Biology subjects

Song, M.

Publications and source records attributed to Song, M..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Dynamic Mode Decomposition for Transient Cavitation Bubbles Imaging in Pulsed High Intensity Focused Ultrasound Therapy

Pulsed high-intensity focused ultrasound (pHIFU) can induce sparse de novo inertial cavitation without the introduction of exogenous contrast agents, promoting mild mechanical disruption in targeted tissue. Because the bubbles are small and rapidly dissolve after each HIFU pulse, mapping transient bubbles and obtaining real-time quantitative metrics correlated to tissue damage are challenging. Prior work introduced Bubble Doppler, an ultrafast power Doppler imaging method as a sensitive means to map cavitation bubbles. The main limitation of that method was its reliance on conventional wall filters used in Doppler imaging and optimized for imaging blood flow rather than transient scatterers. This study explores Bubble Doppler enhancement using dynamic mode decomposition (DMD) of a matrix created from a Doppler ensemble for mapping and extracting the characteristics of transient cavitation bubbles. DMD was first tested in silico with a numerical dataset mimicking the spatiotemporal characteristics of backscattered signal from tissue and bubbles. The performance of DMD filter was compared to other widely used Doppler wall filters - singular value decomposition (SVD) and infinite impulse response (IIR) highpass filter. DMD was then applied to an ex vivo tissue dataset where each HIFU pulse was immediately followed by a plane wave Doppler ensemble. In silico DMD outperformed SVD and IIR high pass filter and ex vivo provided physically interpretable images of the modes associated with bubbles and their corresponding temporal decay rates. These DMD modes can be trackable over the duration of pHIFU treatment using k-means clustering method, resulting in quantitative indicators of treatment progression. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/582222v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@f9f858org.highwire.dtl.DTLVardef@11f6844org.highwire.dtl.DTLVardef@f67926org.highwire.dtl.DTLVardef@18bb15c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Molecular and cellular dynamics of the developing human neocortex at single-cell resolution

The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation1. Here, we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence. In parallel, we performed spatial transcriptomic analysis on a subset of the samples to illustrate spatial organization and intercellular communication. This atlas enables us to catalog cell type-, age-, and area-specific gene regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification, and lineage-tracing experiments, we have untangled the complex lineage relationships among progenitor subtypes during the transition from neurogenesis to gliogenesis in the human neocortex. We identified a tripotential intermediate progenitor subtype, termed Tri-IPC, responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells, and astrocytes. Remarkably, most glioblastoma cells resemble Tri-IPCs at the transcriptomic level, suggesting that cancer cells hijack developmental processes to enhance growth and heterogeneity. Furthermore, by integrating our atlas data with large-scale GWAS data, we created a disease-risk map highlighting enriched ASD risk in second-trimester intratelencephalic projection neurons. Our study sheds light on the gene regulatory landscape and cellular dynamics of the developing human neocortex.

neuroscience↗

bioRxiv2024

The lateral habenula integrates age and experience to promote social transitions in developing rats

Social behavior deficits are an early-emerging marker of psychopathology and are linked with early caregiving quality. However, the infant neural substrates linking early care to social development are poorly understood. Here, we focused on the infant lateral habenula (LHb), a highly-conserved brain region at the nexus between forebrain and monoaminergic circuits. Despite its consistent links to adult psychopathology, this brain region has been understudied in development when the brain is most vulnerable to environmental impacts. In a task combining social and threat cues, suppressing LHb principal neurons had opposing effects in infants versus juveniles, suggesting the LHb promotes a developmental switch in social approach behavior under threat. We observed that early caregiving adversity (ECA) disrupts typical growth curves of LHb baseline structure and function, including volume, firing patterns, neuromodulatory receptor expression, and functional connectivity with cortical regions. Further, we observed that suppressing cortical projections to the LHb rescued social approach deficits following ECA, identifying this microcircuit as a substrate for disrupted social behavior. Together, these results identify immediate biomarkers of ECA in the LHb and highlight this region as a site of early social processing and behavior control.

neuroscience↗

bioRxiv2023

Long-term abstinence reduces optimal energy required for transitions from the exogenous networks to the frontoparietal network in methamphetamine addicts

Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52{+/-}99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r [~] 0.35, P <0.01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (PFDR<0.05), with strong alterations in somatomotor regions (PFDR<0.05) and moderate alterations in high-level association networks (PFDR<0.05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics.

neuroscience↗

bioRxiv2023

Inhalation Delivered RNA Aptamer for Therapeutics against SARS-CoV2

The continual emergence and re-emergence of infectious diseases has led to a pressing need for the development of swift and targeted therapeutic interventions. SARS-CoV-2, the causative agent of COVID-19, is a prime example of such a rapidly spreading virus[1]. The global crisis caused by this virus has propelled researchers to explore and adopt novel techniques in the hopes of effectively combating its spread[2]. One such innovative approach is the use of aptamers--single-stranded RNA molecules that can bind targets with high specificity.

molecular biology↗

bioRxiv2023

Synaptic plasticity via receptor tyrosine kinase / G protein-coupled receptor crosstalk

Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and physiological roles of crosstalk between receptors, especially those from different superfamilies, are poorly understood. We find that the receptor tyrosine kinase (RTK), TrkB, and the G protein-coupled receptor (GPCR), metabotropic glutamate receptor 5 (mGluR5), together mediate a novel form of hippocampal synaptic plasticity in response to brain-derived neurotrophic factor (BDNF). Activated TrkB enhances constitutive mGluR5 activity to initiate a mode-switch that drives BDNF-dependent sustained, oscillatory Ca2+ signaling and enhanced MAP kinase activation. This crosstalk is mediated, in part, by synergy between G{beta}{gamma}, released by TrkB, and Gq-GTP, released by mGluR5, to enable a previously unidentified form of physiologically relevant RTK/GPCR crosstalk.

cell biology↗

bioRxiv2023

ASD mutation of Katnal2 impairs ependymal ciliary motion and causes hydrocephalus

Katanin catalytic subunit A1 like 2 (KATNAL2) is a high-risk gene associated with autism spectrum disorders (ASD), however its impact on brain development and disease remains unclear. The present study revealed an unexpected role of KATNAL2 in regulating ependymal ciliary motion and cerebrospinal fluid flow during brain development, an important contributing factor for ASD. We discovered a distinct expression pattern of KATNAL2 in multiciliated ependymal cells of both human and mouse brains. Notably, an ASD-associated mutation of Katnal2 disrupted its molecular function and resulted in ASD-related behavioral deficits in mice. Additionally, this mutation affected the polarized organization and beating of ependymal cilia, leading to delayed cerebrospinal fluid flow and sustained ventricular enlargement from the early postnatal stage. Conditional ablation of Katnal2 specifically in the ependymal cells of neonatal mice is sufficient to cause ventricular dilation, whereas no such effect was observed in adult mice. Our findings highlight the importance of ependymal motile cilia and hydrocephalus in ASD, offering insights into its pathogenesis and potential intervention.

neuroscience↗

bioRxiv2023

Insights from the Early Cretaceous: The promise of Lycoptera aDNA sequencing

Obtaining high-quality ancient DNA (aDNA) is a crucial process for advancements in molecular paleontology. However, current research is restricted to a limited range of fossil types due to DNA degradation and contamination from environmental DNA (eDNA). Utilizing the technology of nanoparticle affinity beads, we successfully extracted DNA from Lycoptera davidi fossils and obtained 1,258,901 DNA sequences. To ascertain their origins, we developed and implemented a novel protocol, the "mega screen method", designed to categorize aDNA fragments. This approach successfully identified 243 Actinopterygii species-specific fragments (SSFs), which subsequent analysis confirmed as original in situ DNA (oriDNA) sequences. Lycoptera davidi, a ray-finned fish from the Early Cretaceous Jehol Biota, dates back approximately 120 million years (Ma). Notably, the absence of deamination in certain oriDNA and paleoenvironmental DNA (paeDNA) fragments calls into question its reliability as a definitive marker for aDNA identification, a phenomenon potentially attributable to the protective effects of fossil diagenesis. Additionally, we identified a novel mechanism, "coding region sliding replication and recombination", responsible for generating new transposase. This mechanism, distinct from conventional processes such as horizontal gene transfer or vertical inheritance from parents, can facilitate a rapid genomic diversification. The transposase CDS insertion into the GAS2 gene of Anabarilius grahami offers molecular insights into the genetic interactions between ancestral carp and Lycoptera and the swift emergence of the expansion of early fish species starting from the early Cretaceous. These findings enhance our understanding of fossil DNA preservation, lay the groundwork for an ancient species DNA database, and introduce innovative tools for exploring evolutionary relationships across geological timescales.

paleontology↗

bioRxiv2023

RealSeq2: a software integrated with UMI identification, error correction, and methylation modifications storing

High-throughput UMI technology sequencing is widely used in early tumor screening, detection, recurrence monitoring, etc. Detecting extremely low-frequency mutations is especially important for monitoring tumor recurrence, so high-precision data, as well as high-quality data, are required. We developed RealSeq2, a new integrated data-preprocessing software based on fastp and gencore, to achieve adapter removal, quality control, UMI identification, and generate consensus reads by clustering and error correction using multithreading in high-throughput next-generation sequencing background. RealSeq2 also supports methylation data of 5-methylcytosine bisulfite-free sequencing. RealSeq2 defined a new tag in SAM for storing methylation information, which is beneficial for co-identifying methylation sites and mutation sites for downstream analysis. RealSeq2 includes three submodules: ReadsProfiler, ReadsCleaner, and ReadsRecycler. In addition, the output format file (BAM or SAM) is universal for downstream analyses. RealSeq2 is the preferred upstream analysis software for the co-detection of ultra-low frequency mutations and bisulfite-free methylation data. The error profile provides data support for downstream analysis. Additionally, XM tags will become a standard protocol for recording methylation signals.

bioinformatics↗

bioRxiv2023

Hierarchical gradient of timescales in the mammalian forebrain

Many anatomical and physiological features of cortical circuits, ranging from the biophysical properties of synapses to the connectivity patterns among different neuron types, exhibit consistent variation along the hierarchical axis from sensory to association areas. Notably, the scale of temporal correlation of neural activity at rest, known as the intrinsic timescale, increases systematically along this hierarchy in both primates and rodents, analogous to the growing scale and complexity of spatial receptive fields. However, how the timescales for task-related activity vary across brain regions and whether their hierarchical organization appears consistently across different mammalian species remain unexplored. Here, we show that both the intrinsic timescale and the timescales of task-related activity follow a similar hierarchical gradient in the cortices of monkeys, rats, and mice. We also found that these timescales covary similarly in both the cortex and basal ganglia, whereas the timescales of thalamic activity are shorter than cortical timescales and do not conform to the hierarchical order predicted by their cortical projections. These results suggest that the hierarchical gradient of cortical timescales might be a universal feature of intra-cortical circuits in the mammalian brain. Significance StatementA gradual increase in the intrinsic timescales of cortical activity along the anatomical hierarchy reflects the functional specialization of cortical circuits. However, it is unknown whether this gradient of timescales is a common feature across distinct mammalian species in both intrinsic and task-related timescales and whether it is also observed in subcortical areas. This study reveals that the hierarchical gradient of multiple cortical timescales is conserved across multiple mammalian species. By contrast, thalamic timescales were shorter than cortical timescales and did not follow the hierarchical order inferred from their cortical projections. These findings imply a crucial role of intra-cortical connections in structuring distinct temporal dynamics observed across the cortex.

neuroscience↗

bioRxiv2023

Directed-evolution mutations of adenine base editor ABE8e improve its DNA-binding affinity and protein stability

Adenine base editors (ABEs), consisting of CRISPR-associated (Cas) nickase and deaminase, can convert the A:T base pair to G:C. Previous studies have shown that ABE8e, a directed-evolution variant of ABE7.10 with eight amino-acid mutations in its deaminase TadA-8e, has higher base editing activity than ABE7.10. However, it remains unclear how the directed-evolution mutations of ABE8e increase its editing activity. Here, we combined molecular dynamics (MD) simulations and experimental measurements to elucidate the molecular origin of the activity enhancement by these mutations. MD simulations and microscale thermophoresis measurements showed that TadA-8e has a higher DNA-binding affinity than TadA-7.10, and the main driving force is electrostatic interactions. The directed-evolution mutations increase the positive charge density in the DNA-binding region, thereby enhancing the electrostatic attractions with DNA. We showed that R111 is the key mutation for the enhanced binding to DNA, which explains why the ABE-8e activity was dramatically reduced when R111 was mutated back to the original T. Unexpectedly, we also found that these mutations improve the thermal stability of TadA-8e by [~]12{degrees}C (Tm). Our results indicate that the editing activities of ABEs are closely related to their DNA-binding affinity and protein stability, thus providing a rational basis for their optimization. Author SummaryAdenine-to-guanine mutations account for 47% of known disease-causing point mutations in humans. Adenine base editors (ABEs), which can restore the guanine mutation to adenine, are a promising tool for precision gene therapy. ABE8e is the most widely used editor today due to its high editing efficacy and was derived from the first-generation base editor ABE7.10 by directed evolution. Compared to ABE7.10, ABE8e contains 8 directed-evolution amino-acid mutations. Understanding how these mutations affect the efficiency of ABE8e is important for the development of efficient base editors. In this study, we combined computational and experimental approaches to investigate how these mutations affect the editing activity of ABE8e. Our results showed that these directed-evolution mutations improve the DNA binding affinity and the protein stability of ABE8e, by enhancing electrostatic and hydrogen bonding interactions. Therefore, our study provides valuable insights for the design of more efficient base editors.

molecular biology↗

bioRxiv2023

Mature microRNA-binding protein QKI promotes microRNA-mediated gene silencing

Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified in genetically engineered AGO-depleted human and mouse cells. We have shown that QKI serves as an auxiliary factor empowering AGO2/let-7b-mediated gene silencing. Depletion of QKI decreases interaction of AGO2 with let-7b and target mRNA, consequently controlling target mRNA decay. QKI, however, also suppresses the dissociation of let-7b from AGO2, and slows assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. We also revealed that QKI suppresses cMYC expression at post-transcriptional level, and decreases proliferation and migration of HeLa cells, demonstrating that QKI is a tumor suppressor gene by in part augmenting let-7b activity. Our data show that QKI is a new type of RBP implicated in the versatile regulation of miRNA-mediated gene silencing.

biochemistry↗

bioRxiv2023

Syntaxin of plants 32 regulates pollen wall development and pollen tube cell wall integrity via controlling secretory pathway

Pollen tubes (PTs) elongate in a polar way to deliver sperm cells to the ovule. Pollen wall development and PT cell wall integrity (CWI) maintenance are critical for PT growth and double fertilization. Pollen wall development mainly relies on secretion of exine precursors in tapetum. RALF4/19-ANX/BUPS-MRI and RALF4/19-LRX-AUN are two distinct signaling pathways but converge to fine-tune CWI during PT growth. Here, we discovered that atsyp32+/-, AtSYP32 RNAi and AtSYP3132 RNAi lines were male sterile. The tapetum development in these lines were disturbed, and the pollen wall structure was impaired resulting in pollen grain and tube bursting and less PTs navigated to micropyles. Strikingly, there were numerous ectopic secretory vesicles retained in pollen cytoplasm, and the abundance or distribution of polysaccharides and AGPs altered significantly in PTs of the mutants and RNAi lines. AtSYP32 interacted with the vesicle transport regulators SEC31B, SEC22 and BET12, the PT CWI regulators RALF19 and LRX11, and the XyG xylosyltransferase XXT5, in the Golgi apparatus. Transcription of some genes related to pollen wall biosynthesis and PT CWI maintenance were seriously affected by AtSYP32 downregulation. Our findings illustrate that AtSYP32 plays essential roles in pollen wall development and PT CWI maintenance via controlling secretory pathway. IN A NUTSHELLO_ST_ABSBackgroundC_ST_ABSPollen wall is the most complex cell wall. Pollen wall development mainly relies on secretion of precursors of exine and pollen coat in tapetal cells. Pollen tubes (PTs) grow in a polar way to deliver sperm cells to the ovule. Maintenance of PT cell wall integrity (CWI) is critical for PT elongation and double fertilization. RALF4/19 ligands interact with BUPS-ANX receptors, signaling it in an autocrine manner to maintain CWI during PT elongation. RALF4/19-LRX-AUN pathway is distinct with RALF4/19-ANX/BUPS-MRI pathway but they converge to fine-tune CWI during PT growth. Biosynthesis of PT cell wall involves multiple subcellular compartments and vesicle transport pathways. Golgi apparatus acts as a hub in vesicle trafficking. Golgi-syntaxin AtSYP31 and AtSYP32 regulate pollen development by controlling intra-Golgi transport and Golgi morphology QuestionWhat is AtSYP32 role in pollen wall and tapetum development? Who are the AtSYP32 partners that regulate secretion of cell wall biosynthesis materials? FindingsWe found that no homozygote progeny was obtained from self-pollinated atsyp32+/- alleles due to pollen sterile. The tapetum development and degeneration in atsyp32+/- mutants was severely delayed, and the pollen wall and PT wall structure were impaired. Strikingly, there were numerous ectopic secretory vesicles retained in pollen cytoplasm in atsyp32+/- mutants, and the abundance or distribution of PT wall polysaccharides and AGPs altered obviously. AtSYP32 interacted with the vesicle transport regulators SEC31B, SEC22 and BET12, the PT CWI regulators RALF19 and LRX11, and XyG xylosyltransferase XXT5, in the Golgi. All these highlight that AtSYP32 regulates pollen wall development and maintenance of PT CWI via controlling secretory pathway. Next stepsThe biological significances and the molecular mechanisms of AtSYP32 interacting with XXT5, RALF19 and LRX11 are elusive but thought-provoking. We are going to clarify the mechanisms.

molecular biology↗

bioRxiv2023

Experiment-based Computational Model Predicts that IL-6 Trans-Signaling Plays a Dominant Role in IL-6 mediated signaling in Endothelial Cells

Inflammatory cytokine mediated responses are important in the development of many diseases that are associated with angiogenesis. Targeting angiogenesis as a prominent strategy has shown limited effects in many contexts such as peripheral arterial disease (PAD) and cancer. One potential reason for the unsuccessful outcome is the mutual dependent role between inflammation and angiogenesis. Inflammation-based therapies primarily target inflammatory cytokines such as interleukin-6 (IL-6) in T cells, macrophages, cancer cells, muscle cells, and there is a limited understanding of how these cytokines act on endothelial cells. Thus, we focus on one of the major inflammatory cytokines, IL-6, mediated intracellular signaling in endothelial cells by developing a detailed computational model. Our model quantitatively characterized the effects of IL-6 classic and trans-signaling in activating the signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and mitogen-activated protein kinase (MAPK) signaling to phosphorylate STAT3, extracellular regulated kinase (ERK) and Akt, respectively. We applied the trained and validated experiment-based computational model to characterize the dynamics of phosphorylated STAT3 (pSTAT3), Akt (pAkt), and extracellular regulated kinase (pERK) in response to IL-6 classic and/or trans-signaling. The model predicts that IL-6 classic and trans-signaling induced responses are IL-6 and soluble IL-6 receptor (sIL-6R) dose-dependent. Also, IL-6 trans-signaling induces stronger downstream signaling and plays a dominant role in the overall effects from IL-6. In addition, both IL-6 and sIL-6R levels regulate signaling strength. Moreover, our model identifies the influential species and kinetic parameters that specifically modulate the pSTAT3, pAkt, and pERK responses, which represent potential targets for inflammatory cytokine mediated signaling and angiogenesis-based therapies. Overall, the model predicts the effects of IL-6 classic and/or trans-signaling stimulation quantitatively and provides a framework for analyzing and integrating experimental data. More broadly, this model can be utilized to identify targets that influence inflammatory cytokine mediated signaling in endothelial cells and to study the effects of angiogenesis- and inflammation-based therapies.

systems biology↗

bioRxiv2022

A human mitofusin 2 mutation causes mitophagic cardiomyopathy

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is ~20x over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of the MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical and functional characteristics of MFN2 Q400 versus wild-type and representative CMT2A-causing MFN2 mutants. All MFN2 mutants we studied suppressed mitochondrial fusion, the canonical MFN2 function. Compared to CMT2A mutants MFN2 R94Q and T105M that lacked catalytic GTPase activity and exhibited normal activation-induced changes in conformation, MFN2 Q400 had normal GTPase activity with impaired conformational shifting. GTPase-defective MFN2 mutants, but not MFN2 Q400, suppressed mitochondrial motility, provoked mitochondrial depolarization and reduced mitochondrial respiration. By contrast, MFN2 Q400 was uniquely defective in recruiting Parkin to mitochondria. CRISPR editing of the R400Q mutation into the mouse Mfn2 gene induced perinatal cardiomyopathy with no other organ involvement. RNA sequencing and metabolomics of cardiomyopathic Mfn2 Q400 hearts revealed signature abnormalities recapitulating experimental mitophagic cardiomyopathy. Indeed, cardiomyoblasts expressing MFN2 Q400 exhibited multiple mitophagy defects, but normal mitochondrial respiration. MFN2 Q400 is the first known natural mitophagy- and shape change-defective MFN2 mutant. Its unique profile of dysfunction evokes mitophagic cardiomyopathy, suggesting a mechanism for its enrichment in clinical cardiomyopathy.

developmental biology↗

bioRxiv2022

Functional traits trade-offs define plant population stability worldwide

O_LIEcological theory posits that temporal stability patterns in plant populations are associated with differences in species ecological strategies. However, empirical evidence is lacking about which traits, or trade-offs, underlie species stability, specially across different ecosystems. C_LIO_LITo address this, we compiled a global collection of long-term permanent vegetation records (>7000 plots from 78 datasets) from a wide range of habitats and combined this with existing trait databases. We tested whether the observed inter-annual variability in species abundance (coefficient of variation) was related to multiple individual traits and multivariate axes of trait variations (PCoA axes). C_LIO_LIWe found that species with greater leaf dry matter content and seed mass were consistently more stable over time (lower variability in species abundance) although other leaf traits played a significant role as well, albeit weaker. Using multivariate axes did not improve predictions by specific traits. C_LIO_LIOur results confirm existing theory, providing compelling empirical evidence on the importance of specific traits, which point at ecological trade-offs in different resource use and dispersal strategies, on the stability of plant populations worldwide. C_LI

ecology↗

bioRxiv2022

Drastic differential CRISPR-Cas9 induced mutagenesis influenced by DNA methylation and chromatin features

CRISPR-Cas9 mediated genome editing has been widely adopted for basic and applied biological research in eukaryotic systems. While many studies considered DNA sequences of CRISPR target sites as the primary determinant for CRISPR mutagenesis efficiency and mutation profiles, increasing evidence revealed the significant role of chromatin context. Nonetheless, most of the prior studies were limited by the lack of sufficient epigenetic resources and/or by only transiently expressing CRISPR-Cas9 in a short time window. In this study, we leveraged the wealth of high-resolution epigenomic resources in Arabidopsis thaliana to address the impact of chromatin features on CRISPR-Cas9 mutagenesis using stable transgenic plants. Our results indicated that DNA methylation and chromatin features could lead to significant variations in mutagenesis efficiency by up to 250 folds. Low mutagenesis efficiencies were mostly associated with repressive heterochromatic features. This repressive effect appeared to persist through cell divisions but could be alleviated through substantial reduction of DNA methylation at CRISPR target sites. Moreover, specific chromatin features, such as H3K4me1, H3.3, and H3.1, appear to be associated with significant variations in CRISPR-Cas9 mutation profiles reflected by the 1 bp insertion rates. Our findings provided strong evidence that specific chromatin features could have significant and lasting impacts on both CRISPR-Cas9 mutagenesis efficiency and DNA double strand break repair outcomes.

plant biology↗

bioRxiv2022

Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex

The prefrontal cortex (PFC) is a highly variable, evolutionarily expanded brain region that is engaged in multiple cognitive processes. The subregions of the PFC mature relatively late compared with other brain regions, and the maturation times vary between these subregions. Among these, the dorsomedial and dorsolateral prefrontal cortex (dmPFC and dlPFC) share a parallel topographic pattern of functional connectivity, while participating in different types of complex behaviors. However, the developmental trajectories of the two areas remain obscure. In this study, we uncovered differences in the developmental trends of the dmPFC and dlPFC. These differences were mainly caused by structural and functional changes in the medial area of the superior frontal gyrus (SFG). The developmentally different arealization patterns were verified using multiple parcellation approaches with multimodal data, including structural magnetic resonance imaging (sMRI), diffusion MRI (dMRI), resting state functional MRI (rfMRI), and a publicly available transcriptomic dataset. Human brain gene expression data was also used to perform downstream analyses, which could inform us about the potential biological mechanisms underlying the developmentally different arealizations. Furthermore, behavioral analyses hinted at the effects of regionalization on ontogeny. In brief, this study revealed a tendency toward a medial-lateral prefrontal division and can provide a fuller understanding of the potential underlying genetic underpinnings as well as of the potential effects on developmental behavior.

neuroscience↗