET) enzymes, as necessary for adult myelin repair.While DNA hydroxy-methylation and high levels of TET1 are detected in young adult mice during myelin regeneration after demyelination, this process is defective in old mice. Constitutive or inducible lineage-specific ablation ofTet1(but not ofTet2) recapitulate the age-related decline of DNA hydroxy-methylation and inefficient remyelination. Genome-wide hydroxy-methylation and transcriptomic analysis identify numerous TET1 targets, including several members of the solute carrier (Slc) gene family. Lower transcripts forSlcgenes, includingSlc12a2, are observed inTet1mutants and old mice and are associated with swelling at the neuroglial interface, a phenotype detected also in zebrafishslc12a2bmutants.We conclude that TET1-mediated DNA hydroxy-methylation is necessary for adult remyelination after injury.
Collateral fitness effects of mutations
Authors: Mehlhoff Jacob D. , Stearns Frank W. , Rohm Dahlia , Wang Buheng , Tsou Erh-Yeh , Dutta Nisita , Hsiao Meng-Hsuan , Gonzalez Courtney E. , Rubin Alan F. , Ostermeier Marc 
Published: October 2019

AbstractThe distribution of fitness effects (DFE) of mutation plays a central role in constraining protein evolution. The underlying mechanisms by which mutations lead to fitness effects are typically attributed to changes in protein specific activity or abundance. Here, we reveal the importance of a mutation’s collateral fitness effects, which we define as effects that do not derive from changes in the protein’s ability to perform its physiological function. We comprehensively measured the collateral fitness effects of missense mutations in theE. coli TEM-1β-lactamase antibiotic resistance gene using growth competition experiments in theabsenceof antibiotic. At least 42% of missense mutations inTEM-1were deleterious, indicating that for some proteins, collateral fitness effects occur as frequently as effects on protein activity and abundance. Deleterious mutations caused improper post-translational processing, incorrect disulfide-bond formation, protein aggregation, changes in gene expression, and pleiotropic effects on cell phenotype. Deleterious collateral fitness effects occurred more frequently inTEM-1than deleterious effects on antibiotic resistance in environments with low concentrations of the antibiotic. The surprising prevalence of deleterious collateral fitness effects suggests they may play a role in constraining protein evolution, particularly for highly-expressed proteins, for proteins under intermittent selection for their physiological function, and for proteins whose contribution to fitness is buffered against mutations with deleterious effects on protein activity and protein abundance.Significance StatementMutations provide the source of genetic variability upon which evolution acts. Deleterious protein mutations are commonly thought of in terms of how they compromise the protein’s ability to perform its physiological function. However, mutations might also be deleterious if they cause negative effects on one of the countless other cellular processes. The frequency and magnitude of such collateral fitness effects is unknown. Our systematic study of mutations in a bacterial protein finds widespread collateral fitness effects that were associated with protein aggregation, improper protein processing, incomplete protein transport across membranes, incorrect disulfide-bond formation, induction of stress-response pathways, and unexpected changes in cell properties. Our results suggest that deleterious collateral fitness effects may be an important constraint on protein evolution.