Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc^−/−) and their wild type (Hdc^+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc^−/− and Hdc^+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc^+/+ mice as histamine deficiency prevented almost all the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.     

Characterization and leachability of electric arc furnace dust made from remelting of stainless steel

Electric arc furnace dust (EAFD) is a toxic waste product made in the remelting of scrap steel. The results of a Toxicity Characteristic Leaching Procedure (TCLP) conducted on a sample of EAFD originating from the remelting of stainless steel scrap showed that the total Cr and Cr (VI) liquor concentrations (9.7 and 6.1 mg/L, respectively) exceeded the Toxicity Characteristic Regulatory Level (TCRL). The EAFD showed a complex heterogeneous mineralogy with spinel minerals group predominance. A sequential extractions method has permitted the determination of the amount of available metals (potentially mobile component) from the EAFD as follows: Cr (3%), Ni (6%), Pb (49%) and Zn (40%). Solubility controls on Cr, Pb, Zn and Ni were identified in the EAFD. This means that the Cr, Pb, Zn and Ni concentrations in solution were controlled by the solubility of some phases from EAFD. The concentrations of Ni and Zn, which are metals not regulated by TCRL were below 0.41 and 1.3 mg/L, respectively. The solubility control on Pb was sufficient to decrease its concentration (<0.24 mg/L) to a level below the TCRL. However, the control on Cr was not sufficient to decrease its concentration (between 117 and 331 mg/L) to below the TCRL.     

Cardiac- versus diaphragm-based respiratory navigation for proton spectroscopy of the heart

Magnetic Resonance Materials in Physics, Biology and Medicine - To study inter-individual differences of the relation between diaphragm and heart motion, the objective of the present study was to...     

Ramping down a clinical 3 T scanner: a journey into MRI and MRS at 0.75 T

Object

Lower-field MR is reemerging as a viable, potentially cost-effective alternative to high-field MR, thanks to advances in hardware, sequence design, and reconstruction over the past decades. Evaluation of lower field strengths, however, is limited by the availability of lower-field systems on the market and their considerable procurement costs. In this work, we demonstrate a low-cost, temporary alternative to purchasing a dedicated lower-field MR system.

Materials and Methods

By ramping down an existing clinical 3 T MRI system to 0.75 T, proton signals can be acquired using repurposed ¹³C transmit/receive hardware and the multi-nuclei spectrometer interface. We describe the ramp-down procedure and necessary software and hardware changes to the system.

Results

Apart from presenting system characterization results, we show in vivo examples of cardiac cine imaging, abdominal two- and three-point Dixon-type water/fat separation, water/fat-separated MR Fingerprinting, and point-resolved spectroscopy. In addition, the ramp-down approach allows unique comparisons of, e.g., gradient fidelity of the same MR system operated at different field strengths using the same receive chain, gradient coils, and amplifiers.

Discussion

Ramping down an existing MR system may be seen as a viable alternative for lower-field MR research in groups that already own multi-nuclei hardware and can also serve as a testing platform for custom-made multi-nuclei transmit/receive coils.

     

Carbon nanotube–polyaniline composites

The last decade has seen a growing interest in hybrid electrically conducting nanocomposites. This article aims to provide a detailed overview of the present status of research in carbon nanotube–polyaniline (CNT/PANI) composites, from processing to structural and property evaluations. CNT/PANI are synthesized by electrochemical and chemical processing. When chemical methods are used, the main challenge is to obtain processable CNT/PANI in the emeraldine salt (ES) form composites. Stable dispersions of ES–CNT in organic media are prepared using the post doping method, inverse emulsion polymerization, or ex situ polymerizations. On the contrary, stable water dispersions of CNT/ES are prepared using hydrophilization of a preformed CNT/ES composite, direct synthesis of micelle–CNT hybrid templates, interfacial polymerization, covalent functionalization of CNT with a water soluble polymer, or using electrostatic interactions between two oppositely charged ES and CNT aqueous colloids. Moreover, the strategies for the synthesis of ternary CNT/PANI composites incorporating noble metal nanoparticles, metal oxide, or graphene sheets are also presented and analyzed in depth. Finally, we give a review of potential applications, including chemical sensors, capacitors, fuel cells and electronic devices.     

Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells

The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.     

An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low-to-sub-micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex-bases) has been successfully coupled to both ribose and 2′-deoxyribose sugars by using the N-deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno-expanded tricyclic heterocyclic base, as well as several distal and proximal flex-bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.     

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.