DNA tetrahedral nanocages as a promising nanocarrier for dopamine delivery in neurological disorders.

Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinson's disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA TD as a carrier for dopamine to cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate that these dopamine-loaded DNA TD nanostructures enhanced cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinson's disease and other neurological disorders.

Extracellular Proteomic Profiling from the Erythrocytes Infected with Plasmodium Falciparum 3D7 Holds Promise for the Detection of Biomarkers.

Plasmodium falciparum (P. falciparum), which causes the most severe form of malaria, if left untreated, has 24 h window in which it can cause severe illness and even death. The aim of this study was to create the most comprehensive and informative secretory-proteome possible by combining high-accuracy and high-sensitivity protein identification technology. In this study, we used Plasmodium falciparum 3D7 (Pf3D7) as the model parasite to develop a label-free quantification proteomic strategy with the main goal of identifying Pf3D7 proteins that are supposed to be secreted outside the infected erythrocytes in the spent media culture during the in-vitro study. The spent culture media supernatant was subjected to differential and ultra-centrifugation steps followed by total protein extraction, estimation, and in-solution digestion using trypsin, digested peptides were analyzed using Nano-LC coupled with ESI for MS/MS. MS/MS spectra were processed using Maxquant software (v2.1.4.0.). Non-infected erythrocytes incubated spent cultured media supernatant were considered as control. Out of discovered 38 proteins, proteins belonging to P. falciparum spp. were EGF-like protein (C0H544), Endoplasmic reticulum chaperone GRP170 (C0H5H0), Small GTP-binding protein sar1 (Q8I1S0), Erythrocyte membrane protein 1, PfEMP1 (Q8I639), aldehyde reductase (Q8ID61), Conserved Plasmodium proteins (Q8IEH3, Q8ILD1), Antigen 332, DBL-like protein (Q8IHN4), Fe-S cluster assembly protein (Q8II78), identified and chosen for further in-depth investigation. This study highlights the value of secretory Plasmodium proteins play crucial roles in various aspects of the disease progression and host-pathogen interactions which can serve as diagnostic markers for malaria infection.

Characterization of G-quadruplexes in the Helicobacter pylori genome and assessment of therapeutic potential of G4 ligands.

Helicobacter pylori, a leading human pathogen associated with duodenal ulcer and gastric cancer, presents a significant threat to human health due to increasing antibiotic resistance rates. This study investigates G-quadruplexes (G4s), which are non-canonical secondary structures form in G-rich regions within the H. pylori genome. Extensive research on G4s in eukaryotes has revealed their role in epigenetically regulating cellular processes like gene transcription, DNA replication, and oncogene expression. However, understanding of G4-mediated gene regulation in other organisms, especially bacterial pathogens, remains limited. Although G4 motifs have been extensively studied in a few bacterial species such as Mycobacterium, Streptococci, and Helicobacter, research on G4 motifs in other bacterial species is still sparse. Like in other organisms such as archaea, mammals, and viruses, G4s in H. pylori display a non-random distribution primarily situated within open reading frames of various protein-coding genes. The occurrence of G4s in functional regions of the genome and their conservation across different species indicates that their placement is not random, suggesting an evolutionary pressure to maintain these sequences at specific genomic sites. Moreover, G-quadruplexes show enrichment in specific gene classes, suggesting their potential involvement in regulating the expression of genes related to cell wall/membrane/envelope biogenesis, amino acid transport, and metabolism. This indicates a probable regulatory role for G4s in controlling the expression of genes essential for H. pylori survival and virulence. Biophysical techniques such as Circular Dichroism spectroscopy and Nuclear Magnetic Resonance were used to characterize G4 motifs within selected H. pylori genes. The study revealed that G-quadruplex ligand inhibited the growth of H. pylori, with minimal inhibitory concentrations in the low micromolar range. This suggests that targeting G4 structures could offer a promising approach for developing novel anti-H. pylori drugs.

Dopamine-Functionalized, Red Carbon Quantum Dots for In Vivo Bioimaging, Cancer Therapeutics, and Neuronal Differentiation.

One of the crucial requirements of quantum dots for biological applications is their surface modification for very specific and enhanced biological recognition and uptake. Toward this end, we present the green synthesis of bright, red-emitting carbon quantum dots derived from mango leaf extract (mQDs). These mQDs are conjugated electrostatically with dopamine to form mQDs-dopamine (mQDs:DOPA) bioconjugates. Bright-red fluorescence of mQDs was used for bioimaging and uptake in cancerous and noncancerous cell lines, tissues, and in vivo models like zebrafish. mQDs exhibited the highest uptake in brain tissue compared to the heart, kidney, and liver. mQD:DOPA conjugates killed breast cancer cells and increased uptake in epithelial RPE-1 cells and zebrafish. Additionally, mQDs:DOPA promoted neuronal differentiation of SH-SY5Y cells to differentiated neurons. Both mQDs and mQDs:DOPA exhibited the potential for higher collective cell migrations, implicating their future potential as next-generation tools for advanced biological and biomedical applications.

Gravity-Driven Separation for Enrichment of Rare Earth Elements Using Lanthanide Binding Peptide-Immobilized Resin.

Rare Earth Elements (REEs) constitute indispensable raw materials and are employed in a diverse range of devices, including but not limited to smartphones, electric vehicles, and clean energy technologies. While there is an increase in demand for these elements, there is a global supply challenge due to limited availability and geopolitical factors affecting their procurement. A crucial step in manufacturing these devices involves utilizing highly pure REEs, often obtained through complex and nonsustainable processes. These processes are vital in isolating individual REEs from mixtures containing non-REEs and other REEs. There exists an urgent requirement to explore alternative techniques that enable the selective recovery of REEs through more energy-efficient processes. To overcome the limitations mentioned above, we developed a microbead-based technology featuring immobilized lanthanide binding peptides (LBPs) for the selective adsorption of REEs. This technology does not require the utilization of external stimuli but uses gravity-based separation processes to separate the bound REE from the unbound REE. We demonstrate this technology's potential by enriching two relevant REEs (Europium and Terbium). Additionally, we propose a mechanism whereby REEs bind selectively to a particular LBP, leveraging the distinctive physicochemical characteristics of both the REE and the LBP. Moreover, these LBPs exhibit no binding affinity toward other frequently encountered industrial ions. Finally, we demonstrate the recovery of REEs through a change in system conditions and assess the reusability of the microbeads for subsequent adsorption cycles. We anticipate that this approach will address the challenges of REE recovery and demonstrate the potential of biomolecular strategies in advancing sustainable resource management.

Ocular and Neuro-ophthalmic Manifestations Post COVID-19 Infection.

A 39-year-old male with a history of COVID-19 infection presented with ocular manifestations: dendritic ulcer in the left eye cornea followed by diplopia in the same eye. Extraocular motility was restricted in the levo-lateral gaze with maximum diplopia measuring 25∆ exotropia. Slit lamp biomicroscopy showed dendritic patterned lesion with diffused superficial punctate keratitis in the cornea. There are various reports associated with COVID-19 and the neuro-ophthalmic system. Although the clinicopathological aspect of COVID-19 and the neurological system is still to explicate. However, the patient showed gradual improvement with topical and systemic antiviral therapy and orthoptic exercise. This points to the need for detailed neurological and ophthalmic workup in symptomatic COVID-19 patients. Taking the risk of viral spread into serious consideration, a thorough evaluation is though mandatory. Keywords: COVID-19; dendritic ulcer; lateral rectus palsy; superficial punctate keratopathy.

Structural, kinetic, and thermodynamic aspects of insulin aggregation.

Given the significance of protein aggregation in proteinopathies and the development of therapeutic protein pharmaceuticals, revamped interest in assessing and modelling the aggregation kinetics has been observed. Quantitative analysis of aggregation includes data of gradual monomeric depletion followed by the formation of subvisible particles. Kinetic and thermodynamic studies are essential to gain key insights into the aggregation process. Despite being the medical marvel in the world of diabetes, insulin suffers from the challenge of aggregation. Physicochemical stresses are experienced by insulin during industrial formulation, storage, delivery, and transport, considerably impacting product quality, efficacy, and effectiveness. The present review briefly describes the pathways, mathematical kinetic models, and thermodynamics of protein misfolding and aggregation. With a specific focus on insulin, further discussions include the structural heterogeneity and modifications of the intermediates incurred during insulin fibrillation. Finally, different model equations to fit the kinetic data of insulin fibrillation are discussed. We believe that this review will shed light on the conditions that induce structural changes in insulin during the lag phase of fibrillation and will motivate scientists to devise strategies to block the initialization of the aggregation cascade. Subsequent abrogation of insulin fibrillation during bioprocessing will ensure stable and globally accessible insulin for efficient management of diabetes.

Endocytic pathways of pathogenic protein aggregates in neurodegenerative diseases.

Endocytosis is the fundamental uptake process through which cells internalize extracellular materials and species. Neurodegenerative diseases (NDs) are characterized by a progressive accumulation of intrinsically disordered protein species, leading to neuronal death. Misfolding in many proteins leads to various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other disorders. Despite the significance of disordered protein species in neurodegeneration, their spread between cells and the cellular uptake of extracellular species is not entirely understood. This review discusses the major internalization mechanisms of the different conformer species of these proteins and their endocytic mechanisms. We briefly introduce the broad types of endocytic mechanisms found in cells and then summarize what is known about the endocytosis of monomeric, oligomeric and aggregated conformations of tau, Aß, α-Syn, Huntingtin, Prions, SOD1, TDP-43 and other proteins associated with neurodegeneration. We also highlight the key players involved in internalizing these disordered proteins and the several techniques and approaches to identify their endocytic mechanisms. Finally, we discuss the obstacles involved in studying the endocytosis of these protein species and the need to develop better techniques to elucidate the uptake mechanisms of a particular disordered protein species.

Catalytic Sabatier Process under Thermally and Magnetically Induced Heating: A Comparative Case Study for Titania-Supported Nickel Catalyst.

In the present paper, we compare the activity, selectivity, and stability of a supported nickel catalyst in classical heating conditions and in magnetically activated catalysis by using iron wool as a heating agent. The catalyst, 5 wt% Ni supported on titania (Degussa P25), was prepared via an organometallic decomposition method and was thoroughly characterized by using elemental, microscopic, and diffraction techniques. In the event of magnetic induction heating, the % CO2 conversion reached a maximum of ~85% compared to ~78% for thermal conditions at a slightly lower temperature (~335 °C) than the thermal heating (380 °C). More importantly, both processes were found to be stable for 45 h on stream. Moreover, the effects of magnetic induction and classical heating over the catalyst evolution were discussed. This study demonstrated the potential of magnetic heating-mediated methanation, which is currently under investigation for the development of pilot-scale reactors.

Rising surface ozone due to anthropogenic activities and its impact on COVID-19 related deaths in Delhi, India.

The rapidity and global spread of the COVID-19 pandemic have left several vital questions in the research community requiring coordinated investigation and unique perspectives to explore the relationship between the spread of disease and air quality. Previous studies have focused mainly on the relation of particulate matter concentration with COVID-19-related mortalities. In contrast, surficial ozone has not been given much attention as surface ozone is a primary air pollutant and directly impacts the respiratory system of humans. Hence, we analyzed the relationship between surface ozone pollution and COVID-19-related mortalities. In this study, we have analyzed the variability of various atmospheric pollutants (particulate matter (PM2.5 and PM10), Nitrogen dioxide (NO2), Carbon monoxide (CO), and Ozone) in the National Capital Region (NCR) of India during 2020-2021 using station data and investigated the relationship of the air-quality parameters with the COVID-19 related deaths. In northern parts of India, the concentration of particulate matter (PM2.5 and PM10), Nitrogen dioxide (NO2), Carbon monoxide (CO), and Ozone remain high during the pre- and post-monsoon seasons due to dust loading and crop residue burning (after winter wheat in April & summer rice in November). The westerly wind brings the polluted airmass from western and northwestern parts to Delhi and National Capital Region during April-June and October-November, and meteorological conditions help raise the concentration of these pollutants. Due to long solar hours and high CO concentrations, the ozone concentration is higher from April to June and September. While comparing major air quality parameters with COVID-19-related deaths, we found a good relationship between surface ozone and COVID-19 mortality in Delhi. We also observed a time lag relationship between ozone concentration and mortality in Delhi, so the exposure to Ozone in a large population of Delhi may have augmented the rise of COVID-19-related deaths. The analysis suggested that ozone has a significant relationship with COVID-19 related mortality in Delhi in comparison to other parameters.

Red emitting fluorescent carbon nanoparticles to track spatio-temporal dynamics of endocytic pathways in model neuroblastoma neurons.

One of the biggest challenges limiting the biological applications of fluorescent carbon-based nanoparticles is their capacity to emit in the red region of the spectrum and simultaneously maintaining the smaller size. These two parameters always go in inverse proportion, thus lagging their applications in biological imaging. Endocytic pathways play important roles in regulating major cellular functions such as cellular differentiation. The Spatio-temporal dynamics of endocytic pathways adopted by various ligands (including nanoparticles) over longer durations in cellular differentiation remain unstudied. Here we have used red-emitting fluorescent carbon nanoparticles to study the endocytic pathways in neuronal cells at different stages of differentiation. These small-sized, bright, red-emitting carbon nanoparticles (CNPs) can be internalized by live cells and imaged for extended periods, thus capturing the Spatio-temporal dynamics of endocytic pathways in model SH-SY5Y derived neuroblastoma neurons. We find that these nanoparticles are preferably taken up via clathrin-mediated endocytosis and follow the classical recycling pathways at all the stages of neuronal differentiation. These nanoparticles hold immense potential for their size, composition, surface and fluorescence tunability, thus maximizing their applications in spatio-temporally tracking multiple cellular pathways in cells and tissues simultaneously.

Designer, Programmable DNA-peptide hybrid materials with emergent properties to probe and modulate biological systems.

The chemistry of DNA endows it with certain functional properties that facilitate the generation of self-assembled nanostructures, offering precise control over their geometry and morphology, that can be exploited for advanced biological applications. Despite the structural promise of these materials, their applications are limited owing to lack of functional capability to interact favourably with biological systems, which has been achieved by functional proteins or peptides. Herein, we outline a strategy for functionalizing DNA structures with short-peptides, leading to the formation of DNA-peptide hybrid materials. This proposition offers the opportunity to leverage the unique advantages of each of these bio-molecules, that have far reaching emergent properties in terms of better cellular interactions and uptake, better stability in biological media, an acceptable and programmable immune response and high bioactive molecule loading capacities. We discuss the synthetic strategies for the formation of these materials, namely, solid-phase functionalization and solution-coupling functionalization. We then proceed to highlight selected biological applications of these materials in the domains of cell instruction & molecular recognition, gene delivery, drug delivery and bone & tissue regeneration. We conclude with discussions shedding light on the challenges that these materials pose and offer our insights on future directions of peptide-DNA research for targeted biomedical applications.

Formulation of Cabotegravir Loaded Gold Nanoparticles: Optimization, Characterization to In-Vitro Cytotoxicity Study.

The effective and preventive treatment of HIV is one of the difficult challenges worldwide. It requires the development of an effective prophylactic strategy to prevent HIV/AIDS. This study aimed to synthesize Cabotegravir (CAB)-biodegradable gold (Au) nanoparticles by using pectin as a reducer and stabilizer. CAB-GNPs were prepared by the slightly modified Turkevich method. CAB-GNPs were optimized using Box Behnken design for independent variables gold chloride (A), pectin (B) and pH range (C). The effects of independent variables were observed on particle size (Y1) and encapsulation efficiency (Y2). The results of the study revealed that the optimized nanoparticles (GLN7) had a particle size of 3.9 ± 0.1 nm and encapsulation efficiency of 97.2 ± 3.9%. TEM study showed the spherical shape particles. The in-vitro drug release revealed 62.1 ± 0.5% release of CAB in simulated gastric buffer (pH 1.2) and 45.5 ± 2.8% in physiological buffer (pH 7.4). In-vitro cytotoxicity study and antibacterial activity depicted the safety of the prepared NPs by showing lesser toxicity than pure CAB. From the results, our experimental outcomes concluded that CAB gold nanoparticles composed of pectin may constitute a preferred embodiment for the delivery of CAB.

Patterns of Macular Edema in Branch Retinal Vein Occlusion Diagnosed by Optical Coherence Tomography.

INTRODUCTION: Branch Retinal vein occlusion is the most common retinal vascular disease after diabetic retinopathy in elderly populations. OBJECTIVES: To describe morphological patterns of macular edema in branch retinal vein occlusion using optical coherence tomography. MATERIALS AND METHODS: It is a hospital based; descriptive, cross-sectional study. All patients with macular edema secondary to branch retinal vein occlusion diagnosed by optical coherence tomography and fulfilling the inclusion criteria from 2017 July 1 to 2018 July 1 were studied. RESULTS: A total of 84 eyes of 84 patients were enrolled. The mean age of the patient was 68.0833 ± 11.22 years (range, 35-74 years). Forty-five (53.57%) were male. Forty-four eyes had right eye involvement. Major and macular branch retinal vein occlusion was found in 50 and 34 eyes respectively. Forty eight eyes had superior and 36 eyes had inferior branch retinal vein occlusion. Morphological patterns of macular edema were classified: cystoid macular edema, cystoid macular edema with serous retinal detachment, diffuse macular edema and diffuse macular edema with serous retinal detachment of which 68 (80.95%) had cystoid macular edema. Out of 84 eyes, 30 (35.71%) had inner and outer segment (IS/OS) junction disruption. CONCLUSION: Optical coherence tomography is a safe and noninvasive technique. Serous retinal detachment and photoreceptors disruption may go unnoticed unless OCT is performed. It can measure the changes in retinal thickness and thus predict the visual outcomes in patients with macular edema.

La-Cu based heterogeneous perovskite catalyst for highly selective benzene hydroxylation under mild conditions.

Direct hydroxylation of benzene towards phenol with high conversion and selectivity remains a great challenge. We report herein an efficient La2 CuO4 perovskite catalyst for one-step oxidation of benzene using hydrogen peroxide under mild conditions. The catalyst was characterized using XRD, TEM, XPS, TG-DTA, and other advanced techniques. The one-pot hydroxylation reaction carried out at 60 °C under optimum reaction conditions in the presence of catalytic material shows benzene to phenol transformation with 51% conversion with >99% selectivity with 65 percent peroxide efficiency, respectively. The influence of reaction conditions such as temperature, amount of oxidant, reaction time and mode of addition of the oxidant was crucial in selectivity optimization.

Emerging Biomedical Applications of the Vesicular Stomatitis Virus Glycoprotein.

Nanoparticles (NPs) made of metals, polymers, micelles, and liposomes are increasingly being used in various biomedical applications. However, most of these NPs are hazardous for long- and short-term use and hence have restricted biomedical applications. Therefore, naturally derived, biocompatible, and biodegradable nanoconstructs are being explored for such applications. Inspired by the biology of viruses, researchers are exploring the viral proteins that hold considerable promise in biomedical applications. The viral proteins are highly stable and further amenable to suit specific biological applications. Among various viral proteins, vesicular stomatitis virus glycoprotein (VSV-G) has emerged as one of the most versatile platforms for biomedical applications. Starting with their first major use in lentivirus/retrovirus packaging systems, the VSV-G-based reagents have been tested for diverse biomedical use, many of which are at various stages of clinical trials. This manuscript discusses the recent advancements in the use of the VSV-G-based reagents in medical, biological research, and clinical applications particularly highlighting emerging applications in biomedical imaging.

Role of Doxorubicin on the Loading Efficiency of ICG within Silk Fibroin Nanoparticles.

The effective loading or encapsulation of multimodal theranostic agents within a nanocarrier system plays an important role in the clinical development of cancer therapy. In recent years, the silk fibroin protein-based delivery system has been drawing significant attention to be used in nanomedicines due to its biocompatible and biodegradable nature. In this study, silk fibroin nanoparticles (SNPs) have been synthesized by a novel and cost-effective ultrasonic atomizer-based technique for the first time. The fabricated SNPs were coencapsulated by the FDA-approved indocyanine green (ICG) dye and the chemotherapeutic drug doxorubicin (DOX). The synthesized SNPs are spherical, with an average diameter of ∼37 ± 4 nm, and the ICG-DOX-coencapsulated SNPs (ID-SNPs) have a diameter size of ∼47 ± 6 nm. For the first time, here we demonstrate that DOX helps in the higher loading of ICG within the ID-SNPs, which enhances the encapsulation efficiency of ICG by ∼99%. This could be attributed to the interaction of ICG and DOX molecules with the silk fibroin protein, which helps ICG to get loaded more efficiently within these nanoparticles. The overall finding of this study suggests that the ID-SNPs could be utilized for enhanced ICG-complemented multimodal deep-tissue bioimaging and synergistic chemo-photothermal therapy.

Peptide functionalized DNA hydrogel enhances neuroblastoma cell growth and differentiation.

Designing programmable biomaterials that could act as extracellular matrices and permit functionalization is a current need for tissue engineering advancement. DNA based hydrogels are gaining significant attention owing to their self-assembling properties, biocompatibility, chemical robustness and low batch to batch variability. The real potential of DNA hydrogels in the biomedical domain remains to be explored. In this work, a DNA hydrogel was coated on a glass surface and coupled to a synthetic IKVAV peptide by a chemical crosslinker. We observe enhanced neuronal differentiation, prolonged neurite length, dynamic movement of microtubules and cytoskeleton, and altered endocytic mechanisms in neuroblastoma-based stem cells for the peptide modified DNA hydrogel compared to the unmodified DNA hydrogel and controls. We anticipate that a peptide-modified DNA hydrogel could emerge as a promising scaffold coating material to develop nerve tissue conduits in the future for application in neuroscience and neuroregeneration.

α-Synuclein fibrils explore actin-mediated macropinocytosis for cellular entry into model neuroblastoma neurons.

Alpha-synuclein (α-Syn), an intrinsically disordered protein (IDP), is associated with neurodegenerative disorders, including Parkinson's disease (PD or other α-synucleinopathies. Recent investigations propose the transmission of α-Syn protein fibrils, in a prion-like manner, by entering proximal cells to seed further fibrillization in PD. Despite the recent advances, the mechanisms by which extracellular protein aggregates internalize into the cells remain poorly understood. Using a simple cell-based model of human neuroblastoma-derived differentiated neurons, we present the cellular internalization of α-Syn PFF to check cellular uptake and recycling kinetics along with the standard endocytic markers Transferrin (Tf) marking clathrin-mediated endocytosis (CME) and Galectin3 (Gal3) marking clathrin-independent endocytosis (CIE). Specific inhibition of endocytic pathways using chemical inhibitors reveals no significant involvement of CME, CIE and caveolae-mediated endocytosis (CvME). A substantial reduction in cellular uptake was observed after perturbation of actin polymerization and treatment with macropinosomes inhibitor. Our results show that α-Syn PFF mainly internalizes into the SH-SY5Y cells and differentiated neurons via the macropinocytosis pathway. The elucidation of the molecular and cellular mechanism involved in the α-Syn PFF internalization will help improve the understanding of α-synucleinopathies including PD, and further design specific inhibitors for the same.

Charge neutralization of lysine via carbamylation reveals hidden aggregation hot-spots in tau protein flanking regions.

Tau protein is found abundantly in neurofibrillary tangles in Alzheimer's disease (AD). The longest human tau isoform (2N4R) has 44 lysine residues. Several lysine-based post-translational modifications (PTMs) such as glycation, acetylation, ubiquitination, and sumoylation have been implicated not only in AD, but also in other tauopathies. Carbamylation is one such lysine neutralizing age-related nonenzymatic PTM which can modulate the aggregation propensity of tau. In this work, we have studied the aggregation potential of lysine-rich regions of tau upon carbamylation which do not aggregate in their native form. Using an array of biophysical and microscopic analyses, such as ThT kinetic assay, fluorescence microscopy, Congo red staining, and scanning electron microscopy, we demonstrate that peptides derived from four of five such regions exhibit robust fibrillar amyloid formation. These regions are found in the N-terminal projection domain that encompasses proline-rich domain (148-153 and 223-230), repeat domain R1 (253-260), as well as fibrillary core region (368-378), and can be described as hidden aggregation hot-spots which become activated upon carbamylation. We have further compared the impact of carbamylation with acetylation on the aggregation propensity of lysine-rich peptide (254 KKVAVV259 ) using biophysical experiments and molecular dynamics simulations and deduced that carbamylation is a much stronger driver of aggregation than acetylation. Our findings may offer more insight into amyloid fibrils' interaction with hidden aggregation-prone nucleating sequences that act as hot-spots for inducing tau fibrillation.