Quantitative Assessment of Serine-8 Phosphorylated β-Amyloid Using MALDI-TOF Mass Spectrometry

The study of the molecular mechanisms of the pathogenesis of Alzheimer’s disease (AD) is extremely important for identifying potential therapeutic targets as well as early markers. In this regard, the study of the role of post-translational modifications (PTMs) of β-amyloid (Aβ) peptides is of particular relevance. Serine-8 phosphorylated forms (pSer8-Aβ) have been shown to have an increased aggregation capacity and may reflect the severity of amyloidosis. Here, an approach for quantitative assessment of pSer8-Aβ based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is proposed. The relative fraction of pSer8-Aβ was estimated in the total Aβ-pool with a detection limit of 1 fmol for pSer8-Aβ (1–16) and an accuracy of 2% for measurements in the reflectron mode. The sensitivity of the developed method is suitable for determining the proportion of phosphorylated peptides in biological samples.     

Tricyclic derivatives of bispidine as AMPA receptor allosteric modulators

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Structural Dynamics and Stereoselectivity of Chiral Benzylideneamine N,C-Chelate Borane Photo–Thermal Isomerization

New chiral N,C-chelate organoboron compounds based on benzylideneamines (bza) with the general formula of B(bza-R)Mes₂ (R=H or Me; Mes=mesityl) are reported. A chiral substituent group R- or S-CH(CH₃)Ph (Ph=phenyl) was introduced to the imine center, which imposed a previously unobserved pseudo- or axial-chirality on the BMes₂, creating distinct diastereomers. NMR spectroscopic studies established that the diastereomers undergo slow exchange in solution at ambient temperature. The chiral N,C-chelate B(bza-R)Mes₂ molecules undergo photoisomerization in the same manner as their non-chiral analogues, generating chiral BN-cyclooctatriene (BN-COT) derivatives. Most significantly, by tracking the photoisomerization with circular dichroism (CD) and ¹H NMR spectra along with time-dependent density functional theory (TD-DFT) computational studies, the photoisomerization was established to proceed in a highly stereoselective manner, that is, one diastereomer converts exclusively to the corresponding diastereomer product in the photoreaction.     

On a notion of partially conditionally identically distributed sequences

A notion of conditionally identically distributed (c.i.d.) sequences has been studied as a form of stochastic dependence weaker than exchangeability, but equivalent to it in the presence of stationarity. We extend such notion to families of sequences. Paralleling the extension from exchangeability to partial exchangeability in the sense of de Finetti, we propose a notion of partially c.i.d. dependence, which is shown to be equivalent to partial exchangeability for stationary processes. Partially c.i.d. families of sequences preserve attractive limit properties of partial exchangeability, and are asymptotically partially exchangeable. Moreover, we provide strong laws of large numbers and two central limit theorems. Our focus is on the asymptotic agreement of predictions and empirical means, which lies at the foundations of Bayesian statistics. Natural examples of partially c.i.d. constructions are interacting randomly reinforced processes satisfying certain conditions on the reinforcement.     

A study of Galerkin method for the heat convection equations

The paper investigates the Galerkin method for an initial boundary value problem for heat convection equations. New error estimates for the approximate solutions and their derivatives in strong norm are obtained.     

Asymmetric synthesis and molecular docking study of enantiomerically pure pyrrolidine derivatives with potential antithrombin activity

The (2R,4R,5S)- and (2S,4S,5R)-enantiomers of 4-(tert-butyl) 2-methyl 5-(4-bromophenyl)-pyrrolidine-2,4-dicarboxylate 3 were synthesized efficiently with an ee of >90% on a gram scale using a FAM-catalytic methodology. Subsequent modification afforded enantiopure N-((4-chlorophenyl)thio)acetyl pyrrolidine derivatives 4, which are potential thrombin inhibitors according to comprehensive molecular docking studies.     

Bispidinone-based molecular switches for construction of stimulus-sensitive liposomal containers

It is demonstrated that new lipid-like amphiphilic compounds, derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one (bispidinone) with long alkyl substituents, can be integrated into liposomal membranes. They can serve as molecular switches changing the conformation from the chair–boat to chair–chair on addition of an aqueous solution of a bivalent copper salt, and thus enhancing the permeability of the lipid bilayer of liposomes and the release of encapsulated compounds.