Bisphenol-A Exposure Induced Neurotoxicity and Synapse and Cytoskeleton Dysfunction in Neuro-2a Cells

Bisphenol A (BPA) is one of the typical environmental endocrine disruptors. BPA was leached from polycarbonate containers into food and water, and it has been detected in collective samples from humans. Microtubule-associated protein 2 (MAP2) and Tau maintain microtubule normal function and promote the normal development of the nervous system. Synaptophysin (SYP) and drebrin (Dbn) proteins are involved in regulating synaptic plasticity. This study aimed to determine the adverse effects of BPA on Neuro-2a cells by investigating the synaptic and cytoskeletal damage. Cells were exposed to 0 (Minimum Essential Medium, MEM), 0.01% (v/v) DMSO and 150 µM BPA for 12, 24, or 36 h. Morphological analysis revealed that the cells in the BPA-treated groups shrank, collapsed, and had a reduced number of synapses compared with those in the control groups. CCK-8 and LDH assays showed that the mortality of Neuro-2a cells increased as the BPA treatment time was prolonged. Transmission electron microscopic analysis further revealed that cells demonstrated nucleolar swelling and nuclear membrane and partial mitochondrial dissolution or condensation following BPA exposure. BPA also significantly decreased the relative protein expression levels of MAP2, Tau, and Dbn (P < 0.01). Interestingly, the relative protein expression levels of SYP increased (P < 0.01). These results indicated that BPA damaged the development and proliferation of Neuro-2a cells by disrupting cytoskeleton and synaptic integrity.

Functionally-oriented composite layered materials with martensitic transformations

The studies carried out show that the task of ensuring the reliability and expanding the functionality of products operating under multifactorial effects (temperature, force, deformation) can be successfully solved by functionally oriented surface composite materials with thermoelastic martensitic transformations (TMT). The authors proposed the technology of layer-by-layer synthesis of functionally-oriented composite layered materials with TMT in argon environment, implemented on patented equipment in a single technological cycle. This technology determines not only the novelty, but also the economic feasibility of technical solutions. We also suggested step-by-step methods of thermal and thermomechanical treatment of composite layered materials with TMT, which contribute to the structure stabilization while decreasing residual stress. On the basis of complex X-ray diffraction and electron microscopic studies, we determined the structural parameters of High Velocity Oxy-Fuel (HVOF) materials obtained by HVOF with subsequent thermal and thermomechanical treatment and ceramic materials ZrO2-Y2O3-CeO2-Al2O3 stabilized with Al2O3 with subsequent heat treatment. We investigated the microhardness of surface high-entropy and ceramic materials. Tests for "friction-wear" and mechanical high-cycle fatigue of steels with a composite surface laminate showed decrease in the wear rate and increase in the cyclic durability.

Sorting Nexin 24 is required for α-granule biogenesis and cargo delivery in megakaryocytes

Germline defects affecting the DNA-binding domain of the transcription factor FLI1 are associated with a bleeding disorder that is characterised by the presence of large, fused α-granules in platelets. We investigated whether the genes showing abnormal expression in FLI1-deficient platelets could be involved in platelet α-granule biogenesis by undertaking transcriptome analysis of control platelets and platelets harbouring a DNA-binding variant of FLI1. Our analysis identified 2276 transcripts that were differentially expressed in FLI1- deficient platelets. Functional annotation clustering of the coding transcripts revealed significant enrichment for gene annotations relating to protein transport, and identified Sorting nexin 24 (SNX24) as a candidate for further investigation. Using an iPSC-derived megakaryocyte model, SNX24 expression was found to be increased during the early stages of megakaryocyte differentiation and downregulated during proplatelet formation, indicating tight regulatory control during megakaryopoiesis. CRISPR-Cas9 mediated knockout (KO) of SNX24 led to decreased expression of immature megakaryocyte markers, CD41 and CD61, and increased expression of the mature megakaryocyte marker CD42b (p=0.0001), without affecting megakaryocyte polyploidisation, or proplatelet formation. Electron microscopic analysis revealed an increase in empty membrane-bound organelles in SNX24 KO megakaryocytes, a reduction in α-granules and an absence of immature and mature multivesicular bodies, consistent with a defect in the intermediate stage of α-granule maturation. Co-localisation studies showed that SNX24 associates with each compartment of α-granule maturation. Reduced expression of CD62P and VWF was observed in SNX24 KO megakaryocytes. We conclude that SNX24 is required for α-granule biogenesis and intracellular trafficking of α-granule cargo within megakaryocytes.

8 Å structure of the outer rings of the Xenopus laevis nuclear pore complex obtained by cryo-EM and AI

The nuclear pore complex (NPC), one of the largest protein complexes in eukaryotes, serves as a physical gate to regulate nucleocytoplasmic transport. Here, we determined the 8 Å resolution cryo-electron microscopic (cryo-EM) structure of the outer rings containing nuclear ring (NR) and cytoplasmic ring (CR) from the Xenopus laevis NPC, with local resolutions reaching 4.9 Å. With the aid of AlphaFold2, we managed to build a pseudoatomic model of the outer rings, including the Y complexes and flanking components. In this most comprehensive and accurate model of outer rings to date, the almost complete Y complex structure exhibits much tighter interaction in the hub region. In addition to two copies of Y complexes, each asymmetric subunit in CR contains five copies of Nup358, two copies of the Nup214 complex, two copies of Nup205 and one copy of newly identified Nup93, while that in NR contains one copy of Nup205, one copy of ELYS and one copy of Nup93. These in-depth structural features represent a great advance in understanding the assembly of NPCs.

A Century of Brain Regeneration Phenomena and Neuromorphological Research Advances, 1890s–1990s—Examining the Practical Implications of Theory Dynamics in Modern Biomedicine

The modern thesis regarding the “structural plastic” properties of the brain, as reactions to injuries, to tissue damage, and to degenerative cell apoptosis, can hardly be seen as expendable in clinical neurology and its allied disciplines (including internal medicine, psychiatry, neurosurgery, radiology, etc.). It extends for instance to wider research areas of clinical physiology and neuropsychology which almost one hundred years ago had been described as a critically important area for the brain sciences and psychology alike. Yet the mounting evidence concerning the range of structural neuroplastic phenomena beyond the significant early 3 years of childhood has shown that there is a progressive building up and refining of neural circuits in adaptation to the surrounding environment. This review essay explores the history behind multiple biological phenomena that were studied and became theoretically connected with the thesis of brain regeneration from Santiago Ramón y Cajal’s pioneering work since the 1890s to the beginning of the American “Decade of the Brain” in the 1990s. It particularly analyzes the neuroanatomical perspectives on the adaptive capacities of the Central Nervous System (CNS) as well as model-like phenomena in the Peripheral Nervous System (PNS), which were seen as displaying major central regenerative processes. Structural plastic phenomena have assumed large implications for the burgeoning field of regenerative or restorative medicine, while they also pose significant epistemological challenges for related experimental and theoretical research endeavors. Hereafter, early historical research precursors are examined, which investigated brain regeneration phenomena in non-vertebrates at the beginning of the 20th century, such as in light microscopic studies and later in electron microscopic findings that substantiated the presence of structural neuroplastic phenomena in higher cortical substrates. Furthermore, Experimental physiological research in hippocampal in vivo models of regeneration further confirmed and corroborated clinical physiological views, according to which “structural plasticity” could be interpreted as a positive regenerative CNS response to brain damage and degeneration. Yet the underlying neuroanatomical mechanisms remained to be established and the respective pathway effects were only conveyed through the discovery of neural stem cells in in adult mammalian brains in the early 1990s. Experimental results have since emphasized the genuine existence of adult neurogenesis phenomena in the CNS. The focus in this essay will be laid here on questions of the structure and function of scientific concepts, the development of research schools among biomedical investigators, as well as the impact of new data and phenomena through innovative methodologies and laboratory instruments in the neuroscientific endeavors of the 20th century.

The teratogenic effect of pregabalin on heart, liver and kidney in rats: a light microscopic, electron microscopic and immunohistochemical study

Background Pregabalin (PGB) was approved as new anti-epileptic drugs with little information about its teratogenic effect. Aim of the work to evaluate the developmental toxicity of PGB. Materials and methods 60 pregnant albino rats were divided into three groups. PGB (500 mg/kg body weight/day) was given to group II, PGB (1250 mg/kg body weight/day) was given to Group III and no medications were given to group I. The pups were normally delivered. Liver, kidney and heart specimens were prepared for histological, immunohistochemical, and morphometric studies. Results A dose of 500 mg of PGB had minimal toxic effects in the form of mild collagen deposition and moderate positive caspase-3 immunoexpression. PGB dose of 1250 mg/kg induced gross toxic effects in form of degenerated cardiac myofibres, ruptured blood vessels, vacuolations in the renal cortex, fibrosis and strong positive caspase-3 immunoexpression. Conclusion PGB at dose of 500 mg/kg revealed minimal toxic changes. PGB cause embryotoxicity in a dose-dependent manner, as the higher dose induced more degenerative changes.

Structural Heterogeneity of an Amorphous-Nanocrystalline Alloy Fe77Cu1Si16B6 in the Nanometer Range

In this article, an alloy of the Finemet type Fe77Cu1Si16B6 obtained by quenching from a liquid state (spinning method) in the initial state is investigated. The main research methods were scanning and transmission electron microscopy. Methods for describing multiscale structural heterogeneities in amorphous-nanocrystalline alloys have been developed, allowing the structural state to be described and its influence on the physicochemical and technical properties to be determined depending on the technological conditions for obtaining these alloys. Representation of electron microscopic images in the form of Fourier spectra made it possible to reveal the nature of the formation of short- and middle-order in amorphous-nanocrystalline alloys according to the principle of self-similar spatial structures. The analysis of electron microscopic images by integral Lebesgue measures revealed density fluctuations over the alloy volume, which corresponds to the hierarchical representation of structural inhomogeneities in amorphous metallic alloys.

Structural insights into an evolutionary turning-point of photosystem I from prokaryotes to eukaryotes

Photosystem I (PSI) contributes to light-conversion reactions; however, its oligomerization state is variable among photosynthetic organisms. Herein we present a 3.8-Å resolution cryo-electron microscopic structure of tetrameric PSI isolated from a glaucophyte alga Cyanophora paradoxa. The PSI tetramer is organized in a dimer of dimers form with a C2 symmetry. Different from cyanobacterial PSI tetramer, two of the four monomers are rotated around 90°, resulting in a totally different pattern of monomer-monomer interactions. Excitation-energy transfer among chlorophylls differs significantly between Cyanophora and cyanobacterial PSI tetramers. These structural and spectroscopic features reveal characteristic interactions and energy transfer in the Cyanophora PSI tetramer, thus offering an attractive idea for the changes of PSI from prokaryotes to eukaryotes.