Exercise during pregnancy mitigates Alzheimer-like pathology in mouse offspring

Physical activity protects brain function in healthy individuals and those with Alzheimer's disease (AD). Evidence for beneficial effects of parental exercise on the health status of their progeny is sparse and limited to nondiseased individuals. Here, we questioned whether maternal running interferes with offspring's AD-like pathology and sought to decipher the underlying mechanisms in TgCRND8 mice. Maternal stimulation was provided by voluntary wheel running vs. standard housing during pregnancy. Following 5 mo of standard housing of transgenic and wild-type offspring, their brains were examined for AD-related pathology and/or plasticity changes. Running during pregnancy reduced β-amyloid (Aβ) plaque burden (-35%, P=0.017) and amyloidogenic APP processing in transgenic offspring and further improved the neurovascular function by orchestrating different Aβ transporters and increasing angiogenesis (+29%, P=0.022). This effect was accompanied by diminished inflammation, as indicated by reduced microgliosis (-20%, P=0.002) and down-regulation of other proinflammatory mediators, and resulted in less oxidative stress, as nitrotyrosine levels declined (-28%, P=0.029). Moreover, plasticity changes (in terms of up-regulation of reelin, synaptophysin, and ARC) were found not only in transgenic but also in wild-type offspring. We conclude that exercise during pregnancy provides long-lasting protection from neurodegeneration and improves brain plasticity in the otherwise unstimulated progeny.     

Soybeans Grown in the Chernobyl Area Produce Fertile Seeds that Have Increased Heavy Metal Resistance and Modified Carbon Metabolism

Plants grow and reproduce in the radioactive Chernobyl area, however there has been no comprehensive characterization of these activities. Herein we report that life in this radioactive environment has led to alteration of the developing soybean seed proteome in a specific way that resulted in the production of fertile seeds with low levels of oil and β-conglycinin seed storage proteins. Soybean seeds were harvested at four, five, and six weeks after flowering, and at maturity from plants grown in either non-radioactive or radioactive plots in the Chernobyl area. The abundance of 211 proteins was determined. The results confirmed previous data indicating that alterations in the proteome include adaptation to heavy metal stress and mobilization of seed storage proteins. The results also suggest that there have been adjustments to carbon metabolism in the cytoplasm and plastids, increased activity of the tricarboxylic acid cycle, and decreased condensation of malonyl-acyl carrier protein during fatty acid biosynthesis.     

Increased contribution of N-methyl-D-aspartate receptors to synaptic transmission inCA1 area of the rat hippocampus after short-term episodes of hypoxia/aglycemia

Effect of hypoxia/aglycemia episodes on excitatory postsynaptic currents (EPSC) evoked in pyramidal neurons of the rat hippocampalCA1 area by electrical stimulation of Schaffer collaterals was studied using voltage-clamp and intracellular perfusion techniques. By 60–80 min after a 10-min-long hypoxia/aglycemia episode, the EPSC amplitude increased and the EPSC decay was considerably slowed down, if compared with control. In contrast to control conditions, under which EPSC decay kinetics did not depend on the stimulus strength, hypoxia/aglycemia was followed by slowing down of the EPSC decay when stimulus intensity increased. The stimulus-dependent posthypoxic “slow” EPSC component was depressed both by D-(−)-2-amino-5-phosphonovaleric acid, an NMDA receptor blocker, and by 6-cyano-7-nitroquinoline-2,3-dion, a non-NMDA receptor blocker, which suggested possible polysynaptic origin of the above EPSC component. We suggest that short-term hypoxia/aglycemia transforms into an active state the NMDA receptors in the synapses of excitatory reccurrent collaterals of theCA1 hippocampal area, which had not functioned before. An increase in the intracellular calcium concentration from 1.5 to 5.0 mM resulted in the effect similar to that produced by hypoxia/aglycemia, which suggests that calcium channels play an important role in the mechanisms responsible for hypoxia-related activation of “silent” NMDA receptors.     

Structural basis for Myf and Psa fimbriae‐mediated tropism of pathogenic strains of Yersinia for host tissues

Three pathogenic species of the genus Yersinia assemble adhesive fimbriae via the FGL‐chaperone/usher pathway. Closely related Y. pestis and Y. pseudotuberculosis elaborate the pH6 antigen (Psa), which mediates bacterial attachment to alveolar cells of the lung. Y. enterocolitica, instead, assembles the homologous fimbriae Myf of unknown function. Here, we discovered that Myf, like Psa, specifically recognizes β1‐3– or β1‐4–linked galactose in glycosphingolipids, but completely lacks affinity for phosphatidylcholine, the main receptor for Psa in alveolar cells. The crystal structure of a subunit of Psa (PsaA) complexed with choline together with mutagenesis experiments revealed that PsaA has four phosphatidylcholine binding pockets that enable super‐high‐avidity binding of Psa‐fibres to cell membranes. The pockets are arranged as six tyrosine residues, which are all missing in the MyfA subunit of Myf. Conversely, the crystal structure of the MyfA‐galactose complex revealed that the galactose‐binding site is more extended in MyfA, enabling tighter binding to lactosyl moieties. Our results suggest that during evolution, Psa has acquired a tyrosine‐rich surface that enables it to bind to phosphatidylcholine and mediate adhesion of Y. pestis/pseudotuberculosis to alveolar cells, whereas Myf has specialized as a carbohydrate‐binding adhesin, facilitating the attachment of Y. enterocolitica to intestinal cells.     

Solution structure of monomeric and trimeric photosystem I of <Emphasis Type="Italic">Thermosynechococcus elongatus</Emphasis> investigated by small-angle X-ray scattering

The structure of monomeric and trimeric photosystem I (PS I) of Thermosynechococcus elongatus BP1 (T. elongatus) was investigated by small-angle X-ray scattering (SAXS). The scattering data reveal that the protein–detergent complexes possess radii of gyration of 58 and 78 Å in the cases of monomeric and trimeric PS I, respectively. The results also show that the samples are monodisperse, virtually free of aggregation, and contain empty detergent micelles. The shape of the protein–detergent complexes can be well approximated by elliptical cylinders with a height of 78 Å. Monomeric PS I in buffer solution exhibits minor and major radii of the elliptical cylinder of about 50 and 85 Å, respectively. In the case of trimeric PS I, both radii are equal to about 110 Å. The latter model can be shown to accommodate three elliptical cylinders equal to those describing monomeric PS I. A structure reconstitution also reveals that the protein–detergent complexes are larger than their respective crystal structures. The reconstituted structures are larger by about 20 Å mainly in the region of the hydrophobic surfaces of the monomeric and trimeric PS I complexes. This seeming contradiction can be resolved by the addition of a detergent belt constituted by a monolayer of dodecyl-β-D-maltoside molecules. Assuming a closest possible packing, a number of roughly 1024 and 1472 detergent molecules can be determined for monomeric and trimeric PS I, respectively. Taking the monolayer of detergent molecules into account, the solution structure can be almost perfectly modeled by the crystal structures of monomeric and trimeric PS I.     

Synthesis,crystal structure and magnetic properties of the spin crossover system [Fe(pq)3]2+

Three new compounds formulated (ClO₄)₂[Fe(pq)₃] (1), (BF₄)₂[Fe(pq)₃] · EtOH (2) and {(ClO₄)[MnCr(C₂O₄)₃][Fe(pq)₂(H₂O)₂]} (3), where pq is 2,2′-pyridylquinoline, have been synthesised and characterised. Despite the different crystal packing exhibited by 1 and 2, the cationic species [Fe(pq)₃]²⁺ are structurally quite similar. At 293 K, the Fe–N bond lengths are characteristic of the iron(II) in the high-spin state. In contrast to 1, 2 undergoes a continuous spin transition. Indeed, at 95 K its structure experiences a noticeable change in the Fe–N bonds and angles, i.e. the Fe–N bonds shorten by 0.194 Å on the average. The magnetic behaviour confirms that 1 is fully high-spin in the 4–300 K temperature range while 2 shows a spin transition centred at T_1/2 = 150 K. The corresponding enthalpy, entropy and interaction parameter are ΔH = 7.49 kJ mol^?1, ΔS = 50 J K^?1 mol^?1and Γ = 1.35 kJ mol^?1. Compound 3 has been obtained as a microcrystalline powder. The magnetic properties of 3 point at the occurrence of ferromagnetic coupling below 100 K and the onset of a ferromagnetic ordering below 10 K (Weiss constant equal to 6.8 K). The Mössbauer spectra of 3 show the occurrence of a magnetic order at T ? 4.2 K.     

Targeted tandem affinity purification of PSD‐95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins

The molecular complexity of mammalian proteomes demands new methods for mapping the organization of multiprotein complexes. Here, we combine mouse genetics and proteomics to characterize synapse protein complexes and interaction networks. New tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD‐95 using gene targeting in mice. Homozygous mice showed no detectable abnormalities in PSD‐95 expression, subcellular localization or synaptic electrophysiological function. Analysis of multiprotein complexes purified under native conditions by mass spectrometry defined known and new interactors: 118 proteins comprising crucial functional components of synapses, including glutamate receptors, K⁺ channels, scaffolding and signaling proteins, were recovered. Network clustering of protein interactions generated five connected clusters, with two clusters containing all the major ionotropic glutamate receptors and one cluster with voltage‐dependent K⁺ channels. Annotation of clusters with human disease associations revealed that multiple disorders map to the network, with a significant correlation of schizophrenia within the glutamate receptor clusters. This targeted TAP tagging strategy is generally applicable to mammalian proteomics and systems biology approaches to disease.     

The negative effect of magnetic nanoparticles with ascorbic acid on peritoneal macrophages

Neurochemical Research - Superparamagnetic iron oxide nanoparticles (SPIOn) are widely used as a contrast agent for cell labeling. Macrophages are the first line of defense of organisms in contact...     

Benchmark of different charges for prediction of the partitioning coefficient through the hydrophilic/lipophilic index

A few different theoretical methods for assigning the partial atomic charges were benchmarked for calculation of the hydrophilic/lipophilic index (HLI). The coefficients were selected to produce the best correlation of the HLI values with the experimental octanol-water partition. Different parameters were checked in calculations of partial charges to get the best performance of the HLI values obtained. Thus, four partitioning schemes (Coulson, Mulliken, Merz-Kollman, Ford-Wang) were benchmarked for calculations of atomic charges with six semiempirical methods (AM1, PM3, RM1, PM6, PM6-D3H4, PM7). Moreover, five distinct types of partial atomic charges (Mulliken, Hirshfeld, Löwdin, CHELPG, NPA), obtained at the Hartree–Fock and DFT levels of theory with three basis sets, were tested for their ability to produce the HLI values with the best correlation to experimental logP coefficients of 50 mono-charged organic anions. In the case of the semiempirical methods, the best correlation between the HLI and logP values (the correlation coefficient r?=?0.9216) was obtained with the AM1 Ford–Wang parametric electrostatic potential charges. The Mulliken and Coulson charges calculated with the PM7 method can be used as an alternative to AM1, with the r values of 0.9107 and 0.8984, respectively. In the case of the DFT, the PBE/def2-TZVP natural population analysis charges produce the best correlation (r?=?0.9220). Nevertheless, in spite of a marginally lower performance (r?=?0.9159), the NPA charges computed at the PBE/def2-SVP level are more robust and can be regarded as the optimum choice for calculating the HLI values.

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Graphical abstract The hydrophilic/lipophilic index (HLI)