Biology subjects

Li, G.

Publications and source records attributed to Li, G..

At least 217 records · Page 12Linked to original sources

bioRxiv2024

A chromosome-level genome assembly of the cabbage aphid Brevicoryne brassicae

The cabbage aphid, Brevicoryne brassicae, is a major pest on Brassicaceae plants, and causes significant yield losses annually. However, lacking genomic resources hinders the progress in understanding this pest at the level of molecular biology. Here, a high-quality, chromosomal-level genome was assembled for B. brassicae based on PacBio HIFI long-read sequencing and Hi-C data. The final assembled size was 429.99 Mb with a scaffold N50 of 93.31 Mb. Importantly, 96.2% of the assembled sequences were anchored to eight chromosomes. The genome recovered 98.50% of BUSCO genes and 92.30% of CEGMA genes, supporting the high level of completeness. By combining high-coverage transcriptome data, a total of 22,671 protein-coding genes and 3,594 lncRNA genes were annotated. Preliminary comparative genomic analyses were focused on genes related to host colonisation, such as chemosensory- and detoxification-related genes, as well as those encoding putative protein effectors and cross-kingdom lncRNA Ya. In summary, our study presents a contiguous and complete genome for B. brassicae that will benefit our understanding of the biology of it and other aphids.

genomics↗

bioRxiv2024

SCIITensor: A tensor decomposition based algorithm to construct actionable TME modules with spatially resolved intercellular communications

Advanced spatial transcriptomics (ST) technology has paved the way for elucidating the spatial architecture of the tumor microenvironment (TME) from multiple perspectives. However, available tools only focus on the static molecular and cellular composition of the TME when analyzing the high-throughput ST data, neglecting to uncover the in-depth spatial co-variation of intercellular communications arising from heterogeneous spatial TMEs. Here, we introduce SCIITensor, which decomposes TME modules from the perspective of spatially resolved intercellular communication by spatially quantifying the cellular and molecular interaction intensities between proximal cells within each domain. It then constructs a three-dimensional matrix, formulating the task as a matrix decomposition problem, and identifies biologically relevant spatial interactions and TME patterns using Non-Negative Tucker Decomposition (NTD). We evaluated the performance of SCIITensor on liver cancer datasets obtained from multiple ST platforms. At the research setting of a single-sample investigation, SCIITensor precisely identified a functional TME module indicating a tumor boundary structure specific domain with co-variant interaction contexts, which were involved in construction of immunosuppressive TME. Moreover, we also proved that SCIITensor was able to construct TME meta-modules across multiple samples and to further identify an immune-infiltration associated and sample-common meta-module. We demonstrate that SCIITensor is applicable for dissecting TME modules from a new perspective by constructing spatial interaction contexts using ST datasets of individual and multiple samples, providing new insights into tumor research and potential therapeutic targets.

bioinformatics↗

bioRxiv2024

Heat stress and recovery induce transcriptomic changes in lactogenic bovine mammary epithelial (MAC-T) cells

Heat stress (HS) in cattle significantly challenges the dairy industry by reducing milk production. However, the molecular mechanism behind mammary gland responses to HS and recovery remains poorly understood. This study aimed to determine the transcriptomic changes in lactogenic bovine mammary epithelial (MAC-T) cells after HS and post-HS recovery. Six culture conditions were analyzed: MAC-T cells cultured in basal medium, cells in lactogenic medium to induce differentiation, differentiated cells at standard temperature (37) or HS (42) for 1 hour. HS cells were collected after incubation at 37 for either 2 or 6 hours to examine the extent of recovery. A total of 1,668 differentially expressed genes (DEGs) were identified. Differentiated cells expressed genes associated with milk lipid synthesis, indicating lactogenic potential. HS suppressed genes involved in cellular differentiation and activated heat shock protein genes. Several transcription factors were identified as potential regulators of HS response. During recovery, chaperon-mediated protein folding genes remained elevated. Apoptosis regulation genes were induced at 2 hours, and cellular homeostasis regulation genes were enriched at 6 hours. Overall, these findings provide a foundation for the molecular mechanisms involved in HS and recovery in cattle.

genomics↗

bioRxiv2024

mosGraphGen: a novel tool to generate multi-omic signaling graphs to facilitate integrative and interpretable graph AI model development

Multi-omics data, i.e., genomics, epigenomics, transcriptomics, proteomics, characterize cellular complex signaling systems from multi-level and multi-view and provide a holistic view of complex cellular signaling pathways. However, it remains challenging to integrate and interpret multi-omics data for mining key disease targets and signaling pathways. Graph AI models have been widely used to analyze graph-structure datasets, and are ideal for integrative multi-omics data analysis because they can naturally integrate and represent multi-omics data as a biologically meaningful multi-level signaling graph and interpret multi-omics data via graph node and edge ranking analysis. However, it is non-trivial for graph-AI model developers to pre-analyze multi-omics data and convert the data into biologically meaningful graphs, which can be directly fed into graph-AI models. To resolve this challenge, we developed mosGraphGen (multi-omics signaling graph generator), generating Multi-omics Signaling graphs (mos-graph) of individual samples by mapping multi-omics data onto a biologically meaningful multi-level background signaling network with data normalization by aggregating measurements and aligning to the reference genome. With mosGraphGen, AI model developers can directly apply and evaluate their models using these mos-graphs. In the results, mosGraphGen was used and illustrated using two widely used multi-omics datasets of TCGA and Alzheimers disease (AD) samples. The code of mosGraphGen is open-source and publicly available via GitHub: https://github.com/FuhaiLiAiLab/mosGraphGen

systems biology↗

bioRxiv2024

Endothelial cannabinoid CB1 receptor deficiency reduces arterial inflammation and lipid uptake in response to atheroprone shear stress

BackgroundPeripherally restricted cannabinoid CB1 receptor antagonists without central side effects hold promise for treating metabolic disorders including diabetes and obesity. In atherosclerosis, the specific effects of peripheral CB1 signaling in vascular endothelial cells (ECs) remain incompletely understood. Methods and resultsEndothelial expression of the CB1 encoding gene CNR1 was detectable in human plaque single-cell RNA sequencing data. In situ hybridization of Cnr1 in murine aortas revealed a significantly increased endothelial expression within atheroprone compared to atheroresistant regions. In vitro, CNR1 was upregulated by oscillatory shear stress (OSS) in human aortic endothelial cells (HAoECs). Endothelial CB1 deficiency (Cnr1EC-KO) in female mice on atherogenic background resulted in pronounced endothelial phenotypic changes, with reduced vascular inflammation and permeability. This resulted in attenuated plaque development with reduced lipid content in female mice, while reduced white and brown adipose tissue mass and liver steatosis were observed in both males and females. Ex vivo imaging of carotid arteries via two-photon microscopy revealed less labeled low density lipoprotein (Dil-LDL) uptake in Cnr1EC-KO. This was accompanied by a significant reduction of aortic endothelial caveolin-1 (CAV1) expression, a key structural protein involved in lipid transcytosis, in female Cnr1EC-KO mice. In vitro, pharmacological blocking with CB1 antagonist AM281 reproduced the inhibition of CAV1 expression and Dil-LDL uptake in response to atheroprone OSS in HAoECs, which was dependent on cAMP-mediated PKA activation. Conversely, the CB1 agonist ACEA increased Dil-LDL uptake and CAV1 expression in HAoECs. Finally, treatment of atherosclerotic mice with the peripheral CB1 antagonist JD-5037 reduced plaque progression, CAV1 and endothelial adhesion molecule expression in female mice. ConclusionsThese results confirm an essential role of endothelial CB1 to the pathogenesis of atherosclerosis. Peripheral CB1 antagonists may hold promise as an effective therapeutic strategy for treating atherosclerosis and related metabolic disorders. NOVELTY AND SIGNIFICANCEWhat is known? O_LIEnhanced endocannabinoid-cannabinoid CB1 receptor signaling has been implicated in metabolic disorders, atherosclerosis, and hypertension, but the cell-specific role of endothelial CB1 in atherosclerosis is not well understood. C_LIO_LIGlobal CB1 antagonists improve metabolic function and inhibit atherosclerotic plaque development in mouse models, but have failed in the clinic due to centrally mediated psychiatric side effects. C_LI What is new? O_LIBased on human single-cell RNA sequencing data, CB1 is expressed in human plaque ECs. C_LIO_LIUsing transgenic mouse models and human primary aortic endothelial cells, we provide evidence for a key role of CB1 in endothelial shear stress response, inflammatory gene expression, and LDL uptake. C_LIO_LIThe underlying signaling pathway of CB1-induced endothelial LDL uptake involves a cAMP-PKA-dependent regulation of caveolin 1 (CAV1) expression, a structural protein of the shear stress sensitive signaling domains of the plasma membrane. C_LIO_LIBy limiting endothelial CAV1 and VCAM1 expression, peripherally restricted CB1 antagonists confer atheroprotection in mice. C_LI Our findings reveal that endothelial CB1 expression is induced by atheroprone shear stress responses and contributes to impaired vascular barrier function, inflammation, and lipid uptake, thereby promoting atherosclerotic lesion formation and progression. By elucidating the transcriptomic pathways regulated by endothelial CB1 and its broad influence on lipid uptake and metabolism in arteries, liver, and brown and white adipose tissue, our study provides insights into novel pathways and potential interventions for the treatment of atherosclerosis and metabolic disorders. The use of peripherally restricted CB1 antagonists that specifically target vascular inflammation and tissue lipid storage could be a complementary and safe therapeutic avenue to treat cardiovascular and metabolic disease comorbidities without altering CB1 signaling in the brain.

immunology↗

bioRxiv2024

ADAPT: Analysis of Microbiome Differential Abundance by Pooling Tobit Models

Microbiome differential abundance analysis remains a challenging problem despite multiple methods proposed in the literature. The excessive zeros and compositionality of metagenomics data are two main challenges for differential abundance analysis. We propose a novel method called "analysis of differential abundance by pooling Tobit models" (ADAPT) to overcome these two challenges. ADAPT uniquely treats zero counts as left-censored observations to facilitate computation and enhance interpretation. ADAPT also encompasses a theoretically justified way of selecting non-differentially abundant microbiome taxa as a reference for hypothesis testing. We generate synthetic data using independent simulation frameworks to show that ADAPT has more consistent false discovery rate control and higher statistical power than competitors. We use ADAPT to analyze 16S rRNA sequencing of saliva samples and shotgun metagenomics sequencing of plaque samples collected from infants in the COHRA2 study. The results provide novel insights into the association between the oral microbiome and early childhood dental caries.

bioinformatics↗

bioRxiv2024

Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control

Inhibitory control is a critical executive function that allows animals to suppress their impulsive behavior in order to achieve certain goals or avoid punishment. We investigated norepinephrine (NE) and acetylcholine (ACh) dynamics and population neuronal activity in the prefrontal cortex (PFC) during inhibitory control. Using fluorescent sensors to measure extracellular levels of NE and ACh, we simultaneously recorded prefrontal NE and ACh dynamics in mice performing inhibitory control tasks. The prefrontal NE and ACh signals exhibited strong coherence at 0.4-0.8 Hz. Although inhibition of locus coeruleus (LC) neurons projecting to the PFC impaired inhibitory control, inhibiting LC neurons projecting to the basal forebrain (BF) caused a more profound impairment, despite an approximately 30% overlap between LC neurons projecting to the PFC and BF, as revealed by our tracing studies. The inhibition of LC neurons projecting to the BF did not diminish the difference in prefrontal NE/ACh signals between successful and failed trials; instead, it abolished the difference in NE-ACh phase synchrony between successful and failed trials, indicating that NE-ACh phase synchrony is a task-relevant neuromodulatory feature. Chemogenetic inhibition of cholinergic neurons that project to the LC region did not impair inhibitory control, nor did it abolish the difference in NE-ACh phase synchrony between successful or failed trials, further confirming the relevance of NE-ACh phase synchrony to inhibitory control. To understand the possible effect of NE-ACh synchrony on prefrontal population activity, we employed Neuropixels to record from the PFC during inhibitory control. The inhibition of LC neurons projecting to the BF not only reduced the number of prefrontal neurons encoding inhibitory control, but also disrupted population firing patterns representing inhibitory control, as revealed by a demixed principal component (dPCA) analysis. Taken together, these findings suggest that the LC modulates inhibitory control through its collective effect with cholinergic systems on population activity in the prefrontal cortex. Our results further indicate that NE-ACh phase synchrony is a critical neuromodulatory feature with important implications for cognitive control.

neuroscience↗

bioRxiv2024

Magnetically Steered Cell Therapy For Functional Restoration Of Intraocular Pressure Control In Open-Angle Glaucoma

Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for nine months after a single dose of only 1500 magnetically-steered hAMSCs, explained by increased outflow through the conventional pathway and associated with an higher TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle three weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically-steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma. One Sentence SummaryA novel magnetic cell therapy provided effective intraocular pressure reduction in a mouse model, motivating future translational studies.

bioengineering↗

bioRxiv2024

Recognition of RNA secondary structures with a programmable peptide nucleic acid-based platform

RNA secondary structures comprise double-stranded (ds) and single-stranded (ss) regions. Antisense peptide nucleic acids (asPNAs) enable the targeting of ssRNAs and weakly formed dsRNAs. Nucleobase-modified dsRNA-binding PNAs (dbPNAs) allow for targeting of relatively stable dsRNAs. A programmable RNA structure-specific targeting strategy is needed for simultaneous recognition of dsRNAs and ssRNAs. Here, we report on combining dbPNAs and asPNAs (designated as daPNAs) for the targeting of dsRNA-ssRNA junctions. Our binding and modeling data suggest that combining traditional asPNA (with a 4-letter code: T, C, A, and G) and dbPNA (with a 4-letter code: T or s2U, L, Q, and E) scaffolds facilitates RNA structure-specific tight binding (nM to M) under physiologically-relevant conditions. We further applied our daPNAs in substrate specific inhibition of Dicer acting on pre-miR-198 in a cell-free assay and regulating ribosomal frameshifting induced by model hairpins in both cell-free and cell culture assays. daPNAs would be a useful platform for developing chemical probes and therapeutic ligands targeting RNA. HighlightO_LIWe demonstrated that sequence- and structure-specific targeting of RNA can be facilitated by nucleobase-modified dsRNA-binding PNAs (dbPNAs) platform in combination with antisense PNAs (asPNAs). We name the novel PNAs as daPNAs. C_LIO_LIdaPNAs can be used in a programmable way for targeting RNAs by formation of a short triplex next to a short duplex at a dsRNA-ssRNA junction. C_LIO_LIWe applied our daPNAs in substrate specific inhibition of Dicer acting on pre-miR-198 in a cell-free assay and regulating ribosomal frameshifting induced by model hairpins in both cell-free and cell culture assays. C_LIO_LIThe daPNAs platform would serve as useful junction-specific molecular glues for the targeting of many biologically important RNA structures in transcriptomes. C_LI

biochemistry↗

bioRxiv2024

StereoMM: A Graph Fusion Model for Integrating Spatial Transcriptomic Data and Pathological Images

Spatially resolved omics technologies generating multimodal and high-throughput data lead to the urgent need for advanced analysis to allow the biological discoveries by comprehensively utilizing information from multi-omics data. The H&E image and spatial transcriptomic data indicate abundant features which are different and complementary to each other. AI algorithms can perform nonlinear analysis on these aligned or unaligned complex datasets to decode tumoral heterogeneity for detecting functional domain. However,the interpretability of AI-generated outcomes for human experts is a problem hindering application of multi-modal analysis in clinic. We presented a machine learning based toolchain called StereoMM, which is a graph fusion model that can integrate gene expression, histological images, and spatial location. StereoMM firstly performs information interaction on transcriptomic and imaging features through the attention module, guaranteeing explanations for its decision-making processes. The interactive features are input into the graph autoencoder together with the graph of spatial position, so that multimodal features are fused in a self-supervised manner. Here, StereoMM was subjected to mouse brain tissue, demonstrating its capability to discern fine tissue architecture, while highlighting its advantage in computational speed. Utilizing data from Stereo-seq of human lung adenosquamous carcinoma and 10X Visium of human breast cancer, we showed its superior performance in spatial domain recognition over competing software and its ability to reveal tumor heterogeneity. The fusion approach for imaging and gene expression data within StereoMM aids in the more accurate identification of domains, unveils critical molecular features, and elucidates the connections between different domains, thereby laying the groundwork for downstream analysis.

bioinformatics↗

bioRxiv2024

Dopamine and acetylcholine correlations in the nucleus accumbens depend on behavioral task states

Dopamine in the nucleus accumbens ramps up as animals approach desired goals. These ramps have received intense scrutiny because they seem to violate long-held hypotheses on dopamine function. Furthermore, it has been proposed that they are driven by local acetylcholine release, i.e., that they are mechanistically separate from dopamine signals related to reward prediction errors. Here, we tested this hypothesis by simultaneously recording accumbal dopamine and acetylcholine signals in rats executing a task involving motivated approach. Contrary to recent reports, we found that dopamine ramps were not coincidental with changes in acetylcholine. Instead, we found that acetylcholine could be positively, negatively, or uncorrelated with dopamine depending on whether the task phase was determined by a salient cue, reward prediction error, or active approach, respectively. Our results suggest that accumbal dopamine and acetylcholine are largely independent but may combine to engage different postsynaptic mechanisms depending on the behavioral task states.

neuroscience↗

bioRxiv2024

Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle

Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird-to-cattle transmission episode. The movement of asymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers in virus populations were detected at low frequency that may lead to changes in transmission efficiency and phenotype after evolution in dairy cattle. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations.

microbiology↗

bioRxiv2024

Heterogeneous Cardiac- and Neural Crest-Derived Aortic Smooth Muscle Cells have Similar Transcriptional Changes after TGFβ Signaling Disruption

Smooth muscle cells (SMCs) of cardiac and neural crest origin contribute to the developing proximal aorta and are linked to disease propensity in adults. We analyzed single-cell transcriptomes of SMCs from mature thoracic aortas in mice to determine basal states and changes after disrupting transforming growth factor-{beta} (TGF{beta}) signaling necessary for aortic homeostasis. A minority of Myh11 lineage-marked SMCs differentially expressed genes suggestive of embryological origin. Additional analyses in Nkx2-5 and Wnt1 lineage-marked SMCs derived from cardiac and neural crest progenitors, respectively, showed both lineages contributed to a major common cluster and each lineage to a minor distinct cluster. Common cluster SMCs extended from root to arch, cardiac subset cluster SMCs from root to mid-ascending, while neural crest subset cluster SMCs were restricted to the arch. The neural crest subset cluster had greater expression of a subgroup of TGF{beta}-dependent genes suggesting specific responsiveness or skewed extracellular matrix synthesis. Nonetheless, deletion of TGF{beta} receptors in SMCs resulted in similar transcriptional changes among all clusters, primarily decreased extracellular matrix molecules and modulators of TGF{beta} signaling. Many embryological markers of murine aortic SMCs were not confirmed in adult human aortas. We conclude: (i) there are multiple subtypes of cardiac- and neural crest-derived SMCs with shared or distinctive transcriptional profiles, (ii) neural crest subset SMCs with increased expression of certain TGF{beta}-inducible genes are not spatially linked to the aortic root predisposed to aneurysms from aberrant TGF{beta} signaling, and (iii) loss of TGF{beta} responses after receptor deletion is uniform among SMCs of different embryological origins.

pathology↗

bioRxiv2024

An AI-designed adenine base editor

Adenine base editors (ABEs) allow the efficient programmable conversion of adenine to guanine without causing DNA double strand breaks. Previous ABEs were generated by multiple rounds of directed evolution or derived by rational design based on the evolved ones. Although powerful, these methods search the local space for ABEs optimizations. Artificial intelligence (AI) based methods have the ability to efficiently explore much larger protein space for protein design. But currently there is no AI-designed ABE with wet experimental validation. Here, we demonstrate the first successful AI-designed ABE, which is named ABE10. ABE10 includes an AI-designed adenine deaminase enzyme fused with SpCas9n. The sequence identity between AI-designed enzyme and other publicly accessible variants is as low as 65.3%. ABE10 shows improved editing efficiency compared to current state-of-the-art ABE8 at multiple human genome sites tested. ABE10 also shows low off-target editing rate and reduced cytosine bystander effect. Our work demonstrates new direction for optimization of gene editing tools.

bioengineering↗

bioRxiv2024

Short-Term Disruption of TGFβ Signaling in Adult Mice Renders the Aorta Vulnerable to Hypertension-Induced Dissection

Hypertension and transient increases in blood pressure from extreme exertion are risk factors for aortic dissection in patients with age-related vascular degeneration or inherited connective tissue disorders. Yet, the common experimental model of angiotensin II-induced aortopathy in mice appears independent of high blood pressure as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by co-treatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice 1 week after disruption of TGF{beta} signaling in smooth muscle cells. Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes that was rescued by hydralazine; results were similar with angiotensin II. Changes in regulatory contractile molecule expression were not of pathological significance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically type XVIII, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure cause dissection in aortas rendered vulnerable by inhibition of TGF{beta}-driven extracellular matrix production by smooth muscle cells. A corollary is that medial fibrosis, a frequent feature of medial degeneration, may afford some protection against aortic dissection.

pathology↗

bioRxiv2024

Genetic and anatomical determinants of olfaction in dogs and wild canids

Understanding the anatomical and genetic basis of complex phenotypic traits has long been a challenge for biological research. Domestic dogs offer a compelling model as they demonstrate more phenotypic variation than any other vertebrate species. Dogs have been intensely selected for specific traits and abilities, directly or indirectly, over the past 15,000 years since their initial domestication from the gray wolf. Because olfaction plays a central role in critical tasks, such as the detection of drugs, diseases, and explosives, as well as human rescue, we compared relative olfactory capacity across dog breeds and assessed changes to the canine olfactory system resulting from domestication. We conducted a cross-disciplinary survey of olfactory anatomy, olfactory receptor (OR) gene variation, and OR gene expression in domestic dogs. Through comparisons to their closest wild canid relatives, the gray wolf and coyote, we show that domestic dogs might have lost functional OR genes commensurate with a documented reduction in nasal morphology during domestication. Critically, within domestic dogs alone, we found no genetic or morphological profile shared among functional or genealogical breed groupings, such as scent hounds, that might indicate evidence of any human-directed selection for enhanced olfaction. Instead, our results suggest that superior scent detection dogs likely owe their success to advantageous behavioral traits and training rather than an "olfactory edge" provided by morphology or genes.

evolutionary biology↗

bioRxiv2024

Highly Pathogenic Avian Influenza A (H5N1) clade 2.3.4.4b Virus detected in dairy cattle

The global emergence of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses poses a significant global public health threat. Until March 2024, no outbreaks of this virus clade had occurred in domestic cattle. We genetically characterize HPAI viruses from dairy cattle showing an abrupt drop in milk production. They share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. B3.13 viruses underwent two reassortment events since 2023 and exhibit critical mutations in HA, M1, and NS genes but lack critical mutations in PB2 and PB1 genes, which enhance virulence or adaptation to mammals. The PB2 E627K mutation in a human case underscores the potential for rapid evolution post-infection, highlighting the need for continued surveillance to monitor public health threats.

microbiology↗

bioRxiv2024

In vivo evaluation of thermally drawn biodegradable optical fibers as brain neural interfaces

Optical fiber technology has a critical role in modern neuroscience towards understanding the complex neuronal dynamics within the nervous system. In this study, we manufactured amorphous thermally drawn poly D, L-lactic acid (PDLLA) optical fibers in different diameters. These fibers were then implanted into the lateral posterior (LP) region of the mouse brain for 4 months, allowing us to assess their degradation characteristics. The gradual dissolution of the implanted PDLLA optical fibers in the brain was confirmed by optical microscope and scanning electron microscopy (SEM), molecular weight measurements, and light transmission spectroscopy. The results indicate that the degradation rate was mainly pronounced during the first week. Degradation after 4 months resulted in the formation of micropores on the surface of the implanted fiber within the gray matter region of the brain. Moreover, the current PDLLA optical fiber implant offers efficient light transmission in the short-wavelength near-infrared (SW-NIR) range. SW-NIR enables deeper tissue penetration and reduced light scattering, making it ideal for optogenetics and functional imaging with therapeutic potential in neurological disorders. We believe that the provided PDLLA optical fiber in this study constitutes a promising candidate for the development of next-generation biocompatible, soft, and biodegradable bi-directional neural interfaces

bioengineering↗