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Herein, we describe the synthesis of a 1,2σ3λ3-oxaphosphetane from ethylene oxide and its reactions with alkyl halides to form β-halo phosphane oxides in an Arbuzov-type reaction. When methyl triflate was used as a hard electrophile, cationic oligomerisation of 1,2-oxaphosphetanes was observed. DFT calculations indicate 1,2-oxaphosphetan-2-iums as intermediates and reveal differences between the Arbuzov and the potential Perkow reaction pathway. [ABSTRACT FROM AUTHOR]

Incorporating hydrolytically sensitive functional groups into polymer backbones provides a feasible strategy to trigger their degradation to the starting monomers, thus enabling chemical recycling of the material. Here, we present two series of copolyesters in which a biobased spirocyclic ketal-functional diester monomer was incorporated into poly(butylene 2,5-furandicarboxylate) (PBLF) and poly(hexamethylene 2,5-furandicarboxylate) (PHLF), respectively. A two-step melt polycondensation resulted in copolyesters with moderate to high molecular weights, as confirmed by intrinsic viscosity and size exclusion chromatography data. Thermogravimetric analysis showed a thermal stability up to 275 °C, and increasing char yields upon incorporation of the spirocyclic monomer. The crystallinity and melting points of the copolyesters decreased with an increasing content of the spirocyclic ketal units in the backbone. Copolyesters containing up to 15% of the spiro-ketal units were semicrystalline, while those containing 20 and 50% spiro-ketal units were completely amorphous. The hydrolytic degradation of copolyesters from the PHLF series was investigated using 3–12 M aq. HCl, and were found to degrade faster than the corresponding homopolyesters. Acid-catalyzed cleavage of the randomly distributed spiro ketal units promoted the rapid fragmentation of the polymer chain into small oligomers, which were subsequently hydrolyzed to the original chemical building blocks. The ketone-terminated telechelic oligomers obtained after the degradation of spirocyclic ketal units were also investigated in a direct polymerization with pentaerythritol. The initial results implied that the oligomers can be re-polymerized into the original polymer. Hence, this work demonstrated a feasible pathway towards chemically recyclable 2,5-furandicarboxylate polyesters with a tuneable degree of crystallinity. [ABSTRACT FROM AUTHOR]

This study investigates the effect of adding oligomers on the rheological properties of polymer nanocomposite melts with the goal of enhancing the processability of nanocomposites. The scaling analysis of plateau modulus (GN) is used in understanding the complex mechanical behavior of entangled poly(methyl acrylate) (PMA) melts upon oligomer addition. Increasing the oligomer amount led to a decrease in GN and an apparent degree of entanglement (Z) in the neat polymer melt. The particle dispersion states at two particle loadings with oligomer addition are examined in transmission electron microscopy (TEM) and small‐angle X‐ray scattering (SAXS). The dilution exponent is found unchanged at 7 and 17 vol% particle loadings for the well‐dispersed PMA‐SiO2 nanocomposites compared to the neat PMA solution. These findings suggest that attractive particles with strong interfacial layers do not influence the tube dilution scaling of the polymer with the oligomer. To the contrary, composites with weak polymer‐particle interfaces demonstrate phase separation of particles when oligomers are introduced and its exponent for tube dilution scaling reaches 4 at a particle loading of 17 vol%, potentially indicating that network‐forming clusters influence chain entanglements in this scenario. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The rapid synthesis of structurally complicated electron donors & acceptors still remains a major challenge in organic solar cells (OSC). In this work, we developed a highly efficient strategy to access long‐chain oligomeric donor and acceptors for OSC applications. A series of cyclopentadithiophene (CPDT) and benzothiadiazole (BT)‐based π‐conjugated oligomers, i.e., three oligomeric acceptors (BTDT)n‐IC (n = 1—3) and one long‐chain oligomeric donor (BTDT)4‐RD, are facilely synthesized by an atom‐ and step‐economical, and labor‐saving direct C—H arylation (DACH) reaction (i.e., C—H/C—Br cross coupling). Note that (BTDT)4‐RD involving five CPDT, four BT and two rhodamine (RD) building blocks is the longest oligomeric donor in the fullerene‐free OSC devices ever reported. The dependence of the structure‐property‐performance correlation of (BTDT)n‐IC (n = 1—3) and (BTDT)4‐RD on the π‐conjugation lengths is thoroughly investigated by opto‐electrochemical measurements, bulk heterojunction (BHJ) OSC devices and microscopies. The (BTDT)1‐IC:PBDB‐T and (BTDT)4‐RD:Y6 BHJs achieve power conversion efficiencies of 9.14% and 4.51%, respectively. Our findings demonstrate that DACH reaction is a powerful tool to tune the opto‐electronic properties and device performances by regulating the lengths of π‐conjugated oligomers with varied numbers of repeating units. [ABSTRACT FROM AUTHOR]

Amyloidosis is a condition involving a disparate group of pathologies characterized by the extracellular deposition of insoluble fibrils composed of broken-down proteins. These proteins can accumulate locally, causing peculiar symptoms, or in a widespread way, involving many organs and. causing severe systemic failure. The damage that is created is related not only to the accumulation of. amyloid fibrils but above all to the precursor oligomers of the fibrils that manage to enter the cell in a very particular way. This article analyzes the current state of research related to the entry of these oligomers into the cell membrane and the theories related to their toxicity. The paper proposed here not only aims to review the contents in the literature but also proposes a new vision of amyloid toxicity. that could occur in a multiphase process catalyzed by the cell membrane itself. In this process, the denaturation of the lipid bilayer is followed by the stabilization of a pore through energetically favorable self-assembly processes which are achieved through particular oligomeric structures. [ABSTRACT FROM AUTHOR]

New data suggest that the aggregation of misfolded native proteins initiates and drives the pathogenic cascade that leads to Alzheimer's disease (AD) and other age-related neurodegenerative disorders. We propose a unifying single toxin theory of brain neurodegeneration that identifies new targets and approaches to the development of disease-modifying treatments. An extensive body of genetic evidence suggests soluble aggregates of beta-amyloid (Aβ) as the primary neurotoxin in the pathogenesis of AD. New insights from fluid biomarkers, imaging, and clinical studies provide further evidence for the decisive impact of toxic Aβ species in the initiation and progression of AD. Understanding the distinct roles of soluble and insoluble amyloid aggregates on AD pathogenesis has been the key missing piece of the Alzheimer's puzzle. Data from clinical trials with anti-amyloid agents and recent advances in the diagnosis of AD demonstrate that the driving insult in biologically defined AD is the neurotoxicity of soluble Aβ aggregates, called oligomers and protofibrils, rather than the relatively inert insoluble mature fibrils and amyloid plaques. Amyloid oligomers appear to be the primary factor causing the synaptic impairment, neuronal stress, spreading of tau pathology, and eventual cell death that lead to the clinical syndrome of AD dementia. All other biochemical effects and neurodegenerative changes in the brain that are observed in AD are a response to or a downstream effect of this initial toxic insult by oligomers. Other neurodegenerative disorders follow a similar pattern of pathogenesis, in which normal brain proteins with important biological functions become trapped in the aging brain due to impaired clearance and then misfold and aggregate into neurotoxic species that exhibit prion-like behavior. These aggregates then spread through the brain and cause disease-specific neurodegeneration. Targeting the inhibition of this initial step in neurodegeneration by blocking the misfolding and aggregation of healthy proteins has the potential to slow or arrest disease progression, and if treatment is administered early in the course of AD and other neurodegenerative disorders, it may delay or prevent the onset of clinical symptoms. [ABSTRACT FROM AUTHOR]

Myelin basic protein (MBP) is the second most abundant protein in the central nervous system and is responsible for structural maintenance of the myelin sheath covering axons. Previously, we showed that MBP has a more proactive role in the oligodendrocyte homeostasis, interacting with membrane-associated proteins, including integral membrane protein 2B (ITM2B or Bri2) that is associated with familial dementias. Here, we report that the molecular dynamics of the in silico-generated MBP-Bri2 complex revealed that MBP covers a significant portion of the Bri2 ectodomain, assumingly trapping the furin cleavage site, while the surface of the BRICHOS domain, which is responsible for the multimerization and activation of the Bri2 high-molecular-weight oligomer chaperone function, remains unmasked. These observations were supported by the co-expression of MBP with Bri2, its mature form, and disease-associated mutants, which showed that in mammalian cells, MBP indeed modulates the post-translational processing of Bri2 by restriction of the furin-catalyzed release of its C-terminal peptide. Moreover, we showed that the co-expression of MBP and Bri2 also leads to an altered cellular localization of Bri2, restricting its membrane trafficking independently of the MBP-mediated suppression of the Bri2 C-terminal peptide release. Further investigations should elucidate if these observations have physiological meaning in terms of Bri2 as a MBP chaperone activated by the MBP-dependent postponement of Bri2 membrane trafficking. [ABSTRACT FROM AUTHOR]

A lignin model oligomer with only β-O-4 linkages and a selectively deuterium-labelled methoxy group at the phenolic terminal units was synthesised to clarify the behaviour of the phenolic end of oligolignols. First, t-butoxycarbonylmethyl vanillin was synthesised and oligomerised by nucleophilic addition, a known method. The terminal of the oligomers was then subjected to nucleophilic addition to [3-OCD3]benzyl vanillin to achieve selective labelling of the terminal units. A deuterium-labelled lignin model oligomer (D-LM) was obtained through debenzylation and subsequent reduction. The results of thioacidolysis after methylation revealed that the degree of polymerisation was about five, and the deuterium-labelled phenylpropane unit was located only at the phenolic terminal moiety. [ABSTRACT FROM AUTHOR]

Protein misfolding and aggregation are crucial pathogenic factors for cataracts, which are the leading cause of visual impairment worldwide. 𝛼-crystallin, as a small molecular chaperone, is involved in preventing protein misfolding and maintaining lens transparency. The chaperone activity of 𝛼-crystallin depends on its oligomeric state. Our previous work identified a natural compound, celastrol, which could regulate the oligomeric state of 𝛼B-crystallin. In this work, based on the UNcle and SEC analysis, we found that celastrol induced 𝛼B-crystallin to form large oligomers. Large oligomer formation enhanced the chaperone activity of 𝛼B-crystallin and prevented aggregation of the cataract-causing mutant 𝛽A3-G91del. The interactions between 𝛼B-crystallin and celastrol were detected by the FRET (Fluorescence Resonance Energy Transfer) technique, and verified by molecular docking. At least 9 binding patterns were recognized, and some binding sites covered the groove structure of 𝛼B-crystallin. Interestingly, 𝛼B-R120G, a cataract-causing mutation located at the groove structure, and celastrol can decrease the aggregates of 𝛼B-R120G. Overall, our results suggested celastrol not only promoted the formation of large 𝛼B-crystallin oligomers, which enhanced its chaperone activity, but also bound to the groove structure of its 𝛼-crystallin domain to maintain its structural stability. Celastrol might serve as a chemical and pharmacological chaperone for cataract treatment. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has been widely used to manage debilitating neurological symptoms in movement disorders such as Parkinson's disease (PD). Despite its well-established symptomatic benefits, our understanding of the mechanisms underlying DBS and its possible effect on the accumulation of pathological proteins in neurodegeneration remains limited. Accumulation and oligomerization of the protein alpha-synuclein ( α -Syn) are implicated in the loss of dopaminergic neurons in the substantia nigra in PD, making α -Syn a potential therapeutic target for disease modification. We examined the effects of high frequency electrical stimulation on α -Syn levels and oligomerization in cell and rodent models. High frequency stimulation, mimicking DBS parameters used for PD, was combined with viral-mediated overexpression of α -Syn in cultured rat primary cortical neurons or in substantia nigra of rats. Bimolecular protein complementation with split fluorescent protein reporters was used to detect and quantify α -Syn oligomers. High frequency electrical stimulation reduced the expression of PD-associated mutant α -Syn and mitigated α -Syn oligomerization in cultured neurons. Furthermore, DBS in the substantia nigra, but not the subthalamic nucleus, decreased overall levels of α -Syn, including oligomer levels, in the substantia nigra. Taken together, our results demonstrate that direct high frequency stimulation can reduce accumulation and pathological forms of α -Syn in cultured neurons in vitro and in substantia nigra in vivo. Thus, DBS therapy could have a role beyond symptomatic treatment, with potential disease-modifying properties that can be exploited to target pathological proteins in neurodegenerative diseases. • High frequency stimulation reduces α -synuclein accumulation in cultured neurons. • Deep brain stimulation of the substantia nigra reduces α -synuclein accumulation in rats. • Deep brain stimulation could have a role beyond symptomatic treatment, with potential disease-modifying properties. One sentence summary: Electrical stimulation reduces α -synuclein accumulation in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The rapid synthesis of structurally complicated electron donors & acceptors still remains a major challenge in organic solar cells (OSC). In this work, we developed a highly efficient strategy to access long‐chain oligomeric donor and acceptors for OSC applications. A series of cyclopentadithiophene (CPDT) and benzothiadiazole (BT)‐based π‐conjugated oligomers, i.e., three oligomeric acceptors (BTDT)n‐IC (n = 1—3) and one long‐chain oligomeric donor (BTDT)4‐RD, are facilely synthesized by an atom‐ and step‐economical, and labor‐saving direct C—H arylation (DACH) reaction (i.e., C—H/C—Br cross coupling). Note that (BTDT)4‐RD involving five CPDT, four BT and two rhodamine (RD) building blocks is the longest oligomeric donor in the fullerene‐free OSC devices ever reported. The dependence of the structure‐property‐performance correlation of (BTDT)n‐IC (n = 1—3) and (BTDT)4‐RD on the π‐conjugation lengths is thoroughly investigated by opto‐electrochemical measurements, bulk heterojunction (BHJ) OSC devices and microscopies. The (BTDT)1‐IC:PBDB‐T and (BTDT)4‐RD:Y6 BHJs achieve power conversion efficiencies of 9.14% and 4.51%, respectively. Our findings demonstrate that DACH reaction is a powerful tool to tune the opto‐electronic properties and device performances by regulating the lengths of π‐conjugated oligomers with varied numbers of repeating units. [ABSTRACT FROM AUTHOR]

This work explores the definition and characterization of synthetic polymeric oligomers, chemical substances comprising a small number of repeated organic molecules. It highlights the lack of clarity surrounding the range of repeated units that can be classified as an oligomer, and how this definition is field-dependent. The present study focused on PET cyclic oligomers and revealed that the progression of the ring length from smaller to longer oligomers followed the well-known odd-even effect. This phenomenon affects the physical and chemical properties of oligomers and can also be observed with analytical techniques such as differential scanning calorimetry (DSC), high resolution mass spectrometry (HR-MS) and NMR. Similarities between PET and PBT oligomers were also observed, and an alternative potential definition for oligomers in the polymeric field is suggested based on physical behaviour of the longer cyclic oligomers. [ABSTRACT FROM AUTHOR]

This study delved into the correlation between the chain length of PEG polymerizable oligomers and the electro-optical properties exhibited by the resultant PDLC films. A range of di(meth)acrylate oligomers derived from polyethylene glycol with varying molecular weights (Mn = 1000, 2000, 4000, and 6000 g mol−1) was synthesized for incorporation as the polymer matrix in PDLC devices. Comprehensive analyses employing 1H-NMR, 13C-NMR, and MALDI-TOF mass spectroscopy were conducted to validate the structure and purity of the synthesized products. The investigation revealed a significant influence of pre-polymer molecular chain length on the thermal properties of the polymer, including amorphousness and crystallinity, which in turn impact the permanent memory effect. Specifically, it was observed that amorphous PEG polymers serve as an ideal matrix for fostering the permanent memory effect in PDLCs. Among the polymerizable PEG oligomers examined, those with a molecular weight of 1000 g/mol yielded polymer chains existing in an amorphous state, exhibiting a glass transition temperature lower than room temperature (−50 °C). This characteristic imparts flexibility and mobility to the polymer matrix chains, facilitating a 37% permanent memory effect. Conversely, longer polymer chains lead to the formation of crystal aggregates, resulting in semi-crystalline polymer matrices. This reduces the malleability of the polymer chains, thereby nullifying the permanent memory effect in the corresponding PDLC devices. [ABSTRACT FROM AUTHOR]

Intra- or extracellular aggregates of proteins are central pathogenic features in most neurodegenerative disorders. The accumulation of such proteins in diseased brains is believed to be the end-stage of a stepwise aggregation of misfolded monomers to insoluble cross-β fibrils via a series of differently sized soluble oligomers/protofibrils. Several studies have shown how α-synuclein, amyloid-β, tau and other amyloidogenic proteins can act as nucleating particles and thereby share properties with misfolded forms, or strains, of the prion protein. Although the roles of different protein assemblies in the respective aggregation cascades remain unclear, oligomers/protofibrils are considered key pathogenic species. Numerous observations have demonstrated their neurotoxic effects and a growing number of studies have indicated that they also possess seeding properties, enabling their propagation within cellular networks in the nervous system. The seeding behavior of oligomers differs between the proteins and is also affected by various factors, such as size, shape and epitope presentation. Here, we are providing an overview of the current state of knowledge with respect to the “prion-like” behavior of soluble oligomers for several of the amyloidogenic proteins involved in neurodegenerative diseases. In addition to providing new insight into pathogenic mechanisms, research in this field is leading to novel diagnostic and therapeutic opportunities for neurodegenerative diseases.

Abstract The deposition of insoluble proteinaceous aggregates in the form of amyloid fibrils within the extracellular space of tissues is associated with numerous diseases. The development of molecular approaches to arrest amyloid formation and prevent cellular degeneration remains very challenging due to the complexity of the process of protein aggregation, which encompasses an infinite array of conformations and quaternary structures. Polyanionic biopolymers, such as glycosaminoglycans and RNAs, have been shown to modulate the self‐assembly of amyloidogenic polypeptides and to reduce the toxicity induced by the formation of oligomeric and/or pre‐fibrillar proteospecies. This study evaluates the effects of double‐stranded DNA (dsDNA) nanostructures (1D, 2D, and 3D) on amyloid self‐assembly, fibril disaggregation, and the cytotoxicity associated with amyloidogenesis. Using the islet amyloid polypeptide (IAPP) whose pancreatic accumulation is the hallmark of type 2 diabetes, it was observed that dsDNA nanostructures inhibit amyloid formation by inducing the formation of spherical complexes in which the peptide adopts a random coil conformation. Interestingly, the DNA nanostructures showed a persistent ability to disassemble enzymatically and thermodynamically stable amyloid fibrils into nanoscale DNA/IAPP entities that are fully compatible with β‐pancreatic cells and are biodegradable by proteolysis. Notably, dsDNA nanostructures avidly trapped highly toxic soluble oligomeric species in complete cell culture media and converted them into non‐toxic binary complexes. Overall, these results expose the potent modulatory effects of dsDNA on amyloidogenic pathways, and these DNA nanoscaffolds could be used as a source of inspiration for the design of molecules to fight amyloid‐related disorders.

Microplastics (MPs) and nanoplastics (NPs) pervade both the environment and the food chain, originating from the degradation of plastic materials from various sources. Their ubiquitous presence raises concerns for ecosystem safety, as well as the health of animals and humans. While evidence suggests their infiltration into mammalian and human tissues and their association with several diseases, the precise toxicological effects remain elusive and require further investigation. MPs and NPs sample preparation and analytical methods are quite scattered without harmonized strategies to exist at the moment.A significant challenge lies in the limited availability of methods for the chemical characterization and quantification of these contaminants. MPs and NPs can undergo further degradation, driven by abiotic or biotic factors, resulting in the formation of cyclic or linear oligomers. These oligomers can serve as indicative markers for the presence or exposure to MPs and NPs. Moreover, recent finding concerning the aggregation of oligomers to form NPs, makes their analysis as markers very important.Recent advancements have led to the development of sensitive and robust analytical methods for identifying and (semi)quantifying these oligomers in environmental, food, and biological samples. These methods offer a valuable complementary approach for determining the presence of MPs and NPs and assessing their risk to human health and the environment.

Poly(3-alkylthiophenes) (P3[Alkyl]T) exhibit high mobility and efficiency of formation of polaronic charge carriers generated by light absorption, thus finding applications in field effect devices. Excited states of π-stacked dimers of tetra-thiophene oligomers (T4), infinite isolated polythiophene (PT) chains, and P3[Alkyl]T crystals are modeled using configuration interaction singles (CIS) calculations. Excited states in cofacial T4 dimers are mostly localized Frenkel states except for two low energy charge transfer (CT) exciton states, which become the ionization potential and electron affinity levels of T4 molecules at large dimer separation. The lowest excited states in infinite, isolated PT chains and P3[Alkyl]T crystals are intra-chain excitons where the electron and hole are localized on the same chain. The next lowest excited states are interchain, CT excitons in which the electron and hole reside on neighboring chains. The former capture almost all optical oscillator strength and the latter may be a route to efficient formation of polaronic charge carriers in P3[Alkyl]T systems. Changes in optical absorption energies of T4 dimers as a function of molecular separation are explained using CIS calculations with four frontier orbitals in the active space. Shifts in optical absorption energy observed on going from isolated chains to P3[Alkyl]T lamellar structures are already present in single-particle transition energies induced by direct π–π interactions at short range. The electroabsorption spectrum of T4 dimers is calculated as a function of dimer separation and states that are responsible for parallel and perpendicular components of the spectrum are identified. [ABSTRACT FROM AUTHOR]

The dielectric constant of water/oligomer mixtures, spanning the range from pure water to pure oligomeric melts, is investigated using molecular dynamics (MD) simulations. As prototypical water-soluble organic substances, we consider neutral poly-glycine, poly-ethylene glycol, and charged monomeric propionic acid. As the water content is reduced, the dielectric constant decreases but does not follow an ideal mixing behavior. The deviations from ideal mixing originate primarily in the non-linear relation between the oligomer mass fraction and collective polarization effects. We find that the dielectric constant is dominated by water polarization, even if the oligomer mass fraction exceeds 50%. By a double extrapolation of the MD simulation results to the limit of vanishing water fraction and to the limit of infinite oligomeric chain length, we estimate the orientational contribution to the dielectric constant of the pure polymeric melts. By this procedure, we obtain ɛ = 17 ± 2 for polyglycine and ɛ = 1 ± 0.3 for polyethylene glycol. The large difference is rationalized by polarization correlations of glycine units. Interestingly, we find constant temperature simulations to outperform replica exchange simulations in terms of equilibration speed. [ABSTRACT FROM AUTHOR]

Abstract Background It is now realized that Parkinson’s disease (PD) pathology extends beyond the substantia nigra, affecting both central and peripheral nervous systems, and exhibits a variety of non-motor symptoms often preceding motor features. Neuroinflammation induced by activated microglia and astrocytes is thought to underlie these manifestations. α-Synuclein aggregation has been linked with sustained neuroinflammation in PD, aggravating neuronal degeneration; however, there is still a lack of critical information about the structural identity of the α-synuclein conformers that activate microglia and/or astrocytes and the molecular pathways involved. Methods To investigate the role of α-synuclein conformers in the development and maintenance of neuroinflammation, we used primary quiescent microglia and astrocytes, post-mortem brain tissues from PD patients and A53T α-synuclein transgenic mice that recapitulate key features of PD-related inflammatory responses in the absence of cell death, i.e., increased levels of pro-inflammatory cytokines and complement proteins. Biochemical and -omics techniques including RNAseq and secretomic analyses, combined with 3D reconstruction of individual astrocytes and live calcium imaging, were used to uncover the molecular mechanisms underlying glial responses in the presence of α-synuclein oligomers in vivo and in vitro. Results We found that the presence of SDS-resistant hyper-phosphorylated α-synuclein oligomers, but not monomers, was correlated with sustained inflammatory responses, such as elevated levels of endogenous antibodies and cytokines and microglial activation. Similar oligomeric α-synuclein species were found in post-mortem human brain samples of PD patients but not control individuals. Detailed analysis revealed a decrease in Iba1Low/CD68Low microglia and robust alterations in astrocyte number and morphology including process retraction. Our data indicated an activation of the p38/ATF2 signaling pathway mostly in microglia and a sustained induction of the NF-κB pathway in astrocytes of A53T mice. The sustained NF-κB activity triggered the upregulation of astrocytic T-type Cav3.2 Ca2+ channels, altering the astrocytic secretome and promoting the secretion of IGFBPL1, an IGF-1 binding protein with anti-inflammatory and neuroprotective potential. Conclusions Our work supports a causative link between the neuron-produced α-synuclein oligomers and sustained neuroinflammation in vivo and maps the signaling pathways that are stimulated in microglia and astrocytes. It also highlights the recruitment of astrocytic Cav3.2 channels as a potential neuroprotective mediator against the α-synuclein-induced neuroinflammation. Graphical Abstract

Abstract Background Soluble oligomeric forms of Tau protein have emerged as crucial players in the propagation of Tau pathology in Alzheimer’s disease (AD). Our objective is to introduce a single-domain antibody (sdAb) named 2C5 as a novel radiotracer for the efficient detection and longitudinal monitoring of oligomeric Tau species in the human brain. Methods The development and production of 2C5 involved llama immunization with the largest human Tau isoform oligomers of different maturation states. Subsequently, 2C5 underwent comprehensive in vitro characterization for affinity and specificity via Enzyme-Linked Immunosorbent Assay and immunohistochemistry on human brain slices. Technetium-99m was employed to radiolabel 2C5, followed by its administration to healthy mice for biodistribution analysis. Results 2C5 exhibited robust binding affinity towards Tau oligomers (Kd = 6.280 nM ± 0.557) and to Tau fibers (Kd = 5.024 nM ± 0.453), with relatively weaker binding observed for native Tau protein (Kd = 1791 nM ± 8.714) and amyloid peptide (Kd > 10,000 nM). Remarkably, this SdAb facilitated immuno-histological labeling of pathological forms of Tau in neurons and neuritic plaques, yielding a high-contrast outcome in AD patients, closely mirroring the performance of reference antibodies AT8 and T22. Furthermore, 2C5 SdAb was successfully radiolabeled with 99mTc, preserving stability for up to 6 h post-radiolabeling (radiochemical purity > 93%). However, following intravenous injection into healthy mice, the predominant uptake occurred in kidneys, amounting to 115.32 ± 3.67, 97.70 ± 43.14 and 168.20 ± 34.52% of injected dose per gram (% ID/g) at 5, 10 and 45 min respectively. Conversely, brain uptake remained minimal at all measured time points, registering at 0.17 ± 0.03, 0.12 ± 0.07 and 0.02 ± 0.01% ID/g at 5, 10 and 45 min post-injection respectively. Conclusion 2C5 demonstrates excellent affinity and specificity for pathological Tau oligomers, particularly in their early stages of oligomerization. However, the current limitation of insufficient blood–brain barrier penetration necessitates further modifications before considering its application in nuclear medicine imaging for humans.

AbstractAA amyloidosis, characterized by the misfolding of serum amyloid A (SAA) protein, is the most common amyloid protein disorder across multiple species. SAA is a positive-acute phase protein synthesized by the liver in response to inflammation or stress, and it normally associates with high-density lipoprotein at its N-terminus. In this study, we focused on the 1-25 amino acid (aa) region of the complete 104 aa SAA sequence to examine the aggregation propensity of AA amyloid. A library comprising eight peptides from different species was assembled for analysis. To access the aggregation propensity of each peptide region, a bioinformatic study was conducted using the algorithm TANGO. Congo red (CR) binding assays, Thioflavin T (ThT) assays, and transmission electron microscopy (TEM) were utilized to evaluate whether the synthesized peptides formed amyloid-like fibrils. All synthetic SAA 1-25 congeners resulted in amyloid-like fibrils formation (per CR and/or ThT staining and TEM detection) at the exception of the ferret SAA1-25 fragment, which generated plaque-like materials by TEM. Ten residues were preserved among SAA 1-25 congeners resulting in amyloid-like fibrils, i.e. F6, E9, A10, G13, D16, M17, A20, Y21, D23, and M24. Amino acid residues highlighted by this study may have a role in increasing the propensity for amyloid-like fibril formation. This study put an emphasis on region 1-25 in the mechanism of SAA1 misfolding.

Protein self-assembly into amyloid fibrils underlies several neurodegenerative conditions, including Alzheimer's and Parkinson's diseases. It has become apparent that the small oligomers formed during this process constitute neurotoxic molecular species associated with amyloid aggregation. Targeting the formation of oligomers represents, therefore, a possible therapeutic avenue to combat these diseases. However, it remains challenging to establish which microscopic steps should be targeted to suppress most effectively the generation of oligomeric aggregates. Recently, we have developed a kinetic model of oligomer dynamics during amyloid aggregation. Here, we use this approach to derive explicit scaling relationships that reveal how key features of the time evolution of oligomers, including oligomer peak concentration and lifetime, are controlled by the different rate parameters. We discuss the therapeutic implications of our framework by predicting changes in oligomer concentrations when the rates of the individual microscopic events are varied. Our results identify the kinetic parameters that control most effectively the generation of oligomers, thus opening a new path for the systematic rational design of therapeutic strategies against amyloid-related diseases. [ABSTRACT FROM AUTHOR]

Acceptor-only oligomers are developed as guest components to construct oligomer-assisted active layers for high performance organic solar cells. Due to the high planarity and structural similarity with the host polymer donor, BDD-based acceptor-only oligomers formed an alloy phase with PM6 and optimized the phase morphology effectively, achieving a stable device displaying 18% efficiency. [ABSTRACT FROM AUTHOR]

To quantify the volatility of organic aerosols (OA), a comprehensive campaign was conducted in the Chinese megacity. Volatility distributions of OA and particle‐phase organic nitrate (pON) were estimated based on five methods: (a) empirical method and (b) kinetic model based on the measurement of a thermodenuder (TD) coupled with an aerosol mass spectrometer; (c) Formula‐based SIMPOL model‐driven method; (d) Element‐based estimations using molecular formula measurements of OA; and (e) gas/particle partitioning. Our results demonstrate that the ambient OA volatility distribution shows good agreement between the two heating methods and the formula‐based method when assuming ambient OA was mainly composed of organic nitrate (pON), organic sulfate and acid groups using the SIMPOL model. However, the element‐based method tends to overestimate the volatility of OA compared to the above three methods, suggesting large uncertainties in the parameterizations or in the representativeness of the molecular measurements that need further refinement. The volatility of ambient OA is generally lower than that of the laboratory‐derived secondary OA, emphasizing the impact of aging. A large fraction at the higher and lower volatility ranges (approximately log C* ≤ −9 and ≥2 μg m−3) was found for pON, implying the importance of both extremely low volatile and semi‐volatile species. Overall, this study evaluates different methods for volatility estimation and gives new insight into the volatility of OA and pON in urban areas. Plain Language Summary: Volatility, which controls the gas/particle partitioning of organic compounds, is one of most the important physiochemistry properties of organic aerosols (OA). Multiple methods have been used to estimate OA volatility, whereas the accuracy of each method is still unclear. The purpose of this study is to verify the volatility of ambient OA and its key component (i.e., particulate organic nitrate, pON) in urban areas by comparing the estimated results using different methods. With the help of state‐of‐art mass spectrometers, the estimation methods, including two heating methods, one formula‐based method, one element‐based method, and one gas/particle partitioning method, were achieved. In general, we found the heating methods show good agreement with the formula‐based method with a reasonable assumption of functional groups contained in OA and pON. In general, we observed a large faction of extremely low volatile compounds exist in OA (30%–40%), and both extremely low volatile and semi‐volatile species exist in pON, suggesting the complex evolution of atmospheric particles. The results provide a better understanding of the volatility of OA and pON in urban areas and benefit accurate volatility estimation that facilitates the model simulations of OA. Key Points: The volatility of ambient organic aerosols (OA) and organic nitrate (pON) estimated from five methods were systematically comparedThe OA volatility from SIMPOL‐driven model under organic sulfate, pON and acid assumption are consistent with those from heating methodThe volatility distribution of pON indicates both extremely low volatility compounds as oligomers and semi‐volatile species exist in pON [ABSTRACT FROM AUTHOR]

A group of misfolded prone-to-aggregate domains in disease-causing proteins has recently been shown to adopt unique conformations that play a role in fundamental biological processes. These processes include the formation of membrane-less sub-organelles, alternative splicing, and gene activation and silencing. The cellular responses are regulated by the conformational switching of prone-to-aggregate domains, independently of changes in RNA or protein expression levels. Given this, targeting the misfolded states of disease-causing proteins to redirect them towards their physiological conformations is emerging as an effective therapeutic strategy for diseases caused by protein misfolding. In our study, we successfully identified baicalein as a potent structure-correcting agent. Our findings demonstrate that baicalein can reconfigure existing TDP-43 aggregates into an oligomeric state both in vitro and in disease cells. This transformation effectively restores the bioactivity of misfolded TDP-43 proteins in cellular models of ALS and premature aging in progeria. Impressively, in progeria cells where defective lamin A interferes with TDP-43-mediated exon skipping, the formation of pathological TDP-43 aggregates is promoted. Baicalein, however, restores the functionality of TDP-43 and mitigates nuclear shape defects in these laminopathic cells. This establishes a connection between lamin A and TDP-43 in the context of aging. Our findings suggest that targeting physiological TDP-43 oligomers could offer a promising therapeutic avenue for treating aging-associated disorders. [ABSTRACT FROM AUTHOR]

The length and mode of conjugation directly affect the molecular electronic structure, which has been extensively studied in through‐bond conjugation (TBC) systems. Corresponding research greatly promotes the development of TBC‐based luminophores. However, how the length and mode of through‐space conjugation (TSC), one kind of weak interaction, influence the photophysical properties of non‐conjugated luminophores remains a relatively unexplored field. Here, we unveil a non‐linear relationship between TSC length and emission characteristics in non‐conjugated systems, in contrast to the reported proportional correlation in TBC systems. More specifically, oligo(phenylene methylene)s (OPM[4]‐OPM[7]) exhibit stronger TSC and prominent blue clusteroluminescence (CL) (≈440 nm) compared to shorter counterparts (OPM[2] and OPM[3]). OPM[6] demonstrates the highest solid‐state quantum yield (40 %), emphasizing the importance of balancing flexibility and rigidity. Further theoretical calculations confirmed that CL of these oligo(phenylene methylene)s was determined by stable TSC derived from the inner rigid Diphenylmethane (DPM) segments within the oligomers instead of the outer ones. This discovery challenges previous assumptions and adds a new dimension to the understanding of TSC‐based luminophores in non‐conjugated systems. [ABSTRACT FROM AUTHOR]

Background: It is now realized that Parkinson's disease (PD) pathology extends beyond the substantia nigra, affecting both central and peripheral nervous systems, and exhibits a variety of non-motor symptoms often preceding motor features. Neuroinflammation induced by activated microglia and astrocytes is thought to underlie these manifestations. α-Synuclein aggregation has been linked with sustained neuroinflammation in PD, aggravating neuronal degeneration; however, there is still a lack of critical information about the structural identity of the α-synuclein conformers that activate microglia and/or astrocytes and the molecular pathways involved. Methods: To investigate the role of α-synuclein conformers in the development and maintenance of neuroinflammation, we used primary quiescent microglia and astrocytes, post-mortem brain tissues from PD patients and A53T α-synuclein transgenic mice that recapitulate key features of PD-related inflammatory responses in the absence of cell death, i.e., increased levels of pro-inflammatory cytokines and complement proteins. Biochemical and -omics techniques including RNAseq and secretomic analyses, combined with 3D reconstruction of individual astrocytes and live calcium imaging, were used to uncover the molecular mechanisms underlying glial responses in the presence of α-synuclein oligomers in vivo and in vitro. Results: We found that the presence of SDS-resistant hyper-phosphorylated α-synuclein oligomers, but not monomers, was correlated with sustained inflammatory responses, such as elevated levels of endogenous antibodies and cytokines and microglial activation. Similar oligomeric α-synuclein species were found in post-mortem human brain samples of PD patients but not control individuals. Detailed analysis revealed a decrease in Iba1Low/CD68Low microglia and robust alterations in astrocyte number and morphology including process retraction. Our data indicated an activation of the p38/ATF2 signaling pathway mostly in microglia and a sustained induction of the NF-κB pathway in astrocytes of A53T mice. The sustained NF-κB activity triggered the upregulation of astrocytic T-type Cav3.2 Ca2+ channels, altering the astrocytic secretome and promoting the secretion of IGFBPL1, an IGF-1 binding protein with anti-inflammatory and neuroprotective potential. Conclusions: Our work supports a causative link between the neuron-produced α-synuclein oligomers and sustained neuroinflammation in vivo and maps the signaling pathways that are stimulated in microglia and astrocytes. It also highlights the recruitment of astrocytic Cav3.2 channels as a potential neuroprotective mediator against the α-synuclein-induced neuroinflammation. [ABSTRACT FROM AUTHOR]

The conversion of native peptides and proteins into amyloid aggregates is a hallmark of over 50 human disorders, including Alzheimer's and Parkinson's diseases. Increasing evidence implicates misfolded protein oligomers produced during the amyloid formation process as the primary cytotoxic agents in many of these devastating conditions. In this review, we analyze the processes by which oligomers are formed, their structures, physicochemical properties, population dynamics, and the mechanisms of their cytotoxicity. We then focus on drug discovery strategies that target the formation of oligomers and their ability to disrupt cell physiology and trigger degenerative processes. [ABSTRACT FROM AUTHOR]

The popularity and rapid spread of new psychoactive substances is why there is an urgent need for their fast monitoring in saliva in the field with electrodes modified with a selective receptor. Oligomers of electrochemically oxidized 3-aminobenzoic acid that are deposited on the surface of a graphite screen-printed electrode (o-3ABA/G/SPE) is proposed as a selector for the analyte of forensic interest. The oligomeric structure and existence of the zwitterionic form of o-3ABA on the G/SPE surface was confirmed using scanning electron microscopy, Raman spectroscopy and cyclic voltammetry techniques. The equilibrium adsorption constants between o-3ABA and 2-aminoindane (primary amine: Kads(2-AI) = 5.31 × 104) and selected synthetic cathinones (secondary amine: Kads(butylone) = 6.12 × 105, tertiary amines: Kads(MDPV) = 3.41 × 104 and Kads(naphyrone) = 1.01 × 104) were estimated using the electrochemical impedance spectroscopy (EIS) technique. The EIS technique was applied for determining a 1.0 μM concentration of 2-AI (RSD 3.5–4.0%) and butylone (RSD 4.9–6.4%) in the model and oral fluid samples. [ABSTRACT FROM AUTHOR]

Background: Soluble oligomeric forms of Tau protein have emerged as crucial players in the propagation of Tau pathology in Alzheimer's disease (AD). Our objective is to introduce a single-domain antibody (sdAb) named 2C5 as a novel radiotracer for the efficient detection and longitudinal monitoring of oligomeric Tau species in the human brain. Methods: The development and production of 2C5 involved llama immunization with the largest human Tau isoform oligomers of different maturation states. Subsequently, 2C5 underwent comprehensive in vitro characterization for affinity and specificity via Enzyme-Linked Immunosorbent Assay and immunohistochemistry on human brain slices. Technetium-99m was employed to radiolabel 2C5, followed by its administration to healthy mice for biodistribution analysis. Results: 2C5 exhibited robust binding affinity towards Tau oligomers (Kd = 6.280 nM ± 0.557) and to Tau fibers (Kd = 5.024 nM ± 0.453), with relatively weaker binding observed for native Tau protein (Kd = 1791 nM ± 8.714) and amyloid peptide (Kd > 10,000 nM). Remarkably, this SdAb facilitated immuno-histological labeling of pathological forms of Tau in neurons and neuritic plaques, yielding a high-contrast outcome in AD patients, closely mirroring the performance of reference antibodies AT8 and T22. Furthermore, 2C5 SdAb was successfully radiolabeled with 99mTc, preserving stability for up to 6 h post-radiolabeling (radiochemical purity > 93%). However, following intravenous injection into healthy mice, the predominant uptake occurred in kidneys, amounting to 115.32 ± 3.67, 97.70 ± 43.14 and 168.20 ± 34.52% of injected dose per gram (% ID/g) at 5, 10 and 45 min respectively. Conversely, brain uptake remained minimal at all measured time points, registering at 0.17 ± 0.03, 0.12 ± 0.07 and 0.02 ± 0.01% ID/g at 5, 10 and 45 min post-injection respectively. Conclusion: 2C5 demonstrates excellent affinity and specificity for pathological Tau oligomers, particularly in their early stages of oligomerization. However, the current limitation of insufficient blood–brain barrier penetration necessitates further modifications before considering its application in nuclear medicine imaging for humans. [ABSTRACT FROM AUTHOR]

Here, we report on the synthesis of discrete oligomers of alkyl‐bridged naphthalenediimides (NDIs) and study their molecular nanostructures both in bulk, in solution, and at the liquid‐solid interface. Via an iterative synthesis method, multiple NDI cores were bridged with short and saturated alkyl‐diamines (C3 and C12) or long and unsaturated alkyl‐diamines (u2C33 to u8C100) at their imide termini. The strong intermolecular interaction between the NDI cores was observed by probing their photophysical properties in solution. In bulk, the discrete NDI oligomers preferentially ordered in lamellar morphologies, irrespective of whether a saturated or unsaturated spacer was employed. Moreover, both the molecular architecture as well as the crystallization conditions play a significant role in the nanoscale ordering. The long unsaturated alkyl chains lead preferably to folded‐chain conformations while their saturated analogues form stretched arrangements. At the solution‐solid interface, well‐defined lamellar regions were observed. These results show that precision in chemical structure alone is not sufficient to reach well‐defined structures of discrete oligomers, but that it must be combined with precision in processing conditions. [ABSTRACT FROM AUTHOR]

New benzidine-based oligomers containing four Schiff base arms with terminal alkoxy chains CnH2n+1 (n = 6–12) were characterized by elemental, spectroscopic (UV, FT-IR, and NMR) and DFT techniques. The thermal-optical behaviors were observed using differential calorimetry and polarized optical microscope. Upon heating the molecules with n = 8, 10, and 12 exhibited endothermic peaks characteristic of the crystal-soft crystal B transition in addition to crystal-crystal subphases. It can be generalized that all oligomers showed unusual curing temperature of which the compounds with odd alkoxy chain carbon numbers possess lower curing temperatures in comparison with the analogous compounds of even parity. [ABSTRACT FROM AUTHOR]

The polymerization of fullerenes is a significant method for obtaining fullerene-based materials that possess intriguing properties. Metallofullerenes, as a notable type of fullerene derivatives, are also capable of undergoing polymerization, potentially resulting in the creation of metallofullerene polymers. However, there is currently limited knowledge regarding the polymerization process of metallofullerenes. In this study, we have selected Ca@C   60 as a representative compound to investigate the polymerization process of metallofullerenes. The objective of this research is to determine whether the polymerization process is energetically favorable and to examine how the electronic properties of the metallofullerene are altered throughout the polymerization process. Ca@C   60 is a unique metallofullerene molecule that exhibits insolubility in common fullerene solvents like toluene and carbon disulfide but is soluble in aniline. This behavior suggests a potential tendency for Ca@C   60 to form oligomers and polymers that resist dissolution. However, the structures and properties of polymerized Ca@C   60 remain unknown. We employed density functional theory calculations to investigate the stability and electronic properties of one-dimensional and two-dimensional Ca@C   60 oligomers and polymers. Our findings indicate that the coalescence of Ca@C   60 monomers is energetically favorable, with a significant contribution from van der Waals interactions between the fullerene cages. The polymerization process of Ca@C   60 also involves the formation of covalent linkages, including four-atom rings and C-C single bonds. The increase in the number of the Ca@C   60 units to three and four in the oligomer leads to a significant decrease in the HOMO-LUMO gap. In the two-dimensional polymerized Ca@C   60 , the organization of the monomers closely resembles the spatial configuration of carbon atoms in graphene. With a direct bandgap of 0.22 eV, the polymerized Ca@C   60 holds potential for utilization in optoelectronic devices. [ABSTRACT FROM AUTHOR]

Oligomeric aggregates of the amyloid-beta (Aβ) peptide have been implicated as the toxic species for Alzheimer's disease by contributing to oxidative cytotoxicity and physical disruption in cell membranes in the brain. Recent evidence points to the ability of the catecholamine neurotransmitter dopamine in the presence of copper ions to both stabilize oligomers and decrease the toxic effects of these oligomers. Based on these results, physical characterization of aggregates and subsequent cell studies with a neuroblastoma line were performed that show both dopamine and the related neurotransmitter, norepinephrine, can stabilize oligomers and decrease toxicity of Aβ aggregates without copper present. To investigate this reduction of toxicity, structural characterization of oligomers in the presence of neurotransmitters was compared to aggregates formed with Aβ alone. Gel electrophoresis and transmission electron microscopy show higher levels of oligomers in the presence of dopamine and norepinephrine, yet the oligomer structure is largely amorphous. Aβ aggregated alone forms the predicted highly organized fibrillar species, with increased levels of dityrosine covalent linkages, which are largely absent in the presence of the neurotransmitters. A proposed mechanism for the observed decrease in cell death by Aβ in the presence of dopamine and norepinephrine suggests the neurotransmitters both block the formation of organized oligomer structures and dityrosine stabilizing linkages while also behaving as antioxidants, providing a dual mechanism for increased cell viability. [ABSTRACT FROM AUTHOR]

The molecular events of protein misfolding and self-aggregation of tau and amylin are associated with the progression of Alzheimer's and diabetes, respectively. Recent studies suggest that tau and amylin can form hetero-tau-amylin oligomers. Those hetero-oligomers are more neurotoxic than homo-tau oligomers. So far, the detailed interactions between the hetero-oligomers and the neuronal membrane are unknown. Using multiscale MD simulations, the lipid binding and protein folding behaviors of hetero-oligomers on asymmetric lipid nanodomains or raft membranes were examined. Our raft membranes contain phase-separated phosphatidylcholine (PC), cholesterol, and anionic phosphatidylserine (PS) or ganglioside (GM1) in one leaflet of the lipid bilayer. The hetero-oligomers bound more strongly to the PS and GM1 than other lipids via the hydrophobic and hydrophilic interactions, respectively, in the raft membranes. The hetero-tetramer disrupted the acyl chain orders of both PC and PS in the PS-containing raft membrane, but only the GM1 in the GM1-containing raft membrane as effectively as the homo-tau-tetramer. We discovered that the alpha-helical content in the heterodimer was greater than the sum of alpha-helical contents from isolated tau and amylin monomers on both raft membranes, indicative of a synergetic effect of tau-amylin interactions in surface-induced protein folding. Our results provide new molecular insights into understanding the cross-talk between Alzheimer's and diabetes. [ABSTRACT FROM AUTHOR]

A relatively simple physical method has been proposed for fabrication of stable oligomers of silver nanoparticles, preliminarily obtained by pulsed laser ablation of a metal target in a liquid. Oligomers of silver nanoparticles are formed in an aqueous solution after prolonged centrifugation at 18 000g and subsequent ultrasonication of the initial colloidal solution of spherical nanoparticles obtained by laser ablation. The plasmon resonance in oligomers is shifted relative to the plasmon resonance in spherical nanoparticles to the long wavelength region by 140 nm. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of isomalto‐oligosaccharide (IMO) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of glucose oligomers with degrees of polymerisation of 3–9, along with various amounts of mono‐ and disaccharides. The NF comes in both syrup and powder form. The applicant intends to extend the current uses of the NF as an ingredient in several foods, and use the NF in food supplements aimed at the general population older than 10 years of age. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. Along with literature data, the applicant carried out a tolerability study in adult volunteers with the NF at doses up to 120 g/day. The Panel concludes that this study provides reassurance that the NF is tolerable at doses of 120 g/day. Conservative intake estimates resulting from the use of the NF as an ingredient according to the currently authorised uses and new proposed uses result in a highest intake estimate in adolescents of 112 g/day at the 95th percentile, and reach 142 g/day in adolescents when the use as a food supplement is included. The Panel notes this amount is higher than the dose of 120 g/day for which tolerability has been demonstrated. However, considering the source, compositional characterisation, production process and nature of the NF, as well as the available nutritional and toxicological data on the NF, the Panel considers that the NF does not present safety concerns under the proposed conditions of use. [ABSTRACT FROM AUTHOR]

Poly(glycerol sebacate) (PGS) belongs to the hyperbranched polyesters family (HBP), which possesses an extensive variety of applications due to its tunable chemical and mechanical properties, together with its biocompatibility and biodegradability. However, the understanding of PGS synthesis becomes a challenge due to the lack of consistency when determining its synthesis parameters. Understanding these parameters is fundamental to control PGS synthesis and obtain a scalable and reproducible final product for biomedical applications. To unveil their effect on diverging PGS properties, diols are used as glycerol analogs and the reaction is chemically and thermally monitored, suggesting a heterogeneous reactivity of the exposed hydroxyl groups. Also, confinement of the prepolymerization is proven to be fundamental In order to maintain the equimolar ratio of initial monomers during synthesis. Early stages of the polycondensation (first 4 h) tend to linear and less branched oligomers by consuming primary hydroxyls rather than secondary hydroxyls. However, physicochemical characterization determines that a high degree of conversion (40%) is reached during these early stages. Afterward, the oligomers tend to condense through the secondary hydroxyls into a more crosslinked elastomer. This study demonstrates how hydroxyl affinity, water presence, and glycerol loss are crucial for the scalability and reproducibility of its final product. [ABSTRACT FROM AUTHOR]

Hexanucleotide repeat expansion in C9orf72 is one of the most common causes of amyotrophic lateral sclerosis and frontotemporal dementia. The hexanucleotide expansion, formed by GGGGCC (G4C2) repeats, leads to the production of five dipeptide protein repeats (DPRs) via repeat-associated non-AUG translation. Among the five dipeptide repeats, Gly-Arg, Pro-Arg, and Gly-Ala form neuronal inclusions that contain aggregates of the peptides. Several studies have attempted to model DPR-associated toxicity using various repeat lengths, which suggests a unique conformation that is cytotoxic and is independent of the repeat length. However, the structural characteristics of DPR aggregates have yet to be determined. Increasing evidence suggests that soluble species, such as oligomers, are the main cause of toxicity in proteinopathies, such as Alzheimer's and Parkinson's disease. To investigate the ability of DPRs to aggregate and form toxic oligomers, we adopted a reductionist approach using small dipeptide repeats of 3, 6, and 12. This study shows that DPRs, particularly glycine-arginine and proline-arginine, form oligomers that exhibit distinct dye-binding properties and morphologies. Importantly, we also identified toxic DPR oligomers in amyotrophic lateral sclerosis and frontotemporal dementia postmortem brains that are morphologically similar to those generated recombinantly. This study demonstrates that, similar to soluble oligomers formed by various amyloid proteins, DPR oligomers are toxic, independent of their repeat length. [ABSTRACT FROM AUTHOR]

Molecular rotor‐based fluorophores (RBFs) activate fluorescence upon increase of micro‐viscosity, thus bearing a broad application promise in many fields. However, it remains a challenge to control how fluorescence of RBFs responds to viscosity changes. Herein, we demonstrate that the formation and regulation of intramolecular hydrogen bonds in the excited state of RBFs could modulate their rotational barrier, leading to a rational control of how their fluorescence can be activated by micro‐viscosity. Based on this strategy, a series of RBFs were developed based on 4‐hydroxybenzylidene‐imidazolinone (HBI) that span a wide range of viscosity sensitivity. Combined with the AggTag method that we previously reported, the varying viscosity sensitivity and emission spectra of these probes enabled a dual‐color imaging strategy that detects both protein oligomers and aggregates during the multistep aggregation process of proteins in live cells. In summary, our work indicates that installing intracellular excited state hydrogen bonds to RBFs allows for a rational control of rotational barrier, thus allow for a fine tune of their viscosity sensitivity. Beyond RBFs, we envision similar strategies can be applied to control the fluorogenic behavior of a large group of fluorophores whose emission is dependent on excited state rotational motion, including aggregation‐induced emission fluorophores. [ABSTRACT FROM AUTHOR]

The work investigated the synthesis of the oligomers with citric acid (CA) and epoxidized soybean oils (ESO) at various temperatures and the effects of the oligomers on the structures and properties of starch‐based bioplastics. CA was bonded effectively onto ESO via ring‐opening polymerization at 90°C as confirmed by the results of Fourier‐transform infrared spectroscopy, thermogravimetric analysis, and carboxylic group contents of CA‐ESO oligomers (CESO). The oligomers exhibited higher thermal stability than ESO. Regarding starch‐based bioplastics, CESO disrupted the hydrogen bonding interaction within starch molecules and formed the esterification reaction with starch. The bioplastics containing CESO exhibited remarkably higher structural homogeneity and opacity as the synthesis temperatures of CESO increased. However, the thermal properties of the bioplastics with various CESO reduced, which might be due to the decomposition of starch by CESO. The films containing CESO also exhibited lower tensile strength than the film with ESO, which might be related to the decomposition, crosslinking, and plasticization effects of CESO on starch. The bioplastics with CESO exhibited lower degradation due to a more intense interaction of CESO and starch. The study demonstrated the potential of CA as an interfacial linker of starch/ESO‐based bioplastics by adjusting the synthetic temperatures of CESO. [ABSTRACT FROM AUTHOR]

In recent years, the evolution of lithium-ion batteries (LIB) has been propelled by the growing demand for energy storage systems that are lightweight, have high energy density, and are long-lasting. This review article examines the use of self-terminated oligomers with hyperbranched architecture (STOBA) as a key electrode additive for the superior performance of LIBs. STOBA has been found to have excellent electrochemical properties, including high specific capacity, low impedance, and good cycling stability when used as an additive in electrode materials. The article discusses the process of synthesis and characterization of STOBA materials, including their potential applications in LIBs as electrode material additives. The article also discusses current research on the optimization of STOBA materials for LIBs, including the use of different solvents, monomers, and initiators. Overall, the review concludes that STOBA materials possess huge potential as a next-generation additive for LIB safety. [ABSTRACT FROM AUTHOR]

The paper focuses on the correction of Illumina WGS sequencing reads. We provide an extensive evaluation of the existing correctors. To this end, we measure an impact of the correction on variant calling (VC) as well as de novo assembly. It shows, that in selected cases read correction improves the VC results quality. We also examine the algorithms behaviour in a processing of Illumina NovaSeq reads, with different reads quality characteristics than in older sequencers. We show that most of the algorithms are ready to cope with such reads. Finally, we introduce a new version of RECKONER, our read corrector, by optimizing it and equipping with a new correction strategy. Currently, RECKONER allows to correct high-coverage human reads in less than 2.5 h, is able to cope with two types of reads errors: indels and substitutions, and utilizes a new, based on a two lengths of oligomers, correction verification technique. [ABSTRACT FROM AUTHOR]

Oligomeric clusters of amyloid-β (Aβ) are one of the major biomarkers for Alzheimer's disease (AD). However, proficient methods to detect Aβ-oligomers in brain tissue are lacking. Here we show that synthetic M13 bacteriophages displaying Aβ-derived peptides on their surface preferentially interact with Aβ-oligomers. When exposed to brain tissue isolated from APP/PS1-transgenic mice, these bacteriophages detect small-sized Aβ-aggregates in hippocampus at an early age, prior to the occurrence of Aβ-plaques. Similarly, the bacteriophages reveal the presence of such small Aβ-aggregates in post-mortem hippocampus tissue of AD-patients. These results advocate bacteriophages displaying Aβ-peptides as a convenient and low-cost tool to identify Aβ-oligomers in post-mortem brain tissue of AD-model mice and AD-patients. Bacteriophages displaying amyloidogenic peptides are able to identify amyloid-beta oligomers in post-mortem brain tissue of APP/PS1-transgenic mice and of Alzheimer patients. [ABSTRACT FROM AUTHOR]