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1
Mendler, M., S. G. Eich-Bender, L. Vaughan, K. H. Winterhalter, and P. Bruckner. "Cartilage contains mixed fibrils of collagen types II, IX, and XI." Journal of Cell Biology 108, no. 1 (January 1, 1989): 191–97. http://dx.doi.org/10.1083/jcb.108.1.191.
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The distribution of collagen XI in fibril fragments from 17-d chick embryo sternal cartilage was determined by immunoelectron microscopy using specific polyclonal antibodies. The protein was distributed throughout the fibril fragments but was antigenically masked due to the tight packing of collagen molecules and could be identified only at sites where the fibril structure was partially disrupted. Collagens II and IX were also distributed uniformly along fibrils but, in contrast to collagen XI, were accessible to the antibodies in intact fibrils. Therefore, cartilage fibrils are heterotypically assembled from collagens II, IX, and XI. This implies that collagen XI is an integral component of the cartilage fibrillar network and homogeneously distributed throughout the tissue. This was confirmed by immunofluorescence.
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Thakur, Garima, Miodrag Micic, Yuehai Yang, Wenzhi Li, Dania Movia, Silvia Giordani, Hongzhou Zhang, and Roger M. Leblanc. "Conjugated Quantum Dots Inhibit the Amyloidβ(1–42) Fibrillation Process." International Journal of Alzheimer's Disease 2011 (2011): 1–15. http://dx.doi.org/10.4061/2011/502386.
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Nanoparticles have enormous potential in diagnostic and therapeutic studies. We have demonstrated that the amyloid beta mixed with and conjugated to dihydrolipoic acid- (DHLA) capped CdSe/ZnS quantum dots (QDs) of size approximately 2.5 nm can be used to reduce the fibrillation process. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used as tools for analysis of fibrillation. There is a significant change in morphology of fibrils when amyloidβ(1–42) (Aβ(1–42)) is mixed or conjugated to the QDs. The length and the width of the fibrils vary under modified conditions. Thioflavin T (ThT) fluorescence supports the decrease in fibril formation in presence of DHLA-capped QDs.
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Birk, D. E., J. M. Fitch, J. P. Babiarz, K. J. Doane, and T. F. Linsenmayer. "Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter." Journal of Cell Science 95, no. 4 (April 1, 1990): 649–57. http://dx.doi.org/10.1242/jcs.95.4.649.
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The small-diameter fibrils of the chick corneal stroma are heterotypic, composed of both collagen types I and V. This tissue has a high concentration of type V collagen relative to other type I-containing tissues with larger-diameter fibrils, suggesting that heterotypic interactions may have a regulatory role in the control of fibril diameter. The interactions of collagen types I and V were studied using an in vitro self-assembly system. Collagens were purified from lathyritic chick embryos in the presence of protease inhibitors. The type V collagen preparations contained higher molecular weight forms of the alpha 1(V) and alpha 2(V) chains constituting 60–70% of the total. Rotary-shadow electron micrographs showed a persistence of a small, pepsin-sensitive terminal region in an amount consistent with that seen by electrophoresis. In vitro, this purified type V collagen formed thin fibrils with no apparent periodicity, while type I collagen fibrils had a broad distribution of large diameters. However, when type I collagen was mixed with increasing amounts of type V collagen a progressive and significant decrease in both the mean fibril diameter and the variance was observed for D periodic fibrils. The amino-terminal domain of the type V collagen molecule was required for this regulatory effect and in its absence little diameter reducing activity was observed. Electron microscopy using collagen type-specific monoclonal antibodies demonstrated that the fibrils formed were heterotypic, containing both collagen types I and V. These data indicate that the interaction of type V with type I collagen is one mechanism modulating fibril diameter and is at least partially responsible for the regulation of collagen fibril formation.
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Boothroyd, Stephen, Alberto Saiani, and Aline F. Miller. "Formation of Mixed Ionic Complementary Peptide Fibrils." Macromolecular Symposia 273, no. 1 (November 2008): 139–45. http://dx.doi.org/10.1002/masy.200851320.
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Accardi, Fabrizio, Valentina Papa, Anna Rita Capozzi, Gian Luca Capello, Laura Verga, Cristina Mancini, Eugenia Martella, et al. "A Rare Case of Systemic AL Amyloidosis with Muscle Involvement: A Misleading Diagnosis." Case Reports in Hematology 2018 (2018): 1–5. http://dx.doi.org/10.1155/2018/9840405.
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Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels. Transmission electron microscopy (TEM) confirmed amyloid fibrils around perimysial vessels associated with collagen fibrils. A stepwise approach to diagnosis and staging of this disorder is critical and involves confirmation of amyloid deposition, identification of the fibril type, assessment of underlying amyloidogenic disorder, and evaluation of the extent and severity of amyloidotic organ involvement.
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Cerofolini, Linda, Enrico Ravera, Sara Bologna, Thomas Wiglenda, Annett Böddrich, Bettina Purfürst, Iryna Benilova, et al. "Mixing Aβ(1–40) and Aβ(1–42) peptides generates unique amyloid fibrils." Chemical Communications 56, no. 62 (2020): 8830–33. http://dx.doi.org/10.1039/d0cc02463e.
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Hilman, A., T. Karo-karo, Azhari, H. Sakdiah, N. A. Salma, and I. Pangestu. "Hydrolysis of alkaline treatment and characterization of cellulose fibrils from processing waste of bengkoang water-soluble polysaccharide." IOP Conference Series: Earth and Environmental Science 977, no. 1 (June 1, 2022): 012087. http://dx.doi.org/10.1088/1755-1315/977/1/012087.
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Abstract Cellulose fibrils are insoluble dietary fibres in the processing waste of bengkoang water-soluble polysaccharides (WSP). The researcher has investigated the characterization of chemical and morphological properties of WSP bengkoang in previous studies. However, the processing waste of the insoluble dietary fibres from WSP bengkoang still needs to be studied. This research aim is to hydrolyze and characterize the cellulose fibrils from bengkoang water-soluble polysaccharides. The results showed that the crude fibres assisted with alkaline treatment would lead to the swollen thread and remove materials like soluble and insoluble lignin to become cellulose fibrils. The morphology of natural fibres has mixed with starch from the processing waste of bengkoang water-soluble polysaccharides. Meanwhile, the cellulose fibrils look clear with a dimension of around 10–14 μm. The FTIR graph shows a degradation in the quantum of linking materials allows in the fibres due to alkaline treatment. The raw fibres characteristic peak does not appear due to alkaline hydrolisis treatment. The peak between 1200 and 1300 cm-1 which decreases due to alkaline treatment is mainly responsible for the wax, lignin, pectin, and other impurities components. The color degree of cellulose fibrils were indicate due to the removal of other impurities and non-cellulosic components.
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Dieriks, Birger Victor, Blake Highet, Ania Alik, Tracy Bellande, Taylor J. Stevenson, Victoria Low, Thomas I.-H. Park, et al. "Human pericytes degrade diverse α-synuclein aggregates." PLOS ONE 17, no. 11 (November 18, 2022): e0277658. http://dx.doi.org/10.1371/journal.pone.0277658.
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Parkinson’s disease (PD) is a progressive, neurodegenerative disorder characterised by the abnormal accumulation of α-synuclein (α-syn) aggregates. Central to disease progression is the gradual spread of pathological α-syn. α-syn aggregation is closely linked to progressive neuron loss. As such, clearance of α-syn aggregates may slow the progression of PD and lead to less severe symptoms. Evidence is increasing that non-neuronal cells play a role in PD and other synucleinopathies such as Lewy body dementia and multiple system atrophy. Our previous work has shown that pericytes—vascular mural cells that regulate the blood-brain barrier—contain α-syn aggregates in human PD brains. Here, we demonstrate that pericytes efficiently internalise fibrillar α-syn irrespective of being in a monoculture or mixed neuronal cell culture. Pericytes cleave fibrillar α-syn aggregates (Fibrils, Ribbons, fibrils65, fibrils91 and fibrils110), with cleaved α-syn remaining present for up to 21 days. The number of α-syn aggregates/cell and average aggregate size depends on the type of strain, but differences disappear within 5 five hours of treatment. Our results highlight the role brain vasculature may play in reducing α-syn aggregate burden in PD.
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Sugimoto, Yasushi, Yoshiki Kamada, Yuhei Tokunaga, Hiroshi Shinohara, Mitsuharu Matsumoto, Takahiro Kusakabe, Takatoshi Ohkuri, and Tadashi Ueda. "Aggregates with lysozyme and ovalbumin show features of amyloid-like fibrils." Biochemistry and Cell Biology 89, no. 6 (December 2011): 533–44. http://dx.doi.org/10.1139/o11-041.
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The interaction of egg-white lysozyme with N-ovalbumin, the native form of egg-white ovalbumin with the denaturation temperature, Tm, of 78 °C, was investigated by the inhibition of lysozyme muramidase activity, differential scanning calorimetry, and circular dichroism assay as indicators. Signals for the interaction were the most prominent when the mixture of lysozyme and N-ovalbumin was co-heated at 72 °C, slightly lower than the Tm of N-ovalbumin. The interaction was also marked when unheated lysozyme was mixed with N-ovalbumin preheated at 72 °C. Moreover, the mixture rapidly formed fibrous precipitates, which were positive for thioflavin T fluorescent emission, a marker for the amyloid fibril formation. Also electron microscopic observation exhibited features of fibrils. The interaction potency of ovalbumin was ascribed to the tryptic fragment ILELPFASGT MSMLVLLPDE VSGLEQLESIINFEK (residues 229–263), derived from the 2B strands 2 and 3 of ovalbumin. From lysozyme, on the other hand, the chymotryptic peptide RNRCKGTDVQAW (residues 112–123), including cluster 6, and the chymotryptic/tryptic peptide GILQINSRW (residues 54–62), including cluster 3, were responsible for the interaction with N-ovalbumin. Interestingly, this nonamer peptide was found to have the ability to self-aggregate. To the authors knowledge, this may be the first report to document the possible involvement of dual proteins in the formation of amyloid-like fibrils.
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Buchanan, L. E., J. K. Carr, A. M. Fluitt, A. J. Hoganson, S. D. Moran, J. J. de Pablo, J. L. Skinner, and M. T. Zanni. "Structural motif of polyglutamine amyloid fibrils discerned with mixed-isotope infrared spectroscopy." Proceedings of the National Academy of Sciences 111, no. 16 (February 18, 2014): 5796–801. http://dx.doi.org/10.1073/pnas.1401587111.
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MacPhee, Cait E., and Christopher M. Dobson. "Formation of Mixed Fibrils Demonstrates the Generic Nature and Potential Utility of Amyloid Nanostructures." Journal of the American Chemical Society 122, no. 51 (December 2000): 12707–13. http://dx.doi.org/10.1021/ja0029580.
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Morgan, Gareth J., Silva Giannini, Andrea M. Hounslow, C. Jeremy Craven, Eva Zerovnik, Vito Turk, Jonathan P. Waltho, and Rosemary A. Staniforth. "Exclusion of the Native α-Helix from the Amyloid Fibrils of a Mixed α/β Protein." Journal of Molecular Biology 375, no. 2 (January 2008): 487–98. http://dx.doi.org/10.1016/j.jmb.2007.10.033.
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Starke, Josefine, Bernhard Wehrle-Haller, and Peter Friedl. "Plasticity of the actin cytoskeleton in response to extracellular matrix nanostructure and dimensionality." Biochemical Society Transactions 42, no. 5 (September 18, 2014): 1356–66. http://dx.doi.org/10.1042/bst20140139.
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Mobile cells discriminate and adapt to mechanosensory input from extracellular matrix (ECM) topographies to undergo actin-based polarization, shape change and migration. We tested ‘cell-intrinsic’ and adaptive components of actin-based cell migration in response to widely used in vitro collagen-based substrates, including a continuous 2D surface, discontinuous fibril-based surfaces (2.5D) and fibril-based 3D geometries. Migrating B16F1 mouse melanoma cells expressing GFP–actin developed striking diversity and adaptation of cytoskeletal organization and migration efficacy in response to collagen organization. 2D geometry enabled keratinocyte-like cell spreading and lamellipod-driven motility, with barrier-free movement averaging the directional vectors from one or several leading edges. 3D fibrillar collagen imposed spindle-shaped polarity with a single cylindrical actin-rich leading edge and terminal filopod-like protrusions generating a single force vector. As a mixed phenotype, 2.5D environments prompted a broad but fractalized leading lamella, with multiple terminal filopod-like protrusions engaged with collagen fibrils to generate an average directional vector from multiple, often divergent, interactions. The migratory population reached >90% of the cells with high speeds for 2D, but only 10–30% of the cells and a 3-fold lower speed range for 2.5D and 3D substrates, suggesting substrate continuity as a major determinant of efficient induction and maintenance of migration. These findings implicate substrate geometry as an important input for plasticity and adaptation of the actin cytoskeleton to cope with varying ECM topography and highlight striking preference of moving cells for 2D continuous-shaped over more complex-shaped discontinuous 2.5 and 3D substrate geometries.
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Edler, Karen, Duygu Celebi, Yun Jin, and Janet Scott. "Partially Oxidised Cellulose Nanofibril Gels for Rheology Modification." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C1320. http://dx.doi.org/10.1107/s2053273314086793.
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Partially C6-oxidised cellulose nanofibrils form a transparent, slightly viscous suspension in water. These materials, sourced from soft-wood waste, have shown excellent potential for use as a rheology modifier in aqueous formulations, when mixed with salt and minimal amounts of anionic surfactants [1] or with short chain alcohols. The interaction with anionic surfactants is particularly surprising as the cellulose fibrils themselves carry a net negative charge. The gels formed are transparent, mild on the skin and have excellent suspending properties while also being strongly shear thinning making application eg via spraying possible. The partially oxidised cellulose nanofibrils can also be used to stabilize oil-in-water Pickering emulsions. Both the gels and emulsions are of interest for use in personal care products such as creams, sanitizers and shower gels. We have probed the micelle-fibril interactions in water and in the presence of ethanol using contrast matching SANS on the gels and also on the cellulose-stabilized Pickering emulsion droplets. SAXS has also been used to probe the effect of short chain alcohols on the nanofibril structures in the gels as a function of alcohol chain length, while neutron reflectivity was used to probe surfactant-fibril binding for anionic and nonionic surfactants in thin nanofibril layers. The nanostructures formed in suspensions of partially oxidised cellulose nanofibrils with a range of salts, alcohols and surfactants will be correlated with their rheological behaviour. These factors will be discussed and brought together to give insights into how and why these systems form gels.
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Barocas, V. H., and R. T. Tranquillo. "A Finite Element Solution for the Anisotropic Biphasic Theory of Tissue-Equivalent Mechanics: The Effect of Contact Guidance on Isometric Cell Traction Measurement." Journal of Biomechanical Engineering 119, no. 3 (August 1, 1997): 261–68. http://dx.doi.org/10.1115/1.2796090.
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We present a method for solving the governing equations from our anisotropic biphasic theory of tissue-equivalent mechanics (Barocas and Tranquillo, 1997) for axisymmetric problems. A mixed finite element method is used for discretization of the spatial derivatives, and the DASPK subroutine (Brown et al., 1994) is used to solve the resulting differential-algebraic equation system. The preconditioned GMRES algorithm, using a preconditioner based on an extension of Dembo’s (1994) adaptation of the Uzawa algorithm for viscous flows, provides an efficient and scaleable solution method, with the finite element method discretization being first-order accurate in space. In the cylindrical isometric cell traction assay, the chosen test problem, a cylindrical tissue equivalent is adherent at either end to fixed circular platens. As the cells exert traction on the collagen fibrils, the force required to maintain constant sample length, or load, is measured. However, radial compaction occurs during the course of the assay, so that the cell and network concentrations increase and collagen fibrils become aligned along the axis of the cylinder, leading to cell alignment along the axis. Our simulations predict that cell contact guidance leads to an increase in the load measured in the assay, but this effect is diminished by the tendency of contact guidance to inhibit radial compaction of the sample, which in turn reduces concentrations and hence the measured load.
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van de Meene, Allison, Lauren McAloney, Sarah M. Wilson, JiZhi Zhou, Wei Zeng, Paul McMillan, Antony Bacic, and Monika S. Doblin. "Interactions between Cellulose and (1,3;1,4)-β-glucans and Arabinoxylans in the Regenerating Wall of Suspension Culture Cells of the Ryegrass Lolium multiflorum." Cells 10, no. 1 (January 11, 2021): 127. http://dx.doi.org/10.3390/cells10010127.
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Plant cell walls (PCWs) form the outer barrier of cells that give the plant strength and directly interact with the environment and other cells in the plant. PCWs are composed of several polysaccharides, of which cellulose forms the main fibrillar network. Enmeshed between these fibrils of cellulose are non-cellulosic polysaccharides (NCPs), pectins, and proteins. This study investigates the sequence, timing, patterning, and architecture of cell wall polysaccharide regeneration in suspension culture cells (SCC) of the grass species Lolium multiflorum (Lolium). Confocal, superresolution, and electron microscopies were used in combination with cytochemical labeling to investigate polysaccharide deposition in SCC after protoplasting. Cellulose was the first polysaccharide observed, followed shortly thereafter by (1,3;1,4)-β-glucan, which is also known as mixed-linkage glucan (MLG), arabinoxylan (AX), and callose. Cellulose formed fibrils with AX and produced a filamentous-like network, whereas MLG formed punctate patches. Using colocalization analysis, cellulose and AX were shown to interact during early stages of wall generation, but this interaction reduced over time as the wall matured. AX and MLG interactions increased slightly over time, but cellulose and MLG were not seen to interact. Callose initially formed patches that were randomly positioned on the protoplast surface. There was no consistency in size or location over time. The architecture observed via superresolution microscopy showed similarities to the biophysical maps produced using atomic force microscopy and can give insight into the role of polysaccharides in PCWs.
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van de Meene, Allison, Lauren McAloney, Sarah M. Wilson, JiZhi Zhou, Wei Zeng, Paul McMillan, Antony Bacic, and Monika S. Doblin. "Interactions between Cellulose and (1,3;1,4)-β-glucans and Arabinoxylans in the Regenerating Wall of Suspension Culture Cells of the Ryegrass Lolium multiflorum." Cells 10, no. 1 (January 11, 2021): 127. http://dx.doi.org/10.3390/cells10010127.
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Plant cell walls (PCWs) form the outer barrier of cells that give the plant strength and directly interact with the environment and other cells in the plant. PCWs are composed of several polysaccharides, of which cellulose forms the main fibrillar network. Enmeshed between these fibrils of cellulose are non-cellulosic polysaccharides (NCPs), pectins, and proteins. This study investigates the sequence, timing, patterning, and architecture of cell wall polysaccharide regeneration in suspension culture cells (SCC) of the grass species Lolium multiflorum (Lolium). Confocal, superresolution, and electron microscopies were used in combination with cytochemical labeling to investigate polysaccharide deposition in SCC after protoplasting. Cellulose was the first polysaccharide observed, followed shortly thereafter by (1,3;1,4)-β-glucan, which is also known as mixed-linkage glucan (MLG), arabinoxylan (AX), and callose. Cellulose formed fibrils with AX and produced a filamentous-like network, whereas MLG formed punctate patches. Using colocalization analysis, cellulose and AX were shown to interact during early stages of wall generation, but this interaction reduced over time as the wall matured. AX and MLG interactions increased slightly over time, but cellulose and MLG were not seen to interact. Callose initially formed patches that were randomly positioned on the protoplast surface. There was no consistency in size or location over time. The architecture observed via superresolution microscopy showed similarities to the biophysical maps produced using atomic force microscopy and can give insight into the role of polysaccharides in PCWs.
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Micsonai, András, Frank Wien, Linda Kernya, Young-Ho Lee, Yuji Goto, Matthieu Réfrégiers, and József Kardos. "Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy." Proceedings of the National Academy of Sciences 112, no. 24 (June 2, 2015): E3095—E3103. http://dx.doi.org/10.1073/pnas.1500851112.
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Circular dichroism (CD) spectroscopy is a widely used technique for the study of protein structure. Numerous algorithms have been developed for the estimation of the secondary structure composition from the CD spectra. These methods often fail to provide acceptable results on α/β-mixed or β-structure–rich proteins. The problem arises from the spectral diversity of β-structures, which has hitherto been considered as an intrinsic limitation of the technique. The predictions are less reliable for proteins of unusual β-structures such as membrane proteins, protein aggregates, and amyloid fibrils. Here, we show that the parallel/antiparallel orientation and the twisting of the β-sheets account for the observed spectral diversity. We have developed a method called β-structure selection (BeStSel) for the secondary structure estimation that takes into account the twist of β-structures. This method can reliably distinguish parallel and antiparallel β-sheets and accurately estimates the secondary structure for a broad range of proteins. Moreover, the secondary structure components applied by the method are characteristic to the protein fold, and thus the fold can be predicted to the level of topology in the CATH classification from a single CD spectrum. By constructing a web server, we offer a general tool for a quick and reliable structure analysis using conventional CD or synchrotron radiation CD (SRCD) spectroscopy for the protein science research community. The method is especially useful when X-ray or NMR techniques fail. Using BeStSel on data collected by SRCD spectroscopy, we investigated the structure of amyloid fibrils of various disease-related proteins and peptides.
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Tian, Jing, Yang Yu, Yao Wang, Haoyi Li, Lujuan Yang, Baoan Du, and Gang Ma. "Tannic Acid-Induced Surface-Catalyzed Secondary Nucleation during the Amyloid Fibrillation of Hen Egg-White Lysozyme." International Journal of Molecular Sciences 19, no. 12 (December 12, 2018): 4009. http://dx.doi.org/10.3390/ijms19124009.
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Amyloid fibrillation by hen egg white lysozyme under the influence of tannic acid was investigated by atomic force microscopy and fluorescence spectroscopy. Tannic acid was found to be able to induce the formation of amyloid fibrils with an interesting mixed morphology. Such morphology features with the existence of areas of thickening alternating with areas of normal height. This novel modulation effect of tannic acid on amyloid fibrillation was interpreted by the established surface-catalyzed secondary nucleation theory. We further performed a fluorescence quenching study to investigate the intermolecular interaction between tannic acid and lysozyme. The results support that lysozyme and tannic acid interact with each other mainly through hydrophobic interactions. We also discussed why hydrogen-bonding interaction is not a dominant factor in the interaction between tannic acid and lysozyme though tannic acid contains a significant amount of hydroxyl groups. Our work provides new insight into the effect of tannic acid, a well-known amyloid inhibitor, on amyloid fibrillation.
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Bykova, N. I., T. L. Kobylkina, V. A. Grigoryan, A. A. Adamchik, and A. V. Arutyunov. "PATHOLOGIC FEATURES OF PERIODONTAL TISSUES IN EXPERIMENTAL OSTEOPOROSIS." Russian Journal of Dentistry 21, no. 2 (April 15, 2017): 76–78. http://dx.doi.org/10.18821/1728-28022017;21(2):76-78.
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The article presents information about some pathological changes in periodontal tissues during experimental osteoporosis. The experiments were conducted on 8 three-year sheep, which have at different times after ovariectomy removed dentoalveolar segments in the region of incisors of the lower jaw. Pathological changes in periodontal animals in experimental osteoporosis were local manifestations of the general condition of the body that are typical of acute hypoxia mixed character. It was found that experimental osteoporosis in periodontal develop processes accompanied by acute circulatory disorders, which worsen the conditions of metabolism, which ultimately leads to destructive changes of argyrophilic and collagen fibrils, as well as individual nerve fibers. Studies have shown that these effects are reversible, and after 120 days to the fore the phenomenon of compensation in periodontal starting to recover basic histological structure. Prolonged hypoxia, as the main link in the pathogenesis of degenerative and inflammatory of forms of periodontal disease may be modified by the proven of efficiency pharmacological means. The detected changes at the osteoporosis models can be the basis for further study of the role of autologous mesenchymal stem cells and materials-matrices of various origins in optimizing the osseointegration process.
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Fu, Wuchang, Xiaoqiang Xu, and Hongwu Wu. "Mechanical and biodegradable properties of l-lactide-grafted sisal fiber reinforced polylactide composites." Journal of Reinforced Plastics and Composites 33, no. 22 (September 29, 2014): 2034–45. http://dx.doi.org/10.1177/0731684414552684.
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Sisal fiber (SF) was grafted with low polymerization degree polylactide (PLA) according to the principle of coordinative ring-opening polymerization of lactide, and then the lactide-grafted sisal fiber (SF-g-LA) was mixed with PLA to make PLA/SF-g-LA composites. The mechanical properties, morphology, and biodegradability of PLA/SF-g-LA composites were systematically investigated, comparing with untreated SF reinforced PLA (PLA/USF) and alkali-treated SF reinforced PLA (PLA/ASF) composites. Results showed that the interfacial properties between SF-g-LA and PLA matrix showed dramatic improvement. The PLA/SF-g-LA composites exhibited noticeably superior tensile and flexural properties; however, their impact strength decreased slightly compared with pure PLA. All of the composites were buried in soil and different degrees of degradation were achieved. Because of better interfacial adhesion between SF-g-LA and PLA matrix, the degradation rate of PLA/SF-g-LA composite was lower than those of PLA/USF and PLA/ASF composites, although still higher than that of pure PLA. The biodegradation of PLA/SF-g-LA composites was marked by appearance of cavities, the exfoliation of fragmental materials, and the degradation of cellulose fibrils.
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Markowitz, G. S., J. T. Cheng, R. B. Colvin, W. M. Trebbin, and V. D. D'Agati. "Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy." Journal of the American Society of Nephrology 9, no. 12 (December 1998): 2244–52. http://dx.doi.org/10.1681/asn.v9122244.
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The most common form of glomerular disease seen in association with hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis, with or without associated cryoglobulinemia. This study examines four cases of fibrillary glomerulonephritis and two cases of immunotactoid glomerulopathy in association with HCV infection. Findings at presentation included proteinuria, renal insufficiency, and hematuria. Renal biopsy revealed a membranoproliferative pattern of glomerular disease in five cases, and a membranous glomerulopathy with mesangial proliferative features in one. On immunofluorescence, all cases stained with IgG and C3. Electron microscopy revealed fibrils of the expected diameter, 16 to 28 nm in fibrillary glomerulonephritis and 33 to 45 nm in immunotactoid glomerulopathy. In only one case were cryoglobulins detected (at low titer and on only one of three assays). Antiviral therapy was not given in any of the six cases. Outcomes were mixed, with progression to renal failure occurring in two patients and persistent proteinuria with stable or improved renal function in three. Follow-up is not available on the sixth case. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have features that overlap with cryoglobulinemic glomerulonephritis. The relatedness of these three entities in a subset of patients with HCV infection suggests a common pathogenic mechanism of glomerular deposition of organized deposits.
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Lim, Wei Lee, Shiplu Roy Chowdhury, Min Hwei Ng, and Jia Xian Law. "Physicochemical Properties and Biocompatibility of Electrospun Polycaprolactone/Gelatin Nanofibers." International Journal of Environmental Research and Public Health 18, no. 9 (April 29, 2021): 4764. http://dx.doi.org/10.3390/ijerph18094764.
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Tissue-engineered substitutes have shown great promise as a potential replacement for current tissue grafts to treat tendon/ligament injury. Herein, we have fabricated aligned polycaprolactone (PCL) and gelatin (GT) nanofibers and further evaluated their physicochemical properties and biocompatibility. PCL and GT were mixed at a ratio of 100:0, 70:30, 50:50, 30:70, 0:100, and electrospun to generate aligned nanofibers. The PCL/GT nanofibers were assessed to determine the diameter, alignment, water contact angle, degradation, and surface chemical analysis. The effects on cells were evaluated through Wharton’s jelly-derived mesenchymal stem cell (WJ-MSC) viability, alignment and tenogenic differentiation. The PCL/GT nanofibers were aligned and had a mean fiber diameter within 200–800 nm. Increasing the GT concentration reduced the water contact angle of the nanofibers. GT nanofibers alone degraded fastest, observed only within 2 days. Chemical composition analysis confirmed the presence of PCL and GT in the nanofibers. The WJ-MSCs were aligned and remained viable after 7 days with the PCL/GT nanofibers. Additionally, the PCL/GT nanofibers supported tenogenic differentiation of WJ-MSCs. The fabricated PCL/GT nanofibers have a diameter that closely resembles the native tissue’s collagen fibrils and have good biocompatibility. Thus, our study demonstrated the suitability of PCL/GT nanofibers for tendon/ligament tissue engineering applications.
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Pozsonyi, Zoltán, Gergely Peskó, Hedvig Takács, Dorottya Csuka, Viktória Nagy, Ágnes Szilágyi, Lidia Hategan, et al. "Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features." Genes 12, no. 8 (July 28, 2021): 1152. http://dx.doi.org/10.3390/genes12081152.
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Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. Methods: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. Results: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. Conclusions: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.
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Kupka, Vojtěch, Eva Dvořáková, Anton Manakhov, Miroslav Michlíček, Josef Petruš, Lucy Vojtová, and Lenka Zajíčková. "Well-Blended PCL/PEO Electrospun Nanofibers with Functional Properties Enhanced by Plasma Processing." Polymers 12, no. 6 (June 22, 2020): 1403. http://dx.doi.org/10.3390/polym12061403.
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Biodegradable composite nanofibers were electrospun from poly(ε-caprolactone) (PCL) and poly(ethylene oxide) (PEO) mixtures dissolved in acetic and formic acids. The variation of PCL:PEO concentration in the polymer blend, from 5:95 to 75:25, revealed the tunability of the hydrolytic stability and mechanical properties of the nanofibrous mats. The degradation rate of PCL/PEO nanofibers can be increased compared to pure PCL, and the mechanical properties can be improved compared to pure PEO. Although PCL and PEO have been previously reported as immiscible, the electrospinning into nanofibers having restricted dimensions (250–450 nm) led to a microscopically mixed PCL/PEO blend. However, the hydrolytic stability and tensile tests revealed the segregation of PCL into few-nanometers-thin fibrils in the PEO matrix of each nanofiber. A synergy phenomenon of increased stiffness appeared for the high concentration of PCL in PCL/PEO nanofibrous mats. The pure PCL and PEO mats had a Young’s modulus of about 12 MPa, but the mats made of high concentration PCL in PCL/PEO solution exhibited 2.5-fold higher values. The increase in the PEO content led to faster degradation of mats in water and up to a 20-fold decrease in the nanofibers’ ductility. The surface of the PCL/PEO nanofibers was functionalized by an amine plasma polymer thin film that is known to increase the hydrophilicity and attach proteins efficiently to the surface. The combination of different PCL/PEO blends and amine plasma polymer coating enabled us to tune the surface functionality, the hydrolytic stability, and the mechanical properties of biodegradable nanofibrous mats.
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Tajima, Asako, Wen Liu, Isha Pradhan, Suzanne Bertera, Robert Lakomy, William A. Rudert, Massimo Trucco, Wilson S. Meng, and Yong Fan. "Generation of functional mini thymus-like units with self-assembling EAK16-II/EAKIIH6 hydrogel." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 209.2. http://dx.doi.org/10.4049/jimmunol.196.supp.209.2.
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Abstract A functional thymus is crucial to produce mature, self-tolerant T cells. Crosstalk between the residing thymic stromal cells, especially the predominant population of thymic epithelial cells (TECs), and the developing thymocytes is essential for thymopoiesis. The survival and proliferation of TECs depend on a unique 3 dimensional (3-D) configuration of the thymus microenvironment. Disorganization of TECs results in a loss of gene expressions essential for TEC growth and survival, as well as inability to produce functional T cells. Recapitulating the property of thymus has been proven to be challenging. In our study, we have incorporated EAK16-II, a low molecular weight peptide that self-assembles into beta-sheet fibrils, and its histidinylated analogue, to induce 3-D aggregation of TECs. When the adaptor complex comprised of anti-EpCAM IgG, anti-His and recombinant protein A/G molecules were mixed with TECs in the hydrogel, TECs were captured into small clusters. TECs cultured in this condition maintained their molecular properties and were viable up to 2 weeks. Furthermore, when the TEC clusters in the hydrogel were transplanted into athymic nude mice, T cell development was observed, and these newly generated T cells proliferated upon stimulation with allogenic cells. These results demonstrate that self-assembling EAK16-II/EAKIIH6 system with addition of tri-component adaptor complex may be a useful tool to organize TECs in a 3-D-like structure to support T cell development, suggesting a possibility to generate injectable mini thymus-like units to restore adaptive immune system.
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Hirai, Jiro, and Takehisa Matsuda. "Venous Reconstruction Using Hybrid Vascular Tissue Composed of Vascular Cells and Collagen: Tissue Regeneration Process." Cell Transplantation 5, no. 1 (January 1996): 93–105. http://dx.doi.org/10.1177/096368979600500114.
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In this study, a tubular hybrid vascular tissue composed of vascular cells and collagen was implanted as a venous substitute, and its remodeling process was histologically investigated. First, a hybrid medial tissue was prepared by pouring a cold mixed solution of canine jugular smooth muscle cells (SMCs) and Type I collagen into a tubular glass mold and subsequent incubation at 37°C. Culture in medium for 10 days produced a dense tubular tissue. Seeding of jugular endothelial cells (ECs) onto the luminal surface of the tissue produced a hybrid vascular tissue with a hierarchical structure. These vascular tissues (inner diameter, 7 mm; length, 3 cm; wall thickness, 1 mm; n = 14) were implanted autologously in the canine posterior vena cava wrapped in Dacron mesh for up to 24 wk. Nine of 14 grafts were patent throughout implantation. In patent grafts, monolayered ECs were oriented in the direction of blood flow at 1 wk. Circumferentially oriented SMCs accumulated at the subendothelial layer and ingrown fibroblasts were sparsely distributed throughout the wall at 12 wk. Contractile phenotype of SMCs was evident at 24 wk. Collagen fibrils, which were sparsely distributed at an early period of implantation, gradually assembled to form fibrous meshes at 24 wk. Sheet-like elastic lamellae were also observed at this time. Marked wall thinning was observed at 12 and 24 wk. The resultant tissues became highly dense. The specific gravity of tissues increased with time, and reached those of natural vessels at 24 wk. Tissue remodeling progressed in a time-dependent manner and appeared to be almost complete within 6 mo of implantation.
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Takeuchi, Masaru, Po-Chuen Shieh, and Chi-Ting Horng. "Treatment of Symptomatic Vitreous Opacities with Pharmacologic Vitreolysis Using a Mixure of Bromelain, Papain and Ficin Supplement." Applied Sciences 10, no. 17 (August 26, 2020): 5901. http://dx.doi.org/10.3390/app10175901.
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Methods: Our research was scheduled in Southern Taiwan between April 2017 and December 2017. A total of 280 patients presenting 280 eyes were enrolled and received a series of ocular examinations. Each of our specially designed capsules contained 190 mg bromelain, 95 mg papain and 95 mg ficin. In Experiment 1, 120 subjects were classified into Group 1 (one symptomatic vitreous opacity (SVO)) and Group 2 (multiple SVOs) which each subject taking two capsules every day. In Experiment 2, 160 eyes with SVOs were randomly divided into four groups including the placebo; low protease group (LPG) (1 capsule/day); middle protease group (MPG) (2 capsules/day); and high protease group (HPG) (3 capsules/day), respectively. Finally, we analyzed the change in SVOs and checked the numbers of SVOs during and after three months in our study. Results: In Experiment 1, 80 subjects with one SVO were reduced to 24 cases (30.0%; 24/80), 40 participants with multiple SVOs were decreased to 11 cases (27.5%; 11/40) three months later. In Experiment 2, the numbers of patients with SVOs in the placebo group was similar after three months. The disappeared rates of SVOs by treatment with fruit enzymes was 65.5%, 70.0% and 75.5% and for those taking one, two and three capsules daily as therapy, respectively. Hence, the results showed that the effects of treating SVOs in a dose-dependent manner; the higher the dose, the greater the SVO reduction. We also suggested that the mechanisms of dissolving and absorbing SVOs may be due to the proteinase and associated hydrolysis and antioxidant activities that may clear the compromised opacity and scavenge free radicals in the vitreous. In addition, there were no serious side effects or discomfort during treatment. Conclusion: We demonstrated that mixed-fruit-enzyme including bromelain, papain and ficin may excise SVOs and even eliminate intraocular hemorrhage by cleaving the collagen fibrils and cellular debris that may induce ocular floaters.
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Chaparro Sosa, Andres F., Sabrina Matos de Oliveira da Silva, Garry P. Morgan, Daniel K. Schwartz, and Joel L. Kaar. "Mixed Phospholipid Vesicles Catalytically Inhibit and Reverse Amyloid Fibril Formation." Journal of Physical Chemistry Letters 11, no. 17 (August 17, 2020): 7417–22. http://dx.doi.org/10.1021/acs.jpclett.0c02074.
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Ma, Yong Qing, Yun Zhong Wu, Hong Tao Gao, Yang Zhang, and Shi Yong Liu. "Microstructure and Mechanical Properties of Copper Clad Aluminium Wire by Drawing at Room Temperature." Key Engineering Materials 334-335 (March 2007): 317–20. http://dx.doi.org/10.4028/www.scientific.net/kem.334-335.317.
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The microstructure and mechanical properties of pure copper clad Aluminum wires in different diameters by drawing at room temperature were studied in this paper. The results show that the microstructure of the cladding wire by drawing at room temperature is vimineous grain as fibril shape from prime equiaxed grain. The fibril diameter is in inverse proportion to deformation and the fibril length is in direct proportion to square of deformation approximately. The ultimate tensile strength of the cladding wire by drawing at room temperature increases in direct proportion to square root of deformation, and the elongation decreases and fluctuates. Basis of the ultimate tensile strength of prime pure copper and aluminum alloy, the ultimate tensile strength of the cladding wires in different diameters can be doped out by mixed principle of composite material.
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Chen, Da, Fang Fang, Enrico Federici, Osvaldo Campanella, and Owen Griffith Jones. "Rheology, microstructure and phase behavior of potato starch-protein fibril mixed gel." Carbohydrate Polymers 239 (July 2020): 116247. http://dx.doi.org/10.1016/j.carbpol.2020.116247.
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Bell, E., M. Rosenberg, P. Kemp, R. Gay, G. D. Green, N. Muthukumaran, and C. Nolte. "Recipes for Reconstituting Skin." Journal of Biomechanical Engineering 113, no. 2 (May 1, 1991): 113–19. http://dx.doi.org/10.1115/1.2891224.
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Reconstituted Living Skin Equivalent™ (LSE™) is made up of a dermal equivalent (DE) on which keratinocytes are plated where they give rise to a multilayered differentiated epidermis. The dermal equivalent develops through interactions between fibroblasts and collagen fibrils that begin to form after the cell-matrix precursor is cast. The gel that forms as a result of collagen polymerization and fluid trapping is contracted uniformly in all dimensions. By securing it at ends and edges in the mold in which it is cast, the final dimensions, strength and morphology of the forming tissue are altered. The same phenomena are seen in casting tubular tissues for the fabrication of small caliber blood vessel equivalents. The cells of the dermal equivalent are biosynthetically active and enrich the matrix to different degrees with secretory products, depending on how the cells are stimulated and on the presence or absence of an epidermis. Collagen biosynthesis by dermal cells in the DE is sensitive to growth factors, ascorbate concentrations and amino acid pools. Both ascorbate and TGFβ1 increase total collagen biosynthesis at least two-fold by one week after tissue formation. With TGFβ1 present, the capacity of cells in the DE to synthesize collagen increases with time, over a two-week period. If ascorbate (200 μg/ml) is added just after the tissue is cast and daily thereafter, contraction lattice is blocked, and collagen biosynthesis is enhanced relative to contracted controls that had received 200 μg/ml ascorbate once. The increase was nearly an order of magnitude over that of controls and was coordinate with a comparable increase in hyaluronate and sulfated glycosaminoglycan (GAG) production as shown by TCA-precipitable glucosamine in the intercellular matrix of the DE. Both the LSE and the Living Dermal Equivalent™ (LDE™) exhibit complex responses to UV radiation and to various chemicals that are greatly different from responses given by monolayered cells. In general, threshold doses are elevated by one or more orders of magnitude for the tissues as compared with cells in monolayer, with the LSE exhibiting higher thresholds than the DE. The immunogenicity of the human LSE has been tested in vitro. Its cells are shown to be unable to stimulate a response in a mixed lymphocyte reaction (MLR) even after Class II antigens are induced by exposure to cytokines. The basis for the immunologic neutrality of the LSE can be referred to the absence of immune system (IS) cells normally present in skin and to the specific antigenic profiles of nonimmune system (NIS) cells that must be different from those of IS cells and which, even after Class II induction, are not allostimulatory. The generality of immunologic neutrality is an essential consideration in the fabrication of tissue and organ equivalents for grafting. The idea that it can be made a graft property has been formalized in the Neutral Allograft Hypothesis.
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Yeo, Yan Ling, Kheng Lim Goh, Liao Kin, Hui Juan Wang, Anne Listrat, and Daniel Bechet. "Structure-Property Relationship of Burn Collagen Reinforcing Musculo-Skeletal Tissues." Key Engineering Materials 478 (April 2011): 87–92. http://dx.doi.org/10.4028/www.scientific.net/kem.478.87.
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An investigation has been conducted on burn ligaments, addressing the specific conditions in burn arising from dehydration and heating, and how these affect the structure-property relationship of collagen for reinforcing the tissue. Collagen fibres were isolated from a sheep’s anterior cruciate ligament, i.e. our model for this study, and divided into six groups. The first group was designated as control; the second (D) group was dehydrated without exposure to elevated temperature. The remaining (DH) groups were dehydrated followed by heating at 120oC for 30 minutes, 2, 4 and 24 hours, respectively. Tensile test to rupture was carried out to derive the fibre modulus of elasticity (E), maximum stress (σ), strain at maximum stress (ε) and strain energy density to maximum stress (u). Electron micrographs of the ruptured ends reveal a mixed mode of fibril pull-out and rupture: fibril pull-out dominates in the control group but fibril rupture dominates increasingly in the other groups, i.e. with increasing exposure time to elevated temperature. Apart from ε, there is significant increase in E, σ and u in the D and DH groups with respect to the control group but there is no evidence of variation among the D and DH groups. The results of this study implicate (1) the removal of water in the hydrated proteoglycan-rich matrix, leading to shrinkages at micrometer length-scale during dehydration, and (2) the alteration of the collagen organisation arising from the underlying changes in the crystallinity and denaturation during heating, on the mechanical properties of burn collagen fibres.
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Bifulco, Aurelio, Brigida Silvestri, Jessica Passaro, Luca Boccarusso, Valentina Roviello, Francesco Branda, and Massimo Durante. "A New Strategy to Produce Hemp Fibers through a Waterglass-Based Ecofriendly Process." Materials 13, no. 8 (April 14, 2020): 1844. http://dx.doi.org/10.3390/ma13081844.
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Natural fibers such as kenaf, hemp, flax, jute, and sisal have become the subject of much research as potential green or eco-friendly reinforcement composites, since they assure the reduction of weight, cost, and CO2 release with less reliance on oil sources. Herein, an inexpensive and eco-friendly waterglass treatment is proposed, allowing the production of silica-coated fibers that can be easily obtained in micro/nano fibrils through a low power mixer. The silica coating has been exploited to improve the chemical compatibility between fibers and the polymer matrix through the reaction of silanol groups with suitable coupling agents. In particular, silica-coated fibers easily functionalized with (3-Aminopropyl) triethoxysilane (APTS) were used as a filler in the manufacturing of epoxy-based composites. Morphological investigation of the composites through Scanning Electron Microscopy (SEM) demonstrated that the filler has a tendency to produce a web-like structure, formed by continuously interconnected fibrils and microfibrils, from which particularly effective mechanical properties may be obtained. Dynamic Mechanical Analysis (DMA) shows that the functionalized fibers, in a concentration of 5 wt%, strongly affect the glass transformation temperature (10 °C increase) and the storage modulus of the pristine resin. Taking into account the large number of organosilicon compounds (in particular the alkoxide ones) available on the market, the new process appears to pave the way for the cleaner and cheaper production of biocomposites with different polymeric matrices and well-tailored interfaces.
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Carnemolla, Barbara, Alessandra Leprini, Germano Querzé, Stefania Urbini, and Luciano Zardi. "Novel self-association fibronectin sites." Biochemistry and Cell Biology 74, no. 6 (December 1, 1996): 745–48. http://dx.doi.org/10.1139/o96-081.
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In this study, we report a strong interaction between two contiguous proteolytic fragments of fibronectin, each having a mass of about 16 kDa. This interaction was stable in 4 M NaCl and 4 M urea and dissociation of the two fragments required buffers containing 0.5% sodium dodecyl sulphate. After purification, these peptides maintained their ability to interact when mixed. One fragment was made up of type III repeat 4 and part of 5, the other by repeat 6 and part of 5. Such strong interaction between two fibronectin regions may play a role in fibronectin conformation as well as during fibronectin fibril formation.Key words: fibronectin, type III repeats interaction.
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Puttawibul, Puttiporn, Soottawat Benjakul, and Jirut Meesane. "Preparation and Characterization of an In Situ Hydrogel of Self-Assembly Type I Collagen from Shark Skin/Methylcellulose for Central Nerve System Regeneration." Journal of Biomimetics, Biomaterials and Biomedical Engineering 24 (July 2015): 14–29. http://dx.doi.org/10.4028/www.scientific.net/jbbbe.24.14.
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Central nerve system degeneration is a crucial problem for many patients. To use an in situ hydrogel formation is an attractive method to treat that problem. An in situ hydrogel was developed for central nerve system regeneration. An acid soluble collagen (ASC) and pepsin soluble collagen (PSC) from the shark skin of the brownbanded bamboo shark (Chiloscyllium punctatum) were used to produce hybridized hydrogels by the biomimetic approach. Collagen was mixed with methylcellulose and used 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as a crosslinker. The hydrogels had various ratios of collagen:methylcellulose: 100:0, 70:30, 50:50, 30:70, and 0:100. Structural, molecular, and morphological organization were characterized and observed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The DSC results showed that the peak of denatured collagen fibril shifted higher in a 30:70 ratio of collagen:methylcellulose in both ASC and PSC. The FT-IR results indicated that the structure of hydrogels from both ASC and PSC were organized into complex structures. The SEM results demonstrated that the collagen fibril networks were formed in both ASC and PSC hydrogels. The results indicated that the samples containing collagen promise to be an in situ hydrogel for central nerve regeneration.
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Shari, Nur Atiqah Syahirah, Nurfarah Aini Mocktar, An'amt Mohamed Noor, Mohd Zahri Abdul Aziz, Mohammed Arifullah, and Mohammad Khairul Azhar Abdul Razab. "Mechanical Enhancement of Composite Bricks Using Kenaf and Oil Palm Cellulose Nanofibrils." Key Engineering Materials 908 (January 28, 2022): 651–57. http://dx.doi.org/10.4028/p-58aq10.
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The application of nanocellulose has been adapted as fillers in composite bricks. Raw kenaf and oil palm empty fruit bunch were treated through chemical treatment and high intensity ultrasonication process to produce cellulose nanofibrils (CNF). One control brick without CNF and ten CNF composite bricks were fabricated. The composite bricks used different amount of CNF which were 40 - 200 ml mixed with filtered sand, portland cement and pebbles. Physical and mechanical characterization was done by using field emission scanning electron microscopy (FESEM) and universal testing machine (UTM) on CNF and composite bricks. FESEM showed the fibril diameter were ranges from 30 - 80 nm for kenaf and 20 - 60 nm for oil palm. The compression tests showed that control brick, 40 ml kenaf CNF composite brick and 40 ml oil palm CNF composite brick were cracked at force 39.01 kN, 50.46 kN and 42.16 kN respectively. Kenaf CNF composite brick has the highest value of Young’s Modulus which is 28.92 N/mm2, followed by oil palm CNF composite brick with 27.8 N/mm2 and control brick (Malaysia Standard) with 25.8 N/mm2. Kenaf and oil palm CNF can increase the strength of the bricks because of enhancement in their mechanical properties.
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Panfilova, O. A., S. I. Vol'fson, N. A. Okhotina, R. K. Sabirov, and I. V. Baranets. "The Structure of Thermoplastic Vulcanisates Based on Rubbers of Different Polarity and Polypropylene." International Polymer Science and Technology 44, no. 5 (May 2017): 15–20. http://dx.doi.org/10.1177/0307174x1704400503.
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To expand the range of properties and the range of types of thermoplastic elastomer (TPE), materials based on ternary blends of polypropylene and polar and non-polar rubbers were produced and investigated. To obtain blended and dynamically vulcanised materials, one- and two-stage methods were tested. It was established that the best properties are possessed by composites produced using master batches (rubber mixes) based on a thermoplastic vulcanisate (TPV) rubber phase, and to improve the combination of polymers of different polarity, functionalised additives modifying the polypropylene are necessary. Optical microscopy was used to study the influence of compounding factors (the ratio of components of the polymer phase, the presence or absence of compatibilisers) and technological factors (the production method) on the structure and properties both of blended and of dynamically vulcanised TPEs. A study of the morphology of blended and vulcanised TPEs showed that, in all cases, in the polypropylene, which is the dispersion medium, there are areas rich in rubber to different degrees. Here, fragments of polar rubber are found both in the polypropylene and in zones rich in non-polar rubber, and the range of particle sizes of the disperse phase depends on the production method. The introduction of a compatibiliser leads to a considerable increase in the homogeneity of distribution of the components throughout the material, and to a reduction in the size range of the disperse phase and in the thickness of the polypropylene-rich surface layer of the extrudate (strand). In the surface layer of the strands, anisotropy of the polypropylene fibrils is observed in the direction of extrusion.
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ANTUNES GUIMARÃES, MATHEUS, HONGHI TRAN, and MARCELO CARDOSO. "A novel method for determining the internal recycled dust load in kraft recovery boilers." August 2014 13, no. 8 (September 1, 2014): 27–34. http://dx.doi.org/10.32964/tj13.8.27.
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In kraft recovery boiler operation, fly ash or dust generated from black liquor combustion is mixed with the virgin black liquor in a mix tank and returned to the boiler with the as-fired black liquor. This internal recycled dust stream varies widely from boiler to boiler and from time to time and can have a great impact on the as-fired black liquor flow and properties and, ultimately, on the boiler thermal performance. A new method has been developed to quickly and accurately determine the amount of internal recycled dust in recovery boilers. The method is based on the difference between the total organic carbon content of the virgin black liquor and that of the as-fired black liquor. Tests using the method were performed on recovery boilers at three of Fibria’s mills in Brazil. The results show that while the specific virgin black liquor solids produced at these mills were about the same, the internal recycled dust load varied widely, from as low as 4 wt% of as-fired black liquor solids fired in the boiler at one mill to as high as 15 wt% at another mill. Instead of total organic carbon values, heating values may also be used, but the result is not as accurate.
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Shu, Qin, Andrzej M. Krezel, Zachary T. Cusumano, Jerome S. Pinkner, Roger Klein, Scott J. Hultgren, and Carl Frieden. "Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation." Proceedings of the National Academy of Sciences 113, no. 26 (June 13, 2016): 7130–35. http://dx.doi.org/10.1073/pnas.1607222113.
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Curli, consisting primarily of major structural subunit CsgA, are functional amyloids produced on the surface ofEscherichia coli, as well as many other enteric bacteria, and are involved in cell colonization and biofilm formation. CsgE is a periplasmic accessory protein that plays a crucial role in curli biogenesis. CsgE binds to both CsgA and the nonameric pore protein CsgG. The CsgG–CsgE complex is the curli secretion channel and is essential for the formation of the curli fibril in vivo. To better understand the role of CsgE in curli formation, we have determined the solution NMR structure of a double mutant of CsgE (W48A/F79A) that appears to be similar to the wild-type (WT) protein in overall structure and function but does not form mixed oligomers at NMR concentrations similar to the WT. The well-converged structure of this mutant has a core scaffold composed of a layer of two α-helices and a layer of three-stranded antiparallel β-sheet with flexible N and C termini. The structure of CsgE fits well into the cryoelectron microscopy density map of the CsgG–CsgE complex. We highlight a striking feature of the electrostatic potential surface in CsgE structure and present an assembly model of the CsgG–CsgE complex. We suggest a structural mechanism of the interaction between CsgE and CsgA. Understanding curli formation can provide the information necessary to develop treatments and therapeutic agents for biofilm-related infections and may benefit the prevention and treatment of amyloid diseases. CsgE could establish a paradigm for the regulation of amyloidogenesis because of its unique role in curli formation.
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Yang, Yanming, Kyung Soo Kim, and Edwin J. Anderson. "Seed Transmission of Cucumber Mosaic Virus in Spinach." Phytopathology® 87, no. 9 (September 1997): 924–31. http://dx.doi.org/10.1094/phyto.1997.87.9.924.
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Spinach (Spinacia oleracea) seed from a commercial breeding line suspected of harboring cucumber mosaic virus (CMV) was analyzed for seed transmission of the virus. Initial seed grow-out tests and enzymelinked immunosorbent assay studies indicated that CMV was present in this seed lot at a level of nearly 15%. To verify these results and gain insight into the mechanism of seed transmission, four combinations of crosses between healthy and/or infected parent plants were conducted. None of the spinach seedlings derived from crossing healthy male and healthy female plants contained CMV, whereas a portion of seedlings derived from all of the other three crosses, i.e., healthy male and infected female, infected male and healthy female, and infected male and infected female plants, were infected with CMV. The results demonstrate that CMV is seed transmitted in spinach and indicate that both male and female parent plants can serve as infection sources. Ultrastructural studies, including immunogold labeling, revealed the presence of virus particles in the cytoplasm of ovary wall cells, ovule integuments and nucellus, anther, and seed-coat cells, as well as fine fibril-containing vesicles and electron-dense inclusions of amorphous aggregates in the central vacuoles of these cells. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify 860-bp cDNA fragments containing the CMV coat protein (CP) gene from the embryo, endosperm, and pollen tissues of CMV-infected plants. Taken together, these studies indicate that CMV occurs in virtually all spinach reproductive tissues. Analysis of several RT-PCR amplified and cloned CP genes and flanking sequences from parent and progeny plants revealed that the spinachinfecting CMV was a member of subgroup II. Furthermore, cDNA sequencing and restriction endonuclease mapping consistently revealed two sequence variants, designated SP103 and SP104, in most plants analyzed. These data suggest that there may have been mixed infections of two distinct, seed-transmitted CMV variants in spinach.
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Wang, Xiaoqin, Wenhui Kou, Weidan Kong, Shujing Ma, Qian Xue, Yuan Zou, and Aixia Song. "Magnetic Resonance Images, Pathological Features of Thrombus, and Expression of NLRP Inflammasome in Patients with Acute Ischemic Stroke." Contrast Media & Molecular Imaging 2022 (August 16, 2022): 1–8. http://dx.doi.org/10.1155/2022/3464042.
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The aim of this study was to investigate imaging features of magnetic resonance imaging (MRI), pathological features of thrombus, and expression of nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome in acute ischemic stroke (AIS). Their relationship with the prognosis of patients was also explored. Sixty patients with AIS admitted to the hospital were selected as the observation group, and 20 healthy objects were in the control group. The shape of the thrombus was observed by MRI, pathological features of the thrombus were observed under hematoxylin-eosin (HE) staining, and the levels of NLRP3 inflammasome and inflammatory factors in serum were detected. The MRI-T2 weighted imaging (T2WI) signal ratio and plaque enhancement rate in the observation group were higher than those in the control group significantly ( P < 0.05 ). In the observation group, the red/mixed thrombus in 6–12 h and 24 h were also much higher than that in 6 h ( P < 0.05 ). The levels of NLRP3, interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in the observation group were higher than those in the control group in 6 h, 6–12 h, and 24 h ( P < 0.05 ), and those reached the highest levels in 24 h. The ratio of fibrins/platelets in the cardiogenic thrombus reached (63.8 ± 15.6) %, which was significantly higher than that in the large-artery atherosclerotic thrombus (49.5 ± 14.2) %, P < 0.05 . The ratio of red blood cells (RBCs) in the large atherosclerotic thrombus was (30.7 ± 14.3) %, considerably lower than (42.9 ± 15.2) %, P < 0.05 . The prognosis of patients with the fibrin/platelet-rich thrombus was highly lower than that with the RBC-rich thrombus ( P < 0.05 ). The levels with poor prognosis were higher than those with good prognosis ( P < 0.05 ). MRI could be used to assist in the assessment of brain conditions in patients with AIS. NLRP3 inflammasome was involved in the inflammatory response of AIS and can be used for predicting the poor prognosis, having a certain clinical application value. In addition, different types of thrombi also laid a certain impact on prognosis.
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Eltit, Felipe, Qiong Wang, Raphaële Charest-Morin, Colm Morrissey, Eva Corey, Rizhi Wang, and Michael E. Cox. "Abstract 273: Prostate cancer metastasis induces irregular bone formation associated to specific androgen dependent phenotypes." Cancer Research 82, no. 12_Supplement (June 15, 2022): 273. http://dx.doi.org/10.1158/1538-7445.am2022-273.
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Abstract Bone metastases (BM) occur in ~80% of advanced prostate cancer (PC) patients, and are a major cause of morbidity. PCBMs are predominantly osteoblastic with mixed, and lytic regions; all of which compromise bone strength. How PCs alter bone structure is unresolved. Prolonged use of modern androgen receptor (AR) targeting agents has increased development of AR pathway-independent PC phenotypes. We hypothesize that defining the structural changes, cellular composition, and PC classification of PCBM-affected bone will help reveal mechanisms of PCBM pathology, and identify potential therapeutic opportunities. We analyze the 3D structure of 14 cadaveric PCBM lumbar vertebrae using micro-computed tomography (microCT). We performed scanning electron microscopy quantitative backscattering electron (qBSE), and energy-dispersive X-ray spectroscopy (EDX) to determine mineral morphology and composition. We analyzed sequential decalcified sections for collagen structure, fibril orientation, and extracellular matrix composition using bright field and polarized light microscopy. We determined lesion structure and cell distribution from two PCBM vertebral specimens resected during decompression surgery using histology and immunohistochemistry, and characterized PCBM cell populations using single cell RNA sequencing (sc RNA Seq) on one vertebral specimen. MicroCT imaging revealed three distinct dysmorphic bone patterns: 1) osteolytic, defined by thinned broken trabecula of well-organized mineral and collagen structures; 2) osteoblastic, with disorganized matrix deposited on pre-existing trabecula; and 3) osteoblastic, with little, if any, residual trabecula, and dominated by accumulation of disorganized mineralized matrix. qBSE and EDX revealed heterogeneous mineral composition, with higher variability in mineral content. Disorganized matrix had a higher voids or “lacunae” density, poorly organized collagen fiber alignment, and higher decorin and pan-proteoglycan content. Sc RNA Seq revealed a PCBM tumor microenvironment composed of a variety of immune cells, hematopoietic progenitors, and bone resident cells. Importantly, we identified AR-high, AR-low, and double-negative PC cells in the same lesion, with minimum neuroendocrine component. Simultaneous presence of these PC phenotypes was confirmed by immunohistochemistry. Morphologically, AR-positive cells adopt two configurations in PCBM, i) clusters within bone cavities in which cells maintain secretory polarization and resemble prostate acini, and ii) diffuse cells in intimate contact with bone-resident cells that lack polarization. PCBM lesions have abnormal bone structures lacking collagen organization, and with mineral heterogeneity consistent with bone weakness. PC cells interact with bone cells, but how distinct PC phenotypes affect bone turnover and structure need further analysis. Citation Format: Felipe Eltit, Qiong Wang, Raphaële Charest-Morin, Colm Morrissey, Eva Corey, Rizhi Wang, Michael E. Cox. Prostate cancer metastasis induces irregular bone formation associated to specific androgen dependent phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 273.
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Sanchorawala, Vaishali, Ashutosh D. Wechalekar, Kihyun Kim, Stefan Schönland, Heather J. Landau, Kwok Fiona, Kenshi Suzuki, et al. "Health-Related Quality of Life and Symptoms Among Patients with Relapsed or Refractory AL Amyloidosis Treated with Ixazomib-Dexamethasone Versus Physician's Choice: Results from a Randomized Phase 3 Trial." Blood 138, Supplement 1 (November 5, 2021): 4771. http://dx.doi.org/10.1182/blood-2021-148689.
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Abstract Introduction Systemic immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys. Management of the disease relies primarily on off-label use of multiple myeloma therapies. No treatments are approved for AL amyloidosis in the relapsed/refractory setting. In the phase 3, open-label TOURMALINE-AL1 trial (NCT01659658), patients with relapsed/refractory AL amyloidosis were randomized 1:1 to receive either oral ixazomib plus dexamethasone (Id) or physician's choice (CH) in 28-day cycles, and followed until progression or unacceptable toxicity. An interim analysis demonstrated that Id was well tolerated and, although the primary endpoint of hematologic response rate was not met, time-to-event efficacy analyses consistently favored Id. We report an analysis of patient-reported outcome (PRO) data on health-related quality of life (HRQOL) and AL amyloidosis symptoms from TOURMALINE-AL1; such data for AL amyloidosis in general have been limited. Methods Four PRO instruments were used to collect data to support PRO-related secondary endpoints during the treatment period: the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale (FACT/GOG-Ntx), an amyloidosis symptom questionnaire (ASQ), the EuroQoL 5-Dimension 3-Level (EQ-5D-3L), and the Visual Analogue Scale (EQ VAS) were collected at screening, day 1 of each cycle, and end of treatment (EOT), and the 36-item Short Form General Health Survey version 2 (SF-36v2) was collected at screening, day 1 of every third cycle, and EOT. Analysis of PRO data included descriptive summaries of means and change from baseline and a linear mixed model (LMM) for repeated measures for patients in the intent-to-treat (ITT) population with a baseline and at least one postbaseline PRO-specific assessment. No adjustment was made for multiple comparisons. Data cutoff date was 20 February 2019. Results The ITT population included 168 patients (Id: n=85; CH: n=83), who completed up to 58 cycles (Id) and up to 43 cycles (CH); median treatment duration was 11.7 vs 5.0 months, respectively. PRO compliance in the treatment period was high for all instruments (Figure). Baseline HRQOL as measured by the SF-36v2 and EQ VAS was similar between treatment arms. During the treatment period, SF-36v2 Mental and Physical Component Summary (MCS and PCS) scores remained stable relative to baseline and were similar between arms; the 8 subscale scores were also generally maintained over time, and mostly similar between arms. Least-squares (LS) mean changes from baseline were significantly higher (better HRQoL) for Id compared with CH at several cycles in the SF-36v2 Role Physical and Vitality subscales (p<0.05) (Figure); no subscales demonstrated significant differences favoring CH. Symptom burden as measured by the FACT/GOG-Ntx and ASQ was low at baseline, leaving little room for improvement. FACT/GOG-Ntx scores were generally maintained over time. In the treatment period, there were small but significant differences in LS mean changes from baseline favoring Id over CH at multiple cycles for 7 of the 11 individual items and the neurotoxicity and sensory summary scores; there were small but significant differences favoring CH over Id for 1 individual item (trouble hearing) at a few later cycles. The ASQ total score trended downward slightly (lower burden) during treatment after the first few cycles in both arms. There were significant differences per the LMM favoring Id over CH at cycles 7 and 21 (p<0.05). In both arms, EQ VAS scores trended upward (better HRQoL) during treatment and then declined slightly at EOT. (LMM analyses were not conducted for EQ-5D.) At EOT, a slight deterioration from baseline was observed in actual scores for SF-36v2 domains and summary scales, FACT/GOG-Ntx neurotoxicity and sensory subscales, and ASQ items and total score for both Id and CH. Conclusions Relapsed/refractory AL amyloidosis patients treated with Id experienced HRQOL and symptoms that were similar to or trended better than patients treated with CH. These data suggest that treatment with Id, although with a substantially longer treatment duration, did not have a negative impact on HRQOL in patients with relapsed/refractory AL amyloidosis, a population with currently no approved treatment options. Figure 1 Figure 1. Disclosures Sanchorawala: Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Oncopeptide: Research Funding; Karyopharm: Research Funding; Sorrento: Research Funding; Pfizer: Honoraria; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Celgene: Research Funding. Wechalekar: Caelum Biosciences: Other: Clinical Trial Funding; Alexion, AstraZeneca Rare Disease: Consultancy; Janssen: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria. Kim: Janssen, BMS: Research Funding. Schönland: Janssen: Honoraria, Other: Travel grants, Research Funding; Takeda: Honoraria, Other: Travel grants; Sanofi: Research Funding; Prothena: Honoraria, Other: Travel grants; Pfizer: Honoraria. Landau: Takeda, Janssen, Caelum Biosciences, Celgene, Pfizer, Genzyme: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Genzyme: Honoraria. Fiona: Pfizer: Research Funding. Suzuki: Janssen: Consultancy, Honoraria; Abie: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; ONO: Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Dispenzieri: Sorrento Therapeutics: Consultancy; Oncopeptides: Consultancy; Pfizer: Research Funding; Alnylam: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Comenzo: Karyopharm: Research Funding; Takeda: Research Funding; Unum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Janssen: Patents & Royalties: WO2016187546A1, Research Funding; Prothena Biosciences: Consultancy, Research Funding; Caelum: Consultancy, Research Funding. Cherepanov: Takeda: Current Employment, Current equity holder in publicly-traded company. Hayden: Takeda: Current Employment, Current equity holder in publicly-traded company. Kumar: Takeda: Current Employment, Current holder of stock options in a privately-held company. Labotka: Takeda: Current Employment. Faller: Takeda Pharmaceuticals Co.: Current Employment; Viracta Therapeutics, Inc: Current holder of stock options in a privately-held company, Ended employment in the past 24 months, Membership on an entity's Board of Directors or advisory committees; Briacell, Inc: Current holder of stock options in a privately-held company. Kastritis: Amgen, Genesis Pharma, Janssen, Takeda: Consultancy; Amgen, Janssen, Pfizer: Research Funding; Amgen, Genesis Pharma, Janssen, Takeda, Pfizer: Honoraria.
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Sanchorawala, Vaishali, Giovanni Palladini, Monique C. Minnema, Arnaud Jaccard, Hans C. Lee, Simon D. Gibbs, Peter Mollee, et al. "Health-Related Quality of Life in Patients with AL Amyloidosis Treated with Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone: Results from the Phase 3 Andromeda Study." Blood 136, Supplement 1 (November 5, 2020): 37–40. http://dx.doi.org/10.1182/blood-2020-139438.
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Background: Systemic AL amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys; there are currently no health authority-approved treatments. Therapies for the treatment of multiple myeloma (MM), including bortezomib, cyclophosphamide, and dexamethasone (VCd), have been shown to improve outcomes in AL amyloidosis, but more effective therapies are needed to achieve deep and rapid hematologic responses, reverse amyloid-mediated organ dysfunction, and improve overall survival. Daratumumab is an anti-CD38 monoclonal antibody approved as monotherapy or in combination with other agents for the treatment of MM. ANDROMEDA (NCT03201965) is a randomized, open-label, active-controlled phase 3 trial of VCd ± daratumumab subcutaneous (DARA SC) in patients with newly-diagnosed AL amyloidosis. After a median follow-up of 11.4 months, the complete hematologic response rate was 53% for DARA SC + VCd (DARA-VCd) and 18% for VCd (odds ratio, 5.1; 95% CI, 3.2-8.2; P<0.0001). Here, we present patient-reported outcomes (PROs) from ANDROMEDA. Methods: Patients with newly-diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage (Mayo 2004) I-IIIA, eGFR ≥20 mL/min, and absence of symptomatic MM were randomized 1:1 to DARA-VCd or VCd and treated for six 28-day cycles; thereafter, patients in the DARA-VCd group received DARA SC alone every 4 weeks for up to 24 cycles. PROs were assessed on Day 1 of Cycles 1-6 for both treatment groups and every 8 weeks thereafter in the DARA-VCd group. PRO assessments included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30), the EuroQol 5-dimensional descriptive system (EQ-5D-5L), and Short Form-36 (SF-36). Improvements in EORTC QLQ-C30 global health status (GHS) and fatigue scale scores and SF-36 mental component summary (MCS) score were secondary endpoints. Assessment of physical functioning, symptom improvement, functional improvement, and health utility as measured by the SF-36, EORTC QLQ-C30 with supplemental symptom items, and the EQ-5D-5L were exploratory outcomes. Patients completed PRO questionnaires prior to study assessments or study drug administration. Analyses of PROs were performed on the intent-to-treat analysis set; patients without a baseline or post-baseline assessment were censored at date of randomization. Compliance with PRO assessments was calculated as the number of assessments received divided by the number of assessments expected at each time point. Descriptive statistics are provided for all PRO endpoints at each time point by treatment group. A distribution-based method was used to define worsening/improvement in scores. Time to worsening/improvement, hazard ratios, and associated 95% confidence intervals were estimated using Kaplan Meier methods and Cox proportional hazards regression. Change from baseline at each time point up to Cycle 6 (Week 24) was calculated using a mixed effects model with repeated measures with patients as a random effect and baseline value, treatment group, time (weeks), treatment-by-time interaction, and stratification factors as fixed effects. Results: A total of 388 patients were randomized (DARA-VCd, n=195; VCd, n=193). Compliance rates for all PRO questionnaires were >90% at baseline and >83% through Cycle 6. Median time to improvement was shorter and median time to worsening was longer in the DARA-VCd group than in the VCd group for EORTC QLQ-C30 GHS and fatigue scales and EQ-5D-5L visual analog scale (VAS) (Table 1). Least squares mean scores for EORTC QLQ-C30 GHS and fatigue, EQ-5D-5L VAS, and SF-36 MCS remained stable in the DARA-VCd group but worsened compared with baseline in the VCd group; between-group differences are shown in Table 2. The greatest between-group differences in PRO score changes from baseline were observed at Week 16 (Cycle 4). After Cycle 6, patients in the DARA-VCd group reported improvements in mean GHS and fatigue scores that continued while on treatment (Figure). Conclusions: Patients with AL amyloidosis treated with DARA-VCd experienced clinical improvements without any decrement in health-related quality of life over 6 cycles. Following Cycle 6, improvements in GHS and fatigue were reported in patients in the DARA-VCd group. These findings further support the value of DARA-VCd in patients with AL amyloidosis. Disclosures Sanchorawala: UpToDate: Patents & Royalties; Abbvie: Other: advisory board; Proclara: Other: advisory board; Caleum: Other: advisory board; Regeneron: Other: advisory board; Oncopeptide: Research Funding; Caelum: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Minnema:Servier: Consultancy; Amgen: Consultancy; Kite, a Gilead Company: Speakers Bureau; Celgene: Other: travel support, Research Funding. Jaccard:Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding; Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding. Lee:Janssen: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding. Gibbs:Janssen, BMS/Celgene, Amgen, Takeda, Pfizer, Caelum, Abbvie and Eidos: Membership on an entity's Board of Directors or advisory committees. Mollee:Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding. Schönland:Janssen: Honoraria, Other: travel support to meetings, Research Funding; Prothena: Honoraria, Other: travel support to meetings, Research Funding; Takeda: Honoraria, Other: travel support to meetings, Research Funding. Suzuki:Bristol-Myers Squibb, Celgene and Amgen: Research Funding; Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria. Kim:BMS, Takeda, Amgen, Celgene, Janssen: Consultancy, Honoraria, Research Funding. Cibeira:Janssen, Akcea Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen, Celgene, Amgen: Honoraria, Other: Educational lectures. Beksac:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Valent:Celgene: Other: Teaching, Speakers Bureau; Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Amgen Inc.: Other: Teaching, Speakers Bureau. Wong:GSK: Research Funding; Roche: Research Funding; Janssen: Research Funding; Bristol Myers Squibb: Research Funding; Fortis: Research Funding; Amgen: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees. Rosenzweig:Janssen: Speakers Bureau. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Qin:Janssen: Current Employment. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Comenzo:Caleum: Consultancy; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Karyopharm: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria. Wechalekar:Takeda: Honoraria, Other: Travel; Celgene: Honoraria; Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory.
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Williams, Tosha, Zachary Sorrentino, Mary Weinrich, Benoit I. Giasson, and Paramita Chakrabarty. "Differential cross-seeding properties of tau and α-synuclein in mouse models of tauopathy and synucleinopathy." Brain Communications 2, no. 2 (2020). http://dx.doi.org/10.1093/braincomms/fcaa090.
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Abstract Co-occurrence of tau and α-synuclein pathologies in a subset of Alzheimer’s disease patients has led to the idea that mixed pathologies may play a unique characteristic role in the Alzheimer’s disease neurodegenerative cascade. To understand the aetiology of such mixed pathologies, we investigated cross-seeding by human recombinant tau and human recombinant α-synuclein fibrillar species in a mouse model of tauopathy (Line PS19) or synucleinopathy (Line M20). Unilateral hippocampal injection of tau fibrils or α-synuclein fibrils, and to a lesser extent tau + α-synuclein copolymer fibrils prepared from co-incubating individual recombinant monomers, induced robust phosphorylated tau pathology in PS19 mice relative to control mice. Though the tau + α-synuclein copolymer fibrils did not modulate induction of pathologies at the site of injection, examination of the whole brain showed that these copolymers exacerbated neuroanatomic transmission of seeded tau pathology compared to tau fibril-injected mice. Only α-synuclein fibrils, but not tau alone or tau + α-synuclein copolymers, triggered modest levels of endogenous phosphorylated α-synuclein pathology. Overall, data from the PS19 mice suggest that human α-synuclein fibrils can efficiently cross-seed human tau and have a modest priming effect on mouse α-synuclein, and the presence of tau fibrils does not exacerbate the priming process. In M20 mice, unilateral hippocampal injection of α-synuclein fibrils or tau fibrils induced robust bilateral phosphorylated α-synuclein pathology, while tau + α-synuclein copolymer injection resulted in restricted phosphorylated α-synuclein pathology predominantly in the ipsilateral cortex. This suggests that human tau fibrils can also induce human α-synuclein pathogenesis, and the presence of combinatorial seeds is not synergistic. None of these aggregates induced phosphorylated tau pathology in M20 mice, showing that mouse tau cannot be primed efficiently by human tau fibrils or human α-synuclein fibrils. Neuropathological analysis of the whole brain of M20 mice showed that tau + α-synuclein copolymer-injected mice had lower abundance of bilaterally transmitted α-synuclein pathologies relative to α-synuclein fibril-injected mice. Thus, the tau + α-synuclein copolymer fibrils show robust transmission properties preferentially in rodent model of tauopathies but not in synucleinopathy, probably signifying an enhanced cooperative relationship between tau and α-synuclein in the tau seeding process. Together, our data highlight the unique cross-seeding properties of tau and αSyn in neurodegenerative proteinopathies.
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Shan, Shengyue, Da Chen, Enrico Federici, Owen G. Jones, and Osvaldo H. Campanella. "The effects of whey protein fibrils on the linear and non-linear rheological properties of a gluten-free dough." Frontiers in Nutrition 9 (July 29, 2022). http://dx.doi.org/10.3389/fnut.2022.909877.
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The increasing awareness of the celiac disease, an autoimmune disorder caused by the consumption of products containing gluten, has led to a growing interest in the development of gluten-free bakery products. In this study, whey protein fibrils (WPFs) were incorporated to mimic the fibrous network of gluten. The rheological properties and microstructure of the developed gluten-free doughs were evaluated and compared with gluten doughs. Protein fibrils were prepared by heating a whey protein isolate (WPI) solution at 80°C in an acidic environment with low salt concentration, and then the fibril lengths were adjusted by leveling up the solution pH to 3.5 and 7. The dimensions of the fibrils were measured by atomic force microscopy (AFM). Rice and potato starches were mixed with fibrils, WPI, gluten, or without protein, to form different doughs for further investigation. Shear tests, including stress sweep, frequency sweep, and creep recovery, were performed to study the viscoelastic properties of doughs under small or large deformation. The strain-hardening properties of doughs under biaxial extension were studied by the lubricated squeezing flow method. The microstructure of the doughs was characterized by cryo-scanning electron microscopy (cryo-SEM). Compared with doughs prepared with WPI and no proteins, doughs incorporating fibrils showed comparable linear viscoelasticity to gluten dough tested with stress sweep, frequency sweep, and creep recovery in the linear viscoelastic region. More differences between the protein fibril doughs were revealed in the rheological properties in the non-linear region. Creep recovery parameters, such as compliance, elastic moduli during the creep, and recovery stages of gluten dough, were like those of WPF pH7 dough, but significantly different from those of the WPF pH3.5 dough. Strain-hardening properties were found in the WPF pH7 dough, although not in WPF pH3.5 dough. Microstructural characterization showed that both fibrils prepared with the different conditions formed a continuous protein phase for the improvement of dough cohesiveness, but the structure of the phase was different between the two fibrils. To summarize, whey protein fibril at pH 7 seemed to have the potential of being used as an ingredient with similar functions to gluten in gluten-free bakery products.
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Chatterjee, Debdeep, Reeba S. Jacob, Soumik Ray, Ambuja Navalkar, Namrata Singh, Shinjinee Sengupta, Laxmikant Gadhe, et al. "Co-aggregation and secondary nucleation in the life cycle of human prolactin/galanin functional amyloids." eLife 11 (March 8, 2022). http://dx.doi.org/10.7554/elife.73835.
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Synergistic-aggregation and cross-seeding by two different proteins/peptides in the amyloid aggregation are well evident in various neurological disorders including Alzheimer’s disease. Here, we show co-storage of human Prolactin (PRL), which is associated with lactation in mammals, and neuropeptide galanin (GAL) as functional amyloids in secretory granules (SGs) of the female rat. Using a wide variety of biophysical studies, we show that irrespective of the difference in sequence and structure, both hormones facilitate their synergic aggregation to amyloid fibrils. Although each hormone possesses homotypic seeding ability, a unidirectional cross-seeding of GAL aggregation by PRL seeds and the inability of cross seeding by mixed fibrils suggest tight regulation of functional amyloid formation by these hormones for their efficient storage in SGs. Further, the faster release of functional hormones from mixed fibrils compared to the corresponding individual amyloid, suggests a novel mechanism of heterologous amyloid formation in functional amyloids of SGs in the pituitary.
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Koo, Bon-Kyung, William Munroe, Edith B. Gralla, Joan Selverstone Valentine, and Julian P. Whitelegge. "A Novel SOD1 Intermediate Oligomer, Role of Free Thiols and Disulfide Exchange." Frontiers in Neuroscience 14 (February 18, 2021). http://dx.doi.org/10.3389/fnins.2020.619279.
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Wild-type human SOD1 forms a highly conserved intra-molecular disulfide bond between C57-C146, and in its native state is greatly stabilized by binding one copper and one zinc atom per monomer rendering the protein dimeric. Loss of copper extinguishes dismutase activity and destabilizes the protein, increasing accessibility of the disulfide with monomerization accompanying disulfide reduction. A further pair of free thiols exist at C6 and C111 distant from metal binding sites, raising the question of their function. Here we investigate their role in misfolding of SOD1 along a pathway that leads to formation of amyloid fibrils. We present the seeding reaction of a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1) to exclude variables caused by these free cysteines. Completely reduced fibril seeds decreasing the kinetic barrier to cleave the highly conserved intramolecular disulfide bond, and accelerating SOD1 reduction and initiation of fibrillation. Presence or absence of the pair of free thiols affects kinetics of fibrillation. Previously, we showed full maturation with both Cu and Zn prevents this behavior while lack of Cu renders sensitivity to fibrillation, with presence of the native disulfide bond modulating this propensity much more strongly than presence of Zn or dimerization. Here we further investigate the role of reduction of the native C57-C146 disulfide bond in fibrillation of wild-type hSOD1, firstly through removal of free thiols by paired mutations C6A, C111S (AS-SOD1), and secondly in seeded fibrillation reactions modulated by reductant tris (2-carboxyethyl) phosphine (TCEP). Fibrillation of AS-SOD1 was dependent upon disulfide reduction and showed classic lag and exponential growth phases compared with wild-type hSOD1 whose fibrillation trajectories were typically somewhat perturbed. Electron microscopy showed that AS-SOD1 formed classic fibrils while wild-type fibrillation reactions showed the presence of smaller “sausage-like” oligomers in addition to fibrils, highlighting the potential for mixed disulfides involving C6/C111 to disrupt efficient fibrillation. Seeding by addition of sonicated fibrils lowered the TCEP concentration needed for fibrillation in both wild-type and AS-SOD1 providing evidence for template-driven structural disturbance that elevated susceptibility to reduction and thus propensity to fibrillate.
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Dregni, Aurelio J., Pu Duan, Hong Xu, Lakshmi Changolkar, Nadia El Mammeri, Virginia M. Y. Lee, and Mei Hong. "Fluent molecular mixing of Tau isoforms in Alzheimer’s disease neurofibrillary tangles." Nature Communications 13, no. 1 (May 27, 2022). http://dx.doi.org/10.1038/s41467-022-30585-0.
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AbstractAlzheimer’s disease (AD) is defined by intracellular neurofibrillary tangles formed by the microtubule-associated protein tau and extracellular plaques formed by the β-amyloid peptide. AD tau tangles contain a mixture of tau isoforms with either four (4R) or three (3R) microtubule-binding repeats. Here we use solid-state NMR to determine how 4R and 3R tau isoforms mix at the molecular level in AD tau aggregates. By seeding differentially isotopically labeled 4R and 3R tau monomers with AD brain-derived tau, we measured intermolecular contacts of the two isoforms. The NMR data indicate that 4R and 3R tau are well mixed in the AD-tau seeded fibrils, with a 60:40 incorporation ratio of 4R to 3R tau and a small homotypic preference. The AD-tau templated 4R tau, 3R tau, and mixed 4R and 3R tau fibrils exhibit no structural differences in the rigid β-sheet core or the mobile domains. Therefore, 4R and 3R tau are fluently recruited into the pathological fold of AD tau aggregates, which may explain the predominance of AD among neurodegenerative disorders.