Biology subjects

Liu, M. H.

Publications and source records attributed to Liu, M. H..

6 recordsLinked to original sources

bioRxiv2025

Assessing Generative Model Coverage of Protein Structures with SHAPES

Recent advances in generative modeling enable efficient sampling of protein structures, but their tendency to optimize for designability imposes a bias toward idealized structures at the expense of loops and other complex structural motifs critical for function. We introduce SHAPES (Structural and Hierarchical Assessment of Proteins with Embedding Similarity) to evaluate five state-of-the-art generative models of protein structures. Using structural embeddings across multiple structural hierarchies, ranging from local geometries to global protein architectures, we reveal substantial undersampling of the observed protein structure space by these models. We use Frechet Protein Distance (FPD) to quantify distributional coverage. Different models are distinct in their coverage behavior across different sampling noise scales and temperatures; the frequency of TERtiary Motifs (TERMs) further supports the observations. More robust sequence design and structure prediction methods are likely crucial in guiding the development of models with improved coverage of the designable protein space.

bioengineering↗

bioRxiv2024

Construction of Discrete Element Model of Different Moisture Hygroscopic Fertilizer Particles and Fertilizer Discharging Verification

The hygroscopic fertilizer particles were characterized based on discrete element simulation, and its accuracy was verified by the simulation of fertilizer discharge. Firstly, the repose angle of the fertilizer particles served as the key metric for assessment. A mathematical model characterizing the relationship between fertilizer moisture content and the repose angle was established, R2=0.9935; and a mathematical representation of the repose angle for fertilizer moisture content was established, R2=0.9933. Then, the moisture absorbing fertilizer particles was developed utilizing the integrated Hertz Mindlin with JKR model within EDEM system to account for particle adhesion; A robust correlation model between the repose angle of hygroscopic fertilizers and the discrete element method was established, p <0.0001; Finally, a correlation model between moisture content and significant parameters within the discrete element method was established, drawing upon the models for moisture content repose angle and repose angle discrete element parameters. The moisture-absorbing fertilizer particles model at moisture contents of 2% and 6% were resolved, with a relative error of the repose angle not exceeding 1.42% and a single circle fertilizer discharge error below 8.32%. The results show that the moisture content discrete element significant parameter correlation model can reliably and precisely forecast the discrete element parameters of various moisture content hygroscopic fertilizers. The hygroscopic fertilizer particle model can represent surface interaction characteristics of hygroscopic fertilizer granules. which has guiding significance for the design of precision fertilizer discharge technology device.

physiology↗

bioRxiv2024

Rapid adaptive evolution of microbial thermal performance curves

Microbial respiration is a key biotic driver of climate change. Warming boosts microbial population growth, which increases biomass and respiration. This feedback might be disrupted by adaptation in thermal performance curves (TPCs) -whose shape describes how temperature drives growth. In this study, we uncover substantial genetic variation (G) in microbial intrinsic population growth rates (r), demonstrate a causal link between G variation in r and G variation in TPC shape, and show how this variation constrains r-TPC shape evolution along specific evolutionary paths across temperatures. We also uncover Gene-by-Environment (G x E) variation in r, which results in specific signatures in TPC shape and predictable temperature-dependent rapid TPC evolution but also lower G, which could reduce future evolutionary potential. Overall, we show how temperature-dependent evolution in a linchpin of global ecosystem function--microbial TPC shape--is determined by a combination of heritable and non-heritable variation in intrinsic growth rates.

ecology↗

bioRxiv2023

Unbiased phosphoproteomics analysis unveils modulation of insulin signaling by extramitotic CDK1 kinase activity in human myotubes

Sensitivity and plasticity of insulin signaling and glucose uptake in skeletal muscle depends on determinants such as genetic variation and obesity. We collected muscle biopsies and isolated myoblasts from a multi-ethnic cohort of lean South Asians (N=10), lean Chinese (N=10), and obese Chinese (N=10), and analysed the proteome and phosphoproteome dynamics in terminally differentiated myotubes after a low-dose insulin stimulation (10nM at 0, 5, 30 min). The myotubes initially responded with increased abundance and phosphorylation level changes along the PI3K/AKT/mTOR axis, decreased abundance of translation initiation factors, and increased phosphorylation levels on proteins involved in mRNA processing at 5 min. After the acute response, protein abundance returned to baseline at 30 min, while phosphorylation changes persisted in proteins including AKT, RPS6 and AS160 (TBC1D4). A joint kinase-substrate statistical analysis revealed that protein abundance changes of AKT, PAK1 and CDK1 showed concordant phosphorylation changes in their respective substrates upon insulin stimulation. We also observed increased phosphorylation of some substrates uniquely in each group, particularly the substrates of CDKs showing stronger changes in South Asians than in Chinese. Pharmacological inhibition and siRNA knockdown of CDK1, a non-myogenic kinase, in terminally differentiated myotubes reduced glucose uptake and desensitized several phosphorylation-mediated signaling on protein translation initiation factors, IRS1, and AS160. Our data suggest that basal extramitotic activity of CDK1 is required for PI3K/AKT/mTORC1 signaling cascade and glucose uptake in insulin-stimulated myotubes. The data also provide a rich resource for studying the role of other kinases in the mechanism of insulin resistance in human myotubes.

physiology↗

bioRxiv2023

Single-strand mismatch and damage patterns revealed by single-molecule DNA sequencing

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other genetic diseases1-4. Almost all of these mosaic mutations begin as nucleotide mismatches or damage in only one of the two strands of the DNA prior to becoming double-strand mutations if unrepaired or misrepaired5. However, current DNA sequencing technologies cannot resolve these initial single-strand events. Here, we developed a single-molecule, long-read sequencing method that achieves single-molecule fidelity for single-base substitutions when present in either one or both strands of the DNA. It also detects single-strand cytosine deamination events, a common type of DNA damage. We profiled 110 samples from diverse tissues, including from individuals with cancer-predisposition syndromes, and define the first single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumors deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples deficient in only polymerase proofreading. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. Since the double-strand DNA mutations interrogated by prior studies are only the endpoint of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable new studies of how mutations arise in a variety of contexts, especially in cancer and aging.

genomics↗

bioRxiv2019

Tongue Kinematics. Cortex-dependent corrections as the mouse tongue reaches for, and misses, targets

AbstractPrecise tongue control is necessary for drinking, eating, and vocalizing1, 2. Yet because tongue movements are fast and difficult to resolve, neural control of lingual kinematics remains poorly understood. Here we combine kilohertz frame-rate imaging and a deep learning based neural network to resolve 3D tongue kinematics in mice drinking from a water spout. Successful licks required previously unobserved corrective submovements (CSMs) which, like online corrections during primate reaches3-10, occurred after the tongue missed unseen, distant, or displaced targets. Photoinhibition of anterolateral motor cortex (ALM) impaired online corrections, resulting in hypometric licks that missed the spout. ALM neural activity reflected upcoming, ongoing, and past CSMs, as well as errors in predicted spout contact. Though less than a tenth of a second in duration, a single mouse lick exhibits hallmarks of online motor control associated with a primate reach, including cortex-dependent corrections after misses.

neuroscience↗