Biology subjects

Xu, L.

Publications and source records attributed to Xu, L..

At least 433 records · Page 24Linked to original sources

bioRxiv2019

Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1

Multisystem manifestations in myotonic dystrophy type 1 (DM1) may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK, including Dmpk and its neighboring genes (Six5 or Dmwd) and downstream Mbnl1. However, the direct evidences are lack. Here, we develop a new strategy to generate mice carrying multigene mutations in one step by injection of haploid embryonic stem cells with mutant Dmpk, Six5 and Mbnl1 into oocytes. The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes. With the additional mutation in Dmwd, quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1. Moreover, muscle stem cells in both models display reduced stemness. Our results suggest that the complex symptoms of DM1 result from the reduced gene dosage of multiple genes.

genetics↗

bioRxiv2019

Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment

There is growing attention surrounding hospital acquired infections (HAIs) due to high associated healthcare costs, compounded by the scourge of widespread multi-antibiotic resistance. Although hospital environment disinfection is well acknowledged to be key for infection control, an understanding of colonization patterns and resistome profiles of environment-dwelling microbes is currently lacking. We report the first extensive genomic characterization of microbiomes (428), common HAI-associated microbes (891) and transmissible drug resistance cassettes (1435) in a tertiary hospital environment based on a 3-timepoint sampling (1 week and >1 year apart) of 179 sites from 45 beds. Deep shotgun metagenomic sequencing unveiled two distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human microbiome influenced environments that display corresponding patterns of divergence over space and time. To study common nosocomial pathogens that were typically present at low abundances, a combination of culture enrichment and long-read nanopore sequencing was used to obtain thousands of high contiguity genomes (2347), phage sequences (1693) and closed plasmids (5910), a significant fraction of which (>60%) are not represented in current sequence databases. These high-quality assemblies and metadata enabled a rich characterization of resistance gene combinations, phage diversity, plasmid architectures, and the dynamic nature of hospital environment resistomes and their reservoirs. Phylogenetic analysis identified multidrug resistant strains as being more widely distributed and stably colonizing across hospital sites. Further genomic comparisons with clinical isolates across multiple species supports the hypothesis that multidrug resistant strains can persist in the hospital environment for extended periods (>8 years) to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in the hospital environment and establishes the feasibility of systematic genomic surveys to help target resources more efficiently for preventing HAIs.

microbiology↗

bioRxiv2019

Clinical Efficacy and Adverse Effects of Antibiotics Used to Treat Mycobacterium abscessus Pulmonary Disease

Treatment of Mycobacterium abscessus pulmonary infection requires long-term administration of multiple antibiotics. Little is known, however, about the impact of each antibiotic on treatment outcomes. A retrospective analysis was conducted to evaluate the efficacy and adverse effects of antibiotics administered in 244 cases of M. abscessus pulmonary disease. Only 110 (45.1%) patients met the criteria for treatment success. Treatment with amikacin (AOR, 3.275; 95% CI, 1.221 - 8.788), imipenem (AOR, 2.078; 95% CI, 1.151 - 3.753), linezolid (AOR, 2.231; 95% CI, 1.078 - 4.616) and tigecycline (AOR, 2.040; 95% CI, 1.079 - 3.857) was successful. The incidence of adverse effects was high (192/244, 78.7%). Severe adverse effects were primarily: ototoxicity (14/60, 23.3%) caused by amikacin; gastrointestinal (14/60, 23.3%) caused by tigecycline; and myelosuppression (5/60, 8.3%) caused by linezolid. In conclusion, the rate of success in treating M. abscessus pulmonary disease is still unsatisfactory; the administration of amikacin, imipenem, linezolid and tigecycline correlated with increased treatment success. Adverse side effects are common due to the long-term and combined antibiotic therapy. Ototoxicity, gastrointestinal and myelosuppression are the most severe.

microbiology↗

bioRxiv2019

Computational staining of pathology images to study tumor microenvironment in lung cancer

The spatial organization of different types of cells in tumor tissues reveals important information about the tumor microenvironment (TME). In order to facilitate the study of cellular spatial organization and interactions, we developed a comprehensive nuclei segmentation and classification tool to characterize the TME from standard Hematoxylin and Eosin (H&E)-stained pathology images. This tool can computationally \"stain\" different types of cell nuclei in H&E pathology images to facilitate pathologists in analyzing the TME.\n\nA Mask Regional-Convolutional Neural Network (Mask-RCNN) model was developed to segment the nuclei of tumor, stromal, lymphocyte, macrophage, karyorrhexis and red blood cells in lung adenocarcinoma (ADC). Using this tool, we identified and classified cell nuclei and extracted 48 cell spatial organization-related features that characterize the TME. Using these features, we developed a prognostic model from the National Lung Screening Trial dataset, and independently validated the model in The Cancer Genome Atlas (TCGA) lung ADC dataset, in which the predicted high-risk group showed significantly worse survival than the low-risk group (pv= 0.001), with a hazard ratio of 2.23 [1.37-3.65] after adjusting for clinical variables. Furthermore, the image-derived TME features were significantly correlated with the gene expression of biological pathways. For example, transcription activation of both the T-cell receptor (TCR) and Programmed cell death protein 1 (PD1) pathways was positively correlated with the density of detected lymphocytes in tumor tissues, while expression of the extracellular matrix organization pathway was positively correlated with the density of stromal cells.\n\nThis study developed a deep learning-based analysis tool to dissect the TME from tumor tissue images. Using this tool, we demonstrated that the spatial organization of different cell types is predictive of patient survival and associated with the gene expression of biological pathways. Although developed from the pathology images of lung ADC, this model can be adapted into other types of cancers.

bioinformatics↗

bioRxiv2019

Extensive genetic diversity of bat-borne polyomaviruses reveals inter-family host-switching events

Polyomaviruses (PyVs) are small, double-stranded DNA tumor viruses carried by diverse vertebrates. PyVs have previously been considered highly host restricted in mammalian hosts, with host-switching events thought rare or nonexistent. Prior investigations have revealed short-range host-switching events of PyVs in two different African bat species within the horseshoe bat genus Rhinolophus. Herein, we have conducted a systematic investigation of PyVs in 1,083 archived bat samples collected from five provinces across China, and identified 192 PyVs from 186 bats from 15 host species within 6 families (Rhinolophidae, Vespertilionidae, Hipposideridae, Emballonuridae, Miniopteridae and Pteropodidae) representing 28 newly-described PyVs, indicative of extensive genetic diversity of bat PyVs. Surprisingly, two PyVs were identified in multiple bat species from different families, and another PyV clustered phylogenetically with PyVs carried by bats from a different host family, indicative of three inter-family PyV host-switching events. The time to most recent common ancestor (tMRCA) of the three events was estimated at 0.02-11.6 million years ago (MYA), which is inconsistent with the estimated tMRCA of their respective bat hosts (36.3-66.7 MYA), and is most parsimoniously explained by host-switching events. PyVs identified from geographically separated Chinese horseshoe bat species in the present study showed close genetic identities, and clustered with each other and with PyVs from African horseshoe bats, allowing assessment of the effects of positive selection in VP1 within the horseshoe bat family Rhinolophidae. Correlation analysis indicated that co-evolution with their hosts contributed much more to evolutionary divergence of PyV than geographic distance. In conclusion, our findings provide the first evidence of inter-family host-switching events of PyV in mammals and challenge the prevailing evolutionary paradigm for strict host restriction of mammalian PyVs.\n\nAuthor summarySince the discovery of murine polyomavirus in the 1950s, polyomaviruses (PyVs) have been considered both genetically stable and highly host-restricted in their mammalian hosts. In this study, we have identified multiple cases of host-switching events of PyVs by large scale surveillance in diverse bat species collected in China. These host-switching events occurred between bat families living in the same colony, indicating that a large population with frequent contacts between different bat species may represent an ecological niche facilitating PyV host-switching. The cases studied involved members of bats from several families, including horseshoe bats, which were previously found to harbor a number of highly virulent viruses to both humans and domestic animals. Our findings have provided evidence that even highly host-specific DNA viruses can transmit between bats of different species and indicate an increased propensity for spillover events involving horseshoe bats. We propose an evolutionary scheme for bat-borne PyVs in which intra-host divergence and host-switching has generated the diverse PyVs in present day bats. This scheme provides a useful model to study the evolution of PyVs in other hosts and, potentially, the modeling of bat zoonoses and the transmission of other DNA viruses in other mammals, including humans.

microbiology↗

bioRxiv2019

Long read sequencing reveals a novel class of structural aberrations in cancers: identification and characterization of cancerous local amplifications

Here we report identification of a new class of local structural aberrations in lung cancers. The whole-genome sequencing of cell lines using a long read sequencer, PromethION, demonstrated that typical cancerous mutations, such as point mutations, large deletions and gene fusions can be detected also on this platform. Unexpectedly, we revealed unique structural aberrations consisting of complex combinations of local duplications, inversions and micro deletions. We further analyzed and found that these mutations also occur in vivo, even in key cancer-related genes. These mutations may elucidate the molecular etiology of patients for whom causative cancerous events and therapeutic strategies remain elusive.

genomics↗

bioRxiv2019

The receptor-like kinases BAM1 and BAM2 promote the cell-to-cell movement of miRNA in the root stele to regulate xylem patterning

Xylem patterning in the root is established through the creation of opposing gradients of miRNAs and their targets, enabled by the cell-to-cell spread of the former. The miRNAs involved in xylem patterning, miR165/6, move through plasmodesmata, but how their trafficking is regulated remains elusive. Here, we describe that the receptor-like kinases BAM1/2 are required for the intercellular movement of miR165/6 in the stele and hence proper xylem patterning in the root.

plant biology↗

bioRxiv2019

A Vibrio cholerae BolA-like protein is required for proper cell shape and cell envelope integrity

BolA family proteins are conserved in gram-negative bacteria and many eukaryotes. While diverse cellular phenotypes have been linked to this protein family, the molecular pathways through which these proteins mediate their effects are not well-described. Here, we investigated the role of BolA family proteins in Vibrio cholerae, the cholera pathogen. Like Escherichia coli, V. cholerae encodes two BolA proteins, BolA and IbaG. However, in marked contrast to E. coli, where bolA is linked to cell shape and ibaG is not, in V. cholerae, bolA mutants lack morphological defects, whereas ibaG proved critical for the generation and/or maintenance of the pathogens morphology. Notably, the bizarre-shaped, multi-polar, elongated and wide cells that predominated in exponential phase {Delta}ibaG V. cholerae cultures were not observed in stationary phase cultures. The V. cholerae {Delta}ibaG mutant exhibited increased sensitivity to cell envelope stressors, including cell wall acting antibiotics and bile, and was defective in intestinal colonization. {Delta}ibaG V. cholerae had reduced peptidoglycan and lipid II and altered outer membrane lipids, likely contributing to the mutants morphological defects and sensitivity to envelope stressors. Transposon-insertion sequencing analysis of ibaGs genetic interactions suggested that ibaG is involved in several processes involved in the generation and homeostasis of the cell envelope. Furthermore, co-purification studies revealed that IbaG interacts with proteins containing iron-sulfur clusters or involved in their assembly. Collectively, our findings suggest that V. cholerae IbaG controls cell morphology and cell envelope integrity through its role in biogenesis or trafficking of iron-sulfur cluster proteins.\n\nImportanceBolA-like proteins are conserved across prokaryotes and eukaryotes. These proteins have been linked to a variety of phenotypes, but the pathways and mechanisms through which they act have not been extensively characterized. Here, we unraveled the role of the BolA-like protein IbaG in the cholera pathogen Vibrio cholerae. The absence of IbaG was associated with dramatic changes in cell morphology, sensitivity to envelope stressors, and intestinal colonization defects. IbaG was found to be required for biogenesis of several components of the V. cholerae cell envelope and to interact with numerous iron-sulfur cluster containing proteins and factors involved in their assembly. Thus, our findings suggest that IbaG governs V. cholerae cell shape and cell envelope homeostasis through its effects on iron-sulfur proteins and associated pathways. The diversity of processes involving iron-sulfur containing proteins is likely a factor underlying the range of phenotypes associated with BolA family proteins.

microbiology↗

bioRxiv2019

FcγRIIB I232T polymorphic change allosterically suppresses ligand binding

Fc{gamma}RIIB bindings to its ligand suppress immune cell activation. A single-nucleotide polymorphic (SNP) change, I232T, in the transmembrane (TM) domain of Fc{gamma}RIIB loses its suppression function, which clinically associates with systemic lupus erythematosus (SLE). Previously, we reported that I232T tilts Fc{gamma}RIIBs TM domain. In this study, combining with molecular dynamics simulations and single-cell FRET assay, we further revealed that such tilting by I232T unexpectedly bends the Fc{gamma}RIIBs ectodomain towards plasma membrane to allosterically impede Fc{gamma}RIIBs ligand association. We then used single-cell biomechanical assay to further find out that I232T also reduces two-dimensional in-situ binding affinities and association rates of Fc{gamma}RIIB interacting with its ligands by three-folds. This allosteric regulation by a SNP provides an intrinsic molecular mechanism for functional loss of Fc{gamma}RIIB-I232T in SLE patients.

immunology↗

bioRxiv2019

GCNA preserves genome integrity and fertility across species

The propagation of species depends on the ability of germ cells to protect their genome in the face of numerous exogenous and endogenous threats. While these cells employ a number of known repair pathways, specialized mechanisms that ensure high-fidelity replication, chromosome segregation, and repair of germ cell genomes remain incompletely understood. Here, we identify Germ Cell Nuclear Acidic Peptidase (GCNA) as a highly conserved regulator of genome stability in flies, worms, zebrafish, and humans. GCNA contains a long acidic intrinsically disordered region (IDR) and a protease-like SprT domain. In addition to chromosomal instability and replication stress, GCNA mutants accumulate DNA-protein crosslinks (DPCs). GCNA acts in parallel with a second SprT domain protein Spartan. Structural analysis reveals that while the SprT domain is needed to limit meiotic and replicative damage, most of GCNAs function maps to its IDR. This work shows GCNA protects germ cells from various sources of damage, providing novel insights into conserved mechanisms that promote genome integrity across generations.\n\nHighlightsGCNA ensures genomic stability in germ cells and early embryos across species\n\nGCNA limits replication stress and DNA double stranded breaks\n\nGCNA restricts DNA-Protein Crosslinks within germ cells and early embryos\n\nThe IDR and SprT domains of GCNA govern distinct aspects of genome integrity\n\nGraphic Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC=\"FIGDIR/small/570804_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (54K):\norg.highwire.dtl.DTLVardef@1928d82org.highwire.dtl.DTLVardef@885ff2org.highwire.dtl.DTLVardef@15322c9org.highwire.dtl.DTLVardef@110c615_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2019

Bioisosterism reveals new structure-odor relationships

The question of structure-odor relationship (SOR) has inspired numerous studies into chemical odorants via their perceptual similarities. Much of this data comes from psychophysical studies on humans, precluding the possibility of direct measurements of receptor or receptor neuron activation. Remarkably, we find that many of the perceptual classifications used by human subjects translate well enough to mouse that we can apply cellular methods to better understand the molecular mechanism, that leads to odor discrimination and perception. Using a well studied and well recognizable odor percept of bitter almond, we have tested an odorant panel of aldehydes and ketones that were reported to share such perceptual qualities. These odorants include aromatic and aliphatic, as well as cyclic and allylic features. When parsing these odorants using chemical descriptors, we have a clear separation of molecules possessing these various features. However, here we show that OSN responses better recapitulate the physiological percept. Using these odorants, we also provide a proof-of-concept for non-classical bioisosterism at work in the olfactory system.

neuroscience↗

bioRxiv2019

Analysis on epidemiological characteristics of 4 species natural-focal diseases in Shandong Province, China in 2009-2017: a descriptive analysis

BackgroundNatural-focal diseases have always been a kind of serious disease that endangers human health. It threatens about 100 million people in Shandong Province, and causes illness in thousands of people each year. However, information on the epidemiological characteristics of natural-focal diseases in Shandong Province has been limited. The purpose of the study is to describe and analyze the epidemiological characteristics of natural-focal diseases in Shandong Province, 2009-2017. MethodsWe describe the incidence and distribution of 4 species natural-focal diseases in Shandong Province using surveillance data from 2009-2017. ResultsFrom 2009-2017, 11123 cases of 4 species natural-focal diseases including 257 deaths were reported in Shandong Province, China. The 4 species natural-focal diseases were severe fever with thrombocytopenia syndrome (SFTS), human granulocytic anaplasmosis (HGA), typhus and scrub typhus respectively. The high-risk groups of the 4 species diseases all were farmers and the elderly. The incidence rate of scrub typhus was significantly higher in females, however, this difference was not seen in the other 3 diseases. The 4 species diseases were mainly clustered in middle-southern part of Shandong (Mount Yimeng) and Shandong Peninsula (Laoshan Mountain). The annual incidence of SFTS and scrub typhus had increased in the mass, typhus had been relatively stable, and HGA had declined. However, the popular range of SFTS had been expanding, HGA had been shrinking, and typhus and scrub typhus were unchanged. The epidemic period of SFTS and HGA was from May to October, typhus was from October to November, scrub typhus was from September to November in Shandong Province. The fatality rates of SFTS, typhus, scrub typhus, HGA were 9.19%, 0%, 0.01%, 2.24%, respectively. ConclusionsOur study described and analyzed the prevalence of natural-focal diseases in Shandong, and confirmed that age was closely related to the SFTS fatality rate. This study may be applicable to an improved understanding of the prevalence of natural-focal diseases in Shandong Province in recent years and the better development of the accurate prevention and control strategies for natural-focal diseases in Shandong Province. Author SummaryNatural-focal diseases are a serious public health problem in Shandong Province, China. It threatens about 100 million people in Shandong Province, and causes illness in thousands of people each year. This study used the monitoring data from Shandong Province for 2009-2017 to describe and analyze the epidemiological characteristics of the 4 species natural-focal diseases. The results showed that the risk population of natural-focal diseases in Shandong Province was farmers and the elderly, the epidemic season was mainly in summer and autumn, the middle-southern part of Shandong Province and Shandong Peninsula were more seriously affected compared with other regions. In addition, the epidemic area of SFTS was expanded, with a fatality rate of 9.19%. These findings indicated that public awareness of natural-focal diseases should be raised in the epidemic focus, especially for farmers, and further efforts should be strengthen specially in high-risk areas and during the epidemic season.

epidemiology↗

bioRxiv2019

Comparison of three different eye-tracking tasks for distinguishing autistic from typically developing children and autistic symptom severity

Altered patterns of visual social attention preference detected using eye-tracking and a variety of different paradigms are increasingly proposed as sensitive biomarkers for autism spectrum disorder. However, few eye tracking studies have compared the relative efficacy of different paradigms to discriminate between autistic compared with typically developing children and their sensitivity to specific symptoms. To target this issue, the current study used three common eye tracking protocols contrasting social versus non-social stimuli in young (2-7 years old) Chinese autistic (n = 35) and typically developing (n = 34) children matched for age and gender. Protocols included dancing people vs. dynamic geometrical images, biological motion (dynamic light point walking human or cat) vs. non-biological motion (scrambled controls) and child playing with toy vs. toy alone. Although all three paradigms differentiated autistic and typically developing children, the dancing people versus dynamic geometry pattern paradigm was the most effective, with autistic children showing marked reductions in visual preference for dancing people and correspondingly increased one for geometric patterns. Furthermore, this altered visual preference in autistic children was correlated with the ADOS social affect score and had the highest discrimination accuracy. Our results therefore indicate that decreased visual preference for dynamic social stimuli may be the most effective visual attention-based paradigm for use as a biomarker for autism in Chinese children. Clinical trial ID: NCT03286621 (clinicaltrials.gov); Clinical trial name: Development of Eye-tracking Based Markers for Autism in Young Children. Lay summaryEye-tracking measures may be useful in aiding diagnosis and treatment of autism, although it is unclear which specific tasks are optimal. Here we compare the ability of three different social eye-gaze tasks to discriminate between autistic and typically developing young Chinese children and their sensitivity to specific autistic symptoms. Our results show that a dynamic task comparing visual preference for social (individuals dancing) versus geometric patterns is the most effective both for diagnosing autism and sensitivity to its social affect symptoms.

clinical trials↗

bioRxiv2019

Re-curation and Rational Enrichment of Knowledge Graphs in Biological Expression Language

The rapid accumulation of new biomedical literature not only causes curated knowledge graphs to become outdated and incomplete, but also makes manual curation an impractical and unsustainable solution. Automated or semi-automated workflows are necessary to assist in prioritizing and curating the literature to update and enrich knowledge graphs. We have developed two workflows: one for re-curating a given knowledge graph to assure its syntactic and semantic quality and another for rationally enriching it by manually revising automatically extracted relations for nodes with low information density. We applied these workflows to the knowledge graphs encoded in Biological Expression Language from the NeuroMMSig database using content that was pre-extracted from MEDLINE abstracts and PubMed Central full text articles using text mining output integrated by INDRA. We have made this workflow freely available at https://github.com/bel-enrichment/bel-enrichment. Database URLhttps://github.com/bel-enrichment/results

systems biology↗

bioRxiv2019

Tumor Copy Number Deconvolution Integrating Bulk and Single-Cell Sequencing Data

Characterizing intratumor heterogeneity (ITH) is crucial to understanding cancer development, but it is hampered by limits of available data sources. Bulk DNA sequencing is the most common technology to assess ITH, but mixes many genetically distinct cells in each sample, which must then be computationally deconvolved. Single-cell sequencing (SCS) is a promising alternative, but its limitations -- e.g., high noise, difficulty scaling to large populations, technical artifacts, and large data sets -- have so far made it impractical for studying cohorts of sufficient size to identify statistically robust features of tumor evolution. We have developed strategies for deconvolution and tumor phylogenetics combining limited amounts of bulk and single-cell data to gain some advantages of single-cell resolution with much lower cost, with specific focus on deconvolving genomic copy number data. We developed a mixed membership model for clonal deconvolution via non-negative matrix factorization (NMF) balancing deconvolution quality with similarity to single-cell samples via an associated efficient coordinate descent algorithm. We then improve on that algorithm by integrating deconvolution with clonal phylogeny inference, using a mixed integer linear programming (MILP) model to incorporate a minimum evolution phylogenetic tree cost in the problem objective. We demonstrate the effectiveness of these methods on semi-simulated data of known ground truth, showing improved deconvolution accuracy relative to bulk data alone.

bioinformatics↗

bioRxiv2019

TooManyCells identifies and visualizes relationships of single-cell clades

Transcriptional programs contribute to phenotypic and functional cell states. While elucidation of cell state heterogeneity and its role in biology and pathobiology has been advanced by studying single cell level measurements, the underlying assumptions of current analytical methods limit the identification and exploration of cell clades. Unlike other methods, which produce a single uni-layer partition of cells ignoring echelons of cell states, we present TooManyCells, a software consisting of a suite of graph-based tools for efficient, global, and unbiased identification and visualization of cell clades while maintaining and presenting the relationship between cell states. TooManyCells provides a set of tools based on a matrix-free efficient divisive hierarchical spectral clustering algorithm wholly different from the prevalent Louvain-based methods. BirchBeer, the visualization component of TooManyCells, introduces a new approach for single cell analysis that is built on a concept intentionally orthogonal to the widely used dimensionality reduction methods. Together, this suite of tools provide a paradigm shift in the analysis and interpretation of single cell data by enabling simultaneous comparisons of cell states at context-and application-dependent scales. A byproduct of this shift is the immediate detection and visualization of rare populations that outperforms previous algorithms as demonstrated by applying these tools to existing single cell RNA-seq data sets from various mouse organs.

bioinformatics↗

bioRxiv2018

Romantic jealousy is positively associated with fronto-striatal, insula and limbic responses to angry faces

Romantic jealousy is a complex social emotion combining the different primary emotions of anger, fear and sadness. Previous evidence has suggested the involvement of fronto-striatal dopaminergic circuitry in clinical pathological jealousy, although little is known about overlaps with the neural representation of primary emotions involved in non-morbid jealousy. In the current study, 85 healthy subjects underwent fMRI during resting state and an emotional face recognition paradigm. A total of 150 faces (happy, angry, fearful, sad, neutral) were presented and subjects were required to identify the expression and rate its intensity. Trait romantic jealousy was assessed using the Multidimensional Jealousy Scale. Behavioral results showed that only intensity ratings of angry faces were positively associated with subjects jealousy scores. During processing of angry versus neutral expression faces, subjects with higher jealousy scores exhibited greater activation in the right thalamus, insula, fusiform gyrus and hippocampus, left dorsal striatum and superior parietal lobule and bilateral cerebellum and inferior frontal gyrus after controlling for trait aggression and sex. Functional connectivity between the inferior frontal gyrus and caudate was also increased. No associations with resting state functional connectivity were found. Overall, the present study demonstrates an association between romantic jealousy and increased intensity ratings of angry faces as well as in activity and functional connectivity of dorsal striatal-inferior frontal circuitry. Thus, increased emotional responsivity to social threat and enhanced activity in limbic regions and dopaminergic fronto-striatal circuitry may be features of both non-morbid and pathological jealousy.

neuroscience↗

bioRxiv2018

The human secretome - the proteins secreted from human cells

The proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnosis and therapy. Here, we present an annotation of all predicted secreted proteins (n=2,623) with information about their spatial distribution in the human body. A high-throughput mammalian cell factory was established to create a resource of recombinant full-length proteins. This resource was used for phenotypic assays involving {beta}-cell dedifferentiation and for development of targeted proteomics assays. A comparison between host cells, including omics analysis, shows that many of the proteins that failed to be generated in CHO cells could be rescued in human HEK293 cells. In conclusion, the human secretome has been mapped and characterized to facilitate further exploration of the human secretome.

molecular biology↗