Biology subjects

Tao, Y.

Publications and source records attributed to Tao, Y..

At least 109 records · Page 6Linked to original sources

bioRxiv2021

OsciDrop: A versatile on-demand droplet generator

Droplet microfluidics is a powerful tool in many biological and clinical applications. Microfluidic chips, such as flow-focusing droplet generators, have been extensively used to high-throughput encapsulate reactions with single-cell and single-molecular resolutions. However, microfabrication is expensive and precision-demanding, preventing it from widespread use in biomedical laboratories and clinical facilities. Herein, we present a versatile chip-free droplet generator, OsciDrop, for generating size-tunable droplets on demand, with high uniformity. OsciDrop segments the fluid flowing out of the orifice of a micropipette tip into droplets by oscillating the tip under the surface of a continuous oil phase. We investigated the factors influencing droplet generation by examining several control parameters. Results show that flow rate, oscillating amplitude, and frequency are key parameters to generate monodisperse droplets on demand. And OsciDrop is able to generate droplets in a flexible and repeatable manner. Importantly, using an optimal asymmetrical oscillation waveform, OsciDrop can controllably generate monodisperse droplets spanning a wide volume range (200 pL - 2 L). To demonstrate the ability of OsciDrop for chip-free droplet assays, a digital loop-mediated isothermal amplification (dLAMP) was performed to absolutely quantify African swine fever virus (ASFV). The OsciDrop method opens up a feasible and versatile avenue to perform droplet-based assays, exhibiting full accessibility for chip-free droplet microfluidics.

bioengineering↗

bioRxiv2021

The Copper Responsive Transcription Factor SPL7 Represses Key Abscisic Acid Biosynthetic Genes to Balance Growth and Drought Tolerance

Plants adapt to adverse environments by turning on defense against abiotic stresses, which is mainly orchestrated by the phytohormone abscisic acid (ABA). But how ABA homeostasis is modulated to balance growth and stress responses is still largely unknown. Here we report that prior treatment of Arabidopsis seedling with high copper retardates growth but enhances draught tolerance at later stages by modulating ABA accumulation. Subsequent genetic, physiological, transcriptomic, and molecular investigations revealed that the copper responsive transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 7 (SPL7) is a strong regulator of ABA accumulation. We showed that SPL7 is destabilized by high copper and consistently suppresses genes encoding three key oxygenases in the ABA biosynthetic pathway of land plants via binding to the GTAC copper response motifs in their promoters. These results revealed a new mechanism whereby copper availability, inversely reflected by SPL7 abundance, modulates de novo ABA biosynthesis to balance growth and drought tolerance. One-sentence summaryHigh copper availability represses SPL7, releasing its suppression on key ABA biosynthetic genes and leading to increased ABA accumulation that inhibits growth but enhances drought tolerance.

plant biology↗

bioRxiv2021

Integration of embryo-endosperm interaction into a holistic and dynamic picture of seed development using a rice mutant with notched-belly grains

The interaction between the embryo and endosperm affects seed development, an essential process in yield formation in crops such as rice. Signals that communicate between embryo and endosperm are largely unknown. Here we use the notched-belly (NB) mutant with impaired communication between embryo and endosperm to evaluate 1) the impact of embryo on developmental staging of the endosperm; 2) signaling pathways emanating from the embryo that regulate endosperm development. Hierachical clustering of mRNA datasets from embryo and endosperm samples collected through development in NB and wild type showed a delaying effect of the embryo on the developmental transition of the endosperm by extending the middle stage. K-means clustering further identified coexpression modules of gene sets specific for embryo and endosperm development. Combined gene expression and biochemical analysis showed that T6P-SnRK1, gibberellin and auxin signalling from the embryo regulate endosperm developmental transition. The data enable us to propose a new seed developmental staging system for rice and the most detailed signature of rice grain formation to date, that will direct genetic strategies for rice yield improvement.

plant biology↗

bioRxiv2021

Butyryl/Caproyl-CoA:Acetate CoA-Transferase: Cloning, Expression and Characterization of the Key Enzyme Involved in Medium-Chain Fatty Acid Biosynthesis

Coenzyme A transferases (CoATs) are important enzymes involved in carbon chain elongation contributing to medium-chain fatty acid (MCFA) biosynthesis. For example, butyryl-CoA:acetate CoA transferase (BCoAT) is responsible for the final step of butyrate synthesis from butyryl-CoA. However, little is known about caproyl-CoA:acetate CoA-transferase (CCoAT), which is responsible for the final step of caproate synthesis from caproyl-CoA. In this study, two CoAT genes from Ruminococcaceae bacterium CPB6 and Clostridium tyrobutyricum BEY8 were identified by gene cloning and expression analysis. The enzyme assays and kinetic studies were carried out using butyryl-CoA or caproyl-CoA as the substrate. CPB6-CoAT can catalyze the conversion of both butyryl-CoA to butyrate and caproyl-CoA to caproate, but its catalytic efficiency with caproyl-CoA as the substrate was 3.8 times higher than that with butyryl-CoA. In contrast, BEY8-CoAT had only BCoAT activity, not CCoAT activity. This demonstrated the existence of a specific CCoAT involved in chain elongation via the reverse {beta}-oxidation pathway. Comparative bioinformatics analysis showed the presence of a highly conserved motif (GGQXDFXXGAXX) in CoATs, which is predicted to be the active center of CoATs. Single point mutations in the conserved motif of CPB6-CoAT (Asp346 and Ala351) led to marked decreases in the activity for butyryl-CoA and caproyl-CoA, indicating that the conserved motif is the active center of CPB6-CoAT, and sites Asp346 and Ala351 were critical residues that affect enzymatic activity. This work provides insight into the function of CCoAT in caproic acid biosynthesis and improves the understanding of the chain elongation pathway for MCFA production.

biochemistry↗

bioRxiv2020

Sustained ErbB activation causes demyelination and hypomyelination by driving necroptosis of mature oligodendrocytes and apoptosis of oligodendrocyte precursor cells

Oligodendrocytes are vulnerable to genetic and environmental insults and its injury leads to demyelinating diseases. The roles of ErbB receptors in maintaining the CNS myelin integrity are largely unknown. Here we overactivate ErbB receptors that mediate signaling of either neuregulin or EGF family growth factors and found their synergistic activation caused deleterious outcomes in white matter. Sustained ErbB activation induced by the tetracycline-dependent mouse tool Plp-tTA resulted in demyelination, axonal degeneration, oligodendrocyte precursor cell (OPC) proliferation, astrogliosis, and microgliosis in white matter. Moreover, there was hypermyelination prior to these inflammatory pathological events. In contrast, sustained ErbB activation induced by another tetracycline-dependent mouse tool Sox10+/rtTA caused hypomyelination in the corpus callosum and optic nerve, which appeared to be a developmental deficit and did not associate with OPC regeneration, astrogliosis, or microgliosis. By tracing the differentiation states of cells expressing tTA/rtTA-dependent transgene or pulse-labeled reporter proteins in vitro and in vivo, we found that Plp-tTA targeted mainly mature oligodendrocytes (MOs), whereas Sox10+/rtTA targeted OPCs and newly-formed oligodendrocytes. The distinct phenotypes of mice with ErbB overactivation induced by Plp-tTA and Sox10+/rtTA consolidated their non-overlapping targeting preferences in the oligodendrocyte lineage, and enabled us to demonstrate that ErbB overactivation in MOs induced necroptosis that caused inflammatory demyelination, whereas in OPCs induced apoptosis that caused non-inflammatory hypomyelination. Early interference with aberrant ErbB activation ceased oligodendrocyte deaths and restored myelin development in both mice. This study suggests that aberrant ErbB activation is an upstream pathogenetic mechanism of demyelinating diseases, providing a potential therapeutic target. Significance statementPrimary oligodendropathy is one of the etiological mechanisms for multiple sclerosis, and oligodendrocyte necroptosis is a pathological hallmark in the disease. Moreover, the demyelinating disease is now a broad concept that embraces schizophrenia, in which white matter lesions are an emerging feature. ErbB overactivation has been implicated in schizophrenia by genetic analysis and postmortem studies. This study suggests the etiological implications of ErbB overactivation in myelin pathogenesis and elucidates the pathogenetic mechanisms.

neuroscience↗

bioRxiv2020

Construction of a third NAD+ de novo biosynthesis pathway

Only two de novo biosynthetic routes to nicotinamide adenine dinucleotide (NAD+) have been described, both of which start from a proteinogenic amino acid and are tightly controlled. Here we establish a C3N pathway starting from chorismate in Escherichia coli as a third NAD+ de novo biosynthesis pathway. Significantly, the C3N pathway yielded extremely high cellular concentrations of NAD(H) in E. coli. Its utility in cofactor engineering was demonstrated by introducing the four-gene C3N module to cell factories to achieve higher production of 2,5-dimethylpyrazine and develop an efficient C3N-based whole-cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms.

synthetic biology↗

bioRxiv2020

Electrostatic Plasma Membrane Targeting is Essential for Dlg Function in Cell Polarity and Tumorigenesis

Discs large (Dlg) is an essential polarity protein and a tumor suppressor originally characterized in Drosophila but is also well conserved in vertebrates. Like the majority of polarity proteins, plasma membrane (PM)/cortical localization of Dlg is required for its function in polarity and tumorigenesis, but the exact mechanisms targeting Dlg to PM remain to be fully elucidated. Here we show that, similar to the recently discovered polybasic polarity proteins such as Lgl and aPKC, Dlg also contains a positively charged polybasic domain that electrostatically binds the PM phosphoinositides PI4P and PI(4,5)P2. Electrostatic targeting by the polybasic domain contributes significantly to the PM localization of Dlg in follicular and early embryonic epithelial cells, and is crucial for Dlg to regulate both polarity and tumorigenesis. The electrostatic PM targeting of Dlg is controlled by a potential phosphorylation-dependent allosteric regulation of its polybasic domain, and is specifically enhanced by the interactions between Dlg and another basolateral polarity protein and tumor suppressor Scrib. Our studies highlight an increasingly significant role of electrostatic PM targeting of polarity proteins in regulating cell polarity.

developmental biology↗

bioRxiv2020

The susceptibility analysis of Echinococcus multilocularis protoscoleces tubulin to mebendazole and RNA interference

Alveolar echinococcosis, caused by the larval (metacestode) stage of the tapeworm Echinococcus multilocularis, is a lethal parasitosis of the liver prevalent in the Northern Hemisphere. For chemotherapy the benzimidazole derivatives mebendazole and albendazole were introduced, which were found to disrupt the microtubules by inhibition of the polymerization of tubulin into microtubules, and {beta}-tubulin was determined to be the drug target molecule. In the present study, we evaluated the chemosensitivity of E. multilocularis protoscoleces tubulin to mebendazole and RNA interference in vitro, and to explore whether the molecular level and ultrastructure of E. multilocularis protoscoleces microtubules change post-mebendazole and RNA interference. We identified that mebendazole is parasitostatic to E. multilocularis protoscoleces through suppression the tubulin expression and change the flame cell morphology in molecular level, besides RNA interference indicated that {beta} 2 tubulin is probably one of the vital tubulin gene to form the flame cell and the protonephridial system tubules (collective tubes) of E. multilocularis protoscoleces. Molecular level and ultrastructure detection were performed by reverse transcription-PCR, western blotting and transmission electron microscope. The RNA interference would be probably as a parasitocidal method to disrupt the survival of PSCs, extend that the relevant tubulin maybe as potential target for drug development against AE.

molecular biology↗

bioRxiv2020

ErbB dysregulation impairs cognition via myelination-dependent and -independent oligodendropathy

White matter abnormalities are an emerging pathological feature of schizophrenia. However, their attributions to the disease remain largely elusive. ErbB receptors and their ligands, some of which are essential for peripheral myelination, confer susceptibility to schizophrenia. By synergistically manipulating ErbB receptor activities in a oligodendrocyte-stage-specific manner in mice after early development, we demonstrate the distinct effects of ErbB signaling on oligodendrocytes at various differentiation states. ErbB overactivation, in mature oligodendrocytes, induces necroptosis causing demyelination, whereas in oligodendrocyte precursor cells, induces apoptosis causing hypomyelination. In contrast, ErbB inhibition increases oligodendrocyte precursor cell proliferation but induces hypomyelination by suppressing the myelinating capabilities of newly-formed oligodendrocytes. Remarkably, ErbB inhibition in mature oligodendrocytes diminishes axonal conduction under energy stress and impairs working memory capacity independently of myelin pathology. This study reveals the etiological implications of oligodendrocyte vulnerability induced by ErbB dysregulation, and elucidates the pathogenetic mechanisms for variable structural and functional white matter abnormalities.

neuroscience↗

bioRxiv2020

Regular Tai Chi Practice Is Associated with Improved Memory as well as Structural and Functional Integrity of the Hippocampal Formation in the Elderly

ObjectiveThe current study aimed at determining effects of Tai Chi as an example of a combined motor-cognitive exercise relative to regular walking as an example of an exercise without cognitive demands on cognitive functioning and the functional and structural integrity of the brain in the elderly. MethodsHealthy elderly women with at least 6 years of regular Tai Chi or brisk walking exercise were recruited and underwent cognitive assessment via the Montreal Cognitive Assessment and brain structural and resting state functional MRI assessments. ResultsEpisodic memory in Tai Chi group was superior to that of the walking group; (2) higher gray matter density in inferior and medial temporal regions, including the hippocampal formation; (3) higher ReHo in temporal regions, specifically the fusiform gyrus and hippocampal formation (4) significant partial correlations were found between the gray matter density of the left hippocampus and episodic memory in the whole sample (5) significant partial correlations were observed between the ReHo in left hippocampus, left parahippocampal, left fusiform and delayed memory task was observed among all subjects. ConclusionThe present study suggest that long-term Tai Chi practice may improve memory performance via remodeling structure and the function of the hippocampal formation.

neuroscience↗

bioRxiv2020

HapSolo: An optimization approach for removing secondary haplotigs during diploid genome assembly and scaffolding.

BackgroundDespite marked recent improvements in long-read sequencing technology, the assembly of diploid genomes remains a difficult task. A major obstacle is distinguishing between alternative contigs that represent highly heterozygous regions. If primary and secondary contigs are not properly identified, the primary assembly will overrepresent both the size and complexity of the genome, which complicates downstream analysis such as scaffolding. ResultsHere we illustrate a new method, which we call HapSolo, that identifies secondary contigs and defines a primary assembly based on multiple pairwise contig alignment metrics. HapSolo evaluates candidate primary assemblies using BUSCO scores and then distinguishes among candidate assemblies using a cost function. The cost function can be defined by the user but by default considers the number of missing, duplicated and single BUSCO genes within the assembly. HapSolo performs hill climbing to minimize cost over thousands of candidate assemblies. We illustrate the performance of HapSolo on genome data from three species: the Chardonnay grape (Vitis vinifera), with a genome of 490Mb, a mosquito (Anopheles funestus; 200Mb) and the Thorny Skate (Amblyraja radiata; 2,650 Mb). ConclusionsHapSolo rapidly identified candidate assemblies that yield improvements in assembly metrics, including decreased genome size and improved N50 scores. Contig N50 scores improved by 35%, 9% and 9% for Chardonnay, mosquito and the thorny skate, respectively, relative to unreduced primary assemblies. The benefits of HapSolo were amplified by down-stream analyses, which we illustrated by scaffolding with Hi-C data. We found, for example, that prior to the application of HapSolo, only 52% of the Chardonnay genome was captured in the largest 19 scaffolds, corresponding to the number of chromosomes. After the application of HapSolo, this value increased to ~84%. The improvements for mosquito scaffolding were similar to that of Chardonnay (from 61% to 86%), but even more pronounced for thorny skate. We compared the scaffolding results to assemblies that were based on another published method for identifying secondary contigs, with generally superior results for HapSolo.

bioinformatics↗

bioRxiv2020

Broad-Range Virus Detection and Discovery Using Microfluidic PCR Coupled with High-throughput Sequencing

There is a need for a comprehensive and sensitive method to test for a broad range of viral pathogens in samples without any identifiable pathogen detected. Real-time PCR assays are sensitive and rapid, but their specificity limits their utility in detecting divergent agents. Shotgun high-throughput sequencing methods provide unbiased sequence identification, however, they have limited sensitivity and require complex analyses. In order to meet the need for a sensitive, high-throughput virus detection and discovery platform with good sensitivity, we combine two existing technologies, broadly-reactive consensus-degenerate pan-viral group PCR and the MiSeq sequencer (Illumina), using the Access Array (Fluidigm), a commercially-available microfluidic PCR system. Pan-viral group primers target conserved regions of virus taxonomic groups and can amplify known and potentially novel species. The Access Array employs dozens of these assays in parallel, which are then sequenced all at once on the MiSeq. In this study, we run a respiratory panel of pan-viral group PCR assays using AA-PCR-Seq. We validate the panel on a collection of representative human and animal samples, comparing it to qPCR and shotgun next-generation sequencing (NGS). AA-PCR-Seq provides a robust, straightforward method for screening large numbers of samples for virus detection and discovery.

genomics↗

bioRxiv2020

Loss of hepatic aldolase B activates Akt and promotes hepatocellular carcinogenesis by destabilizing Aldob/Akt/PP2A protein complex

Loss of hepatic fructose-1, 6-bisphosphate aldolase B (Aldob) leads to a paradoxical upregulation of glucose metabolism to favor hepatocellular carcinogenesis but the upstream signaling events remain poorly defined. Akt is highly activated in HCC and targeting Akt is being explored as a potential therapy for HCC. Herein we demonstrate that Aldob suppresses Akt activity through a protein complex containing Aldob, Akt, and protein phosphatase 2A (PP2A), leading to inhibition of cell viability, cell cycle progression, glucose metabolism and tumor growth. Interestingly, Aldob directly interacts with phosphorylated Akt (p-Akt) and promotes the recruitment of PP2A to dephosphorylate p-Akt, and this scaffolding effect of Aldob is independent of its enzymatic activity. Loss of Aldob or disruption of Aldob/Akt interaction in Aldob R304A mutant restores Akt activity and tumor promoting effects. Consistently, Aldob and p-Akt expression are inversely correlated in human HCC tissues, and Aldob downregulation coupled with p-Akt upregulation predicts a poor prognosis for HCC. We have further discovered that a specific small-molecule activator of PP2A (SMAP) efficiently attenuates HCC tumorigenesis in Aldob-deficient cell lines and xenografts. Our work reveals a novel non-glycolytic role of Aldob in negative regulation of Akt activation, suggesting that inhibiting Akt activity and reactivating PP2A may be a potential therapeutic approach for HCC treatment.

cancer biology↗

bioRxiv2020

Peptide YY: a novel Paneth cell antimicrobial peptide that maintains fungal commensalism

Perturbed interactions between the intestinal microbes and host correlate with emergence of fungal virulence. Here we report a previously unknown role for peptide YY (PYY), a described endocrine molecule, as an antimicrobial peptide (AMP) expressed by gut immune epithelial Paneth Cells (PC). PC-PYY differs from other AMPs, including lysozyme, because of limited antibacterial activity, packaging in discrete secretory granules, and selective antifungal activity to virulent hyphae, but not yeast forms of Candida albicans. The latter action is through binding of cationic PC-PYY to the anionic hyphal surface, resulting in membrane disruption and killing. PC-PYY is compartmentalized to surface mucus, which optimizes activity and prevents conversion to endocrine PYY by dipeptidyl peptidase-IV (DPP-IV). We conclude PC-PYY is a unique AMP with selective antifungal activity that maintains gut fungal commensalism. Compromised PC-PYY action from PC dysfunction and/or mucus depletion in ileal Crohns disease may initiate or contribute to disease via fungal pathogenesis. Highlights Paneth Cell PYY (PC-PYY) is an antimicrobial peptide that differs from endocrine-PYY PC-PYY is a selective anti-fungal peptide, targeting the virulent form of C. albicans PC-PYY is separately packaged, retained by mucus, and released by C. albicans hyphae PC-PYY is proposed as essential for maintenance of fungal commensalism in the gut Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY Model for Paneth cell (PC) PYY action and regulation of fungal commensalisms and potential role in the pathogenesis of ileal Crohns Disease (iCD) (A) In a healthy ileum, commensal yeast reside and do not stimulate PYY1-36 release from PCs. (B) Increased virulent hyphae (purple hyphae) results in PYY1-36 release from crypt PCs into the mucus. Hyphae are targeted by PYY1-36 and killed (red hyphae) to manage the increased fungi community in gut. (C) In a diseased ileum such as iCD, hyphal load induces immune activation and increased inflammation through PC dysfunction (gray PCs) and decreased PYY1-36 release or mucus depletion and PC dysfunction. C_FIG_DISPLAY

molecular biology↗

bioRxiv2020

Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A

The epithelial-mesenchymal transition (EMT) imparts properties of cancer stem-like cells, including resistance to frequently used chemotherapy, necessitating the identification of molecules that induce cell death specifically in stem-like cells with EMT properties. Herein, we demonstrate that breast cancer cells enriched for EMT features are more sensitive to cytotoxicity induced by ophiobolin A (OpA), a sesterterpenoid natural product. Using a model of experimentally induced EMT in human mammary epithelial (HMLE) cells, we show that EMT is both necessary and sufficient for OpA sensitivity. Moreover, prolonged, sub-cytotoxic exposure to OpA is sufficient to reduce migration, sphere formation, and resistance to doxorubicin. OpA is well-tolerated in mice and treatment with OpA alone reduces tumor burden. These data identify a driver of EMT-driven cytotoxicity with significant potential for use either in combination with standard chemotherapy or for tumors enriched for EMT features.

cancer biology↗

bioRxiv2020

Rapid, sensitive, full genome sequencing of Severe Acute Respiratory Syndrome Virus Coronavirus 2 (SARS-CoV-2)

SARS-CoV-2 recently emerged, resulting a global pandemic. Rapid genomic information is critical to understanding transmission and pathogenesis. Here, we describe validated protocols for generating high-quality full-length genomes from primary samples. The first employs multiplex RT-PCR followed by MinION or MiSeq sequencing. The second uses singleplex, nested RT-PCR and Sanger sequencing.

genomics↗

bioRxiv2020

Genome-wide identification, characterization and expression analysis of the monovalent cation-proton antiporter superfamily, and their function analysis in maize salt tolerance.

Na+, K+ and pH homeostasis are important for plant life and they are controlled by the monovalent cation proton antiporter (CPA) superfamily. The roles of ZmCPAs in salt tolerance are not fully elucidated. In this study, we identified 35 ZmCPAs comprising 13 Na+/H+ exchangers (ZmNHXs), 16 cation/H+ exchanger (ZmCHXs), and 6 K+ efflux antiporters (ZmKEAs). All ZmCPAs have transmembrane domains and maize protoplasts transient expression showed that ZmNHX5 and ZmCHX17 localized to cell membrane system. ZmCHXs were specifically highly expressed in anthers, while ZmNHXs and ZmKEAs showed high expression in various tissues. ZmNHX5 and ZmKEA2 were up-regulated in maize seedlings under both NaCl and KCl stresses. Yeast complementation experiments revealed the roles of ZmNHX5, ZmKEA2 in NaCl tolerance. Analyses of the maize mutants further validated the salt tolerance functions of ZmNHX5 and ZmKEA2. Our study highlights comprehensive information of ZmCPAs and provides new gene targets for salt tolerance maize breeding.

plant biology↗

bioRxiv2020

Parkinson's disease-related phosphorylation at Tyr39 rearranges α-synuclein amyloid fibril structure revealed by cryo-EM

Post-translational modifications (PTMs) of -synuclein (-syn), e.g. phosphorylation, play an important role in modulating -syn pathology in Parkinsons disease (PD) and -synucleinopathies. Accumulation of phosphorylated -syn fibrils in Lewy bodies and Lewy neurites is the histological hallmark of these diseases. However, it is unclear how phosphorylation relates to -syn pathology. Here, by combining chemical synthesis and bacterial expression, we obtained homogeneous -syn fibrils with site-specific phosphorylation at Y39, which exhibits enhanced neuronal pathology in rat primary cortical neurons. We determined the cryo-EM structure of pY39 -syn fibril, which reveals a new fold of -syn with pY39 in the center of the fibril core forming electrostatic interaction network with eight charged residues in the N-terminal region of -syn. This structure composed of residues 1-100 represents the largest -syn fibril core determined so far. This work provides structural understanding on the pathology of pY39 -syn fibril, and highlights the importance of PTMs in defining the polymorphism and pathology of amyloid fibrils in neurodegenerative diseases.

biophysics↗