Iron metabolism in diabetes-induced Alzheimer’s disease: a focus on insulin resistance in the brain

Alzheimer’s disease (AD) is characterized by an excessive accumulation of toxic amyloid beta (Aβ) plaques and memory dysfunction. The onset of AD is influenced by age, genetic background, and impaired glucose metabolism in the brain. Several studies have demonstrated that diabetes involving insulin resistance and glucose tolerance could lead to AD, ultimately resulting in cognitive dysfunction. Even though the relationship between diabetes and AD was indicated by significant evidences, the critical mechanisms and metabolic alterations in diabetes induced AD are not clear until now. Recently, iron metabolism has been shown to play multiple roles in the central nervous system (CNS). Iron deficiency and overload are associated with neurodegenerative diseases. Iron binds to Aβ and subsequently regulates Aβ toxicity in the CNS. In addition, previous studies have shown that iron is involved in the aggravation of insulin resistance. Considering these effects of iron metabolism in CNS, we expect that iron metabolism may play crucial roles in diabetic AD brain. Thus, we review the recent evidence regarding the relationship between diabetes-induced AD and iron metabolism.     

Effect of cement industry flue gas simulation on the physiology and photosynthetic performance of <Emphasis Type="Italic">Chlorella sorokiniana</Emphasis>

Cement plants account for significant emissions of CO₂ and other pollutants into the atmosphere. As a means for its mitigation, we tested the effect of a cement industry-based flue gas simulation (FGS — 18% CO₂, 9% O₂, 300 ppm NO₂, 140 ppm SO₂) on the green alga, Chlorella sorokiniana. Culture pH, cell density, cell viability and productivity, specific growth rates, photosynthetic performance, and biochemical composition were monitored. The treatments consisted of different FGS volumes (0.1, 0.3, 0.8, 1.5, 6, and 48 L day^?1) that were applied in a series of laboratory-scale semi-continuous batch cultures under controlled conditions. Controls were exposed to 18% CO₂ enriched air. Cell density showed that C. sorokiniana was able to grow in all treatments, but compared to the controls, low pH (~ 5.0) caused by 48 L FGS day^?1 led to 27% decrease in specific growth rate. Increasing FGS exposure decreased maximum and operational quantum yields obtained by pulse amplitude modulated fluorometry, while photochemical quenching remained constant (~ 0.93). The α and rETR _max parameters calculated from rapid light curves decreased with increasing FGS exposure. Total proteins and carbohydrates (per cell basis) increased after 6 and 48 L FGS day^?1, which can be advantageous for biotechnological applications, but cell productivity (cells L^?1 day^?1) decreased. Despite the effects in physiology, C. sorokiniana could withstand a pH range of 6.0–5.0 imposed by 48 L FGS day^?1. Overall, C. sorokiniana can be considered a robust species in flue gas bioremediation.     

Enhanced resistance to citrus canker in transgenic mandarin expressing Xa21 from rice

Genetic engineering approaches offer an alternative method to the conventional breeding of Citrus sp. ‘W. Murcott’ mandarin (a hybrid of ‘Murcott’ and an unknown pollen parent) is one of the most commercially important cultivars grown in many regions around the world. Transformation of ‘W. Murcott’ mandarin was achieved by direct DNA uptake using a protoplast transformation system. DNA construct (pAO3), encoding Green Fluorescent Protein (GFP) and the cDNA of Xa21, a Xanthomonas resistance gene from rice, was used to transform protoplasts of ‘W. Murcott’ mandarin. Following citrus protoplast culture and regeneration, transformed micro calli were microscopically designated via GFP expression, physically isolated from non-transformed tissue, and cultured on somatic embryogenesis induction medium. More than 150 transgenic embryos were recovered and from them, ten transgenic lines were regenerated and cultured on rooting medium for shoot elongation. Transgenic shoots were micrografted and established in the greenhouse with 3–5 replicates per line. The insertion of Xa21 and GFP was confirmed by PCR and southern blot analysis. GFP expression was verified by fluorescence microscopy and western blot analysis revealed expression of Xa21 although it was variable among transgenic lines, as shown by RT-qPCR. Transgenic plants challenged with the citrus canker pathogen by syringe inoculation showed a reduction in lesion number and bacterial populations within lesions compared to non-transgenic control plants. Transgenic ‘W. Murcott’ mandarin lines with improved canker resistance via protoplast transformation from embryogenic callus with the Xa21 gene from rice are being evaluated under field conditions to validate the level of resistance.     

The Protective Effect of Selenium on Bovine Mammary Epithelial Cell Injury Caused by Depression of Thioredoxin Reductase

To elucidate the effect of selenium (Se) on antioxidant function of mammary glands in dairy cows and the underlying mechanism, an experiment was conducted using a single-factor completely randomized design study. Bovine mammary epithelial cells (BMECs) were randomly divided into four groups: control, Se treatment, 2,4-dinitrochlorobenzene (DNCB) inhibition, and Se prevention. Treatment of BMECs with Se was found to significantly reverse decreased cell proliferation and the expression of thioredoxin reductase (TrxR) after DNCB exposure. DNCB-induced activation of apoptosis signaling kinase-1 (ASK-1), which activates the mitogen-activated protein kinase (MAPK) pathway, was reduced in BMECs treated with Se. Additionally, our results indicated that Se treatment resulted in lower intracellular accumulation of arachidonic acid (ARA) and 15-hydroperoxyeicosatetraenoic acid (15-HPETE) due to suppressed expression of cytosolic phospholipase A₂ (cPLA₂) regulated by p38MAPK and c-Jun N-terminal kinase (JNK) in DNCB-stimulated BMECs. Taken together, these findings suggest that Se treatment improved the antioxidant function of dairy cow mammary glands and protected cells from oxidative damage primarily by increasing the activity of TrxR, inhibiting the activation of the MAPK signaling pathway, and thus decreasing the content of ARA and its related metabolites.     

Genome-wide association study identified genetic variations and candidate genes for plant architecture component traits in Chinese upland cotton

Key message

Thirty significant associations between 22 SNPs and five plant architecture component traits in Chinese upland cotton were identified via GWAS. Four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits. A candidate gene, Gh_D03G0922, might be responsible for plant height in upland cotton.

Abstract

A compact plant architecture is increasingly required for mechanized harvesting processes in China. Therefore, cotton plant architecture is an important trait, and its components, such as plant height, fruit branch length and fruit branch angle, affect the suitability of a cultivar for mechanized harvesting. To determine the genetic basis of cotton plant architecture, a genome-wide association study (GWAS) was performed using a panel composed of 355 accessions and 93,250 single nucleotide polymorphisms (SNPs) identified using the specific-locus amplified fragment sequencing method. Thirty significant associations between 22 SNPs and five plant architecture component traits were identified via GWAS. Most importantly, four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits, and these SNPs were harbored in one linkage disequilibrium block. Furthermore, 21 candidate genes for plant architecture were predicted in a 0.95-Mb region including the four peak SNPs. One of these genes (Gh_D03G0922) was near the significant SNP D03_31584163 (8.40 kb), and its Arabidopsis homologs contain MADS-box domains that might be involved in plant growth and development. qRT-PCR showed that the expression of Gh_D03G0922 was upregulated in the apical buds and young leaves of the short and compact cotton varieties, and virus-induced gene silencing (VIGS) proved that the silenced plants exhibited increased PH. These results indicate that Gh_D03G0922 is likely the candidate gene for PH in cotton. The genetic variations and candidate genes identified in this study lay a foundation for cultivating moderately short and compact varieties in future Chinese cotton-breeding programs.

     

Insights into the fluoride-resistant regulation mechanism of <Emphasis Type="Italic">Acidithiobacillus ferrooxidans</Emphasis> ATCC 23270 based on whole genome microarrays

Acidophilic microorganisms involved in uranium bioleaching are usually suppressed by dissolved fluoride ions, eventually leading to reduced leaching efficiency. However, little is known about the regulation mechanisms of microbial resistance to fluoride. In this study, the resistance of Acidithiobacillus ferrooxidans ATCC 23270 to fluoride was investigated by detecting bacterial growth fluctuations and ferrous or sulfur oxidation. To explore the regulation mechanism, a whole genome microarray was used to profile the genome-wide expression. The fluoride tolerance of A. ferrooxidans cultured in the presence of FeSO₄ was better than that cultured with the S⁰ substrate. The differentially expressed gene categories closely related to fluoride tolerance included those involved in energy metabolism, cellular processes, protein synthesis, transport, the cell envelope, and binding proteins. This study highlights that the cellular ferrous oxidation ability was enhanced at the lower fluoride concentrations. An overview of the cellular regulation mechanisms of extremophiles to fluoride resistance is discussed.     

The Evolution of the Ribonucleotide Reductases: Much Ado About Oxygen

Ribonucleotide reduction is the only known biological means for de novo production of deoxyribonucleotides, the building blocks of DNA. These are produced from ribonucleotides, the building blocks of RNA, and the direction of this reaction has been taken to support the idea that, in evolution, RNA preceded DNA as genetic material. However, an understanding of the evolutionary relationships among the three modern-day classes of ribonucleotide reductase and how the first reductase arose early in evolution is still far off. We propose that the diversification of this class of enzymes is inherently tied to microbial colonization of aerobic and anaerobic niches. The work is of broader interest, as it also sheds light on the process of adaptation to oxygenic environments consequent to the evolution of atmospheric oxygen.     

Effects of Dexmedetomidine and Oxycodone on Neurocognitive and Inflammatory Response After Tourniquet-Induced Ischemia–Reperfusion Injury

To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia–reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n?=?48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p < 0.05), while Oxy had no significant effect on it. Compared with I/R group, Dex and Oxy treatment down-regulated the expression of NF-κB, TLR4, TNF-α and CD68 (all p < 0.05), while no significantly different was found in CD206 and IL-10. In addition, Dex treatment down-regulated the expression of NR2B and reduced the frequency and amplitude of sEPSCs in I/R model mice (all p < 0.05), while Oxy had no significant effect on them. Tourniquet-induced I/R could impair the neurocognitive function of mice. Dex treatment could alleviate I/R-induced neurocognitive disorder by inhibiting abnormal synaptic transmission in hippocampal neurons. Both Dex and Oxy could alleviate the inflammatory response likely by inhibiting the polarization of microglia toward M1 phenotype via TLR4/NF-κB pathway. Future studies are needed to further examine the effects of Dex on neurocognitive disorder after tourniquet-induced I/R injury and investigate the exact mechanism.

     

Neuroprotection of Bone Marrow-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicle-Enclosed miR-410 Correlates with HDAC4 Knockdown in Hypoxic-Ischemic Brain Damage

Neurochemical Research - Evidence exists reporting that miR-410 may rescue neurological deficits, neuronal injury, and neuronal apoptosis after experimental hypoxic ischemia. This study aimed to...