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Highlights: [•] The N-terminal 1–83 residues of apoA-I have a propensity to form amyloid fibrils. [•] ApoA-I 1–43 peptide forms amyloid fibrils with transition to β-sheet-rich structure. [•] The G26R point mutation enhances the fibril formation of apoA-I 1–43 peptide. [•] The extreme N-terminal region plays a crucial role in fibril formation by apoA-I. [ABSTRACT FROM AUTHOR]

A number of naturally occurring mutations of apolipoprotein (apo) A-I, the major protein of HDL, are known to be associated with hereditary amyloidosis and atherosclerosis. Here, we examined the effects of the G26R point mutation in apoA-I (apoA-IIowa) on the structure, stability, and aggregation propensity to form amyloid fibril of full-length apoA-I and the N-terminal fragment of apoA-I. Circular dichroism and fluorescence measurements demonstrated that the G26R mutation destabilizes the N-terminal helix bundle domain of full-length protein, leading to increased hydrophobic surface exposure, whereas it has no effect on the initial structure of the N-terminal 1-83 fragment, which is predominantly a random coil structure. Upon incubation for extended periods at neutral pH, the N-terminal 1-83 variants undergo a conformational change to β-sheet-rich structure with a great increase in thioflavin T fluorescence, whereas no structural change is observed in fulllength proteins. Comparison of fibril-forming propensity among substituted mutants at Gly-26 position of 1-83 fragments demonstrated that the G26R mutation enhances the nucleation step of fibril formation, whereas G26K and G26E mutations have small or inhibiting effects on the formation of fibrils. These fibrils of the 1-83 variants have long and straight morphology as revealed by atomic force microscopy and exhibited significant toxicity with HEK293 cells. Our results indicate dual critical roles of the arginine residue at position 26 in apoAIIowa: destabilization of the N-terminal helix bundle structure in full-length protein and enhancement of amyloid fibril formation by the N-terminal 1-83 fragment. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare surgical outcomes following conventional laparoscopic hysterectomy (LH) (C-LH) versus the combination method of LH plus laparoscopic myomectomy (LM) (LH+LM) for the treatment of large uterine fibroids.Study Design: This study was performed in 56 patients (uterine weights ≥500g) who underwent either C-LH or LH+LM performed by the same surgeon between May 2010 and May 2016. LH+LM was performed when C-LH was problematic because of poor visibility and/or mobility due to uterine fibroids.Results: The C-LH and LH+LM groups consisted of 27 (48%) and 29 (52%) patients, respectively. The clinical characteristics of patients differed significantly only in the median sizes of the dominant fibroid. The sizes of the dominant fibroid in the C-LH and LH+LM groups were 9.5cm and 10.7cm (P=0.04), respectively. Regarding the surgical outcomes for the C-LH and LH+LM groups, the median uterine weights were 558g and 737g (P=0.03), respectively, the median operating times were 156min and 173min (P=0.23), respectively, and the median intraoperative blood losses were 150g and 300g (P=0.0004), respectively. In all patients, LH was performed without conversion to laparotomy and there were no cases of bladder, ureteral, or gastrointestinal tract injury. There were no postoperative complications of Clavien-Dindo scale≥III in either group.Conclusions: When C-LH cannot be performed because of large uterine fibroids that cause poor visibility and/or mobility, LH+LM may allow the procedure to be successfully completed without conversion to laparotomy. However, the latter approach increases the risk for intraoperative blood loss. [ABSTRACT FROM AUTHOR]

Apolipoprotein A-I is amenable to a number of specific mutations associated with hereditary systemic amyloidoses. Amyloidogenic properties of apoA-I are determined mainly by its N-terminal fragment. In the present study Förster resonance energy transfer between tryptophan as a donor and Thioflavin T as an acceptor was employed to obtain structural information on the amyloid fibrils formed by apoA-I variant 1-83/G26R/W@8. Analysis of the dye-fibril binding data provided evidence for the presence of two types of ThT binding sites with similar stoichiometries (bound dye to monomeric protein molar ratio ∼10), but different association constants (∼6 and 0.1μM−1) and ThT quantum yields in fibril-associated state (0.08 and 0.05, respectively). A β-strand–loop–β-strand structural model of 1-83/G26R/W@8 apoA-I fibrils has been proposed, with potential ThT binding sites located in the solvent-exposed grooves of the N-terminal β-sheet layer. Reasoning from the expanded FRET analysis allowing for heterogeneity of ThT binding centers and fibril polymorphism, the most probable locations of high- and low-affinity ThT binding sites were attributed to the grooves T16_Y18 and D20_L22, respectively. [ABSTRACT FROM AUTHOR]

A terahertz linear polarizer was developed with a single crystal of methyl 4-nitrobenzoate. Several IR-active vibrations with parallel moments of transition were concentrated in a frequency range around 2.7 THz. These results establish a new category of polarizers. [Display omitted] • A terahertz linear polarizer was made of an organic single crystal. • A single crystal of methyl 4-nitrobenzoate has clear anisotropy. • The anisotropy is mainly due to one or two parallel fundamental modes. • The same strategy will allow the development of higher quality polarizers. A terahertz linear polarizer was developed using a single crystal of methyl 4-nitrobenzoate. Flat molecules are arranged in parallel in the crystal and the intramolecular vibrations efficiently absorb terahertz waves with high anisotropy. Several infrared-active intramolecular vibrations with parallel moments of transition concentrate in a frequency band between 2.2 and 3.2 THz. The highest degree of polarization of 76% was achieved at 2.74 THz (T max = 80%, T min = 11%). This result establishes a new category of polarizer that can be manufactured in a simple process at low cost. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are an intriguing class of protein aggregates with distinct physicochemical, structural and morphological properties. They display peculiar membrane-binding behavior, thus adding complexity to the problem of protein-lipid interactions. The consensus that emerged during the past decade is that amyloid cytotoxicity arises from a continuum of cross-β-sheet assemblies including mature fibrils. Based on literature survey and our own data, in this chapter we address several aspects of fibril-lipid interactions, including (i) the effects of amyloid assemblies on molecular organization of lipid bilayer; (ii) competition between fibrillar and monomeric membrane-associating proteins for binding to the lipid surface; and (iii) the effects of lipids on the structural morphology of fibrillar aggregates. To illustrate some of the processes occurring in fibril-lipid systems, we present and analyze fluorescence data reporting on lipid bilayer interactions with fibrillar lysozyme and with the N-terminal 83-residue fragment of amyloidogenic mutant apolipoprotein A-I, 1-83/G26R/W@8. The results help understand possible mechanisms of interaction and mutual remodeling of amyloid fibers and lipid membranes, which may contribute to amyloid cytotoxicity.