Biology subjects

Yang, N.

Publications and source records attributed to Yang, N..

At least 91 records · Page 5Linked to original sources

bioRxiv2021

Portrait of a genus: the genetic diversity of Zea

Maize is a globally valuable commodity and one of the most extensively studied genetic model organisms. However, we know surprisingly little about the extent and potential utility of the genetic variation found in the wild relatives of maize. Here, we characterize a high-density genomic variation map from ~700 genomes encompassing maize and all wild taxa of the genus Zea, identifying over 65 million single nucleotide polymorphisms (SNPs), 8 million Insertion/Deletion (InDel) polymorphisms, and over one thousand novel inversions. The variation map reveals evidence of selection within taxa displaying novel adaptations such as perenniality and regrowth. We focus in detail on evidence of convergent adaptation in highland teosinte and temperate maize. This study not only indicates the key role of hormone related pathways in highland adaptation and flowering time related pathways in high latitude adaptation, but also identifies significant overlap in the genes underlying adaptations to both environments. To show how this data can identify useful genetic variants, we generated and characterized novel mutant alleles for two flowering time candidate genes. This work provides the most extensive sampling to date of the genetic diversity inherent in the genus Zea, resolving questions on evolution and identifying adaptive variants for direct use in modern breeding.

evolutionary biology↗

bioRxiv2021

EgGLUT1 is crucial for the viability of larvae of Echinococcus granulosus sensus lato by involving its glucose uptake

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus granulosus sensu lato (s.l.) cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, presence and role of GLUT1 in E. granulosus s.l. (EgGLTU1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) from E. granulosus sensu stricto (s.s.) and found EgGLUT1-ss was crucial for glucose uptake of the protoscoleces of E. granulosus s.s.. WZB117, a GLUT1 inhibitor, inhibited glucose uptake of E. granulosus s.s. and the viability of the metacestode in vitro. In addition, WZB117 showed potent therapeutic activity in E. granulosus s.s.-infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts as well as the reference drug, albendazole. Our data have defined EgGLUT1 as a key E. granulosus s.l. vulnerability target, involved in its glucose uptake from the host; this opens a new avenue to identify drugs with an ideal activity profile for the treatment of CE.

microbiology↗

bioRxiv2021

Brucella outer membrane proteins to control maturation and antigen presentation of mouse dendritic cells

Brucellosis is a highly contagious zoonotic disease, which seriously endangers animal husbandry in China. Bone marrow-derived dendritic cells (DCs) are full-time antigen presenting cells (APC) that play an important role in the interaction between pathogens and host immunity. DCs were stimulated with Brucella major outer membrane proteins (OMPs: OMP10, OMP19, OMP25, BP26 and OMP31) and Brucella mutants ({Delta} omp10, {Delta} omp19, {Delta} omp25, {Delta} bp26, {Delta} omp31) to examine effects on DC maturity and antigen presentation. Brucella OMP10, OMP19 and BP26; Brucella mutants {Delta} omp10, {Delta} omp19, {Delta} omp25, {Delta} bp26, {Delta} omp31 and Brucella RB51 induced DC maturation and antigen presentation efficiency in mice, activated proliferation of T lymphocytes, and decreased apoptosis, which helped the host recognize antigens and eliminate pathogens. However, B. abortus 2308 evaded the host immune function and established chronic infection by maintaining a balance between intracellular replication and inducing apoptosis, thus reducing DC maturation and antigen presentation to T cells. Toll-like receptor (TLR) -mediated signaling pathways were involved in the DC maturation and antigen presentation induced by Brucella OMPs. These results enhance understanding of Brucella pathogenesis and the host protective immune response mechanism and lay the foundation for the rational design of Brucella vaccines.

microbiology↗

bioRxiv2021

DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma

While molecular targeted therapies have improved prognoses of advanced stage lung adenocarcinoma expressing oncogenic driver mutations, acquired therapeutic resistance continues to be a major problem. Epidermal growth factor receptor (EGFR) activating mutations are among the most common targetable genetic alterations in lung adenocarcinoma, and EGFR tyrosine kinase inhibitors (TKIs) are recommended first-line therapy for EGFR mutation positive cancer patients. Unfortunately, most patients develop resistance to EGFR TKIs and rapid disease progression occurs. A better mechanistic understanding of therapy refractory cancer progression is necessary to develop new therapeutic approaches to predict and prevent acquired resistance to EGFR TKIs. Here, we identify a new mechanism of ERBB3-mediated resistance to EGFR TKIs in human lung adenocarcinoma. Specifically, we show that dopamine and cyclic AMP-regulated phosphoprotein, Mr 32000 (DARPP-32) physically recruits ERBB3 to EGFR to mediate a switch from EGFR homodimers to EGFR:ERBB3 heterodimers to bypass EGFR TKI-mediated inhibition to potentiate ERBB3-dependent activation of oncogenic AKT and ERK signaling that drives therapy refractory tumor cell survival. In a cohort of paired tumor specimens derived from 30 lung adenocarcinoma patients before and after the development of EGFR TKI refractory disease progression, we reveal that DARPP-32 as well as kinase-activated EGFR and ERBB3 proteins are overexpressed upon acquired EGFR TKI resistance. In vivo studies suggest that ablation of DARPP-32 protein activity sensitizes gefitinib-resistant lung tumor xenografts to EGFR TKI treatment, while DARPP-32 overexpression increases gefitinib-refractory lung cancer progression in gefitinib-sensitive lung tumors orthotopically xenografted into mice. Taken together, our findings introduce a DARPP-32-mediated, ERBB3-dependent mechanism used by lung tumor cells to evade EGFR TKI-induced cell death, potentially paving the way for the development of new therapies to prevent or overcome therapy-refractory lung adenocarcinoma progression.

cancer biology↗

bioRxiv2021

Elucidating Mechanisms of Antitumor Immunity Mediated by Live Oncolytic Vaccinia and Heat-Inactivated Vaccinia

BackgroundViral-based immunotherapy has the potential to overcome resistance to immune checkpoint blockade (ICB) and to fill the unmet needs of many cancer patients. Oncolytic viruses (OVs) are defined as engineered or naturally occurring viruses that selectively replicate in and kill cancer cells. OVs also induce antitumor immunity. The purpose of this study is to compare the antitumor effects of live OV-GM expressing murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) versus inactivated OV-GM and elucidate the underlying immunological mechanisms. MethodsIn this study, we engineered a replication-competent, oncolytic vaccinia virus (OV-GM) by inserting a murine GM-CSF gene into the thymidine kinase (TK) locus of a mutant vaccinia E3L{Delta}83N, which lacks the Z-DNA-binding domain of vaccinia virulence factor E3. We compared the antitumor effects of intratumoral (IT) delivery of live OV-GM vs. heat-inactivated OV-GM (heat-iOV-GM) in a murine B16-F10 melanoma bilateral implantation model. ResultsHeat-iOV-GM infection of dendritic cells (DCs) and tumor cells in vitro induces type I IFN and pro inflammatory cytokines and chemokines, whereas live OV-GM does not. IT live OV-GM is less effective in generating systemic antitumor immunity compared with heat-iOV-GM. Similar to heat-iOV-GM, the antitumor effects of live OV-GM also require Batf3-dependent CD103+ dendritic cells. IT heat-iOV-GM induces higher numbers of infiltrating activated CD8+ and CD4+ T cells as well as higher levels of type I IFN, proinflammatory cytokines, and chemokines in the distant non-injected tumors, which is dependent on CD8+ T cells. When combined with systemic delivery of ICB, IT heat-iOV-GM is more effective in eradicating tumors compared with live OV-GM. ConclusionsTumor lysis induced by the replication of oncolytic DNA viruses has a limited effect on the generation of systemic antitumor immunity. The activation of Batf3-dependent CD103+ DCs is critical for antitumor effects induced by both live OV-GM and heat-iOV-GM. Heat-iOV-GM is more potent than live OV-GM in the induction of innate and adaptive immunity in both the injected and distant non-injected tumors. We propose that evaluations of both innate and adaptive immunity induced by IT oncolytic viral immunotherapy at injected and non-injected tumors should be included as potential biomarkers.

immunology↗

bioRxiv2021

Transposable element landscape changes are buffered by RNA silencing in aging Drosophila

Genetic mechanisms that repress transposable elements (TEs) in young animals decline during aging, as reflected by increased TE expression in aged animals. Does increased TE expression during aging lead to more genomic TE copies in older animals? To answer this question, we quantified TE Landscapes (TLs) via whole genome sequencing of young and aged Drosophila strains of wild-type and mutant backgrounds. We quantified TLs in whole flies and dissected brains and validated the feasibility of our approach in detecting new TE insertions in aging Drosophila genomes when natural defenses like RNA interference (RNAi) pathways are compromised. By also incorporating droplet digital PCR to validate genomic TE loads, we confirm TL changes can occur in a single lifespan of Drosophila when TEs are not suppressed. We also describe improved sequencing methods to quantify extra-chromosomal DNA circles (eccDNAs) in Drosophila as an additional source of TE copies that accumulate during aging. Lastly, to combat the natural progression of aging-associated TE expression, we show that knocking down PAF1, a conserved transcription elongation factor that antagonizes RNAi pathways, may bolster suppression of TEs during aging and extend lifespan. Our study suggests that RNAi mechanisms generally mitigate genomic TL expansion despite the increase in TE transcripts during aging.

genomics↗

bioRxiv2020

Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patients immunological status, and found dramatic changes in the IGH within the patients immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones during 2-3 weeks of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34 and IGHV4-39 in COVID-19 patients were more abundant than that of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

immunology↗

bioRxiv2020

A meta-analysis and experiment assessing phage-based FMDV vaccine

Foot-and-mouth disease (FMD) is a pathological disease caused by the foot- and-mouth disease virus (FMDV), which mainly affects cloven-hoofed animals. This study was conducted to a meta-analysis and experiment on the effect of bacteriophages used in the development of FMDV vaccines. A systematic search was conducted for the collection of the protection effect for the phage-based FMDV vaccine using sensitive search strategies. The extracted data were analyzed using Rev-Man 5.4 software. This experiment used the T7 phage to express the capsid protein VP1 of the OHM-02 strain, and the recombinant VP1 phage was termed OHM-T7. Antibodies and cytokines levels were assessed after immunizing BALB/C mice with OHM-T7. The results showed that a total of 115 articles were retrieved, and 4 of them met the inclusion criteria. There was no heterogeneity with I2 = 0%, 20% or 43%. We used a fixed-effect model for meta-analysis, and the results showed a protective effect on FMDV between the phage group and control group (P<0.01) and between FMDV group and control group (P<0.01). Furthermore, when the phage group was compared to the FMDV group, there was also no significant difference (P>0.05). After successfully obtained the ohm-t7 strain and immunized the mice, it could induce high levels of IFN-{gamma} levels in mice with little effect on IL-4 levels. OHM-T7 could be used to detect antibodies produced by mice immunized with different FMDV antigens and produce high levels of anti-FMD antibodies. In summary, these results showed the potential of phage-based FMDV vaccines in FMDV prevention.

immunology↗

bioRxiv2020

A novel copper-sensing two-component system for activating Dsb genes in bacteria

Copper is an essential element for biological systems but becomes toxic when present in excess. In Pseudomonas aeruginosa, an important human pathogen, the resistance to copper requires the induction of dsbDEG operon encoding proteins involved in disulfide-bond formation (Dsb). However, it is unknown how the copper stress induces the transcription of the operon. Here, we report that the exogenous copper induces the transcription of the dsbDEG operon through a new copper-sensing two-component system named DsbRS. The dsbRS is divergently transcribed from the dsbDEG operon, and the response regulator DsbR binds to the intergenic region between the operons. In the absence of copper, the sensor kinase DsbS acts as a phosphatase toward DsbR and thus blocks the transcription of the operons. However, in the presence of copper, the metal ion directly binds to the sensor domain of DsbS, for which the Cys82 residue plays a critical role. The copper-binding appears to inhibit the phosphatase activity of DsbS, leading to activation of DsbR. The copper resistance of the dsbRS knock-out mutant was restored by ectopic expression of the dsbDEG operon, confirming the critical role of the operon in the resistance to copper. Strikingly, cognates of dsbRS-dsbDEG pair are widely distributed across eubacteria. Also, a DsbR-binding site, which contains the consensus sequence 5-TAA-N7-TTAAT-3, is detected in the promoter region of dsbDEG homologs in those species. Thus, regulation of Dsb genes by DsbRS represents a novel mechanism by which bacterial cells cope with copper stress. ImportanceCopper is an essential redox active cofactor that becomes highly cytotoxic when present in excess. Therefore, in order to evade copper toxicity, bacteria must perceive copper stress and tightly regulate genes expression. In the present study, we identify a new copper-sensing two-component system (designated DsbRS) in Pseudomonas aeruginosa, an important human pathogen. We provide multiple lines of evidence that upon copper binding to the periplasmic domain of DsbS, its phosphatase activity is blocked, and the phosphorylated DsbR directly activates the transcription of a number of copper-induced genes including those involved in protein disulfide-bond formation (Dsb). This study suggests that regulation of Dsb genes by DsbRS may be an underappreciated regulatory mechanism by which bacteria sense and respond to copper.

microbiology↗

bioRxiv2020

Lapatinib protects against epileptic seizures via halting glutathione peroxidase 4-dependent ferroptosis

Background and PurposeRepetitive epileptic seizures trigger massive neuronal death. Therefore, neuroprotection plays a role in preventing neuronal death and inversely suppresses seizure generation. Additionally, some studies have shown ferroptosis, featured by lipid peroxidation (a dominant form of oxidative stress in the brain), is of paramount importance in epileptic seizures. Lapatinib can play a first-line anti-tumor role by targeting oxidative stress and a recent work illustrates the improvement of encephalomyelitis in rodent models after lapatinib treatment. We hypothesize whether lapatinib can protect against ferroptosis in epileptic seizures via regulating lipid peroxidation. Experimental ApproachThe epileptic behavior of the mice was recorded after intracranial injection of KA. Western blot and RT-qPCR were used to detect the protein expression of 4-hydroxynonenal (4-HNE) and glutathione peroxidase 4 (GPX4) and the mRNA expression of prostaglandin endoperoxide synthase 2 (PTGS2) in vivo and in vitro. The level of lipid reactive oxygen species (lipid ROS) in cells pretreated with lapatinib was analyzed by flow cytometry. Key ResultsLapatinib remarkably prevented KA-induced epileptic seizures in mice and ferroptosis was involved in the neuroprotection of lapatinib. Compared with the model group, western blot showed that lapatinib significantly upregulated the levels of GPX4. In the ferroptotic cell death model, lapatinib exerted neuroprotection via up-regulating GPX4. Treatment with Ras-selective lethal small molecule 3 (RSL3), a selective GPX4 inhibitor abrogated its anti-ferroptotic potential. Conclusions and ImplicationsThese results illustrated that lapatinib has neuroprotective potential against KA-triggered epileptic seizures via suppressing GPX4-dependent ferroptosis. What is already knownO_LIActivation of ferroptosis occurs in epileptic seizures. C_LI What this study addsO_LILapatinib protects brain against epileptic seizures via blocking ferroptosis. C_LIO_LIGPX4-dependent ferroptosis is involved in the neuroprotection of lapatinib. C_LI What is the clinical significanceO_LIInhibition of ferroptosis by lapatinib represents a potential neuroprotective strategy for epileptic patients. C_LI

neuroscience↗

bioRxiv2020

Oxytocinergic modulation of threat-specific amygdala sensitization in humans is critically mediated by serotonergic mechanisms

BackgroundOverarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking. MethodsTo determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/ desensitization, we conducted a parallel-group randomized placebo-controlled double-blind experiment during which n = 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD, TRYP-) or the corresponding placebo-control protocols before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity towards threatening stimuli (angry faces) as assessed by fMRI served as the primary outcome. ResultsNo treatment main or interaction effects on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with TRYP-. ConclusionsThe present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization and adjunct up-regulation of 5-HT neurotransmission may facilitate OXTs anxiolytic potential. The trial was preregistered on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03426176, ID NCT03426176)

neuroscience↗

bioRxiv2020

Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against an acute vaccinia infection in the lungs

The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How the two immune components cross-talk during an acute viral infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we report that vaccinia host range protein C7 is a critical virulence factor. Vaccinia virus with deletion of C7 (VACV{Delta}C7L) is non-pathogenic in wild-type C57BL/6J mice, but it gains virulence in mice lacking STAT2, or IFNAR1, or MDA5/STING. We provide evidence that lung type II alveolar epithelial cells (AECs) provide first-line of defense against VACV{Delta}C7L infection by inducing IFN-{beta} and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways. This leads to recruitment of CCR2+ inflammatory monocytes into the lungs to fight against viral dissemination.

immunology↗

bioRxiv2020

Alterations of human lung and gut microbiome in non-small cell lung carcinomas and distant metastasis

BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. ResultsWe surveyed the fecal and sputum (as a proxy for lung) microbiota in healthy controls and NSCLC patients of various stages, and found significant perturbations of gut- and sputum-microbiota in patients with NSCLC and DM. Machine-learning models combining both microbiota (mixed models) performed better than either dataset in patient stratification, with the highest area under the curve (AUC) value of 0.842. Sputum-microbiota contributed more than the gut in the mixed models; in addition, sputum-only models performed similarly to the mixed models in most cases. Several microbial-biomarkers were shared by both microbiota, indicating their similar roles at distinct body sites. Microbial-biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for distant metastasis could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating distinct types of DMs could have different microbial-biomarkers. ConclusionOur results indicate that alterations of sputum-microbiota have stronger relationships with NSCLC and distant metastasis than the gut, and strongly support the feasibility of metagenome-based non-invasive disease diagnosis and risk evaluation.

microbiology↗

bioRxiv2020

ZEAMAP, a comprehensive database adapted to the maize multi-omics era

As one of the most extensively cultivated crops, maize (Zea mays L.) has been extensively studied by researchers and breeders for over a century. With advances in high-throughput detection of various omics data, a wealth of multi-dimensional and multi-omics information has been accumulated for maize and its wild relative, teosinte. Integration of this information has the potential to accelerate genetic research and generate improvements in maize agronomic traits. To this end, we constructed ZEAMAP (http://www.zeamap.com), a comprehensive database incorporating multiple reference genomes, annotations, comparative genomics, transcriptomes, open chromatin regions, chromatin interactions, high-quality genetic variants, phenotypes, metabolomics, genetic maps, genetic mapping loci, population structures and domestication selection signals between teosinte and maize. ZEAMAP is user-friendly, with the ability to interactively integrate, visualize and cross-reference multiple different omics datasets.

bioinformatics↗

bioRxiv2019

Boron deficiency-induced root growth inhibition is mediated by BR signal regulation in Arabidopsis

Brassinosteroid (BR) is a pivotal phytohormone involved in regulating root development. Boron (B) is an essential micronutrient for plant growth and development, and root growth of plants is rapidly inhibited under B deficiency condition, but the mechanisms are still elusive. Here, we demonstrate that BR plays crucial roles in these processes. We identify BR-related processes underlying B deficiency at the physiological, genetic, molecular/cell biological and transcriptome levels, and provide strong evidences that B deficiency can affect BR signalling, thereby altering root growth. RNA-sequencing analysis reveals a high co-regulation between BR-regulated genes and B deficiency-responsive genes. We found that low B negatively regulates BR signalling to control BR signalling-dependent root elongation, bes1-D exhibits insensitivity to low B stress, and bri1-301 mutants fails to respond to B depletion. Exogenous eBL application can rescue the inhibition of root growth under B deficiency condition, and application of BR biosynthesis inhibitor BRZ aggravates root growth inhibition of wild-type under B deficiency condition. B deficiency reduces the nuclear signal of BES1. We further found that B deficiency reduces the accumulation of brassinolide (BL) by reducing BR6ox1 and BR6ox2 mRNA level to down-regulate BR signalling and modulate root elongation. Altogether, our results uncover a role of BR signalling in root elongation under B deficiency. One-sentence summaryB deficiency reduces the accumulation of brassinolide by reducing BR6ox1 and BR6ox2 mRNA level to down-regulate BR signalling and modulate root elongation.

physiology↗

bioRxiv2019

Generating Templates and Growth Charts for School-Aged Brain Development

Standard brain templates and growth charts provide an invaluable resource for basic science research, with the eventual goal of contributing to the clinical care of neuropsychiatric conditions. Here, we report on a protocol to generate MRI brain templates in children and adolescents at one-year intervals from 6-to-18 years of age, with their corresponding growth charts, using a large-scale neuroimaging data resource (948 brain images from China and United States). To assure that the brain templates and growth charts are reliable and accurate, we developed a refined pipeline consisting of template construction, image registration, brain area labeling and growth chart modeling. The pipeline comprises multiple modular workflows that can be used for multiple applications. In our approach, population- and age-specific templates were first constructed to avoid systemic bias in registration. Brain areas were then labeled based on the appropriate templates, and their morphological metrics were extracted for modeling associated growth curves. We implemented warp cost as a function of age differences between individual brains and template brains. A strong U-shaped cost function was revealed, indicating larger age differences are associated with greater registration errors. This validates the necessity of age-specific reference templates in pediatric brain imaging studies. Growth chart analyses revealed preferential shape differences between Chinese and US samples in lateral frontal and parietal areas, aspects of cortex which are most variable across individuals with regard to structure and function as well as associated behavioral performance. This growth distinction is largely driven by neurodevelopmental differences between Chinese and US age-specific brain templates. The pipeline together with the brain templates and charts are publicly available and integrated into the Connectome Computation System.

neuroscience↗

bioRxiv2019

Slc7a11 modulated by POU2F1 is involved in pigmentation in rabbit

Solute carrier family 7 member 11 (Slc7a11) codes for a cystine/glutamate xCT transporter and can control production of pheomelanin pigment to change fur and skin colors of animals. Previous studies found that the skin expression levels of Slc7a11 varied significantly with the fur colors of the Rex Rabbit. However, it is not yet known the molecular regulation mechanism of Slc7a11 in pigmentation. Here rabbit melanocytes were first isolated and identified. The distribution and expression pattern of Slc7a11 was confirmed in rabbit skin with different fur colors. Slc7a11 could affect the expression of pigmentation related genes and thus affect melanogenesis. Meanwhile, Slc7a11 decreased melanocytes apoptosis, but inhibition of Slc7a11 enhanced apoptosis. Furthermore, it was found that POU2F1 protein bound to the -713 to -703 bp region of Slc7a11 promoter to inhibite its activity by dual-luciferase reporter and site-directed mutagenesis assay. This study uncover the function of the Slc7a11 in melanogenesis and provided in-depth analysis of the mechanism of fur pigmentation.

molecular biology↗

bioRxiv2019

Dynamic chromosome rearrangements of the white-spotted bamboo shark shed light on cartilaginous fish diversification mechanisms

Cartilaginous fishes have a very high phenotypical diversity, a phenomenon for which the mechanisms have been largely unexplored. Here, we report the genome of the white-spotted bamboo shark as the first chromosome-level genome assembly of cartilaginous fish. Using this genome, we illustrated a dynamic chromosome rearrangement process in the bamboo shark, which resulted in the formation of 13 chromosomes, all of which were sparsely distributed with conserved genes and fast-evolving. We found the fast-evolving chromosomes to be enriched in immune-related genes with two chromosomes harboring the major genes for developing the single-chain antibody. We also found chromosome rearrangements to have resulted in the loss of two genes (p2rx3 and p2rx5) which we also showed were involved in cartilage development using a CRISPR/Cas9 approach in zebrafish. Our study highlighted the significance of chromosome rearrangements in the phenotypical evolution of cartilaginous fishes, providing clues to inform further studies on mechanisms for fish diversification.

genomics↗