Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids

The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)_n-O2Oc-NH₂, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]₈-O2Oc-NH₂ and typical for large proteins.     

The Causes and Potential Injurious Effects of Elevated Serum Leptin Levels in Chronic Kidney Disease Patients

Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.     

Role of Chiral Configuration in the Photoinduced Interaction of D- and L-Tryptophan with Optical Isomers of Ketoprofen in Linked Systems

The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer’s and Parkinson’s diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor–acceptor dyad with (R)- and (S)-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: (R,S)-, (S,R)-, and (S,S)-. Thus, the ET efficiency is identical for (S,R)- and (R,S)-enantiomers, while RET differs by 1.6 times. For (S,S)-, the CIDNP coefficient is almost an order of magnitude greater than for (R,S)- and (S,R)-. To understand the source of this difference, hyperpolarization of (S,S)-and (R,S)- has been calculated using theory involving the electron dipole–dipole interaction in the secular equation.     

A medical hand tool physical interaction evaluation approach for prototype testing using patient care simulators

The purpose of this study was to develop and test a physical ergonomics assessment approach for medical device handles. The method assesses wrist posture and force of exertion simultaneously by task element. Electrogoniometers and EMG sensors were connected through a data acquisition module for synchronization with video recordings of trials. Task analysis of video recordings were performed offline with Observer XT software. Average posture and force data across several repetitions of individual task elements were calculated and presented in a format suitable for informing product designers of specific issues during a test trial. A handle comfort questionnaire is proposed to survey subjective responses. The evaluation approach was applied to an endoscope needle in sampling a biopsy from the stomach wall using a gastrointestinal track simulator with ten physician surrogates. The results showed that for all task elements the wrist was in extension (33(°)-45(°)). Peak muscle forces ranged from 28% to 68% MVC across the three muscles studied. Muscle peak forces were above ACGIH HAL maximum threshold limits for four of the seven task elements, and above the action limit for all seven task elements for two muscles. The handle comfort questionnaire data also supported the high muscle force findings, and also on force distribution on the handle due to contact stresses. This combined approach could be used to collect and report detailed early stage ergonomics data from user trials on patient care simulators. The approach is proposed for use by medical device designers at the design stage of new products using prototypes, but it could also be used on existing products with real patients.     

Obtaining complete 2 D view representation of polyhedra using concept of seedling single-view area

This article deals with construction of complete 2 D exact view models of polyhedral objects for visual identification systems. In particular, a new method and an algorithm views generation using the view sphere with perspective concept are described. A set of views generated by this method forms a complete view representation of the object. The method of ensuring completeness of the view representation by controlling covering of the view space (by single-view areas) is used in the presented algorithm. The perspective projection used for calculating the views, the total, tight covering of the view sphere by the single-view areas and -dimensionality of the views ensure, in our opinion, unambiguous and proper identification of polyhedral objects. The method consists in calculating single (any) view, determining the corresponding single-view area (so-called seedling single-view area) and then spiral propagation of neighbouring single-view areas until the whole view sphere is covered by them (i.e., until the border register containing the border between the covered and uncovered parts of the view sphere becomes empty). Having a complete set of single-view areas, we get a complete set of views as well. A method of determining single-view areas for convex polyhedra is also presented.     

Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders

Mental disorders represent common brain diseases characterized by substantial impairments of social and cognitive functions. The neurobiological causes and mechanisms of psychopathologies still have not been definitively determined. Various forms of brain proteinopathies, which include a disruption of protein conformations and the formation of protein aggregates in brain tissues, may be a possible cause behind the development of psychiatric disorders. Proteinopathies are known to be the main cause of neurodegeneration, but much less attention is given to the role of protein impairments in psychiatric disorders’ pathogenesis, such as depression and schizophrenia. For this reason, the aim of this review was to discuss the potential contribution of protein illnesses in the development of psychopathologies. The first part of the review describes the possible mechanisms of disruption to protein folding and aggregation in the cell: endoplasmic reticulum stress, dysfunction of chaperone proteins, altered mitochondrial function, and impaired autophagy processes. The second part of the review addresses the known proteins whose aggregation in brain tissue has been observed in psychiatric disorders (amyloid, tau protein, α-synuclein, DISC-1, disbindin-1, CRMP1, SNAP25, TRIOBP, NPAS3, GluA1, FABP, and ankyrin-G).     

Sensing Magnetic Field and Intermolecular Interactions in Diamagnetic Solution Using Residual Dipolar Couplings of Zephycandidine

An unusual residual dipolar coupling of methylene protons was recorded in NMR spectra because aromatic zephycandidine has preferential orientation at the external magnetic field. The observed splitting contains contribution from the dipole–dipole D-coupling and the anisotropic component of J-coupling. Absolute values of the anisotropy of magnetic susceptibility |Δχ_ax| are larger for protic solvents because of the hydrogen-bonding compared to aprotic solvents for which polar and dispersion forces are more important. The energy barrier for the reorientation due to hydrogen-bonding is 1.22 kJ/mol in methanol-d_4, 0.85 kJ/mol in ethanol-d₆ and 0.87 kJ/mol in acetic acid-d₆. In dimethyl sulfoxide-d₆, 1.08 kJ/mol corresponds to the interaction of solvent lone pair electrons with π-electrons of zephycandidine. This energy barrier decreases for acetone-d₆ which has smaller electric dipole moment. In acetonitrile-d₃, there is no energy barrier which suggests solvent ordering around the solute due to the solvent-solvent interactions. The largest absolute values of the magnetic anisotropy are observed for aromatic benezene-d₆ and tolune-d₈ which have their own preferential orientation and enhance the order in the solution. The magnetic anisotropy of “isolated” zephycandidine, not hindered by intermolecular interaction could be estimated from the correlation between Δχ_ax and cohesion energy density.