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The conformational possibilities of the casoxin D (Tyr1-Val2-Pro3-Phe4-Pro5-Pro6-Phe7) molecule were studied by theoretical conformational analysis. The potential function of the system is chosen as the sum of non-valence, electrostatic and torsion interactions and the energy of hydrogen bonds. The low-energy conformations of the casoxin D molecule, the dihedral angles of the main and side chains of the amino acid residues that make up the molecule were found, and the energy of intra- and interresidual interactions was estimated. It has been shown that the spatial structure of the casoxin D molecule is represented by conformations of eight shapes of the peptide skeleton. The results obtained can be used to elucidate the structural and structural-functional organisation of casoxin molecules. [ABSTRACT FROM AUTHOR]

Organic chromophores emerged as diverse functional materials in the areas of organic catalysis, toxic materials sensing, bio-imaging, and organic electronic devices. With rich chemical and electronic structures, main-group elements have been extensively implanted in organic chromophores to fine-tune the chemical/electronic structures and optoelectronic properties. In this Synpact article, we present a concise overview of the development of phosphorus (P)-containing organic chromophores, further highlighting our recent contributions in the field. A new aspect of combining the P element with the indole moiety was pursued to construct a new series of seven-membered P-organic chromophores; namely, indole-functionalized phosphepines. The new combination endowed the system with rich chemical and electronic structures, for which intriguing photophysical properties were consequently revealed. The combination provided an efficient synthetic protocol to access new P-heterocycles and also offered a new strategy to design functional organic chromophores. [ABSTRACT FROM AUTHOR]

The topic of participation in Christ has remained a distinctive area in Pauline scholarship throughout the twentieth and twenty-first centuries. Scholars have raised a pressing critique, however, that "participation" has become a vague concept such that its use for exegesis of Paul is limited. This recent critique resembles E. P. Sanders's earlier concern in the late 1970s that scholars appear to lack a category of "reality" that corresponds to Paul's experience of participating in Christ. In light of this problem, I argue that the interpretive category of participation can be expanded further without losing its coherence. To develop this argument, I first chart a history of scholarship by focusing on participatory motifs that scholars have recently identified. Then, in the following sections, I analyze two motifs that have not been sufficiently integrated into this research on participation: (1) reasoning in accordance with Christ in Rom 15:5; (2) the form of the body conformed to Christ's glorified body in Phil 3:21. Finally, I discuss the conceptual linkage between these two Pauline passages. In conclusion, these two motifs will allow scholarship to move toward more nuanced perspectives on how Paul envisions participation in Christ. [ABSTRACT FROM AUTHOR]

Circular RNA is a group of covalently closed, single-stranded transcripts with unique biogenesis, stability, and conformation that play distinct roles in modulating cellular functions and also possess a great potential for developing circular RNA-based therapies. Importantly, due to its circular conformation, circular RNA generates distinct intramolecular base pairing that is different from the linear transcript. In this perspective, we review how circular RNA conformation can affect its turnover and modes of action, as well as what factors can modulate circular RNA conformation. We also discuss how understanding circular RNA conformation can facilitate learning about their functions as well as the remaining technological issues to further address their conformation. These efforts will ultimately inform the design of circular RNA-based platforms for biomedical applications. Circular RNAs play distinct cellular roles and possess great potential for developing RNA-based therapies. Liu et al. discuss how one can leverage circular RNA conformation for a better understanding of its turnover and function as well as for a better design of circular RNA-based modalities. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Polyphenols present in sunflower meal act on sunflower proteins by reacting directly with their structures and thus influencing their purity, solubility, crystallinity, and functionality. However, the effect on these properties of varying concentrations of ethanol used in dephenolization has yet to be explored. The present study aimed to explore the impact of dephenolization using varying ethanol concentrations (60%, 70%, 80%, and 90%) on the physicochemical, color, thermal, structural, functional, and flow behavior of protein isolates extracted from sunflower meal.Protein isolates originating from meals that were dephenolized using higher ethanol concentrations exhibited a protein content of 836.10 g kg−1. As the concentration of ethanol increased, a reduction in crystallinity was observed from 24% to 14.15%. Fourier transform infrared (FTIR) spectroscopy revealed marked shifts in major peaks within the 1600 to 1700 cm−1 wavelength range, indicating significant structural and conformational changes. Sodium dodecyl‐sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) results demonstrated that dephenolization caused decline in molecular weight ranging from 25 kDa to 60 kDa. Dephenolization induced significant changes in surface morphology resulting in more heterogeneous and disordered surfaces as indicated by field emission–scanning electron microscopy (FE‐SEM) micrographs. Overall improvement in the functional properties was observed, with an increase in solubility from 15.20% to 22.03%. Improvement in the flow behavior with an increase in porosity from 38% to 60% was also observed, due to dephenolization.Dephenolization using 90% ethanol induced structural changes that enhanced physicochemical and functional characteristics of sunflower protein isolates by improving purity and solubility, reducing crystallinity, and increasing flow behavior. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

D‐Glucose‐to‐L‐sorbose isomerization on Lewis acidic zeolite is a highly attractive avenue for sorbose production. But the L‐sorbose yield is limited by the competing D‐glucose‐to‐D‐fructose isomerization and reaction equilibrium. In this work, it is suggested that ethanol directs the glucose conformation for selective D‐glucose‐to‐L‐sorbose isomerization. It also reacts with the produced L‐sorbose to form ethyl‐sorboside, which allows the D‐glucose‐to‐L‐sorbose isomerization to proceed beyond the thermodynamic equilibrium limit. It is shown that a bifunctional zeolite Beta containing framework titanium (Ti) and boron (B) is a selective catalyst for this tandem reaction: Lewis acidic framework Ti catalyzes the D‐glucose‐to‐L‐sorbose isomerization via an intramolecular 5,1‐hydride shift process as confirmed by isotopic tracing experiments followed by 13C‐NMR, while weak Brønsted acid framework B selectively promotes the sorbose ketalization with ethanol. A remarkably high yield of L‐sorbose with a high fraction of sugar (>95 %: 27 % unreacted glucose, 11.4 % fructose, 57 % sorbose) was obtained after the mixture produced in ethanol was hydrolyzed. [ABSTRACT FROM AUTHOR]

Cyclisation of peptides by forming thioether (lanthionine), disulfide (cystine) or methylene thioacetal bridges between side chains is established as an important tool to stabilise a given structure, enhance metabolic stability and optimise both potency and selectivity. However, a systematic comparative study of the effects of differing bridging modalities on peptide conformation has not previously been carried out. In this paper, we have used the NMR deconvolution algorithm, NAMFIS, to determine the conformational ensembles, in aqueous solution, of three cyclic analogues of angiotensin(1–7), incorporating either disulfide, or non‐reducible thioether or methylene thioacetal bridges. We demonstrate that the major solution conformations are conserved between the different bridged peptides, but the distribution of conformations differs appreciably. This suggests that subtle differences in ring size and bridging structure can be exploited to fine‐tune the conformational properties of cyclic peptides, which may modulate their bioactivities. [ABSTRACT FROM AUTHOR]

Neutral bis(amino acidato)copper(II) [Cu(aa)2] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa)2, two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa)2 compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group's research on structural properties of physiological Cu(aa)2 calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa)2 compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu2+ binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa)2 in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling. [ABSTRACT FROM AUTHOR]

The amyloid β (Aβ) peptide has a central role in Alzheimer's disease (AD) pathology. The peptide length can vary between 37 and 49 amino acids, with Aβ1‐42 being considered the most disease‐related length. However, Aβ1‐40 is also found in Aβ plaques and has shown to form intertwined fibrils with Aβ1‐42. The peptides have previously also shown to form different fibril conformations, proposed to be related to disease phenotype. To conduct more representative in vitro experiments, it is vital to uncover the impact of different fibril conformations on neurons. Hence, we fibrillized different Aβ1‐40:42 ratios in concentrations of 100:0, 90:10, 75:25, 50:50, 25:75, 10:90 and 0:100 for either 24 h (early fibrils) or 7 days (aged fibrils). These were then characterized based on fibril width, LCO‐staining and antibody‐staining. We further challenged differentiated neuronal‐like SH‐SY5Y human cells with the different fibrils and measured Aβ content, cytotoxicity and autophagy function at three different time‐points: 3, 24, and 72 h. Our results revealed that both Aβ1‐40:42 ratio and fibril maturation affect conformation of fibrils. We further show the impact of these conformation changes on the affinity to commonly used Aβ antibodies, primarily affecting Aβ1‐40 rich aggregates. In addition, we demonstrate uptake of the aggregates by neuronally differentiated human cells, where aggregates with higher Aβ1‐42 ratios generally caused higher cellular levels of Aβ. These differences in Aβ abundance did not cause changes in cytotoxicity nor in autophagy activation. Our results show the importance to consider conformational differences of Aβ fibrils, as this can have fundamental impact on Aβ antibody detection. Overall, these insights underline the need for further exploration of the impact of conformationally different fibrils and the need to reliably produce disease relevant Aβ aggregates. [ABSTRACT FROM AUTHOR]

N-(2-(diphenylphosphino)ethyl)-4,6,7-trifluoro-2,1,3-benzothiadiazol-5-amine (Ph2PCH2CH2NH-btd-F3 (PCCN)) is prepared by the reaction of 4,5,6,7-tetrafluoro-2,1,3-benzothiadiazole (btd-F4) with 2-(diphenylphosphino)ethyl-1-amine (Ph2PCH2CH2NH2) leading to the nucleophilic substitution of F– by a phosphinamide fragment (Ph2PCH2CH2NH)– in btd-F4. Phase 1 (a product of cocrystallization of PCCN (85%) and its oxide Ph2P(O)CH2CH2NH–btd-F3 (POCCN, 15%)) is obtained by the separation of the mixture of products by thin-layer chromatography and subsequent evaporation of the solution. POCCN is obtained preparatively using the oxidation of PCCN by hydrogen peroxide. Phase 1, two polymorphs of POCCN (2 and 4), and the POCCN·C6H6 solvatomorph (3) are characterized by XRD. The P–C–C–N fragment in these phases adopts either a bent gauche-conformation with an intramolecular N–H⋯O hydrogen bond or an anti-conformation stabilized by a pair of intermolecular hydrogen bonds combining the molecules into a dimer. According to the DFT data, gauche-POCCN has a larger negative electrostatic potential at F and N than anti-POCCN, i.e. the btd-F3 fragment of the first conformation is more likely to participate in predominantly electrostatic intermolecular interactions. [ABSTRACT FROM AUTHOR]

Hydrazidase from Microbacterium hydrocarbonoxydans was revealed to catalyze synthetic hydrazide compounds, enabling the bacteria to grow with them as a sole carbon source, but natural substrates have remained unknown. In this study, kinetic analyses of hydrazidase with parabens showed that the compounds can be substrates. Then, methylparaben induced gene expressions of the operon containing hydrazidase and ABC transporter, and the compound as a sole carbon source was able to grow the bacteria. Furthermore, homology search was carried out revealing that several actinomycetes possess hydrazidase homologs in the operon. Among those bacteria, an amidase from Pseudonocardia acaciae was subjected to a kinetic analysis and a structure determination revealing similar but not identical to those of hydrazidase. Since parabens are reported to exist in plants and soil, and several actinomycetes code the homologous operon, the enzymes with those operons may play a physiologically important role for bacterial survival with use of parabens. [ABSTRACT FROM AUTHOR]

The interplay between conformation and hydrogen bond pattern was studied in 211 (C(O)NH)(N)2P(O)-based phosphoric triamides retrieved from the Cambridge Structural Database (CSD) and one new molecular structure, (CHCl2C(O)NH)(CH3CH2CH2NH)2P(O). The O═C–N–P and C–N–P═O torsion angles were extracted for the conformational study of the C(O)NP(O) segment, and the conformations of ±sp±ap, ±sp±sc and ±ap±sp were found (sp = synperiplanar, ap = antiperiplanar, sc = synclinal). The conformations of hydrogen bond donor group(s) with respect to the acceptor group(s) were also considered. The investigated structures belong to three classes of (RC(O)NH)(R1R2N)2P(O) (R1 and R2 ≠ H), (RC(O)NH)(R1NH)2P(O) (R1 ≠ H) and heterocyclic (RC(O)NH)P(O)[NR1]2R2 phosphoric triamides (R1 = H or ≠ H, R2 = a hydrocarbon fragment), and the hydrogen bond patterns include dimer, tetramer, chain, tape, ladder, two-dimensional assembly and three-dimensional architecture. In the new structure, the conformation of the C(O)NP(O) fragment is –sp+ap, and molecules are assembled in a tape arrangement (parallel to the [110] axis) through NCP–H···O═P and NP–H···O═C hydrogen bonds (NCP is the nitrogen atom of the C(O)NHP(O) fragment and NP is the other N atom bonded to phosphorus). The interplay between conformation and hydrogen bond pattern was studied in 211 (C(O)NH)(N)2P(O)-based phosphoric triamides retrieved from the Cambridge Structural Database (CSD) and one new structure, (CHCl2C(O)NH)(CH3CH2CH2NH)2P(O). [ABSTRACT FROM AUTHOR]

The microtubule associated protein, tau, is implicated in a multitude of neurodegenerative disorders that are collectively termed as tauopathies. These disorders are characterized by the presence of tau aggregates within the brain of afflicted individuals. Mutations within the MAPT gene that encodes the tau protein form the genetic backdrop for familial forms of tauopathies, such as frontotemporal dementia (FTD), but the molecular consequences of such alterations and their pathological effects are unclear. We sought to investigate the conformational properties of the aggregates of three tau mutants: A152T, P301L, and R406W, all implicated within FTD, and compare them to those of the native form (WT‐Tau 2N4R). Our immunochemical analysis reveals that mutants and WT tau oligomers exhibit similar affinity for conformation‐specific antibodies but have distinct morphology and secondary structure. Additionally, these oligomers possess different dye‐binding properties and varying sensitivity to proteolytic processing. These results point to conformational variety among them. We then tested the ability of the mutant oligomers to cross‐seed the aggregation of WT tau monomer. Using similar array of experiments, we found that cross‐seeding with mutant aggregates leads to the formation of conformationally unique WT oligomers. The results discussed in this paper provide a novel perspective on the structural properties of oligomeric forms of WT tau 2N4R and its mutant, along with shedding some light on their cross‐seeding behavior. [ABSTRACT FROM AUTHOR]

Cellulose has garnered attention in the textile industry, but it exhibits limitations in applications that require high strength and modulus. In this study, regenerated cellulose fiber with enhanced mechanical properties was fabricated from a gel-like N-methylmorpholine N-oxide (NMMO)–cellulose solution by modulating the intermolecular interaction and conformation of the cellulose chains. To control the interaction, two types of co-solvents (dimethyl acetamide (DMAc) and dimethyl formamide (DMF)) were added to the cellulose solutions at varying concentrations (10, 20, and 30 wt%). Rheological analysis showed that the co-solvents reduced the solution viscosity by weakening intermolecular interactions. The calculated distance parameter (Ra) in Hansen space confirmed that the co-solvent disrupted intermolecular hydrogen bonding within cellulose chains. The solutions were spun into fiber via a simple wet spinning process and were characterized by X-ray diffraction (XRD) and universal testing machine (UTM). The addition of co-solvent led to an increased crystallinity index (C.I.) owing to the extended cellulose chains. The modulus of the resulting fiber was increased when the co-solvent concentration was 10 wt%, regardless of the co-solvent type. This study demonstrates the potential for enhancing the mechanical properties of cellulose-based products by modulating the conformation and interaction of cellulose chains through the addition of co-solvent. [ABSTRACT FROM AUTHOR]

Neutral bis(amino acidato)copper(II) [Cu(aa)2] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa)2, two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa)2 compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group’s research on structural properties of physiological Cu(aa)2 calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa)2 compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu2+ binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa)2 in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling.

In the present study, conformations and aromaticity of seventeen [13], [23] and [33] double-stranded cyclophanes composed of three benzene moieties were investigated at B3LYP level of density functional theory. The stability of these conformers is different depending on the type of cycloalkane-like cycles formed by (CH2) n bridges and the peripheral benzene rings, and also the curvature of the latter. In [13] cyclophane, this leads to only one conformer containing puckered cyclobutane-like cycle, at an angle of about 37◦. In comparison, in cyclophanes [23] and [33], the corresponding cycles are cyclohexane-like and cyclooctane-like, respectively. While conformer 2a having TB-like cycles is the most stable member of the [23] family, of eight ground-state conformers obtained for [33], 3a with two Chair-Chair-like and one Twist-Chair-like cycles is the most stable one, and 3h with three Twist-Boat-like cycles being 6.5 kcal higher in energy than the former is the least stable member of series. In addition to the conformational analysis, the aromaticity of the series has been assessed using different indexes, including magnetic criteria nucleus-independent chemical shifts (NICS-based) at the cage and at the ring centers, HNMR chemical shift, Magnetic Susceptibility, HOMA and relative energy (RE). [ABSTRACT FROM AUTHOR]

Background: Peach gum (PG) is an exudate of the peach tree (Prunus persica of the Rosaceae family), which consists primarily of polysaccharides with a large molecular weight and branching structure. Consequently, PG can only swell in water and does not dissolve easily, which severely limits its application. Current conventional extraction methods for PG polysaccharide (PGPS) are time consuming and inefficient. This study investigated the impact of ultrasonic‐assisted extraction (UAE) on PGPS structure and conformation, and their relationship to hypoglycemic activity in vitro. Results: In comparison with conventional aqueous extraction, UAE enhanced PGPS yielded from 28.07–32.83% to 80.37–84.90% (w/w) in 2 h. It drastically decreased the molecular size and conformational parameters of PGPS, including weight‐average molecular weight (Mw), number‐average molecular weight (Mn), z‐average radius of gyration (Rg), hydrodynamic radius (Rh) and instrinsic viscosity ([η]) values. Peach gum polysaccharide conformation converted extended molecules to flexible random coil chains or compact spheres with no obvious primary structure alteration. Furthermore, UAE altered the flow behavior of PGPS solution from that of a non‐Newtonian fluid to that of a Newtonian fluid. As a result, PGPS treated with UAE displayed weaker inhibitory activity than untreated PGPS, mostly because UAE weakens the binding strength of PGPS to α‐glucosidase. However, this negative effect of UAE on PGPS activity was compensated by the increased solubility of polysaccharide. This enabled PGPS to achieve a wider range of doses. Conclusion: Ultrasonic‐assisted extraction is capable of degrading PGPS efficiently while preserving its primary structure, resulting in a Newtonian fluid solution. The degraded PGPS conformations displayed a consistent correlation with their inhibitory effect on α‐glucosidase activity. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Two new 6,17‐di‐tert‐butyl‐[3]metacyclo[3](1,3)‐pyrenophane‐2,11‐diones 8 a–b were synthesized by the coupling reaction of 1,3‐bis(bromomethyl)‐7‐tert‐butylpyrene 5 with the corresponding TosMIC‐adducts 7 a–b in CH2Cl2 and water under phase‐transfer conditions, followed by acid treatment. Wolff–Kishner reduction of 8 a–b afforded in good yields the corresponding 6,17‐di‐tert‐butyl‐[3]metacyclo[3](1,3)‐pyrenophanes 9 a–b. The spectroscopic data of both 8 a and 8 b show that they adopt anti‐conformations. In contrast, both pyrenophanes 9 a and 9 b adopt syn‐conformations. Variable‐temperature 1H NMR studies were carried out to determine the conformational behavior of the pyrenophanes. A single crystal X‐ray structure of 8 a shows that it also has an anti‐conformation in the solid state. Density functional theory (DFT) computations of 8 a–b and 9 a–b were used to determine their energy‐minimized structures and the total energies of their different conformers. [ABSTRACT FROM AUTHOR]

Without stereogenic carbon centers, organic molecules can be chiral when they have large energy barriers for conformational inversion. In this work, conformational behaviors are investigated for a series of tricyclic propellane skeletons with increasing 6‐membered‐ring peripheral moieties fused with aromatic rings. According to theoretical calculations, trinaphtho[3.3.3]propellane has three vertical naphthalene rings like triptycene shape without torsion along the central C−C single bond. On the other hand, hexabenzo[4.4.4]propellane shows hexaphenylethane‐like ca. 60° twist along the bond with large activation energy of 64 kcal mol−1 for twist inversion because of the high congestion caused by three 6‐membered‐ring loops. Indeed, the [4.4.4]propellane gives a stable pair of chiroptical enantiomers toward heating at 146 °C. By contrast, a hybrid [4.3.3]propellane exhibits fast interconversion between two twisted conformations even at −80 °C. [ABSTRACT FROM AUTHOR]

The unresolved phylogenetic framework within the Selaginellaceae subfamily Gymnogynoideae (ca. 130 species) has hindered our comprehension of the diversification and evolution of Selaginellaceae, one of the most important lineages in land plant evolution. Here, based on plastid and nuclear data extracted from genomic sequencing of more than 90% species of all genera except two in Gymnogynoideae, a phylogenomic study focusing on the contentious relationships among the genera in Gymnogynoideae was conducted. Our major results included the following: (1) Only single-copy region (named NR) and only one ribosomal operon was firstly found in Afroselaginella among vascular plants, the plastome structure of Gymnogynoideae is diverse among the six genera, and the direct repeats (DR) type is inferred as the ancestral state in the subfamily; (2) The first strong evidence was found to support Afroselaginella as a sister to Megaloselaginella. Alternative placements of Ericetorum and Gymnogynum were detected, and their relationships were investigated by analyzing the variation of phylogenetic signals; and (3) The most likely genus-level relationships in Gymnogynoideae might be: ((Bryodesma, Lepidoselaginella), (((Megaloselaginella, Afroselaginella), Ericetorum), Gymnogynum)), which was supported by maximum likelihood phylogeny based on plastid datasets, maximum likelihood, and Bayesian inference based on SCG dataset and concatenated nuclear and plastid datasets and the highest proportion of phylogenetic signals of plastid genes. [ABSTRACT FROM AUTHOR]

We report a three-stage scheme (1) Pbt–NH2 + CS2 → (Pbt–NH)2C=S (1) (Pbt = 4-(1′,3′-benzothiazole-2′-yl)phenyl), (2) 1 + PPh3 + I2 → Pbt–N=C=N–Pbt (2), (3) 2 + Ph2PH → (Pbt–N)(Pbt–NH)CPPh2 (3) for the synthesis of a novel luminescent phosphoguanidine 3 with an unprecedentedly high yield (90%) at the last catalyst-free stage. It is demonstrated by the density functional theory (DFT) method that high reactivity of 2, leading to such an yield, is explained by a high electrostatic potential at the central carbon atom. For 3, two polymorphs 3α, 3β and a solvatomorph 3γ·THF are prepared. The structures of 2, 3α, 3β, and 3γ·THF are determined by single-crystal XRD. The tendency of crystals of different phenylbenzothiazole derivatives to form different conformations is explained by the computational (DFT) data indicating that the energy change of the molecule of 3 considered as a function of the torsion angle between phenyl and benzothiazole fragments does not exceed 2 kJ/mol in the –15...30° range. Photophysical properties of 3β and 3γ·THF phases are studied. It is shown that these compounds exhibit photoluminescence with an emission maximum at 510 nm. [ABSTRACT FROM AUTHOR]

Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins. Synopsis: Hyperactivation of kinesins has been linked to neurodegenerative conditions. This study shows that a hyperactive version of OSM-3, a member of kinesin-2 superfamily that drives anterograde intraflagellar transport in C. elegans, is expelled from neurons for degradation in glial cells. Hyperactive OSM-3CA kinesin is absent from cilia and forms dynamic puncta within the neurites of sensory neurons. OSM-3CA puncta are ejected from sensory neurons and engulfed by neighboring cephalic sheath glia cells in a manner dependent of the phagocytic receptor CED-1. Mutations that reduce OSM-3CA activity or increase its microtubule binding protect OSM-3CA and restore normal cilia. ALS-linked hyperactive kinesin-1 is also expelled from neurons when ectopically expressed in C. elegans. Phagocytic receptor CED-1 enables glial uptake and subsequent degradation of hyperactive kinesins in C. elegans. [ABSTRACT FROM AUTHOR]

Background: The risk of carpal injury in racehorses may be related to the morphology, yet whether carpal morphologies are set from birth or change through growth remains unclear. Objective: To quantify carpal bone changes through growth. Method: Twenty privately owned Thoroughbred foals born between January 2022 and May 2023 were radiographed bimonthly from birth to 10 months of age. Imprint training was used to take radiographs safely without chemical restraints. Fifteen individual and 11 relative angular carpal parameters were measured using ImageJ on dorsopalmar radiographs of the carpus at zero degrees of vertical and horizontal rotation. Associations with age (growth), sex and the differences between left and right limbs were analysed separately using a linear mixed effects model. Results: Six individual carpal parameters changed with age (radial carpal joint [RCJ], Prx.dor. radial carpal [Cr], Prx.Cu, Dis.dor. third carpal [C3], Dis.pal.C3 and Dis.pal. intermediate carpal), and one was influenced by side, that is higher in the left carpus (Dis.pal.Cr). Seven relative parameters changed with age, and one relative parameter was influenced by side, that is higher in the left (Ra.met‐RCJ). The proximo‐dorsal bone surface angle of Cr and disto‐dorsal bone surface angle of C3 became flatter over time, which may be associated with the re‐direction of the load towards the sagittal carpal plane. Sex did not influence any of the carpal parameters, nor did the combined effect of age, side of the limb and sex. Conclusion: Specific individual and relative angular carpal parameters changed significantly over time and some differed between the left and right limb, whereas other parameters did not change. The steeper carpal bone angles achieved proximally with the parameters that did change may improve stability by redirecting the load more medially through the carpus and the proximal and distal bones. [ABSTRACT FROM AUTHOR]

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Hexaazamacrocyclic Schiff bases have been extensively combined with lanthanoid (Ln) ions to obtain complexes with a highly axial geometry. However, the use of flexible hexaazatetraamine macrocycles containing two pyridines and acyclic spacers is rather uncommon. Accordingly, we obtained [DyL(OAc)2]OAc·7H2O·EtOH and [DyLMe2(Cl)2]Cl·2H2O, where L and LMe2 are the 18-membered macrocycles 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane and 3,10-dimethyl-3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane, respectively, which contain ethylene and methylethylene spacers between their N3 moieties. [DyL(OAc)2]OAc·7H2O·EtOH represents the first crystallographically characterized lanthanoid complex of L, while [DyLMe2(Cl)2]Cl·2H2O contributes to increasing the scarce number of LnIII compounds containing LMe2. Furthermore, the crystal structure of L·12H2O was solved, and it was compared with those of other related macrocycles previously published. Likewise, the crystal structures of the DyIII complexes were compared with those of the lanthanoid and d-metal complexes of other 18-membered N6 donor macrocycles. This comparison showed some effect of the spacers employed, as well as the influence of the size of the ancillary ligands and the metal ion. Additionally, the distinct folding behaviors of these macrocycles influenced their coordination geometries. Moreover, the luminescent properties of [DyL(OAc)2]OAc·7H2O·EtOH and [DyLMe2(Cl)2]Cl·2H2O were also investigated, showing that both complexes are fluorescent, with the emission being sensitized by the ligands. [ABSTRACT FROM AUTHOR]

All current theories concerning the conductivity of polyelectrolytes ignore the dielectric friction effect undergone by the polyion chains according to their conformation. Indeed, Manning's theory is limited to the case of stretched chains and only takes into account hydrodynamic, electrophoretic and ionic frictions; while scaling approach theories take into account the formation of different types of blobs within the chain but are restricted to hydrodynamic and electrophoretic frictions. In this work, we present a different approach that explains the variation of the equivalent conductivity of polyions having coiled or almost or completely stretched conformations and that takes into account the four frictions. In addition, the introduction of the dielectric friction effect allowed us to interpret the dependency of the equivalent conductivity of a polyion λP,X on the nature of its counterions X. A likely correlation between this effect and Hofmeister's is discussed. [ABSTRACT FROM AUTHOR]

Comprehending and discussing Koreans' experiences of inter-religious dialogue requires a precise understanding of their religious hybridity. To this end, this article first delves into South Korea's multireligious and syncretic landscape. Subsequently, it focuses on the concept of chungch'ŭng-sinang, or multilayered faith, highlighting how Koreans have constructed their own religiously multilayered and open internal structures based on their historical encounters with various religions. Finally, building on this understanding, this article examines how an in-depth understanding of Korean religious hybridity transforms our understanding of their experiences in inter-religious dialogue. Acknowledging their hybridity facilitates an understanding of experiences that go beyond mere acquisition of knowledge about others and a deepening sense of their identities—involving the discovery of internal otherness. While this approach may weaken the logic of religion, it can foster dialogue that is more liberating, formative, and humanizing. [ABSTRACT FROM AUTHOR]

A lot of literature sources discuss diseases associated with the hemoglobin protein [1-2]. In the modern world, more than 800 million people suffer from anemia [3]. Assessing the level of hemoglobin in the circulatory system is one of the ways to diagnose anemia. Hemoglobin protein is also a promising source of bioactive peptides [4]. The aim of the work was to identify the reasons leading to conformation changes of this protein. It still remains unclear what exactly causes disruption of its functionality. Human hemoglobin from Sigma H7379 was studied in the work; all experiments were conducted on a dynamic light scattering spectrometer—Photocor Complex. Experimental data were obtained using optical methods of static and dynamic light scattering. The work included an analysis of the behaviour of hemoglobin protein molecules in aqueous and aqueous-saline solutions with changes in solution parameters (pH, addition of iron chloride III). At values of pH and pH , the hemoglobin molecule underwent conformational changes, resulting in the disintegration of the quaternary structure into -dimers and individual - and -globules. As a result of the study, it was found that the addition of FeCl to aqueous solutions of hemoglobin increases the size and mass of scattering particles, which can be explained by the adsorption of Fe ions on the protein surface. However, upon reaching a certain concentration of FeCl , the pH of the solution was lowered to such an extent that it caused conformational changes in hemoglobin, leading to the disintegration of its quaternary structure. These results can be taken into account when creating medicinal drugs for the treatment of anemia and other diseases associated with the hemoglobin protein. [ABSTRACT FROM AUTHOR]

Conformation traits are important in the selection and distinction between horse breeds, but tend to be evaluated subjectively within a breed and cannot be compared between them. The horse shape space model, using a combination of 253 landmarks and semi-landmarks, provides objective information on the shape of a horse photographed from the side that can be compared between breeds. In this dataset, we are providing the full set of 253 landmarks for 1241 horses from seven breeds, including an R code file to extract joint angle information and transform the raw data into csv files for further analysis, such as breed comparisons, heritability or genome-wide association studies (single- or multibreed). The repeatability of the joint angles are also reported.

Bovine lactoferrin (bLF) is a multifunctional protein used in the food and pharmaceutical industries. Various commercially available bLF powders (bLFPs) have different ratios of protein monomers to aggregates, which affects the aggregation rate. However, the changes in molecular structure and interactions during aggregation are unclear. This study investigated changes in the structure and interactions of stored bLFPs during aggregation. Five commercially available bLFPs with different molecular weight distributions were analyzed before and after storage using size-exclusion chromatography and X-ray diffraction (XRD) to monitor aggregation and β-strand interaction, respectively. These bLFPs were stored for four weeks under high temperature and humidity conditions as a stress test. The XRD results revealed changes in peak II (around 2θ = 20°), corresponding to β-strand interactions. The peak II change rate suggested that the aggregation occurs due to partial structural fluctuations and interaction changes. Furthermore, time-course analysis of peak II and correlations with the pre-storage monomer ratio and aggregation phase index demonstrated that β-strand interactions decreased during the transformation of monomers to low-molecular-weight (LMW) aggregates, while it increased during the LMW-to-high-molecular-weight aggregate phase. These results provide novel insights into the conformational changes and molecular interactions of bLFPs during aggregation.

Molecular simulations have become a key tool in molecular and materials design. Machine learning (ML)‐based potential energy functions offer the prospect of simulating complex molecular systems efficiently at quantum chemical accuracy. In previous work, we have introduced the ML‐based PairF‐Net approach to neural network potentials, that adopts a pairwise interatomic scheme to predicting forces within a molecular system. Here, we further develop the PairF‐Net model to intrinsically incorporate energy conservation and couple the model to a molecular mechanical (MM) environment within the OpenMM package. The updated PairF‐Net model yields energy and force predictions and dynamical distributions in good agreement with the rMD17 dataset of ten small organic molecules in the gas‐phase. We further show that these in vacuo ML models of small molecules can be applied to force predictions in aqueous solution via hybrid ML/MM simulations. We present a new benchmark dataset for these ten molecules in solution, obtained from QM/MM simulations, which we denote as rMD17‐aq (https://zenodo.org/records/10048644); and assess the ability of PairF‐Net to reproduce the molecular energy, atomic forces and dynamical distributions of these solution conformations via ML/MM simulations. [ABSTRACT FROM AUTHOR]

Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C−CF2−C>∠C−CH2−C): this provides a handle to modulate physicochemistry (e.g. pKa). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95 % yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93 : 7 e.r.) together with X‐ray structural analyses and product derivatization. [ABSTRACT FROM AUTHOR]

β-1,3-glucans are a kind of natural polysaccharide with immunomodulatory, antitumor, and anti-inflammatory properties. Curdlan, as the simplest linear β-1,3-glucan, possesses a variety of biological activities and thermogelation properties. However, due to the complexity and variability of the conformations of curdlan, the exact structure–activity relationship remains unclear. We prepare a chemically crosslinked curdlan hydrogel with the unique single-helical skeleton (named S gel) in 0.4 wt% NaOH at 40 °C, confirmed by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). X-ray diffractometry (XRD) data show that S gel maintains the single-helical crystal structure, and the degree of crystallinity of the S gel is ~24%, which is slightly lower than that of the raw powder (~31%). Scanning electron microscopy (SEM) reveals that S gel has a continuous network structure, with large pores measuring 50–200 μm, which is consistent with its high swelling property. Using the 13C high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) method, we determine that most of the single-helical skeleton carbon signals in the swollen S gel are visible, suggesting that the single-helical skeleton of S gel exhibits fascinating mobility at room temperature. Finally, we reveal that the binding of S gel to coagulation Factor G from tachypleus amebocyte lysate increases and saturates at 20 μL tachypleus amebocyte lysate per mg of S gel. Our prepared S gel can avoid the transformation of curdlan conformations and retain the bioactivity of binding to coagulation Factor G, making it a valuable material for use in the food industry and the pharmaceutical field. This work deepens the understanding of the relationship between the single-helical structure and the activity of curdlan, promoting the development and application of β-1,3-glucans. [ABSTRACT FROM AUTHOR]

To develop peptide drugs targeting integrin receptors, synthetic peptide ligands endowed with well-defined selective binding motifs are necessary. The snake venom KTS-containing disintegrins, which selectively block collagen α1β1 integrin, were used as lead compounds for the synthesis and structure–activity relationship of a series of linear peptides containing the KTS-pharmacophore and alternating natural amino acids and 3-aminobenzoic acid (MABA). To ensure a better stiffness and metabolic stability, one, two and three MABA residues, were introduced around the KTS pharmacophore motif. Molecular dynamics simulations determined that the solution conformation of MABA peptide 4 is more compact, underwent larger conformational changes until convergence, and spent most of the time in a single cluster. The peptides' binding affinity has been characterized by an enzyme linked immunosorbent assay in which the most potent peptide 4 inhibited with IC50 of 324 ± 8 µM and 550 ± 45 µM the binding of GST-α1-A domain to collagen IV fragment CB3, and the cell adhesion to collagen IV using α1-overexpressor cells, respectively. Docking studies and MM-GBSA calculations confirmed that peptide 4 binds a smaller region of the integrin near the collagen-binding site and penetrated deeper into the binding site near Trp1. Peptide 4 inhibited tube formation by endothelial cell migration in the Matrigel angiogenesis in vitro assay. Peptide 4 was acutely tolerated by mice, showed stability in human serum, decreased tumor volume and angiogenesis, and significantly increased the survival of mice injected with B16 melanoma cells. These findings propose that MABA-peptide 4 can further serve as an α1β1-integrin antagonist lead compound for further drug optimization in angiogenesis and cancer therapy. [ABSTRACT FROM AUTHOR]

The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease for which there is no cure. HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218–298) to form four different fibrillar vaccine candidates, each displaying a specific conformational epitope present on the surface of α-synuclein fibrils. Vaccination with these four vaccine candidates prolonged the survival of immunized TgM83+/− mice challenged with α-synuclein fibrils by 8% when injected into the brain to model brain-first Parkinson's disease or by 21% and 22% when injected into the peritoneum or gut wall, respectively, to model body-first Parkinson's disease. Antibodies from fully immunized mice recognized α-synuclein fibrils and brain homogenates from patients with Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Conformation-specific vaccines that mimic epitopes present only on the surface of pathological fibrils but not on soluble monomers, hold great promise for protection against Parkinson's disease, related synucleinopathies and other amyloidogenic protein misfolding disorders. [ABSTRACT FROM AUTHOR]

In this study, 2 flexible and pre-organized tetraamide compounds derived from N-6-[(4- pyridylmethylamino)carbonyl]-pyridine-2-carboxylic acid methyl ester namely 1,2-bis[N,N'-6-(4- pyridylmethylamido)pyridyl-2-carboxyamido]pentane (L1) and 1,2-bis[N,N'-6-(4- pyridylmethylamido)pyridyl-2-carboxyamido]hexane (L2) have been successfully synthesized when reacted with diamines in 1:2 ratio. These new compounds were built from combination of 3 main components, as a trend requires for anion receptor which are (i) 2,6-pyridine dicarboxamide moieties as targeted anion binding host, (ii) amino methyl pyridine pendants arms as the flexible moieties and (iii) pentyl (-C5H10-) and hexyl (-C6H12-) unit as the spacer. Compounds L1-L2 were fully characterized by using elemental analyzer, Fourier transform infrared (FTIR) spectroscopy, gas chromatography-mass spectroscopy (GC-MS), ¹H, 2D NOESY and 13C Nuclear Magnetic Resonance (NMR) spectroscopies, and Ultraviolet-visible (UV-Vis) spectroscopies. In this study, anion titration methods were used to identify the affinity towards selected anions. The results showed that L1 (having a pentyl spacer) had the highest affinity towards phosphate anions as compared to L2, where the red shift changes were observed in the UV-vis spectrum at the amide region. [ABSTRACT FROM AUTHOR]

This review emphasizes the practical importance of laser light scattering methods for characterizing cellulose and its derivatives. The physicochemical parameters like molecular weights, the radius of gyration, hydrodynamic radius, and conformation will be considered when the reproducibility of polymer behavior in solution is necessary for the subsequent optimization of the property profile of a designed product. Since there are various sources of cellulose, and the methods of cellulose extraction and chemical modification have variable yields, materials with variable molecular weights, and size polydispersity will often result. Later, the molecular masses will influence other physicochemical properties of cellulosic materials, both in solution and solid state. Consequently, the most rigorous determination of these quantities is imperative. In this regard, the following are presented and discussed in this review: the theoretical foundations of the light scattering phenomenon, the evolution of the specific instrumentation and detectors, the development of the detector-coupling techniques which include a light scattering detector, and finally, the importance of the specific parameters of polymers in solution, resulting from the data analysis of light scattering signals. All these aspects are summarized according to the chemical classification of the materials: celluloses, esters of cellulose, co-esters of cellulose, alkyl esters of cellulose, ethers of cellulose, and other heterogeneous cellulose derivatives with applications in life sciences. [ABSTRACT FROM AUTHOR]

The relevance of the work was to determine whether the loin eye area of m. longissimus dorsi as a criterion for evaluating the yield of high-value cuts from beef carcasses, is associated with beef characteristics from bulls of the Ukrainian Black-and-White dairy breed. The purpose of the study was to establish correlations between the loin eye area and the slaughter characteristics by the chemical composition, sensory, physical and technological properties of beef. The correlation between the cross-sectional area of the oblong muscle and slaughter indicators, the quality of carcasses, the chemical composition, sensory, physical and technological properties of beef was studied in the bulls of Ukrainian Black-and-White dairy breed (UBWDB) aged from 18 to 24 months. A linear correlation was established between the loin eye area and the slaughter weight (r = 0.404; P > 0.95), the amount of muscle tissue (r = 0.355; P > 0.95), including the highest (r = 0.680; P > 0.999) and the first (r = 0.501; P > 0.99) grades, the content of fat tissue in the carcass (r = 0.477; P > 0.99). The loin eye area correlated inversely (r = -0.607; P > 0.95) with the amount lost in boiling beef, the amount of second-class muscle tissue (r = -0.377; P > 0.95), the development of subcutaneous fat (r = -0.395; P > 0.95), the total ash mass (r = -0.560; P > 0.95), the juiciness of boiled meat (r = -0.522; P > 0.95), taste and aroma of broth (r = -0.587; P > 0.95). There was a tendency for an inverse correlation between the loin eye area and the total fat content of beef (r = -0.119), protein (r = -0.401), dry matter (r = -0.403), acidity (r = -0.458), muscle tissue colour (r = -0.126), conformation (r = -0.127), penetration (r = -0.477), taste (r = -0.214) and aroma (r = -0.363) of boiled meat, tenderness (r = -0.256), residue after chewing (r = -0.442), the thickness of broth (r = -0.207), and to a linear correlation - with the amount of tendons and ligaments (r = 0.331), marbling (r = 0.162), the colour of fat tissue on the carcass (r = 0.276), transparency of the broth (r = 0.180). The practical significance of the data is to obtain knowledge that allows formulating marketing strategies for predicting food quality, quantity of premium and first-grade beef, its technological properties and intended use based on the correlation between the loin eye area of m. longissimus dorsi. [ABSTRACT FROM AUTHOR]

The π-π interaction is acknowledged as the predominant factor to determine the molecular packing in organic photovoltaic materials, while other non-covalent intermolecular interactions especially the σ-π hyperconjugation are often ignored. Herein, a perylene diimide (PDI) derivative named FIDT-PDI is designed and synthesized to shed light into the effect of hyperconjugation on the molecular packing and further the photovoltaic performance. Dynamic NMR and 2D NOE NMR demonstrate the formation of intermolecular σ-π hyperconjugation between the C--H bond of the PDI moiety in one molecule and the phenyl sidechain in another molecule of FIDT-PDI. Benefiting from the σ-π hyperconjugation, FIDT-PDI with twisted backbone reversely exhibits more ordered packing and stronger crystallinity compared with another PDI derivative FIDTT-PDI which has better planarity, consequently achieving superior PCE and higher carrier mobility. This contribution is the first paradigm to unravel the structure-property relationship between σ-π hyperconjugation of conjugated materials and corresponding photovoltaic performance. [ABSTRACT FROM AUTHOR]

Small‐molecule dyes are generally designed based on well‐understood electronic effects. However, steric hindrance can promote excited‐state geometric relaxation, increasing the difference between the positions of absorption and emission bands (the Stokes shift). Accordingly, we hypothesized that sterically induced central ring puckering in xanthene dyes could be used to systematically increase their Stokes shift. Through a combined experimental/quantum‐chemical approach, we screened a group of (9‐acylimino)‐pyronin dyes with a perturbed central ring geometry. Our results showed that an atom with sp3 hybridization in position 10 of (9‐acylimino)‐pyronins induces central ring puckering and facilitates excited‐state geometric relaxation, thereby markedly enhancing their Stokes shifts (by up to ~2000 cm−1). Thus, we prepared fluorescent (9‐acylimino)‐pyronin pH sensors, which showed a Stokes shift disparity between acid and base forms of up to ~8700 cm−1. Moreover, the concept of ring puckering‐enhanced Stokes shift can be applied to a wide range of xanthene analogues found in the literature. Therefore, central ring puckering may be reliably used as a strategy for enhancing Stokes shifts in the rational design of dyes. [ABSTRACT FROM AUTHOR]

It is increasingly evident that the association of glycans with the prion protein (PrP), a major post-translational modification, significantly impacts the pathogenesis of prion diseases. A recent bioassay study has provided evidence that the presence of PrP glycans decreases spongiform degeneration and disease-related PrP (PrPD) deposition in a murine model. We challenged (PRNP N181Q/197Q) transgenic (Tg) mice expressing glycan-free human PrP (TgGlyc−), with isolates from sporadic Creutzfeldt–Jakob disease subtype MM2 (sCJDMM2), sporadic fatal insomnia and familial fatal insomnia, three human prion diseases that are distinct but share histotypic and PrPD features. TgGlyc− mice accurately replicated the basic histotypic features associated with the three diseases but the transmission was characterized by high attack rates, shortened incubation periods and a greatly increased severity of the histopathology, including the presence of up to 40 times higher quantities of PrPD that formed prominent deposits. Although the engineered protease-resistant PrPD shared at least some features of the secondary structure and the presence of the anchorless PrPD variant with the wild-type PrPD, it exhibited different density gradient profiles of the PrPD aggregates and a higher stability index. The severity of the histopathological features including PrP deposition appeared to be related to the incubation period duration. These findings are clearly consistent with the protective role of the PrP glycans but also emphasize the complexity of the conformational changes that impact PrPD following glycan knockout. Future studies will determine whether these features apply broadly to other human prion diseases or are PrPD-type dependent. [ABSTRACT FROM AUTHOR]

Simple Summary: The welfare of purebred dogs and cats is being undermined by fashion trends that popularize extreme shapes. Official descriptions of breeds require their distinctive characteristics to be compatible with good health. Nevertheless, extremes within breeds that compromise health, referred to as hypertypes, have become trendy. For example, when flat faces are taken to the extreme, dogs and cats may be unable to breathe normally, which affects all aspects of their lives. Individuals such as breeders, owners and veterinarians, and organizations in the whole community surrounding purebred dogs and cats must collaborate to prevent the breeding of hypertypes. Fashion-fueled breeding of hypertypes, whether or not illegal, must also be tackled because its negative effects can extend beyond what is visible to unsuspecting owners choosing their puppy or kitten. The problem is complex, and the solution involves many bodies working together. However, the message is simple: health, temperament, and well-being must be prioritized over appearance. Putting this into practice will help protect the much-valued diversity of breeds. Fashions in the appearance of purebred dogs and cats are encouraged by celebrity culture, social media, and online impulse buying. The popularity of characteristics perceived as cute, quirky, and anthropomorphic has driven increasingly exaggerated breed features appealing to aesthetics rather than health. 'Hypertypes' of some breeds have emerged that take a breed's distinctive appearance to extremes beyond the intended interpretation of breed standards. This has severe, direct and indirect health and welfare consequences. Extreme conformations are associated with chronic health conditions including brachycephalic obstructive airway disorder, ocular, dental, skin, and musculoskeletal disorders. Puppy and kitten farms and illegal traders that meet the demand for hypertypes are associated with poor husbandry that neglects the physical, behavioral, and mental health of parents and offspring. A multidimensional approach involving collaboration between breeders, geneticists, owners, veterinarians, kennel clubs, cat fanciers' associations, animal charities, the academic and research communities, commercial enterprises, and governments is needed to safeguard breeds and tackle these challenges. There are many ongoing initiatives by national kennel clubs and global partnerships to educate pet owners and support responsible pet ownership and sustainable breeding. The resounding message is that health, temperament, and well-being must be prioritized over appearance. [ABSTRACT FROM AUTHOR]

Invisible orthodontic aligners are having a great impact on tooth movement in an aesthetic and effective way. Different techniques, models, and clinical aspects have been studied for their proper use. However, the aim of this research has been to determine the effect of the shaping process on mechanical properties and their bacterial behavior. For this study, 40 original polyurethane plates and 40 identical models, obtained by hot forming the original plates, were used. The static tensile mechanical properties were studied with a Zwick testing machine using testing speeds of 5 mm/min at a temperature of 37 °C. The original plate and the aligner have been studied with a creep test by subjecting the samples to a constant tension of 30 N, and determining the elongation using a long-distance, high-resolution microscope at different time periods between 1 and 720 h. Studies of water absorption has been realized with artificial saliva for 5 h. Bacterial cultures of Streptococcus oralis and Actinomyces viscosus strains were grown on the original plates and on new and used models, to determine the proliferation of each bacterium through metabolic activity, colony-forming units, and LIVE/DEAD assays. The mechanical results showed an increase in the strength of the inserts with respect to the models obtained from 3.44 to 3.95 MPa in the elastic limit and a lower deformation capacity. It has been proven that the transition zone in the creep curves lasts longer in the original plate, producing the rapid increase in deformation at a shorter time (400 h) in the aligner. Therefore, the shaping process reduces the time of dental correction exerted by the aligner. The results of the bacterial culture assays show an increase in the number of bacterial colonies when the aligners have been used and when the polyurethane is conformed due to the internal energy of the model, with respect to the original polyurethane. It has been observed that between the original plate and the aligner there are no statistically significant differences in water absorption and therefore the forming process does not affect water absorption. A slight increase in water absorption can be observed, but after five hours of exposure, the increase is very small. [ABSTRACT FROM AUTHOR]

Introduction: Different serovars of Salmonella enterica cause systemic diseases in humans including enteric fever, caused by S. Typhi and S. Paratyphi A, and invasive nontyphoidal salmonellosis (iNTS), caused mainly by S. Typhimurium and S. Enteritidis. No vaccines are yet available against paratyphoid fever and iNTS but different strategies, based on the immunodominant O-Antigen component of the lipopolysaccharide, are currently being tested. The O-Antigens of S. enterica serovars share structural features including the backbone comprising mannose, rhamnose and galactose as well as further modifications such as O-acetylation and glucosylation. The importance of these O-Antigen decorations for the induced immunogenicity and cross-reactivity has been poorly characterized. Methods: These immunological aspects were investigated in this study using Generalized Modules for Membrane Antigens (GMMA) as delivery systems for the different O-Antigen variants. This platform allowed the rapid generation and in vivo testing of defined and controlled polysaccharide structures through genetic manipulation of the O-Antigen biosynthetic genes. Results: Results from mice and rabbit immunization experiments highlighted the important role played by secondary O-Antigen decorations in the induced immunogenicity. Moreover, molecular modeling of O-Antigen conformations corroborated the likelihood of cross-protection between S. enterica serovars. Discussion: Such results, if confirmed in humans, could have a great impact on the design of a simplified vaccine composition able to maximize functional immune responses against clinically relevant Salmonella enterica serovars. [ABSTRACT FROM AUTHOR]

Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule, is a seemingly improbable event, on a closer look, it is almost inevitable that some homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic "ocean". Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. Furthermore, a concept of physical compartmentalization based on rock nanopores in analogy to nanocavities of digital immunoassays is introduced to suggest that complex cell walls or membranes were also not required for the first steps of chemical evolution. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth. [ABSTRACT FROM AUTHOR]

Ribitol (C5H12O5) is an acyclic sugar alcohol that was recently identified in O-mannose glycan on mammalian α-dystroglycan. The conformation and dynamics of acyclic sugar alcohols such as ribitol are dependent on the stereochemistry of the hydroxyl groups; however, the dynamics are not fully understood. To gain insights into the conformation and dynamics of sugar alcohols, we carried out comparative analyses of ribitol, d-arabitol and xylitol by a crystal structure database search, solution NMR analysis and molecular dynamics (MD) simulations. The crystal structures of the sugar alcohols showed a limited number of conformations, suggesting that only certain stable conformations are prevalent among all possible conformations. The three-bond scholar coupling constants and exchange rates of hydroxyl protons were measured to obtain information on the backbone torsion angle and possible hydrogen bonding of each hydroxyl group. The 100 ns MD simulations indicate that the ribitol backbone has frequent conformational transitions with torsion angles between 180° and ±60°, while d-arabitol and xylitol showed fewer conformational transitions. Taking our experimental and computational data together, it can be concluded that ribitol is more flexible than d-arabitol or xylitol, and the flexibility is at least in part defined by the configuration of the OH groups, which may form intramolecular hydrogen bonds. [ABSTRACT FROM AUTHOR]

Natural polyamines play a fundamental role in the cell cycle. Despite being recognized as the most abundant organic counterions of DNA in the cell nucleus, their interactions with DNA have not been fully characterized. In a recent work [S. Perepelytsya, T. Vasiliu, A. Laaksonen, L. Engelbrecht, G. Brancato, and F. Mocci, J. Molec. Liq.389, 122828 (2023)], we have shown how the interactions between spermidine3+ and the DNA double helix induce significant conformational variations in the polyamine molecule. Specifically, we found that DNA induces conformations that are not observed in solution. Following that study, we present here a detailed investigation of the most compact conformation of the polyamine, analyzing its connection to the interaction with the DNA duplex. The analysis reveals that anomalous bent conformations of the spermidine3+ molecule result from the interaction of all three amino groups of the polyamine with the DNA phosphate groups on the minor groove side of the double helix. The changes in dihedral angles of the bent spermidine3+ molecule can be explained in terms of conformational transformations of six- and seven-membered rings, analogous to cyclohexane and cycloheptane. The analysis of the position of spermidine3+ molecule along the DNA surface reveals a sequence specificity of this binding mode with a marked preference for the narrow minor groove of A-tracts. The formation of the anomalous bent conformations of spermidine3+ in the complex with the DNA double helix is expected to be of paramount importance in understanding the mechanisms underlying DNA's biological function. [ABSTRACT FROM AUTHOR]

Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses. To characterize further antibodies to Z-DNA, we used an ELISA assay with brominated poly(dGdC) as a source of Z-DNA and determined the isotype of these antibodies and their binding properties. Results of these studies indicate that NHS sera contain IgM and IgA as well as IgG anti-Z-DNA antibodies. As shown by the effects of ionic strength in association and dissociation assays, the anti-Z-DNA antibodies bind primarily by electrostatic interactions; this type of binding differs from that of induced anti-Z-DNA antibodies from immunized animals which bind by non-ionic interactions. Furthermore, urea caused dissociation of NHS anti-Z-DNA at molar concentrations much lower than those for the induced antibodies. These studies also showed IgA anti-Z-DNA antibodies in fecal water. Together, these studies demonstrate that antibodies to Z-DNA occur commonly in normal immunity and may arise as a response to Z-DNA of bacterial origin. [ABSTRACT FROM AUTHOR]

This study investigated the production of methyl formate from carbon monoxide (CO) in the presence of copper oxide nanoparticles (CuO-NPs). The configurations (cis, intermediate state (TS), and trans) of the methyl formate and halogen derivatives (methyl fluoro-formate, methyl chloro-formate, and methyl bromo-formate) are also investigated by density function theory (DFT) and Natural Bond Orbital (NBO) methods. After simulating and optimizing the geometrical structure of the CuO-NPs nano-catalyst with a monoclonal structure, the reaction mechanism of methyl formate production from CO is investigated under suitable temperature conditions in a gaseous environment by LC-WPBE, PM2, and B3LYP based on 6-311 + G**. The results show that the cis configuration of these compounds is more stable than their trans, and when halogen enters the compounds, electron transfer increases, and their anomeric property increases. The gap energy (Eg) for the cis configuration is higher than for the trans, which indicates the stability of its structure, and as the radius of the halogen atom increases in the compounds, the stability of the cis configuration increases. [ABSTRACT FROM AUTHOR]