Biology subjects

Teng, L.

Publications and source records attributed to Teng, L..

10 recordsLinked to original sources

bioRxiv2026

In Vivo Surface Reconstruction of Three Signal-defined Intracortical Layers Using 5T 3D FLAIR MR Imaging

BackgroundIn vivo whole-cortex quantification of intracortical signal-defined layering on the routinely acquired structural MRI remains limited. PurposeTo develop and validate an automated framework to reconstruct three intracortical signal-defined layers from 5T three-dimensional (3D) T2-weighted fluid-attenuated inversion recovery (FLAIR) and to characterize whole-cortex morphometrics and regional organization across a prespecified cortical organizational framework. Materials and MethodsIn this retrospective study, 5T 3D FLAIR images were acquired between February and July 2024. Brain Multi-Layer Surface Reconstruction (BrainMLSR) reconstructed three intracortical signal-defined layers, and derived intracortical layer thickness and surface area measures and ratios. Performance was evaluated against manual annotations and assessed for test-retest repeatability (n=13) and cross-site feasibility (n=2). Paired two-tailed t-tests and linear mixed-effects models were used. A proof-of-concept analysis compared Heschls gyrus ratios between 19 patients with temporal lobe epilepsy (TLE) and 19 age-matched healthy controls (HC). ResultsA total of 270 healthy participants (mean age, 54.4{+/-}14.5 years; 146 men) were included. Agreement with manual hypointense-layer annotations was high (Dice, 0.960{+/-}0.003), and was similar in the cross-site dataset (Dice, 0.954{+/-}0.009). In the test-retest dataset, average symmetric surface distance was less than 0.1 mm. Across prespecified systems, thickness and surface area ratios varied by region; within an auditory-perisylvian hierarchy, banksSTS showed a localized turning point with an increased hyperintense layer thickness ratio and decreased hypointense layer thickness ratio, accompanied by inflections in surface area ratios (P < .001). In bilateral Heschls gyrus, hypointense (left: 0.619{+/-}0.262 vs 0.881{+/-}0.102; right: 0.607{+/-}0.310 vs 0.907{+/-}0.141 mm) and isointense (left: 0.406{+/-}0.225 vs 0.678{+/-}0.128; right: 0.478{+/-}0.232 vs 0.808{+/-}0.176 mm) layer thicknesses were lower in TLE than in HC (all P<.001). ConclusionBrainMLSR enabled accurate and repeatable in vivo reconstruction of three intracortical signal-defined layers from a single 5T 3D T2-weighted FLAIR acquisition and provided whole-cortex boundary-based morphometry with interpretable regional organization. Key ResultsO_LIIn this retrospective study of 270 participants, Brain Multi-Layer Surface Reconstruction (BrainMLSR) showed high agreement with hypointense-layer annotations (Dice, 0.960{+/-}0.003). C_LIO_LIWithin an auditory-perisylvian hierarchy, the hyperintense-layer thickness ratio peaked (0.620{+/-}0.003) and the hypointense-layer ratio was the lowest (0.156{+/-}0.002) in the bank of the superior temporal sulcus (P < .001). C_LIO_LIIn a proof-of-concept analysis, patients with temporal lobe epilepsy (vs healthy controls) had higher hyperintense-layer thicknesses ratio in the left hemisphere (0.523{+/-}0.085 vs 0.417{+/-}0.036, P<.001). C_LI SummaryAn automated multiple-layer surface reconstruction framework (BrainMLSR), applied to 5T 3D T2-weighted FLAIR images, produced reproducible whole-cortex, signal-defined laminar morphometry and demonstrated coherent patterns across prespecified cortical organizational framework.

neuroscience↗

bioRxiv2026

Genetic analysis and mapping of adult plant stripe rust resistance loci in CIMMYT wheat 'Kijil under Mexican and Chinese field environments

Stripe rust, caused by Puccinia striiformis f. sp. tritici, can cause severe yield losses in wheat (Triticum aestivum L.) during epidemics. Breeding resistant wheat varieties remains the most cost-effective approach to manage this disease; and the identification of new resistance loci is essential for maintaining genetic diversity. The CIMMYT-derived wheat line Kijil was highly resistant to stripe rust in both Mexican and Chinese environments. A population of 153 F recombinant inbred lines (RILs) was derived from a cross between Kijil and the susceptible parent Apav#1. The population was phenotyped for stripe rust resistance across seven environments in two countries and genotyped using a genotyping-by-sequencing (GBS) platform. Inclusive composite interval mapping (ICIM) was uesd to construct a genetic map and identify significant resistance quantitative trait loci (QTLs) using 5,468 polymorphic markers. Mapping revealed the known resistance loci Yr29, Yr30 and QYr.hzau-3AS, along with two novel loci, QYr.hzau-2BS and QYr.hzau-5DL, across both Chinese and Mexican rust environments. Among these, QYr.hzau-2BS accounted for 11.75% to 19.19% of the phenotypic variance. A corresponding KASP marker, KASP_2BS, was developed to facilitate maker-assisted selection. Based on the mapping interval, four candidate genes underlying this locus were predicted. Further analysis revealed that Yr29 showed significant additive effects with other stripe rust resistance genes/loci, and the combination of Yr29, Yr30, and QYr.hzau-2BS reduced disease severity by up to 67.8%. Our findings suggest that Kijil and RILs carrying Yr29, Yr30, and QYr.hzau-2BS can serve as valuable donors for breeding wheat varieties with improved stripe rust resistance. Author summaryStripe rust is an important disease that seriously threatens the yield and quality of wheat. It is crucial to explore new resistant resources and cultivate durable resistant varieties in the current breeding programme. In this study, we analysed the genetic basis of resistance to stripe rust in the wheat line "Kijil", which has broad-spectrum resistance to stripe rust. Through genetic mapping, we identified five quantitative trait loci for stripe rust, including two new resistance loci. A closely linked KASP marker, KASP_2BS, was developed for the QYr.hzau-2BS, which can be used for rapid and accurate screening of resistant plants in early breeding populations. Meanwhile, within this QTL region, we screened four candidate genes based on expression analysis. In addition, it was found that polymerization of QYr.hzau-2BS with known resistance genes, Yr29 and Yr30, significantly enhanced resistance and reduced disease severity to low levels and near immunity. In conclusion, this study provides new genetic resources, practical molecular markers and effective gene polymerization strategies for breeding wheat for stripe rust resistance. Kijil and the lines containing resistance loci have important breeding utilization value.

plant biology↗

bioRxiv2025

Proteomic profiling of Elp1-deficient trigeminal ganglia reveals disruption of neurotrophic and metabolic pathways in a familial dysautonomia mouse model

BackgroundElp1, a subunit of the Elongator complex, is essential for tRNA modification and neuronal development. Mutations in ELP1 underlie familial dysautonomia (FD), a disorder marked by sensory and autonomic neuropathy. While loss of Elp1 disrupts trigeminal ganglion formation and survival, the downstream molecular consequences remain poorly defined. ResultsWe performed quantitative proteomic profiling of trigeminal ganglia from Elp1 conditional knockout (CKO) and control embryos at E13.5. Across 5,650 detected proteins, 25 were significantly upregulated and 26 downregulated in Elp1 CKO embryos. EnrichR analysis revealed enrichment of upregulated proteins in amino acid transport and tRNA aminoacylation pathways, with links to neuromuscular and neuropathic diseases. Downregulated proteins were associated with RNA modification, cholesterol biosynthesis, and synaptic organization. Validation by immunohistochemistry confirmed decreased expression of the neurotrophic receptor Gfra3 and the neuropeptide Galanin, and increased levels of the chromatin regulator Chd1, in Elp1 CKO embryos relative to controls. ConclusionsThese findings demonstrate that Elp1 loss disrupts metabolic, RNA modification, and neurotrophic signaling pathways in the developing trigeminal ganglion. Proteomic analysis thus provides new insight into the molecular consequences of Elp1 deficiency and highlights candidate mechanisms contributing to sensory neuron vulnerability in FD.

developmental biology↗

bioRxiv2025

Structure and iron-transporting mechanism of brain organic cation transporter 1

Brain organic cation transporter 1 (BOCT1), also known as the solute carrier family 22 member 17 (SLC22A17) or the receptor for lipocalin-2 (LCN2), plays critical roles in health and disease. Its deficiency in mice results in early postnatal mortality and severe neurogenesis impairments. Despite its importance in physiology and pathophysiology, BOCT1s structure and transport mechanism remain elusive. Here, we integrate cryo-electron microscopy (cryo-EM), functional assays, biochemical experiments, and molecular dynamics simulations to elucidate the structure, substrate recognition, and transport mechanism of mouse BOCT1 (mBOCT1). The high-resolution cryo-EM structure reveals a distinctive N-terminal domain with a unique folding pattern dominated by a transmembrane loop atop TM6 (TML6), diverging from both known structures of SLC22 transporters and AlphaFold predictions. Notably, mBOCT1 functions as a high-capacity, low-affinity iron transporter independent of LCN2 binding. Iron transport is facilitated by a substrate gating mechanism involving TML6. These findings establish a structural basis for BOCT1s role as an independent iron transporter, enhancing our understanding of the transport mechanisms within major facilitator superfamily (MFS) transporters and providing new insights into brain iron homeostasis.

biophysics↗

bioRxiv2025

Prostate cancer associated fibroblasts have distinct morphomechanical features that are associated with patient outcome

Tumour development and progression reshape the physical properties of the surrounding tumour microenvironment (TME) including its biomechanical traits. This is driven by a prominent cell type in the TME, cancer associated fibroblasts (CAFs), which increases tissue stiffness via extracellular matrix deposition and remodelling. Currently, it is unclear whether there are also physical changes to CAFs at the cellular level and, if so, how they relate to patient outcome. Here we show that CAFs have distinct morphological and biomechanical features from normal fibroblasts. We examined matched, patient-derived CAFs and non-malignant prostate fibroblasts (NPFs) from 35 patients with primary prostate cancer. Morphologically, CAFs had more aligned stress fibres, and larger and more elongated nuclei, based on quantitative image analysis of confocal microscopy images. In addition, single-cell mechanical measurements using real-time deformability cytometry showed that CAFs are larger and stiffer than NPFs. These changes were consistent across patients and validated with atomic force microscopy. A combined morphomechanical score encompassing these features was significantly associated with patient outcome. In transcriptomic analyses, the score was correlated with microtubule dynamics and a myofibroblast phenotype. Importantly, we also demonstrated that morphomechanical features of prostate fibroblasts are modified by approved treatments for prostate cancer, such as docetaxel, and other small molecular inhibitors, such as axitinib. In summary, changes in cellular morphomechanical properties are a consistent feature of CAFs and associated with patient outcome. Moreover, cellular morphomechanical properties can be therapeutically targeted, potentially providing a new strategy for manipulating the TME to control cancer progression.

cancer biology↗

bioRxiv2024

Mutation of GmDMP genes triggers haploid induction in soybean

The development of homozygous lines is a key step in plant breeding and production. Generally, homozygous lines can be obtained through traditional time-consuming way of several generations selfing or through a way of doubled haploid (DH) technology, which has obvious advantages to accelerate breeding. However, no effective haploid production system so far has been established in soybean. Here we show that mutations of the soybean GmDMP1 and GmDMP2 genes can be used to induce haploid with an average haploid induction rate of 0.61%. We also found that 22.9% of soybean haploids can produce seeds through spontaneous chromosome doubling. Those findings laid a solid foundation for establishing DH technology in soybean, which will accelerate soybean breeding.

genetics↗

bioRxiv2023

Self-assembly vascularized human cardiac organoids model cardiac diseases in petri dishes and in mice

In this study, we generated self-assembly cardiac organoids (COs) from human pluripotent stem cells by dual-phase modulation of Wnt/{beta}-catenin pathway, utilizing CHIR99021 and IWR-1-endo. The resulting COs exhibited a diverse array of cardiac-specific cell lineages, cardiac cavity-like structures and demonstrated the capacity of spontaneous beating and vascularization in vitro. We further employed these complex and functional COs to replicate conditions akin to human myocardial infarction and SARS-CoV-2 induced fibrosis. These models accurately captured the pathological characteristics of these diseases, in both in vitro and in vivo settings. In addition, we transplanted the COs into NOD SCID mice and observed that they survived and exhibited ongoing expansion in vivo. Impressively, over a span of 75-day transplantation, these COs not only established blood vessel-like structures but also integrated with the host mices vascular system. It is noteworthy that these COs developed to a size of approximately 8 mm in diameter, slightly surpassing the dimensions of the mouse heart. This innovative research highlighted the potential of our COs as a promising avenue for cardiovascular research and therapeutic exploration.

cell biology↗

bioRxiv2020

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. In consequence, PLANE promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor patient outcomes. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.

cancer biology↗

bioRxiv2018

Polar targeting and assembly of the Legionella Dot/Icm type IV secretion system (T4SS) by T6SS-related components

Legionella pneumophila, the causative agent of Legionnaires disease, survives and replicates inside amoebae and macrophages by injecting a large number of protein effectors into the host cells cytoplasm via the Dot/Icm type IVB secretion system (T4BSS). Previously, we showed that the Dot/Icm T4BSS is localized to both poles of the bacterium and that polar secretion is necessary for the proper targeting of the Legionella containing vacuole (LCV). Here we show that polar targeting of the Dot/Icm core-transmembrane subcomplex (DotC, DotD, DotF, DotG and DotH) is mediated by two Dot/Icm proteins, DotU and IcmF, which are able to localize to the poles of L. pneumophila by themselves. Interestingly, DotU and IcmF are homologs of the T6SS components TssL and TssM, which are part of the T6SS membrane complex (MC). We propose that Legionella co-opted these T6SS components to a novel function that mediates subcellular localization and assembly of this T4SS. Finally, in depth examination of the biogenesis pathway revealed that polar targeting and assembly of the Legionella T4BSS apparatus is mediated by an innovative \"outside-inside\" mechanism.

microbiology↗

bioRxiv2018

Bi-clustering interpretation and prediction of correlation between gene expression and protein abundance

Most organisms transcript and protein level only moderately correlate for various reasons, such as regulation of transcription and protein degradation. Better prediction and understanding the correlation between gene expression and protein abundance has been possible by harnessing the matching RNA/protein datasets produced by modern high-throughput RNA-Seq and mass spectrometry methods. In this work, we have utilized some well-studied matching RNA/protein datasets, and explored for the first time a bi-clustering method to cluster genes that have consistent correlation patterns between gene expression and protein abundance. The clustering results have been interpreted from the perspective of both transcriptomic and proteomic features, which show that mRNA half-life, protein half-life and protein structure in concert significantly affect the correlation of gene expression and protein abundance. With these and other carefully selected features, a prediction model based on individual clusters, called Cluster-based Linear prediction Model (CLM), was built and tested on mouse liver mitochondrial, mouse brainstem mitochondrial, Saccharomyces cerevisiae and Danio rerio datasets. CLM could find genes for which protein abundance can be predicted from mRNA data. In summary, based on bi-clustering, feature selection and CLM model, we have established a new and valuable cluster-based protein abundance prediction method.

bioinformatics↗