Biology subjects

Xu, J.

Publications and source records attributed to Xu, J..

At least 397 records · Page 22Linked to original sources

bioRxiv2023

Liver Protects Cytoarchitecture, Neuron Viability and Electrocortical Activity in Post-Cardiac Arrest Brain Injury

BACKGROUNDBrain injury is the major reason for patient deaths in victims who survive after cardiac arrest. Clinical studies have shown that the presence of hypoxic hepatitis and pre-cardiac arrest liver disease is associated with increased mortality and inferior neurological recovery. However, how the liver might impact the pathogenesis of post-cardiac arrest is still unknown. METHODSAn in vivo global cerebral ischemia model was established to assess how simultaneous liver ischemia affected the recovery of brain ischemic injury. In addition, an ex vivo brain normothermic machine perfusion (NMP) model was established to evaluate how addition of a functioning liver might impact the circulation, cytoarchitecture, neuron viability and electrocortical activity of the reperfused brain post-cardiac arrest. RESULTSIn the in vivo model, we observed a larger infarct area in the frontal lobe, elevated tissue injury scores in the CA1 region, as well as increased intravascular immune cell adhesion in the reperfused brains with hepatic ischemia, compared to those without simultaneous hepatic ischemia. The results of the ex vivo model demonstrated that the addition of a functioning liver to the brain NMP circuit significantly reduced post-cardiac arrest brain injury, increased neuronal viability and improved electrocortical activity. Furthermore, we observed significant alterations in gene expressions and metabolites in the presence or absence of hepatic ischemia. CONCLUSIONSOur research highlights the crucial role of the liver in the pathogenesis of post-cardiac arrest brain injury. These findings shed lights on a cardio-pulmonary-hepatic brain resuscitation strategy for patients with cardiac arrest.

neuroscience↗

bioRxiv2023

Structural variation discovery in wheat using PacBio high-fidelity sequencing

BackgroundStructural variations (SVs) pervade plant genomes and contribute substantially to the phenotypic diversity. However, most SVs were ineffectively assayed because of their complex nature and the limitations of early genomic technologies. The recent advance in third-generation sequencing, particularly the PacBio high-fidelity (HiFi) sequencing technology, produces highly accurate long-reads and offers an unprecedented opportunity to characterize SVs structure and functionality. As HiFi sequencing is relatively new to population genomics, it is imperative to evaluate and optimize HiFi sequencing based SV detection before applying the technology at scale. ResultsWe sequenced wheat genomes using HiFi reads, followed by a comprehensive evaluation of mainstream long-read aligners and SV callers in SV detection. The results showed that the accuracy of deletion discovery is markedly influenced by callers, which account for 87.73% of the variance, while both aligners (38.25%) and callers (49.32%) contributed substantially to the accuracy variance for insertions. Among the aligners, Winnowmap2 and NGMLR excelled in detecting deletions and insertions, respectively. For SV callers, SVIM achieved the best performance. We demonstrated that combining the aligners and callers mentioned above is optimal for SV detection. Furthermore, we evaluated the effect of sequencing depth on the accuracy of SV detection, showing that low-coverage HiFi sequencing is sufficiently robust for high-quality SV discovery. ConclusionsThis study thoroughly evaluated SV discovery approaches using HiFi reads, establishing optimal workflows to investigate structural variations in the wheat genome. The notable accuracy of SV discovery from low-coverage HiFi sequencing indicates that skim HiFi sequencing is effective and preferable to characterize SVs at the population level. This study will help advance SV discovery and decipher the biological functions of SVs in wheat and many other plants.

genomics↗

bioRxiv2023

Spatially resolved molecular and cellular atlas of the mouse brain

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.

neuroscience↗

bioRxiv2023

Satellite glial GPR37L1 regulates maresin and potassium channel signaling for pain control

G protein coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR and its function remains largely unknown. Here we report that GPR37L1 transcript is highly expressed compared to all known GPCRs in mouse and human dorsal root ganglia (DRGs) and selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy following diabetes and chemotherapy by streptozotocin and paclitaxel resulted in downregulations of surface GPR37L1 in mouse and human DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptom (mechanical allodynia), whereas overexpression of Gpr37l1 in mouse DRGs can reverse neuropathic pain. Notably, GPR37L1 is co-expressed and coupled with potassium channels in SGCs. We found striking species differences in potassium channel expression in SGCs, with predominant expression of KCNJ10 and KCNJ3 in mouse and human SGCs, respectively. GPR37L1 regulates the surface expression and function of KCNJ10 and KCNJ3. We identified the pro-resolving lipid mediator maresin 1 (MaR1) as a GPR37L1 ligand. MaR1 increases KCNJ10/KCNJ3-mediated potassium influx in SGCs via GPR37L1. MaR1 protected chemotherapy-induced suppression of KCNJ13/KCNJ10 expression and function in SGCs. Finally, genetic analysis revealed that the GPR37L1-E296K variant is associated with increased chronic pain risk by destabilizing the protein. Thus, GPR37L1 in SGCs offers a new target for neuropathy protection and pain control.

neuroscience↗

bioRxiv2023

Stereopy: modeling comparative and spatiotemporal cellular heterogeneity via multi-sample spatial transcriptomics

Tracing cellular dynamic changes across conditions, time, and space is crucial for understanding the molecular mechanisms underlying complex biological systems. However, integrating multi-sample data in a unified and flexible way to explore cellular heterogeneity remains a major challenge. Here, we present Stereopy, a flexible and versatile framework for modeling and dissecting comparative and spatiotemporal patterns in multi-sample spatial transcriptomics with interactive data visualization. To optimize this flexible framework, we have developed three key components: a multi-sample tailored data container, a scope controller, and an analysis transformer. Furthermore, Stereopy showcases three transformative applications supported by pivotal algorithms. Firstly, the multi-sample cell community detection (CCD) algorithm introduces an innovative capability to detect specific cell communities and identify genes responsible for pathological changes in comparable datasets. Secondly, the spatially resolved temporal gene pattern inference (TGPI) algorithm represents a notable advancement in detecting important spatiotemporal gene patterns while concurrently considering spatial and temporal features, which enhances the identification of important genes, domains and regulatory factors closely associated with temporal datasets. Finally, the 3D niche-based regulation inference tool, named NicheReg3D, reconstructs the 3D cell niches to enable the inference of cell-gene interaction network within the spatial texture, thus bridging intercellular communications and intracellular regulations to unravel the intricate regulatory mechanisms that govern cellular behavior. Overall, Stereopy serves as both a bioinformatics toolbox and an extensible framework that provides researchers with enhanced data interpretation abilities and new perspectives for mining multi-sample spatial transcriptomics data.

bioinformatics↗

bioRxiv2023

Targeting endothelial FOXO1 protects diabetic β-cells and improves wound healing

The forkhead box O1 (FOXO1) transcription factor plays critical roles in regulating not only metabolic activity but also angiogenesis in the vascular endothelium1-4. Our previous studies show that epsin endocytic adaptors can regulate both angiogenesis and lymphangiogenesis5-7. Endothelial cells (ECs) lining the inside of blood vessels are continuously exposed to circulating insulin and insulin-like growth factors (IGFs). Emerging evidences suggest that ECs can affect {beta}-cell function8-11. Excessive IGF2, especially elevated local IGF2 levels in islets, may represent a risk factor for developing diabetes12-15; however, the underlying molecular mechanisms by which aberrant angiogenesis and endothelium-derived factors regulate pancreatic {beta}-cell function in diabetes remain unclear. Here, we report that the pancreas of diabetic patients as well as the pancreas, skin, and plasma of streptozotocin/high fat diet (STZ/HFD)-induced diabetic mice and db/db mice contains excess IGF2, which can lead to {beta}-cell dysfunction and apoptosis. Single-cell transcriptomics combined with mass spectrometry analysis reveal that endothelial-specific knockout of FOXO1 increases circulating soluble and cell-membrane or intracellular expression levels of IGF type 2 receptor (IGF2R) and CCCTC-binding factor (CTCF), while decreasing IGF2 levels in diabetes. Both IGFR215-17 and CTCF18-21 can reduce IGF2 levels and may ameliorate {beta}-cell decline associated with excess IGF2 in diabetes. Furthermore, depletion of FOXO1, epsins, or knockdown of ULK1 inhibits autophagy formation in ECs, preventing degradation of vascular endothelial growth factor receptor 2 (VEGFR2) to promote angiogenesis and improve wound healing in diabetes. Our findings reveal that endothelial FOXO1 regulates epsin-dependent angiogenesis and affects {beta}-cell function and fate through CTCF and IGF2-IGF2R, providing a potential strategy for ameliorating diabetes and accelerating cutaneous wound healing.

cell biology↗

bioRxiv2023

A foundational atlas of autism protein interactions reveals molecular convergence

Translating high-confidence (hc) autism spectrum disorder (ASD) genes into viable treatment targets remains elusive. We constructed a foundational protein-protein interaction (PPI) network in HEK293T cells involving 100 hcASD risk genes, revealing over 1,800 PPIs (87% novel). Interactors, expressed in the human brain and enriched for ASD but not schizophrenia genetic risk, converged on protein complexes involved in neurogenesis, tubulin biology, transcriptional regulation, and chromatin modification. A PPI map of 54 patient-derived missense variants identified differential physical interactions, and we leveraged AlphaFold-Multimer predictions to prioritize direct PPIs and specific variants for interrogation in Xenopus tropicalis and human forebrain organoids. A mutation in the transcription factor FOXP1 led to reconfiguration of DNA binding sites and altered development of deep cortical layer neurons in forebrain organoids. This work offers new insights into molecular mechanisms underlying ASD and describes a powerful platform to develop and test therapeutic strategies for many genetically-defined conditions.

systems biology↗

bioRxiv2023

A deep lung cell atlas reveals cytokine-mediated lineage switching of a rare cell progenitor of the human airway epithelium

The human airway contains specialized rare epithelial cells whose roles in respiratory disease are not well understood. Ionocytes express the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), while chemosensory tuft cells express asthma-associated alarmins. However, surprisingly, exceedingly few mature tuft cells have been identified in human lung cell atlases despite the ready identification of rare ionocytes and neuroendocrine cells. To identify human rare cell progenitors and define their lineage relationship to mature tuft cells, we generated a deep lung cell atlas containing 311,748 single cell RNA-Seq (scRNA-seq) profiles from discrete anatomic sites along the large and small airways and lung lobes of explanted donor lungs that could not be used for organ transplantation. Of 154,222 airway epithelial cells, we identified 687 ionocytes (0.45%) that are present in similar proportions in both large and small airways, suggesting that they may contribute to both large and small airways pathologies in CF. In stark contrast, we recovered only 3 mature tuft cells (0.002%). Instead, we identified rare bipotent progenitor cells that can give rise to both ionocytes and tuft cells, which we termed tuft-ionocyte progenitor cells (TIP cells). Remarkably, the cycling fraction of these TIP cells was comparable to that of basal stem cells. We used scRNA-seq and scATAC-seq to predict transcription factors that mark this novel rare cell progenitor population and define intermediate states during TIP cell lineage transitions en route to the differentiation of mature ionocytes and tuft cells. The default lineage of TIP cell descendants is skewed towards ionocytes, explaining the paucity of mature tuft cells in the human airway. However, Type 2 and Type 17 cytokines, associated with asthma and CF, diverted the lineage of TIP cell descendants in vitro, resulting in the differentiation of mature tuft cells at the expense of ionocytes. Consistent with this model of mature tuft cell differentiation, we identify mature tuft cells in a patient who died from an asthma flare. Overall, our findings suggest that the immune signaling pathways active in asthma and CF may skew the composition of disease-relevant rare cells and illustrate how deep atlases are required for identifying physiologically-relevant scarce cell populations.

cell biology↗

bioRxiv2023

Giotto Suite: a multi-scale and technology-agnostic spatial multi-omics analysis ecosystem

Emerging spatial omics technologies continue to advance the molecular mapping of tissue architecture and the investigation of gene regulation and cellular crosstalk, which in turn provide new mechanistic insights into a wide range of biological processes and diseases. Such technologies provide an increasingly large amount of information content at multiple spatial scales. However, representing and harmonizing diverse spatial datasets efficiently, including combining multiple modalities or spatial scales in a scalable and flexible manner, remains a substantial challenge. Here, we present Giotto Suite, a suite of open-source software packages that underlies a fully modular and integrated spatial data analysis toolbox. At its core, Giotto Suite is centered around an innovative and technology-agnostic data framework embedded in the R software environment, which allows the representation and integration of virtually any type of spatial omics data at any spatial resolution. In addition, Giotto Suite provides both scalable and extensible end-to-end solutions for data analysis, integration, and visualization. Giotto Suite integrates molecular, morphology, spatial, and annotated feature information to create a responsive and flexible workflow for multi-scale, multi-omic data analyses, as demonstrated here by applications to several state-of-the-art spatial technologies. Furthermore, Giotto Suite builds upon interoperable interfaces and data structures that bridge the established fields of genomics and spatial data science, thereby enabling independent developers to create custom-engineered pipelines. As such, Giotto Suite creates an immersive ecosystem for spatial multi-omic data analysis.

bioinformatics↗

bioRxiv2023

Phylogeny-metabolism dual-directed single-cell genomics for dissecting and mining ecosystem function

Although microbiome-wide association studies (MWAS) have uncovered many marker organisms for an ecosystem trait, mechanisms of most microbiota-mediated processes remain elusive, due to challenges in validating the markers in situ metabolic activities and tracing such activities to individual genomes. Here we introduced a phylogeny-metabolism dual-directed single-cell genomics approach called Fluorescence-In-Situ-Hybridization-guided Single-Cell Raman-activated Sorting and Sequencing (FISH-scRACS-Seq). It directly localizes individual cells from target taxon via a FISH probe for marker organism, profiles their in situ metabolic functions via single-cell Raman spectra, sorts cells of target taxonomy and target metabolism, and produces indexed, high-coverage and precisely-one-cell genomes. From cyclohexane-contaminated seawater, cells representing the MWAS-derived marker taxon of {gamma}-Proteobacteria and that are actively degrading cyclohexane in situ were directly identified via FISH and Raman respectively, then sorted and sequenced for one-cell full genomes. In such a Pseudoalteromonas fuliginea cell, we discovered a three-component cytochrome P450 system that can convert cyclohexane to cyclohexanol in vitro, representing a previously unknown group of cyclohexane-degrading enzymes and organisms. By culture-independently unveiling enzymes, pathways, genomes and their in situ functions specifically for those single-cells with ecological relevance, FISH-scRACS-Seq is a rational and generally applicable approach for dissecting and mining microbiota functions. TeaserFISH-scRACS-Seq is a new strategy to dissect microbiota functional mechanism at single-cell resolution.

microbiology↗

bioRxiv2023

Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes

Programmed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood. We discovered in mice that efficient biogenesis of DSB-machinery clusters requires seeding by axial IHO1 platforms, which are based on a DBF4-dependent kinase (DDK)-modulated interaction between IHO1 and the chromosomal axis component HORMAD1. IHO1-HORMAD1-mediated seeding of the DSB-machinery on axes ensures sufficiency of DSBs for efficient pairing of homologous chromosomes. Without IHO1-HORMAD1 interaction, residual DSBs depend on ANKRD31, which enhances both the seeding and the growth of DSB-machinery clusters. Thus, recombination initiation is ensured by complementary pathways that differentially support seeding and growth of DSB-machinery clusters, thereby synergistically enabling DSB-machinery condensation on chromosomal axes.

cell biology↗

bioRxiv2023

Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors must rely on transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces the biocompatibility, or limits the portability. Here, we develop a set of millimeter-scale, chip-less and battery-less magnetic implants that can measure biophysical and biochemical signals wirelessly. In particular, the implants form two-way communications with a fully integrated wearable device, where the wearable device can induce a large-amplitude damped vibration of the magnetic implants and capture their subsequent motions in a wireless manner. Such damped vibrations reflect not only the biophysical conditions surrounding the implants movements, but also the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities in measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure (ICP), and CSF glucose levels. This miniaturized system opens possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.

bioengineering↗

bioRxiv2023

Aalbo1200: global genetic differentiation and variability of the mosquito Aedes albopictus

The mosquito Aedes albopictus transmits human viruses including dengue and chikungunya and is an extremely successful invasive species expanding into new regions of the world. New tools are needed to complement existing tools to help monitor and control this species. Genomic resources are improving for this species including genome reference sequences, and whole genome sequencing data will help to catalog genetic diversity in this species and further enable genetic analysis. We collected populations of Ae. albopictus from throughout its distribution and generated whole genome sequencing data from population samples. These data will be used to address a number of basic and applied questions for this species. Here, we show genetic differentiation patterns among the tropical and temperate forms, as well as finer scale genetic clustering at the regional and population scale. These data and results will be a valuable resource for further study and tool development for this species.

evolutionary biology↗

bioRxiv2023

De novo Design of Peptides that Bind Specific Conformers of α-Synuclein

Insoluble amyloids rich in cross-{beta} fibrils are observed in a number of neurodegenerative diseases. Depending on the clinicopathology, the amyloids can adopt distinct supramolecular assemblies, termed conformational strains. However, rapid methods to study amyloid in a conformationally specific manner are lacking. We introduce a novel computational method for de novo design of peptides that tile the surface of -synuclein fibrils in a conformationally specific manner. Our method begins by identifying surfaces that are unique to the conformational strain of interest, which becomes a "target backbone" for the design of a peptide binder. Next, we interrogate structures in the PDB database with high geometric complementarity to the target. Then, we identify secondary structural motifs that interact with this target backbone in a favorable, highly occurring geometry. This method produces monomeric helical motifs with a favorable geometry for interaction with the strands of the underlying amyloid. Each motif is then symmetrically replicated to form a monolayer that tiles the amyloid surface. Finally, amino acid sequences of the peptide binders are computed to provide a sequence with high geometric and physicochemical complementarity to the target amyloid. This method was applied to a conformational strain of -synuclein fibrils, resulting in a peptide with high specificity for the target relative to other amyloids formed by -synuclein, tau, or A{beta}40. This designed peptide also markedly slowed the formation of -synuclein amyloids. Overall, this method offers a new tool for examining conformational strains of amyloid proteins.

biophysics↗

bioRxiv2023

Senescent cells impair fracture repair through elevating ubiquitin-proteasome system activity in aged mice.

Senescent cells accumulate in multiple tissues with aging. Depletion of senescent cells benefits the aging related disease, such as aging bone fracture. However, the molecular mechanisms by which senescent cells regulate their neighboring bone cells are still not well-known. We reported that proteasome inhibitor enhanced fracture repair in aged mice. Senescent cells are major source of chronic inflammatory cytokines, which in turn induced protein ubiquitination. We reported that PDGFR{beta} was one of the highly ubiquitinated proteins in mesenchymal progenitors (MPCs) and TGF{beta} was the most increased SASP. In the current study, we found TGF{beta} induced PDGFR{beta} ubiquitination and proteasomal degradation through its E3 ligases. TGF{beta} neutralizing antibody blocked the inhibited callus derived MPC growth and increased Ub-PDGFR{beta} by senescent cells, which could be further prevented PDGFR{beta} inhibitor. These findings suggested senescent cells derived TGF{beta} impaired fracture repair in aged mice through elevating ubiquitination of PDGFR{beta}. The discovery of TGF{beta}-PDGFR{beta} pathway triggered by senescent cells opens avenues for optimizing treatment strategies for aging related disease by combination with the ligand of PDGFR{beta}.

cell biology↗

bioRxiv2023

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma

Myeloid cells are abundant and plastic immune cell subsets in the liver, to which pro-tumorigenic, inflammatory and immunosuppressive roles have been assigned in the course of tumorigenesis. Yet several aspects underlying their dynamic alterations in hepatocellular carcinoma (HCC) progression remain elusive, including the impact of distinct genetic mutations in shaping a cancer-permissive tumor microenvironment (TME). Here, we generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations and subsequent pathway activation that faithfully recapitulated different human HCC subclasses. We identified cancer genetics specific and stage-dependent alterations of the liver TME associated with distinct histopathological and malignant HCC features. These models ranged from T cell-rich, more indolent HCC to aggressive tumors exhibiting heightened myeloid cell infiltration. Interestingly, MAPK-activated, NrasG12D-driven tumors presented a mixed phenotype of prominent inflammation and immunosuppression in a T cell-excluded TME, contrasting with NrasG12V HCC, enriched in adaptive immune cells. Mechanistically, we identified a NrasG12D cancer cell-driven, MEK-ERK1/2-SP1-dependent GM-CSF secretion enabling the accumulation of immunosuppressive and proinflammatory monocyte-derived Ly6Clow cells. GM-CSF blockade curbed the accumulation of this myeloid cell subset, reduced inflammation, induced cancer cell death and prolonged animal survival. Furthermore, the anti-tumor effect of GM-CSF neutralization synergized with the clinically-approved inhibition of the vascular endothelial growth factor (VEGF) to inhibit HCC outgrowth. These findings underscore the striking alterations of the myeloid TME consequential to MAPK pathway activation intensity and the potential of GM-CSF inhibition as a myeloid-centric therapy tailored to subsets of HCC patients.

cancer biology↗

bioRxiv2023

Effects of Gene Dosage and Development on Subcortical Nuclei Volumes in Individuals with 22q11.2 Copy Number Variations

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in 22qDel (n=96, 53.1% female), 22qDup (n=37, 45.9% female), and TD controls (n=80, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the effect of 22q11.2 gene dosage was examined using linear mixed models. Age-related changes were characterized with general additive mixed models (GAMMs). Positive gene dosage effects (22qDel < TD < 22qDup) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age- related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

neuroscience↗

bioRxiv2023

The rapid diversification of Boletales is linked to Early Eocene and Mid-Miocene Climatic Optima

O_LIInvestigating the mechanisms that underpin the diversity and distribution patterns of species is fundamental in ecology and evolution. However, the study of fungi, particularly the ectomycorrhizal group, has been relatively constrained in this field. C_LIO_LIWe conducted a high-resolution phylogenomic analysis of Boletales, an ecologically and economically significant group of fungi, covering 83 genera across 15 families. We subsequently investigated its evolutionary history using sequences at four genes obtained from 984 species across 121 genera within 15 families. C_LIO_LIThe findings unveiled that Boletales likely originated in Early Jurassic and underwent two remarkable episodes of rapid diversification, commencing in early Eocene ([~]54 Mya) and early Miocene ([~]17 Mya) epochs. The notable surges were predominantly driven by ectomycorrhizal clades, with a specific emphasis on East Asia and North America. These expansions were strongly correlated with the warm-humid paleoclimates during the Early Eocene Climatic Optimum and Mid-Miocene Climatic Optimum, as well as the rapid expansion of Fagales and Pinaceae hosts. C_LIO_LIThis study provides novel insights into the spatiotemporal evolution of fungi, highlighting the synergistic impact of abiotic factors, such as warm and humid paleoclimates, and the biotic factor of rapid diversification of host plants on the fungal diversification. C_LI

evolutionary biology↗