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Background Titin truncating variants ( TTN tv-s) are the most common genetic cause of dilated cardiomyopathy (DCM). Only rare TTN tv-s in the constitutively expressed exons of the A-band of the protein titin are associated with DCM according to the guidelines, however, studies in large cohorts of patients with DCM suggest that the region where TTN tv-s are associated with DCM is wider, extending at least into the I-band. The aim of this study was to describe the molecular pathology of TTN tv-s in Slovenian patients with cardiomyopathy and to clinically characterise the most recurrent TTN tv. Results We collected all TTN tv-s identified in patients with cardiomyopathy using next-generation sequencing genetic testing between 2010 and July 2024, resulting in 42 unique variants identified in 54 patients. The TTN :c.12478del variant, affecting not the A-band but the proximal I-band, specifically the cardiac-specific N2Bus region, was found to be the most recurrent variant, present in seven (11.6%) probands with DCM. Genetic characterisation revealed a probable founder origin of the variant. Clinical characterisation of these probands revealed a phenotype consistent with DCM and severely reduced left ventricular ejection fraction in all probands. Three (43%) of the probands had atrial fibrillation and/or non-sustained ventricular tachycardia. Based on literature reports and evidence supporting the pathogenicity of the TTN :c.12478del variant affecting the proximal I-band, we classified all rare TTN tv-s in constitutively expressed exons of the I-band as (likely) pathogenic. Therefore, 33 (78.6%) TTN tv-s were classified as (likely) pathogenic (13 in the I-band, affecting 19 probands and 20 in the A-band affecting 25 probands), meaning that TTN tv-s were identified in 44 genotype-positive Slovenian probands with DCM, explaining 73.3% of the molecular pathology of DCM. Conclusion We report an almost threefold higher diagnostic yield of TTN tv-s in probands with DCM compared to previously reported findings in cohorts of patients with DCM from other populations. We also highlight the need for screening for rare TTN tv-s in the constitutively expressed exons of the I-band and for TTN :c.12478del in patients with DCM in this geographical region.

For valence change memory (VCM)‐type synapses, a large number of vacancies help to achieve very linearly changed dynamic range, and also, the low activation energy of vacancies enables low‐voltage operation. However, a large number of vacancies increases the current of artificial synapses by acting like dopants, which aggravates low‐energy operation and device scalability. Here, mixed‐dimensional formamidinium bismuth iodides featuring in‐situ formed type‐I band structure are reported for the VCM‐type synapse. As compared to the pure 2D and 0D phases, the mixed phase increases defect density, which induces a better dynamic range and higher linearity. In addition, the mixed phase decreases conductivity for non‐paths despite a large number of defects providing lots of conducting paths. Thus, the mixed phase‐based memristor devices exhibit excellent potentiation/depression characteristics with asymmetricity of 3.15, 500 conductance states, a dynamic range of 15, pico ampere‐scale current level, and energy consumption per spike of 61.08 aJ. A convolutional neural network (CNN) simulation with the Canadian Institute for Advanced Research‐10 (CIFAR‐10) dataset is also performed, confirming a maximum recognition rate of approximately 87%. This study is expected to lay the groundwork for future research on organic bismuth halide‐based memristor synapses usable for a neuromorphic computing system. Mixed‐dimensional formamidinium bismuth iodides exhibit highly linear potentiation/depression characteristics with energy consumption as low as 61.08 aJ for the convolutional neural network (CNN) due to a large number of defects and in‐situ formed type I band alignment.

Spinal muscular atrophy (SMA) is caused by a deletion or mutation of the survival motor neuron 1 ( SMN1 ) gene. Reduced SMN levels lead to motor neuron degeneration and muscular atrophy. SMN protein localizes to the cytoplasm and Cajal bodies. Moreover, in myofibrils from Drosophila and mice, SMN is a sarcomeric protein localized to the Z-disc. Although SMN participates in multiple functions, including the biogenesis of spliceosomal small nuclear ribonucleoproteins, its role in the sarcomere is unclear. Here, we analyzed the sarcomeric organization of SMN in human control and type I SMA skeletal myofibers. In control sarcomeres, we demonstrate that human SMN is localized to the titin-positive M-band and actin-positive I-band, and to SMN-positive granules that flanked the Z-discs. Co-immunoprecipitation assays revealed that SMN interacts with the sarcomeric protein actin, α-actinin, titin, and profilin2. In the type I SMA muscle, SMN levels were reduced, and atrophic (denervated) and hypertrophic (nondenervated) myofibers coexisted. The hypertrophied myofibers, which are potential primary targets of SMN deficiency, exhibited sites of focal or segmental alterations of the actin cytoskeleton, where the SMN immunostaining pattern was altered. Moreover, SMN was relocalized to the Z-disc in overcontracted minisarcomeres from hypertrophic myofibers. We propose that SMN could have an integrating role in the molecular components of the sarcomere. Consequently, low SMN levels might impact the normal sarcomeric architecture, resulting in the disruption of myofibrils found in SMA muscle. This primary effect might be independent of the neurogenic myopathy produced by denervation and contribute to pathophysiology of the SMA myopathy.

The aim of this research was to study which kind of conformational changes in gluten proteins were induced by addition of four dietary fibre (apple-cranberry, cacao, carob and oat) by using FT-Raman spectroscopy and to find relationships between conformational changes and rheological behaviour of bread dough in mixing and extensional tests. Structural studies showed that all fibres induced formation of β-like structures between two protein molecules (pseudo-β-sheets) with the band at 1616 cm −1 in the Raman spectrum. According to Principal Component Analysis, the strongest dependence was between changes in gluten structure and two extensographic parameters (resistance to extension and extensibility). Resistance to extension was positively correlated with content of α-helix and pseudo-β-sheets, while a negative correlation was observed between the parameter and content of β-sheets and β-turns. Gauche-gauche-gauche conformation of disulphide bridges and ability of tyrosine residues to hydrogen bonds creation improved mixing properties as stability of dough.

Raman spectroscopy, which is a suitable tool to elucidate the structural properties of intrinsically disordered proteins, was applied to investigate the changes in both the structure and the conformational heterogeneity of the DNA-binding domain (DBD) belonging to the intrinsically disordered protein p53 upon its binding to Azurin, an electron-transfer anticancer protein from Pseudomonas aeruginosa. The Raman spectra of the DBD and Azurin, isolated in solution or forming a complex, were analyzed by a combined analysis based on peak inspection, band convolution, and principal component analysis (PCA). In particular, our attention was focused on the Raman peaks of Tyrosine and Tryptophan residues, which are diagnostic markers of protein side chain environment, and on the Amide I band, of which the deconvolution allows us to extract information about α-helix, β-sheet, and random coil contents. The results show an increase of the secondary structure content of DBD concomitantly with a decrease of its conformational heterogeneity upon its binding to Azurin. These findings suggest an Azurin-induced conformational change of DBD structure with possible implications for p53 functionality.

The study investigates the structural and chemical properties of brown rice flour (WRF), black rice flour (BRF) and their mixtures in ratios of 25%, 50% and 75% to provide reference information for the gluten-free bakery industry. BRF contains higher concentrations of proteins, lipids, total minerals, crude fiber, total polyphenols, proanthocyanidins and flavonoids than WRF. A higher amylose content in BRF than in WRF resulted in flour mixtures with slower starch digestion and a lower glycemic response depending on the BRF ratio added. Differences in the chemical composition of WRF and BRF led to improved composition of the flour mixtures depending on the BRF ratio. The presence of anthocyanidins and phenolic acids in higher concentrations in the BRF resulted in a red–blue color shift within the flour mixtures. The deconvoluted FTIR spectra showed a higher proportion of α-helixes in the amide I band of BRF proteins, indicating their tighter folding. An analysis of the FTIR spectra revealed a more compact starch structure in BRF than in WRF. By processing reflection spectra, nine optically active compound groups were distinguished in rice flour, the proportion in BRF being 83.02% higher than in WRF. Due to co-pigmentation, the bathochromic shift to higher wavelengths was expressed by the proanthocyanins and phenolic acids associated with the wavelengths 380 nm to 590 nm and at 695 nm. Anthocyanins, protein–tannin complexes, methylated anthocyanins and acylated anthocyanins, associated with wavelengths 619, 644 and 668 nm, exhibited a hypsochromic effect by shifting the wavelengths to lower values. This research represents a first step in the development of rice-based products with increased nutritional value and a lower glycemic index.

A mid-infrared free-electron laser (FEL) is operated as a pulsed and linearly polarized laser with tunable wavelengths within infrared region. Although the FEL can ablate soft tissues with minimum collateral damage in surgery, the potential of FEL for dissecting protein aggregates is not fully understood. Protein aggregates such as amyloid fibrils are in some cases involved in serious diseases. In our previous study, we showed that amyloid-like lysozyme fibrils could be disaggregated into the native form with FEL irradiation specifically tuned to the amide I band (1,620 cm −1 ). Here, we show further evidence for the FEL-mediated disaggregation of amyloid-like fibrils using insulin fibrils. Insulin fibrils were prepared in acidic solution and irradiated by the FEL, which was tuned to either 1,620 or 2,000 cm −1 prior to the experiment. The Fourier transform infrared spectroscopy (FT-IR) spectrum after irradiation with the FEL at 1,620 cm −1 indicated that the broad peak (1,630–1,660 cm −1 ) became almost a single peak (1,652 cm −1 ), and the β-sheet content was reduced to 25 from 40 % in the fibrils, while that following the irradiation at 2,000 cm −1 remained at 38 %. The Congo Red assay as well as transmission electron microscopy observation confirmed that the number of fibrils was reduced by FEL irradiation at the amide I band. Size-exclusion chromatography analysis indicated that the disaggregated form of fibrils was the monomeric form. These results confirm that FEL irradiation at the amide I band can dissect amyloid-like protein fibrils into the monomeric form in vitro.

Amyloid fibrils are causal substances for serious neurodegenerative disorders and amyloidosis. Among them, polyglutamine fibrils seen in multiple polyglutamine diseases are toxic to neurons. Although much efforts have been made to explore the treatments of polyglutamine diseases, there are no effective drugs to block progression of the diseases. We recently found that a free electron laser (FEL), which has an oscillation wavelength at the amide I band (C = O stretch vibration mode) and picosecond pulse width, was effective for conversion of the fibril forms of insulin, lysozyme, and calcitonin peptide into their monomer forms. However, it is not known if that is also the case in polyglutamine fibrils in cells. We found in this study that the fibril-specific β-sheet conformation of polyglutamine peptide was converted into nonfibril form, as evidenced by the infrared microscopy and scanning-electron microscopy after the irradiation tuned to 6.08 μm. Furthermore, irradiation at this wavelength also changed polyglutamine fibrils to their nonfibril state in cultured cells, as shown by infrared mapping image of protein secondary structure. Notably, infrared thermography analysis showed that temperature increase of the cells during the irradiation was within 1 K, excluding thermal damage of cells. These results indicate that the picosecond pulsed infrared laser can safely reduce amyloid fibril structure to the nonfibril form even in cells.

Bacterial strains from chitin/chitosan-rich soils, from two industries, were screened for their chitinolytic, antifungal, and mineral phosphate solubilization abilities. The isolate SMA-1-SDCH02, positive for all three properties, was selected and identified as Paenibacillus elgii based on morphological and biochemical characters and supported by 16S rRNA gene sequence analysis. P. elgii enhanced the growth of groundnut in terms of shoot height, root length, total chlorophyll, and fresh and dry weight when applied alone or in combination with chitosan. The plant growth-promoting activity of P. elgii was seen in tobacco in a specially designed gnotobiotic setup indicating its capability to promote growth of at least groundnut and tobacco. Metabolite changes in the bacteria, studied using attenuated total reflectance-infrared (ATR-IR) spectroscopy, revealed split bands of amide I at the 1659- and 1636-cm⁻¹ regions when grown in minimal media amended with tobacco root exudates. The difference in ATR-IR bands in the presence of tobacco root exudates indicated production of compounds with differences in functional groups.

The current status of the Davydov/Scott model for energy transfer in proteins is reviewed. After a brief introduction to the theoretical framework and to the basic results, the problems of finite temperature dynamics and of the full quantum and mixed quantum-classical approximations are described, as well as recent results obtained within each of these approximations. A short survey of experimental evidence in support of the Davydov/Scott model is made and absorption spectra are calculated that show the same temperature dependence as that measured in crystalline acetanilide. Future applications of the Davydov/Scott model to protein folding and function and to misfolding diseases are outlined.