bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved motion correction of submillimetre 7T fMRI time series with boundary-based registration (BBR)
Authors: Huang Pei , Carlin Johan D. , Henson Richard N. , Correia Marta M. 
Published: August 2019

AbstractUltra-high field functional magnetic resonance imaging (fMRI) has allowed us to acquire images with submillimetre voxels. However, in order to interpret the data clearly, we need to accurately correct head motion and the resultant distortions. Here, we present a novel application of Boundary Based Registration (BBR) to realign functional Magnetic Resonance Imaging (fMRI) data and evaluate its effectiveness on a set of 7T submillimetre data, as well as millimetre 3T data for comparison. BBR utilizes the boundary information from high contrast present in structural data to drive registration of functional data to the structural data. In our application, we realign each functional volume individually to the structural data, effectively realigning them to each other. In addition, this realignment method removes the need for a secondary aligning of functional data to structural data for purposes such as laminar segmentation or registration to data from other scanners. We demonstrate that BBR realignment outperforms standard realignment methods across a variety of data analysis methods. Further analysis shows that this benefit is an inherent property of the BBR cost function and not due to the difference in target volume. Our results show that BBR realignment is able to accurately correct head motion in 7T data and can be utilized in preprocessing pipelines to improve the quality of 7T data.
Heart Disease in a Mutant Mouse Model of Spontaneous Eosinophilic Myocarditis Maps to Three Highly Significant Loci
Authors: Zimmermann Nives , Gibbons William J. , Homan Shelli M. , Prows Daniel R. 
Published: August 2019

AbstractBackgroundHeart disease (HD) is the major cause of morbidity and mortality in patients with hypereosinophilic diseases. Due to a lack of adequate animal models, our understanding of the pathophysiology of eosinophil-mediated diseases with heart complications is limited. We have discovered a mouse mutant, now maintained on an A/J inbred background, that spontaneously develops hypereosinophilia in multiple organs. Cellular infiltration into the heart causes an eosinophilic myocarditis, with affected mice of the mutant line (i.e.,A/JHD) demonstrating extensive myocardial damage and remodeling that leads to HD and premature death, usually by 15-weeks old. Maintaining the A/JHDline for many generations established that the HD trait was heritable and implied the mode of inheritance was not too complex. Backcross and intercross populations generated from mating A/JHDmales with females from four different inbred strains produced recombinant populations with highly variable rates of affected offspring, ranging from none in C57BL/6J intercrosses, to a few mice with HD using 129S1/SvImJ intercrosses and C57BL/6J backcrosses, but nearly 8% of intercrosses and >17% of backcrosses from SJL/J related populations developed HD. Linkage analyses of these SJL/J derived recombinants identified three highly significant loci: a recessive locus mapping to distal chromosome 5 (LOD=4.88; namedEmhd1foreosinophilicmyocarditis toheartdisease-1); and two dominant variants mapping to chromosome 17, one (Emhd2; LOD=7.51) proximal to the major histocompatibility complex, and a second (Emhd3; LOD=6.89) that includes the major histocompatibility region. Haplotype analysis identified the specific crossovers that defined theEmhd1(2.65Mb),Emhd2(8.46Mb) andEmhd3(14.59Mb) intervals. These results indicate the HD trait in this mutant mouse model of eosinophilic myocarditis is oligogenic with reduced penetrance, due to multiple segregating variants and possibly additional genetic or nongenetic factors. The A/JHDmouse model represents a unique and valuable tool to understand the interplay of causal factors that underlie the pathology of this newly discovered eosinophil-associated disease with cardiac complications.
Transcriptome analysis reveals the difference between “healthy” and “common” aging and their connection with age-related diseases
Authors: Zeng Lu , Yang Jialiang , Peng Shouneng , Zhu Jun , Zhang Bin , Suh Yousin , Tu Zhidong 
Published: August 2019

AbstractA key goal of aging research is to understand mechanisms underlying healthy aging and use them to develop methods to promote the human healthspan. One approach is to identify gene regulations differentiating healthy aging from aging in the general population (i.e., “common” aging). In this study, we leveraged GTEx (Genotype-Tissue Expression) project data to investigate “healthy” and “common” aging in humans and their interconnection with diseases.We selected GTEx donors who were not annotated with diseases to approximate a “healthy” aging cohort. We then compared the age-associated genes derived from this cohort with age-associated genes from our “common” aging cohort which included all GTEx donors; we also compared the “healthy” and “common” aging gene expressions with various disease-associated gene expression to elucidate the relationships among “healthy”, “common” aging and disease. Our analyses showed that 1. “healthy” and “common” aging shared a large number of gene regulations; 2. Despite the substantial commonality, “healthy” and “common” aging genes also showed distinct function enrichment, and “common” aging genes had a higher enrichment for disease genes; 3. Disease-associated gene regulations were overall different from aging gene regulations. However, for genes regulated by both, their regulation directions were largely consistent, implying some aging processes could increase the susceptibility to disease development; and 4. Possible protective mechanisms were associated with the “healthy” aging gene regulations.In summary, our work highlights several unique features of human “healthy” aging program. This new knowledge can be used for the development of therapeutics to promote human healthspan.
Plasmids persist in a microbial community by providing fitness benefit to multiple phylotypes
Authors: Li Liguan , Dechesne Arnaud , Madsen Jonas Stenløkke , Nesme Joseph , Sørensen Søren J. , Smets Barth F. 
Published: August 2019

AbstractThe current epidemic of antibiotic resistance has been facilitated by the wide and rapid horizontal dissemination of antibiotic resistance genes (ARGs) in microbial communities. Indeed, ARGs are often located on plasmids, which can efficiently shuttle genes across diverse taxa. While the existence conditions of plasmids have been extensively studied in a few model bacterial populations, their fate in complex bacterial communities is poorly understood. Here, we coupled plasmid transfer assays with serial growth experiments to investigate the persistence of the broad-host-range IncP-1 plasmid pKJK5 in microbial communities derived from a sewage treatment plant. The cultivation conditions combined different nutrient and oxygen levels, and were non-selective and non-conducive for liquid-phase conjugal transfer. Following initial transfer, the plasmid persisted in almost all conditions during a 10-day serial growth experiment (equivalent to 60 generations), with a transient transconjugant incidence up to 30%. By combining cell enumeration and sorting with amplicon sequencing, we mapped plasmid fitness effects across taxa of the microbial community. Unexpected plasmid fitness benefits were observed in multiple phylotypes ofAeromonas,PseudomonasandEnterobacteriaceae, which resulted in community-level plasmid persistence. We demonstrate, for the first time, that plasmid fitness effects across community members can be estimated in a high-throughput way without prior isolation. By gaining a fitness benefit when carrying plasmids, members within complex microbial communities might have a hitherto unrecognized potential to maintain plasmids for long-term community-wide access.
Transition from background selection to associative overdominance promotes diversity in regions of low recombination
Authors: Gilbert Kimberly J. , Pouyet Fanny , Excoffier Laurent , Peischl Stephan 
Published: August 2019

SummaryLinked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworthet al.1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao & Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao & Charlesworth (2016) identified the conditions when AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants co-segregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD. We derive the conditions for a transition from BGS to AOD due to pseudo-overdominance (Ohta & Kimura 1970), i.e. a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans (Pouyetet al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.
The tooth on-a-chip: a microphysiologic model system mimicking the pulp-dentin interface and its interaction with biomaterials
Authors: França Cristiane Miranda , Tahayeri Anthony , Rodrigues Nara Sousa , Ferdosian Shirin , Puppin-Rontani Regina , Ferracane Jack L. , Bertassoni Luiz E. 
Published: August 2019

AbstractThe tooth has a unique configuration with respect to biomaterials that are used for its treatment. Cells inside of the dental pulp interface indirectly with biomaterials via a calcified permeable membrane, formed by a dentin barrier which is composed of several thousands of dentinal tubules (~2 µm in diameter) connecting the dental pulp tissue to the outer surface of the tooth. Although the cytotoxic response of the dental pulp to biomaterials has been extensively studied, there is a shortage of in vitro model systems that mimic the dentin-pulp interface, enabling an improved understanding of the morphologic, metabolic and functional influence of biomaterials on live dental pulp cells. To address this shortage, here we developed an organ-on-a-chip model system which integrates cells cultured directly on a dentin wall within a microdevice which replicates some of the architecture and dynamics of the dentin-pulp interface. The tooth-on-a-chip is made out of molded polydimethylsiloxane (PDMS) with a design consisting of two chambers separated by a dentin fragment. To characterize pulp cell responses to dental materials on-chip, stem cell-derived odontoblasts were seeded onto the dentin surface, and observed using live-cell microscopy. Standard dental materials used clinically (2-hydroxyethylmethacrylate - HEMA, Phosphoric Acid - PA, and Adper-Scotchbond - SB) were tested for cytotoxicity, cell morphology and metabolic activity on-chip, and compared against standardized off-chip controls. All dental materials had cytotoxic effects in both on-chip and off-chip systems in the following order: HEMA>SB>PA (p<0.05), and cells presented consistently higher metabolic activity on-chip than off-chip (p<0.05). Furthermore, the tooth-on-a-chip enabled real-time tracking of odontoblast monolayer formation, remodeling, and death in response to biomaterial treatments, and gelatinolytic activity in a model hybrid layer (HL) formed in the microdevice. In conclusion, the tooth-on-a-chip is a novel platform that replicates near-physiologic conditions of the pulp-dentin interface, and enables live-cell imaging to study dental pulp cell response to biomaterials.
Low frequency of pathogenic allelic variants in the 46,XY differences of sex development (DSD)-related genes in small for gestational age children with hypospadias
Authors: Braga Barbara L. , Gomes Nathalia L. , Nishi Mirian Yumie , Freire Bruna Lucheze , Batista Rafael Loch , Lerario Antonio Marcondes , de Assis Funari Mariana Ferreira , Frade Costa Elaine Maria , Domenice Sorahia , Faria Junior José Antonio D. , Lima Jorge Alexander Augusto , Mendonca Berenice Bilharinho 
Published: August 2019

AbstractBackgroundHypospadias is a congenital disorder of male genital formation where the urinary opening is not on the head of the penis and genetic factors play an important role in the incidence of this early developmental defect in 46,XY individuals, in both isolated and syndromic forms. Children born small for gestational age (SGA) present a high frequency of hypospadias of undetermined etiology, ranging from 15 to 30%, but the detection of hypospadias’ etiology remains low.Patients and methodsfrom a cohort of 46,XY DSD patients, we identified 25 SGA children with medium or proximal hypospadias; four of them with associated syndromic characteristics. DNA samples from subjects were studied by massively parallel targeted sequencing (MPTS) using a targeted panel. MLPA was used for molecular diagnosis in two children with clinical phenotype of Silver Russel syndrome.ResultsLoss of DNA methylation (11p15 LOM) at ICR1 was identified in two out of four syndromic children. The other syndromic patient had 3M syndrome phenotype and two novel likely-pathogenic variants in compound heterozygous state were found in CUL7 gene. The last syndromic subject had Mulibrey nanism and, a homozygous variant in TRIM37 was identified in the patient and confirmed in heterozygous state in the mother. Among non-syndromic children seven rare heterozygous variants with uncertain significance in six DSD-related genes were identified: two children had DHX37 variants associated with GATA4 and WWOX variants, respectively; three children had heterozygous variants, in WT1, IGF1R, and BMP8B genes.ConclusionPathogenic or likely-pathogenic variants in DSD-related genes were not identified in non-syndromic SGA children with hypospadias, suggesting that multi-factorial causes, unknown genes or unidentified environmental factors (epigenetic defects), may be involved in the etiology of this condition.
The fasciola cinereum subregion of the hippocampus is important for the acquisition of visual contextual memory
Authors: Park Seong-Beom , Lee Eun-Young , Lim Heung-Yeol , Yoo Seung-Woo , Lee Eunsoo , Jung Hyun-Suk , Sun Woong , Lee Inah 
Published: August 2019

SummaryThe fasciola cinereum (FC) is a subregion of the hippocampus that has received relatively little research attention compared with other hippocampal subregions with respect to anatomical characteristics and functional significance. Here, we show that the FC exhibits clear anatomical borders with CA1. The FC consists of granule cells, but adult neurogenesis was not found. The FC receives inputs from the lateral entorhinal cortex and perirhinal cortex while projecting to the crest of the dentate gyrus (DG). Neurotoxic lesioning of the FC using colchicine impaired the acquisition, but not retrieval, of visual contextual memory in rats. FC lesions also impaired place recognition and object-in-place memory. Place cells in the FC showed robust place fields but fired only transiently in their fields compared with those in CA1. Our findings suggest that the FC may play critical roles in learning a novel environment by facilitating pattern separation in the DG of the hippocampus.
Evolution in interacting species alters predator life history traits, behavior and morphology in experimental microbial communities
Authors: Cairns Johannes , Moerman Felix , Fronhofer Emanuel A. , Altermatt Florian , Hiltunen Teppo 
Published: August 2019

AbstractPredator-prey interactions are key for the dynamics of many ecosystems. An increasing body of evidence suggests that rapid evolution and co-evolution can alter these interactions, with important ecological implications, by acting on traits determining fitness, including reproduction, anti-predatory defense and foraging efficiency. However, most studies to date have focused only on evolution in the prey species, and the predator traits in (co-)evolving systems remain poorly understood. Here we investigated changes in predator traits after ~600 generations in a predator-prey (ciliate-bacteria) evolutionary experiment. Predators independently evolved on seven different prey species, allowing generalization of the predator’s evolutionary response. We used highly resolved automated image analysis to quantify changes in predator life history, morphology and behavior. Consistent with previous studies, we found that prey evolution impaired growth of the predator. In contrast, predator evolution did not cause a clear increase in fitness when feeding on ancestral prey. However, predator evolution affected morphology and behavior, increasing size, speed and directionality of movement, which have all been linked to higher prey search efficiency. These results show that in (co-)evolving systems, predator adaptation can occur in traits relevant to offense level without translating into an increased ability of the predator to grow on the ancestral prey type.
Female resource limitation does not make the opportunity for selection more female biased
Authors: Martinossi-Allibert Ivain , Rönn Johanna Liljestrand , Immonen Elina 
Published: August 2019

AbstractEnvironmental and physiological conditions affect how individual variation is expressed and translated into variance in fitness, the opportunity for natural selection. Competition for limiting resources can magnify variance in fitness and therefore selection, while abundance of resources should reduce it. But even in a common environment the strength of selection can be expected to differ across the sexes, as their fitness is often limited by different resources. Indeed most taxa show a greater opportunity for selection in males than in females, a bias often ascribed to intense competition among males for access to mating partners. This sex-bias could reverberate on many aspects of evolution, from speed of adaptation to genome evolution. It is unclear however, whether the sex-bias in opportunity for selection is robust to variations in environment or physiological condition that limit sex-specific resources. Here we test this in the model speciesC. maculatusby comparing female and male variance in relative fitness (opportunity for selection) under mate competition (i) with and without limitation of quality oviposition sites, and (ii) under delayed age at oviposition. Decreasing the abundance of the resource key to females or increasing their reproductive age was indeed challenging as shown by a reduction in mean fitness, however variance in fitness remained male-biased across the three treatments, with even an increased male-bias when females were limited by oviposition sites. This suggests that males remain the more variable sex independent of context, and that the opportunity for selection through males is indirectly affected by female-specific resource limitation.
Dissecting adaptive traits with nested association mapping: Genetic architecture of inflorescence morphology in sorghum
Authors: Olatoye Marcus O. , Marla Sandeep R. , Hu Zhenbin , Bouchet Sophie , Perumal Ramasamy , Morris Geoffrey P. 
Published: August 2019

ABSTRACTIn the cereal crop sorghum (Sorghum bicolor) inflorescence morphology variation underlies yield variation and confers adaptation across precipitation gradients, but its genetic basis is poorly understood. Here we characterized the genetic architecture of sorghum inflorescence morphology using a global nested association mapping (NAM) population (2200 recombinant inbred lines) and 198,000 phenotypic observations from multi-environment trials for four inflorescence morphology traits (upper branch length, lower branch length, rachis length, and rachis diameter). Trait correlations suggest that lower and upper branch length are under largely independent genetic control, while lower branch length and rachis diameter are pleiotropic. Joint linkage and genome-wide association mapping revealed an oligogenic architecture with 1–22 QTL per trait, each explaining 0.1%–5.0% of variation across the entire NAM population. Overall, there is a significant enrichment (2.4-fold) of QTL colocalizing with homologs of grass inflorescence genes, notably with orthologs of maize (Ramosa2) and rice (Aberrant Panicle Organization1, TAWAWA1) inflorescence regulators. In global georeferenced germplasm, allelic variation at the major inflorescence morphology QTL is significantly associated with precipitation gradients, consistent with a role for these QTL in adaptation to agroclimatic zones. The findings suggest that global inflorescence diversity in sorghum is largely controlled by oligogenic, epistatic, and pleiotropic variation in ancestral regulatory networks. This genotype-phenotype trait dissection in global germplasm provides a basis for genomics-enabled breeding of locally-adapted inflorescence morphology.
The choreography of human attraction: physiological synchrony in a blind date setting
Authors: Prochazkova E. , Sjak-Shie E. E. , Behrens F. , Lindh D. , Kret M. E. 
Published: August 2019

AbstractHumans are social animals whose mental wellbeing is shaped by the ability to attract and connect with each other. In a dating world, in which success can be determined by brief interactions, apart from physical features, there is a whole choreography of movements, physical reactions and subtle expressions that drive humans’ sexual attraction. To determine what drives attraction, we measured nonverbal dynamics between people during real-life interactions outside the laboratory, where dating is most relevant. Participants wore eye-tracking glasses with embedded cameras, and devices to measure physiological signals including heart rate and skin conductance. Crucially, visible signals that can be controlled, such as facial expressions or gaze, did not predict attraction. Instead, attraction was predicted by synchrony in heart rate and skin conductance between partners, which are unconscious and difficult to regulate. Our findings suggest that shared emotionality is vital for mutual attraction. Moreover, physiological synchrony may provide a medium for translating visible expressions into embodied emotions, which can turn into intentions via somatosensory simulation.Significance StatementIn our modern world where millions of people meet online without interacting face-to-face, the question “what defines attraction” has become very relevant. In this study, we used modern technologies to lay down a foundation for the processes that drive human attraction during real-life interactions. Contrary to common belief, we found that attraction is not predicted by a frequency of expression or eye fixation duration, nor is linearly related to the participant’s autonomic nervous system activity. Importantly, we found that the more a participant synchronized their heart rate and skin conductance with their partner, the more they felt attracted toward that person. This study reveals a fundamental physiological process that plays a role in the formation of romantic relations.