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1.
Mol Psychiatry ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266711

RESUMO

The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown. Here, we aggregate structural magnetic resonance imaging data from 38,696 healthy controls (HC) and 1256 psychosis-related conditions, including first-degree relatives of schizophrenia (SCZ) and schizoaffective disorder (SAD) patients (n = 160), individuals who had psychotic experiences (n = 157), patients who experienced a first episode of psychosis (FEP, n = 352), and individuals with chronic SCZ or SAD (n = 587). Using a normative modeling approach, we generated centile scores for cortical gray matter (GM) phenotypes, identifying deviations in regional volumes below the expected trajectory for all conditions, with a greater impact on the clinically diagnosed ones, FEP and chronic. Additionally, we mapped 46 neurobiological features from healthy individuals (including neurotransmitters, cell types, layer thickness, microstructure, cortical expansion, and metabolism) to these abnormal centiles using a multivariate approach. Results revealed that neurobiological features were highly co-localized with centile deviations, where metabolism (e.g., cerebral metabolic rate of oxygen (CMRGlu) and cerebral blood flow (CBF)) and neurotransmitter concentrations (e.g., serotonin (5-HT) and acetylcholine (α4ß2) receptors) showed the most consistent spatial overlap with abnormal GM trajectories. Taken together these findings shed light on the vulnerability factors that may underlie atypical brain maturation during different stages of psychosis.

2.
Small ; 20(27): e2307202, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38308381

RESUMO

Thin-films of metal-organic frameworks (MOFs) have widespread potential applications, especially with the emergence of glass-forming MOFs, which remove the inherent issue of grain boundaries and allow coherent amorphous films to be produced. Herein, it is established that atomic layer deposition (ALD) of zinc oxide lends excellent control over the thickness and localization of resultant polycrystalline and glass zeolitic imidazole framework-62 (ZIF-62) thin-films within tubular α-alumina supports. Through the reduction of the chamber pressure and dose times during zinc oxide deposition, the resultant ZIF-62 films are reduced from 38 µm to 16 µm, while the presence of sporadic ZIF-62 (previously forming as far as 280 µm into the support) is prevented. Furthermore, the glass transformation shows a secondary reduction in film thickness from 16 to 2 µm.

3.
Biomacromolecules ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276065

RESUMO

The self-assembly of Janus-type amphiphilic hybrid block copolymers composed of hydrophilic/hydrophobic layers has shown promise for drug encapsulation and delivery. Saccharides have previously been incorporated to improve the biocompatibility of self-assembled structures; however, glycopolymer block copolymers have been less explored, and their structure-property relationships are not well understood. In this study, novel glycopolymer-branched poly(lactic acid) (PLA) block copolymers were synthesized via thiol-ene coupling and their composition-dependent morphologies were elucidated. Stability as a function of pH, dye uptake capabilities, and cytotoxicity were evaluated. Systems with a hydrophilic weight ratio of 30% were found to produce bilayer nanoparticles, while systems with a hydrophilic weight ratio of 60% form micelles upon self-assembly in aqueous media. Regardless of composition and morphology, all systems exhibited uptake of both hydrophobic (curcumin, DL % from 4.25 to 11.55) and hydrophilic (methyl orange, DL % from 4.08 to 5.88) dye molecules with release profiles dependent on composition. Furthermore, all of the nanoparticles exhibited low cytotoxicity, confirming their potential for biomedical applications.

4.
Soft Matter ; 19(27): 5150-5159, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37386911

RESUMO

Proteinaceous amyloids are well known for their widespread pathological roles but lately have emerged also as key components in several biological functions. The remarkable ability of amyloid fibers to form tightly packed conformations in a cross ß-sheet arrangement manifests in their robust enzymatic and structural stabilities. These characteristics of amyloids make them attractive for designing proteinaceous biomaterials for various biomedical and pharmaceutical applications. In order to design customizable and tunable amyloid nanomaterials, it is imperative to understand the sensitivity of the peptide sequence for subtle changes based on amino acid position and chemistry. Here we report our results from four rationally-designed amyloidogenic decapeptides that subtly differ in hydrophobicity and polarity at positions 5 and 6. We show that making the two positions hydrophobic renders the peptide with enhanced aggregation and material properties while introducing polar residues in position 5 dramatically changes the structure and nanomechanical properties of the fibrils formed. A charged residue at position 6, however, abrogates amyloid formation. In sum, we show that subtle changes in the sequence do not make the peptide innocuous but rather sensitive to aggregation, reflected in the biophysical and nanomechanical properties of the fibrils. We conclude that tolerance of peptide amyloid for changes in the sequence, however small they may be, should not be neglected for the effective design of customizable amyloid nanomaterials.


Assuntos
Amiloide , Peptídeos , Peptídeos/química , Amiloide/química , Sequência de Aminoácidos , Aminoácidos
5.
Biophys J ; 121(11): 2107-2126, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35490297

RESUMO

Cytoplasmic inclusions containing aberrant proteolytic fragments of TDP-43 are associated with frontotemporal lobar degeneration (FTLD) and other related pathologies. In FTLD, TDP-43 is translocated into the cytoplasm and proteolytically cleaved to generate a prion-like domain (PrLD) containing C-terminal fragments (C25 and C35) that form toxic inclusions. Under stress, TDP-43 partitions into membraneless organelles called stress granules (SGs) by coacervating with RNA and other proteins. To study the factors that influence the dynamics between these cytoplasmic foci, we investigated the effects of cysteine-rich granulins (GRNs 1-7), which are the proteolytic products of progranulin, a protein implicated in FTLD, on TDP-43. We show that extracellular GRNs, typically generated during inflammation, internalize and colocalize with PrLD as puncta in the cytoplasm of neuroblastoma cells but show less likelihood of their presence in SGs. In addition, we show GRNs and PrLD coacervate to undergo liquid-liquid phase separation (LLPS) or form gel- or solid-like aggregates. Using charge patterning and conserved cysteines among the wild-type GRNs as guides, along with specifically engineered mutants, we discover that the negative charges on GRNs drive LLPS while the positive charges and the redox state of cysteines modulate these phase transitions. Furthermore, RNA and GRNs compete and expel one another from PrLD condensates, providing a basis for GRN's absence in SGs. Together, the results help uncover potential modulatory mechanisms by which extracellular GRNs, formed during chronic inflammatory conditions, could internalize and modulate cytoplasmic TDP-43 inclusions in proteinopathies.


Assuntos
Esclerose Lateral Amiotrófica , Proteínas de Ligação a DNA , Degeneração Lobar Frontotemporal , Granulinas , Esclerose Lateral Amiotrófica/metabolismo , Proteínas de Ligação a DNA/metabolismo , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia , Granulinas/metabolismo , Humanos , Oxirredução , Agregação Patológica de Proteínas , RNA/metabolismo
6.
FASEB J ; 35(2): e21318, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33508158

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects cognition and memory. Recent advances have helped identify many clinical sub-types in AD. Mounting evidence point toward structural polymorphism among fibrillar aggregates of amyloid-ß (Aß) to being responsible for the phenotypes and clinical manifestations. In the emerging paradigm of polymorphism and prion-like propagation of aggregates in AD, the role of low molecular weight soluble oligomers, which are long known to be the primary toxic agents, in effecting phenotypes remains inconspicuous. In this study, we present the characterization of three soluble oligomers of Aß42, namely 14LPOs, 16LPOs, and GM1Os with discreet biophysical and biochemical properties generated using lysophosphatidyl glycerols and GM1 gangliosides. The results indicate that the oligomers share some biophysical similarities but display distinctive differences with GM1Os. Unlike the other two, GM1Os were observed to be complexed with the lipid upon isolation. It also differs mainly in detection by conformation-sensitive dyes and conformation-specific antibodies, temperature and enzymatic stability, and in the ability to propagate morphologically-distinct fibrils. GM1Os also show distinguishable biochemical behavior with pronounced neuronal toxicity. Furthermore, all the oligomers induce cerebral amyloid angiopathy (CAA) and plaque burden in transgenic AD mice, which seems to be a consistent feature among all lipid-derived oligomers, but 16LPOs and GM1Os displayed significantly higher effect than the others. These results establish a correlation between molecular features of Aß42 oligomers and their distinguishable effects in transgenic AD mice attuned by lipid characteristics, and therefore help bridge the knowledge gap in understanding how oligomer conformers could elicit AD phenotypes.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Lipídeos/farmacologia , Amiloide/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Dicroísmo Circular , Difusão Dinâmica da Luz , Gangliosídeo G(M1)/farmacologia , Imuno-Histoquímica , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Transgênicos , Microscopia de Força Atômica , Fosfatidilgliceróis/farmacologia , Placa Amiloide/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Biomacromolecules ; 23(1): 34-46, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-34793129

RESUMO

The black-legged tick (Ixodes scapularis) is the primary vector for bacteria that cause Lyme disease (Borrelia burgdorferi), where numerous glycosylated tick proteins are involved at the interface of vector-host-pathogen interactions. Reducing the expression of key tick proteins, such as selenoprotein K (SelK), through RNA interference is a promising approach to reduce pathogen transmission, but efficient delivery of nucleic acids to arthropods has proven challenging. While cationic glycopolymers have been used as nonviral gene delivery vehicles in mammalian cells, their use in arthropod or insect gene transfection has not been established. In this study, statistical acrylamide-based cationic glycopolymers with glucose or galactose pendant groups were synthesized by reversible addition-fragmentation chain transfer polymerization, and the effects of the saccharide pendant group and cationic monomer loading on polymer cytotoxicity, RNA complexation, and SelK gene knockdown in ISE6 cells were evaluated. All polymers exhibited low cytotoxicity, yet RNA/copolymer complex cell uptake and gene knockdown were highly dependent on the saccharide structure and the N:P (amino to phosphate groups) ratio.


Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Animais , Proteínas de Artrópodes/metabolismo , Borrelia burgdorferi/metabolismo , Ixodes/genética , Ixodes/metabolismo , Ixodes/microbiologia , Doença de Lyme/genética , Doença de Lyme/microbiologia , Interferência de RNA
8.
Macromol Rapid Commun ; 43(24): e2200487, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35822234

RESUMO

Incorporating dynamic covalent bonds into block copolymers provides useful molecular level information during mechanical testing, but it is currently unknown how the incorporation of these units affects the resultant polymer morphology. High-molecular-weight polyisobutylene-b-polystyrene block copolymers containing an anthracene/maleimide dynamic covalent bond are synthesized through a combination of postpolymerization modification, reversible addition-fragmentation chain-transfer polymerization, and Diels-Alder coupling. The bulk morphologies with and without dynamic covalent bond are characterized by atomic force microscopy  and small-angle X-ray scattering, which reveal a strong dependence on annealing time and casting solvent. Morphology is largely unaffected by the inclusion of the mechanophore. The high-molecular-weight polymers synthesized allow interrogation of a large range of polymer domain sizes.

9.
Macromol Rapid Commun ; 43(24): e2200249, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35856189

RESUMO

Likened to both thermosets and thermoplastics, vitrimers are a unique class of materials that combine remarkable stability, healability, and reprocessability. Herein, this work describes a photopolymerized thiol-ene-based vitrimer that undergoes dynamic covalent exchanges through uncatalyzed transamination of enamines derived from cyclic ß-triketones, whereby the low energy barrier for exchange facilitates reprocessing and enables rapid depolymerization. Accordingly, an alkene-functionalized ß-triketone, 5,5-dimethyl-2-(pent-4-enoyl)cyclohexane-1,3-dione, is devised which is then reacted with 1,6-diaminohexane in a stoichiometrically imbalanced fashion (≈1:0.85 primary amine:triketone). The resulting networks exhibit subambient glass transition temperature (Tg = 5.66 °C) by differential scanning calorimetry. Using a Maxwell stress-relaxation fit, the topology-freezing temperature (Tv ) is calculated to be -32 °C. Small-amplitude oscillatory shear rheological analysis enables to identify a practical critical temperature above which the vitrimer can be successfully reprocessed (Tv,eff ). Via the introduction of excess primary amines, this work can readily degrade the networks into monomeric precursors, which are in turn reacted with diamines to regenerate reprocessable networks. Photopolymerization provides unique spatiotemporal control over the network topology, thereby opening the path for further investigation of vitrimer properties. As such, this work expands the toolbox of chemical upcycling of networks and enables their wider implementation.

10.
Proc Natl Acad Sci U S A ; 116(19): 9604-9609, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31004051

RESUMO

Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case-control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case-control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case-control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.


Assuntos
Encéfalo , Regulação da Expressão Gênica , Rede Nervosa , Vias Neurais , Neuroimagem , Transtornos Psicóticos , Esquizofrenia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/metabolismo , Rede Nervosa/patologia , Vias Neurais/metabolismo , Vias Neurais/patologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/metabolismo
11.
Brain Behav Immun ; 98: 299-309, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34450247

RESUMO

OBJECTIVE: There is increasing evidence for a subgroup of major depressive disorder (MDD) associated with heightened peripheral blood inflammatory markers. In this study, we aimed to understand the mechanistic brain-immune axis in inflammation-linked depression by investigating associations between functional connectivity (FC) of brain networks and peripheral blood immune markers in depression. METHODS: Resting-state functional magnetic resonance imaging (fMRI) and peripheral blood inflammatory markers (C-reactive protein; CRP, interleukin-6; IL-6 and immune cells) were collected on N = 46 healthy controls (HC; CRP ≤ 3 mg/L) and N = 83 cases of depression, stratified further into low CRP cases (loCRP cases; ≤ 3 mg/L; N = 50) and high CRP cases (hiCRP cases; > 3 mg/L; N = 33). In a two-part analysis, network-based statistics (NBS) was firstly used to ascertain whole-brain FC differences in HC vs hiCRP cases. Secondly, we investigated the association between this network of interconnected brain regions and continuous measures of peripheral CRP (N = 83), IL-6 (N = 72), neutrophils and CD4+ T-cells (N = 36) in depression cases only. RESULTS: Case-control NBS testing revealed a single network of abnormally attenuated FC in the high CRP depression cases compared to healthy controls. Connections within this network were mainly between brain regions located in the left insula/frontal operculum and posterior cingulate cortex, which were assigned to ventral attention and default mode canonical fMRI networks respectively. Within-group analysis across all depression cases, secondarily demonstrated that FC within the identified network significantly negatively scaled with CRP, IL-6 and neutrophils. CONCLUSIONS: The findings suggest that inflammation is associated with disruption of functional connectivity within a brain network deemed critical for interoceptive signalling, e.g. accurate communication of peripheral bodily signals such as immune states to the brain, with implications for the pathogenesis of inflammation-linked depression.


Assuntos
Transtorno Depressivo Maior , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
12.
Biomacromolecules ; 21(10): 4280-4293, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32786526

RESUMO

Saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition processes and protein binding. Synthetic glycopolymers with pendant saccharides of controlled stereochemistry provide an attractive approach for the design of polysaccharide-inspired biomaterials. Acrylamide-based polymers containing either ß,d-glucose or ß,d-galactose pendant groups, designed to mimic GM1 ganglioside saccharides, and their small-molecule analogues were used to evaluate the effect of stereochemistry on glycopolymer solution aggregation processes alone and in the presence of Aß42 peptide using dynamic light scattering, gel permeation chromatography-multiangle laser light scattering, and fluorescence assays. Fourier transform infrared and nuclear magnetic resonance (NMR) were employed to determine hydrogen bonding patterns of the systems. The galactose-containing polymer displayed significant intramolecular hydrogen bonding and self-aggregation and minimal association with Aß42, while the glucose-containing glycopolymers showed intermolecular interactions with the surrounding environment and association with Aß42. Saturation transfer difference NMR spectroscopy demonstrated different binding affinities for the two glycopolymers to Aß42 peptide.


Assuntos
Peptídeos beta-Amiloides , Polímeros , Gangliosídeo G(M1) , Galactose , Ligação de Hidrogênio
13.
J Chem Phys ; 150(7): 075101, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795679

RESUMO

As the primary toxic species in the etiology of Alzheimer disease (AD) are low molecular weight oligomers of Aß, it is crucial to understand the structure of Aß oligomers for gaining molecular insights into AD pathology. We have earlier demonstrated that in the presence of fatty acids, Aß42 peptides assemble as 12-24mer oligomers. These Large Fatty Acid-derived Oligomers (LFAOs) exist predominantly as 12mers at low and as 24mers at high concentrations. The 12mers are more neurotoxic than the 24mers and undergo self-replication, while the latter propagate to morphologically distinct fibrils with succinct pathological consequences. In order to glean into their functional differences and similarities, we have determined their structures in greater detail by combining molecular dynamic simulations with biophysical measurements. We conjecture that the LFAO are made of Aß units in an S-shaped conformation, with the 12mers forming a double-layered hexamer ring (6 × 2) while the structure of 24mers is a double-layered dodecamer ring (12 × 2). A closer inspection of the (6 × 2) and (12 × 2) structures reveals a concentration and pH dependent molecular reorganization in the assembly of 12 to 24mers, which seems to be the underlying mechanism for the observed biophysical and cellular properties of LFAOs.


Assuntos
Peptídeos beta-Amiloides/química , Ácidos Graxos/química , Fragmentos de Peptídeos/química , Multimerização Proteica , Simulação de Dinâmica Molecular , Estrutura Quaternária de Proteína
14.
Biomacromolecules ; 18(10): 3359-3366, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-28893064

RESUMO

GM1 ganglioside is known to promote amyloid-ß (Aß) peptide aggregation in Alzheimer's disease. The roles of the individual saccharides and their distribution in this process are not understood. Acrylamide-based glycomonomers with either ß-d-glucose or ß-d-galactose pendant groups were synthesized to mimic the stereochemistry of saccharides present in GM1 and characterized via 1H NMR and electrospray ionization mass spectrometry. Glycopolymers of different molecular weights were synthesized by aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization and characterized by NMR and GPC. The polymers were used as models to investigate the effects of molecular weight and saccharide unit type on Aß aggregation via thioflavin-T fluorescence and PAGE. High molecular weight (∼350 DP) glucose-containing glycopolymers had a profound effect on Aß aggregation, promoting formation of soluble oligomers of Aß and limiting fibril production, while the other glycopolymers and negative control had little effect on the Aß propagation process.


Assuntos
Acrilamida/química , Peptídeos beta-Amiloides/química , Materiais Biomiméticos/síntese química , Gangliosídeo G(M1)/química , Galactose/análogos & derivados , Glucose/análogos & derivados , Benzotiazóis , Materiais Biomiméticos/química , Polimerização , Agregados Proteicos , Tiazóis/química
15.
Biomacromolecules ; 16(12): 3845-52, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26558609

RESUMO

Naturally occurring antimicrobial peptides (AMPs) display the ability to eliminate a wide variety of bacteria, without toxicity to the host eukaryotic cells. Synthetic polymers containing moieties mimicking lysine and arginine components found in AMPs have been reported to show effectiveness against specific bacteria, with the mechanism of activity purported to depend on the nature of the amino acid mimic. In an attempt to incorporate the antimicrobial activity of both amino acids into a single water-soluble copolymer, a series of copolymers containing lysine mimicking aminopropyl methacrylamide (APMA) and arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared via aqueous RAFT polymerization. Copolymers were prepared with varying ratios of the comonomers, with degree of polymerization of 35-40 and narrow molecular weight distribution to simulate naturally occurring AMPs. Antimicrobial activity was determined against Gram-negative and Gram-positive bacteria under conditions with varying salt concentration. Toxicity to mammalian cells was assessed by hemolysis of red blood cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed for APMA homopolymer and copolymers with low concentrations of GPMA against all bacteria tested, with low toxicity toward mammalian cells.


Assuntos
Acrilamidas/química , Aminas/química , Peptídeos Catiônicos Antimicrobianos/síntese química , Guanidinas/química , Peptidomiméticos/síntese química , Polímeros/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Arginina/química , Sobrevivência Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Lisina/química , Células MCF-7 , Estrutura Molecular , Peptidomiméticos/farmacologia , Polimerização , Polímeros/farmacologia
16.
Chemosphere ; : 143338, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278320

RESUMO

Environmental MPs are complex mixtures of plastic polymers and sorbed chemical pollutants with high degrees of heterogeneity, particularly in terms of particle size, morphology and degree of weathering. Currently, limitations exist in sampling sufficient amounts of environmental particles for laboratory studies to assess toxicity endpoints with statistical rigor and to examine chemical pollutant interactions. This study seeks to bridge this gap by investigating environmental plastic particle mimetics and pollutant-polymer interactions by mixing polymer particles with persistent organic pollutants (POPs) at set concentrations over time. Solutions containing combinations of polymers including polystyrene (PS), polypropylene (PP), polyethylene terephthalate (PET), and polyamide (PA) and POPs including 2,3,7,8 -Tetrachlorodibenzo-p-dioxin (TCDD), bisphenol A (BPA), and atrazine, were stirred for up to 19 weeks and monitored using assays to test for aryl hydrocarbon (AhR) and estrogen receptor (ER) activity which are cell signaling pathways impacted by environmental pollutants. TCDD induced AhR activity decreased over time in the presence of PS in a surface area dependent manner. BPA and atrazine also exhibited AhR antagonist activity in the presence of TCDD. The addition of BPA slowed the loss of activity but atrazine did not, suggesting that polymer chemistry impacts interactions with POPs. We also observed potential differences in TCDD sorption with different plastic polymers and that higher concentrations of PS particles may inhibit BPA-induced estrogen receptor activation. These results emphasize the need for additional understanding of how POPs and polymer chemistry impacts their interaction and toxicity.

17.
Eco Environ Health ; 3(3): 347-354, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39281073

RESUMO

This project reports on the use of a novel nanomembrane filtering technology to isolate and analyze the bioactivity of microplastic (MP)-containing debris from Lake Ontario water samples. Environmental MPs are a complex mixture of polymers and sorbed chemicals that are persistent and can exhibit a wide range of toxic effects. Since human exposure to MPs is unavoidable, it is necessary to characterize their bioactivity to assess potential health risks. This work seeks to quantify MP presence in the nearshore waters of Lake Ontario and begin to characterize the bioactivity of the filtrate containing MPs. We utilized silicon nitride (SiN) nanomembrane technology to isolate debris sized between 8 and 20 µm from lake water samples collected at various times and locations. MPs were identified with Nile red staining. Cell-based assays were conducted directly on the filtered debris to test for cell viability, aryl hydrocarbon receptor (AhR) activity, and interleukin 6 (IL-6) levels as a measure of proinflammatory response. All samples contained MPs. None of the isolated debris impacted cell viability. However, AhR activity and IL-6 levels varied over time. Additionally, no associations were observed between the amount of plastic and bioactivity. Observed differences in activity are likely due to variations in the physiochemical properties of debris between samples. Our results highlight the need for increased sampling to fully characterize the bioactivity of MPs in human cells and to elucidate the role that sample physiochemical and spatiotemporal properties play in this activity.

18.
Curr Protoc ; 4(7): e1104, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39018010

RESUMO

Microplastics (MPs; 1 µm to 5 mm) are a persistent and pervasive environmental pollutant of emergent and increasing concern. Human exposure to MPs through food, water, and air has been documented and thus motivates the need for a better understanding of the biological implications of MP exposure. These impacts are dependent on the properties of MPs, including size, morphology, and chemistry, as well as the dose and route of exposure. This overview offers a perspective on the current methods used to assess the bioactivity of MPs. First, we discuss methods associated with MP bioactivity research with an emphasis on the variety of assays, exposure conditions, and reference MP particles that have been used. Next, we review the challenges presented by common instrumentation and laboratory materials, the lack of standardized reference materials, and the limited understanding of MP dosimetry. Finally, we propose solutions that can help increase the applicability and impact of future studies while reducing redundancy in the field. The excellent protocols published in this issue are intended to contribute toward standardizing the field so that the MP knowledge base grows from a reliable foundation. © 2024 Wiley Periodicals LLC.


Assuntos
Exposição Ambiental , Microplásticos , Microplásticos/toxicidade , Humanos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Monitoramento Ambiental/métodos
19.
bioRxiv ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39211215

RESUMO

Interest in utilizing amyloids to develop biomaterials is increasing due to their potential for biocompatibility, unique assembling morphology, mechanical stability, and biophysical properties. However, challenges include the complexity of peptide chemistry and the practical techniques required for processing amyloids into bulk materials. In this work, two decapeptides with fibrillar and globular morphologies were selected, blended with poly(ethylene oxide), and fabricated into composite mats via electrospinning. Notable enhancements in mechanical properties were observed, attributed to the uniform distribution of the decapeptide assemblies within the PEO matrix. Morphological differences, such as the production of thinner nanofibers, are attributed to the increased conductivity from the zwitterionic nature of the decapeptides. Blend rheology and post-processing analysis revealed how processing might affect the amyloid aggregation and secondary structure of the peptides. Both decapeptides demonstrated good biocompatibility and strong antioxidant activity, indicating their potential for safe and effective use as biomaterials. By evaluating these interdependencies, this research lays the foundation for understanding the structure-property-processing relationships of peptide-polymer blends and highlights the strong potential for developing applications in biotechnology.

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