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Biology subjects

Ou, H.

Publications and source records attributed to Ou, H..

7 recordsLinked to original sources

Neuroscience-Inspired Deep Learning Brain-Machine Interface Decoder

Brain-machine interfaces (BMIs) aim to decode motor intentions from neural activity to enable direct control of external devices. However, most existing decoders rely on monolithic architectures that fail to capture the distinct neural representations of different joint movement directions, limiting their generalizability. In this work, we propose a Single-Direction CNN-LSTM decoder inspired by motor cortex encoding mechanisms, which separately models extension and flexion dynamics through parallel CNN-LSTM branches. Each branch extracts spatial-temporal features from neural spike data and predicts directional joint variables, which are then combined by subtraction to yield the net angular velocity and torque of upper-limb joints. Using invasive recordings from a macaque during a 2D center-out reaching task, we demonstrate that our decoder achieves comparable performance to a conventional CNN-LSTM when trained on all tasks, while significantly outperforming both CNN-LSTM and linear regression baselines in cross-target generalization scenarios. Moreover, the model can capture physiologically meaningful co-contraction patterns, providing richer insights into motor control. These results suggest that incorporating neuroscience-inspired modular decoding into deep neural architectures enhances robustness and adaptability across tasks, offering a promising pathway for BMI applications in prosthetics and rehabilitation.

bioengineering↗

Analyzing the Naming Conventions of Life Science Data Resources to Inform Human and Computational Findability

This study aimed to evaluate the names of life science data resources and consider the impacts on findability, a core feature of the FAIR (Findability, Accessibility, Interoperability, and Reusability) Principles. Utilizing a previously published list of unique data resources, we identified and validated data resources with both common and full names available (n = 1153). From this set, we analyzed characteristics of resource names to identify if any naming conventions have emerged organically. Additionally, since common names are often used in the absence of a resources full name, we performed a test to evaluate our ability to infer any meaning from common names. Our results highlight suboptimal naming practices and a wide-spread opaqueness in common names, which poses challenges to resource identification and retrieval by both human-and computationally-centric methods. These results are informative for those who establish and promote data resources as well as for those who search for data to use in individual research projects, develop data discovery systems, analyze the scientific literature, or assess research infrastructure. The findings underscore the value of findability in the FAIR Principles and the current efforts to develop infrastructure that supports more efficient communication and global connectedness.

bioinformatics↗

Imputation for Lipidomics and Metabolomics (ImpLiMet): Online optimization and method selection for missing data imputation

MotivationMissing values are often unavoidable in modern high-throughput measurements due to various experimental or analytical reasons. Imputation, the process of replacing missing values in a dataset with estimated values, plays an important role in multivariate and machine learning analyses. Three missingness patterns have been conceptualized: missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). Each describes unique dependencies between the missing and observed data. As a result, the optimal imputation method for each dataset depends on the type of data, the cause of the missing data, and the nature of relationships between the missing and observed data. The challenge is to identify the optimal imputation solution for a given dataset. ResultsImpLiMet: is a user-friendly UI-platform that enables users to impute missing data using eight different methods. For the users dataset, ImpLiMet can suggest the optimal imputation solution through a grid search-based investigation of the error rate for imputation across three missingness data simulations. The effect of imputation can be visually assessed by histogram, kurtosis and skewness analyses, as well as principal component analysis (PCA) comparing the impact of the chosen imputation method on the distribution and overall behaviour of the data. Availability and implementationImpLiMet is freely available at https://complimet.ca/shiny/implimet/ with software accessible at https://github.com/complimet/ImpLiMet Contactsteffanyann.bennett@uottawa.ca and miroslava.cuperlovic-culf@nrc-cnrc.gca. Supplementary informationSupplementary data are available at Bioinformatics Advances online.

bioinformatics↗

Two subtypes of GTPase-activating proteins coordinate tip growth and cell size regulation in Physcomitrium patens

The establishment of cell polarity is a prerequisite for many developmental processes. However, how it is achieved during tip growth in plants remains elusive. Here, we show that the RHO OF PLANTs (ROPs), ROP GUANINE NUCLEOTIDE EXCHANGE FACTORs (RopGEFs), and ROP GTPASE-ACTIVATING PROTEINs (RopGAPs) assemble into membrane domains in tip-growing cells of the moss Physcomitrium patens. The confinement of membrane domains requires redundant global inactivation of ROPs by PpRopGAPs and the PLECKSTRIN HOMOLOGY (PH) domain-containing RenGAP PpREN. Unexpectedly, PpRopGAPs and PpREN exert opposing effects on domain size and cell width upon overexpression. Biochemical and functional analyses indicate that PpRopGAPs are recruited to the membrane by active ROPs to restrict domain size through clustering, whereas PpREN rapidly inactivates ROPs and inhibits PpRopGAP-induced clustering. We propose that the activity- and clustering-based domain organization by RopGAPs and RenGAPs is a general mechanism for coordinating polarized cell growth and cell size regulation in plants. SignificanceUsing the moss Physcomitrium patens, we show that PpRopGAPs and PpRenGAP redundantly regulate tip growth by inactivating ROP GTPases and influencing their membrane organization. They display distinct GAP activities and binding capacities to ROPs and could oppositely regulate cell width when overexpressed. We propose that tip growth and cell size regulation are coordinated by two subtypes of GTPase-activating proteins that act together to maintain an optimal amount of active ROPs but reversely regulate the membrane clustering of ROPs. The involvement of functionally diverged GAPs in modulating ROP activity and localization may represent a general mechanism for cell morphology regulation in plants.

plant biology↗

Interleukin-16/STAT6 recruits CBP/p300 to upregulate TIMP-3 and promote atherosclerotic plaque stability

BackgroundAtherosclerotic plaque rupture increases the risk of ischemic heart disease and stroke and commonly causes sudden death. High levels of circulating or intraplaque interleukin 16 (IL-16) are clinically associated with a reduced incidence of cardiovascular events. Here, we investigated the effects of IL-16 on plaque phenotypic modification and identified the molecules involved in smooth muscle cells (SMCs). MethodsWe deleted IL-16 in ApoE-/- mice to generate IL16-/-ApoE-/- mice, and the double mutant was used for plaque phenotype analysis after a 24-week high-fat diet. RNA sequencing was performed to identify the changes in cellular processes and molecule expression in response to IL-16 defects. Affinity purification-mass spectrometry was used to identify the STAT6 binding protein. Bone marrow transplantation was used to investigate the effects of hematopoietic IL-16 deficiency or reconstitution on plaque stability. ResultsIL-16 deficiency reduced collagen deposition and increased the necrotic core area in the plaques of the brachiocephalic artery and aortic root lesions. Intraplaque TIMP-3 levels were found to be decreased in association with an increase in the proteolytic activity of MMPsinIL16-/-ApoE-/- mice. Next, we demonstrated that IL-16 activates the CD4/JAK2/STAT6 pathway and that STAT6 directly binds the TIMP-3 promoter in SMCs. Furthermore, IL-16 treatment increased the interaction of cAMP-response element binding protein (CBP)/p300 with STAT6, which promoted STAT6 acetylation and increased histone H3 acetylation in the TIMP-3 promoter. Inhibition of CBP/p300 resulted in decreased acetylation of STAT6 and TIMP-3 promoter histone H3 and TIMP-3 expression, suggesting a requirement for CBP/p300 as a coactivator. Finally, we found that hematopoietic-derived IL-16 from ApoE-/- mice or overexpression of TIMP-3 successfully attenuated plaque instability in IL16-/-ApoE-/- mice. ConclusionsIL-6 upregulates TIMP-3 expression and remodels the intraplaque extracellular matrix toward a stable phenotype, suggesting IL-16 as a potential target for intervening in atherosclerosis at later stages.

pathology↗

Potent in vitro Neutralization of SARS-CoV-2 by Hetero-bivalent Alpaca Nanobodies Targeting the Spike Receptor-Binding Domain

Cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain (RBD) of the viral Spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). As such, RBD has become the major target for vaccine development, while RBD-specific antibodies are pursued as therapeutics. Here, we report the development and characterization of SARS-CoV-2 RBD-specific VHH/nanobody (Nb) from immunized alpacas. Seven RBD-specific Nbs with high stability were identified using phage display. They bind to SARS-CoV-2 RBD with affinity KD ranging from 2.6 to 113 nM, and six of them can block RBD-ACE2 interaction. The fusion of the Nbs with IgG1 Fc resulted in homodimers with greatly improved RBD-binding affinities (KD ranging from 72.7 pM to 4.5 nM) and nanomolar RBD-ACE2 blocking abilities. Furthermore, fusion of two Nbs with non-overlapping epitopes resulted in hetero-bivalent Nbs, namely aRBD-2-5 and aRBD-2-7, with significantly higher RBD binding affinities (KD of 59.2 pM and 0.25 nM) and greatly enhanced SARS-CoV-2 neutralizing potency. The 50% neutralization dose (ND50) of aRBD-2-5 and aRBD-2-7 was 1.22 ng/mL ([~]0.043 nM) and 3.18 ng/mL ([~]0.111 nM), respectively. These high-affinity SARS-CoV-2 blocking Nbs could be further developed into therapeutics as well as diagnosis reagents for COVID-19. ImportanceTo date, SARS-CoV-2 has caused tremendous loss of human life and economic output worldwide. Although a few COVID-19 vaccines have been approved in several countries, the development of effective therapeutics including SARS-CoV-2 targeting antibodies remains critical. Due to their small size (13-15 kDa), highly solubility and stability, Nbs are particularly well suited for pulmonary delivery and more amenable to engineer into multi-valent formats, compared to the conventional antibody. Here, we report a serial of new anti-SARS-CoV-2 Nbs isolated from immunized alpaca and two engineered hetero-bivalent Nbs. These potent neutralizing Nbs showed promise as potential therapeutics against COVID-19.

immunology↗

Transcriptome Profile Analysis of Twisted Leaf Disease Response in Susceptible Sugarcane with Narenga porphyrocoma Genetic Background

Sugarcane is an important industrial crop with a high sugar yield that has become a leading energy crop worldwide. It is widely cultivated in tropical and subtropical regions. Various diseases beset the cultivation of sugarcane. The molecular study of disease resistance in sugarcane is limited by its complicated genome. In our study, RNA-seq was employed to detect the mechanism of twisted leaf disease tolerance in modern cultivar sugarcane, which derived from Narenga porphyrocoma. We completed high-throughput transcriptomic sequencing of 12 samples, including three stages of a susceptible (NSBC1_T \"H3-8\") and an unsusceptible cultivar (NSBC1_CK \"H-19\") with two biological repeats, respectively. Using the Saccharum spontaneum genome as reference, the average mapping ratio of the clean data was over 70%. Among the differentially expressed genes between H3-8 and H3-19, we focused on the analysis of hormone pathways and resistance (R) genes. The results showed that twisted leaf disease triggers hormone networks and around 40% of R genes conditioned lower expression in the susceptible cultivar. One of the possible reasons for H3-8 being susceptible to twisted leaf disease might be the null/retarded response of R genes, especially in pre-onset stage (46% down-regulated) of pathogens infection.

genomics↗