Methylarsonous Acid Transport by Aquaglyceroporins

Many mammals methylate trivalent inorganic arsenic in liver to species that are released into the bloodstream and excreted in urine and feces. This study addresses how methylated arsenicals pass through cell membranes. We have previously shown that aquaglyceroporin channels, including Escherichia coli GlpF, Saccharomyces cerevisiae Fps1p, AQP7, and AQP9 from rat and human, conduct trivalent inorganic arsenic [As(III)] as arsenic trioxide, the protonated form of arsenite. One of the initial products of As(III) methylation is methylarsonous acid [MAs(III)], which is considerably more toxic than inorganic As(III). In this study, we investigated the ability of GlpF, Fps1p, and AQP9 to facilitate movement of MAs(III) and found that rat aquaglyceroporin conducted MAs(III) at a higher rate than the yeast homologue. In addition, rat AQP9 facilitates MAs(III) at a higher rate than As(III). These results demonstrate that aquaglyceroporins differ both in selectivity for and in transport rates of trivalent arsenicals. In this study, the requirement of AQP9 residues Phe-64 and Arg-219 for MAs(III) movement was examined. A hydrophobic residue at position 64 is not required for MAs(III) transport, whereas an arginine at residue 219 may be required. This is similar to that found for As(III), suggesting that As(III) and MAs(III) use the same translocation pathway in AQP9. Identification of MAs(III) as an AQP9 substrate is an important step in understanding physiologic responses to arsenic in mammals, including humans

Selenite inhibits notch signaling in cells and mice

Selenium is an essential micronutrient with a wide range of biological effects in mammals. The inorganic form of selenium, selenite, is supplemented to relieve individuals with selenium deficiency and to alleviate associated symptoms. Additionally, physiological and supranutritional selenite have shown selectively higher affinity and toxicity towards cancer cells, highlighting their potential to serve as chemotherapeutic agents or adjuvants. At varying doses, selenite extensively regulates cellular signaling and modulates many cellular processes. In this study, we report the identification of Delta–Notch signaling as a previously uncharacterized selenite inhibited target. Our transcriptomic results in selenite treated primary mouse hepatocytes revealed that the transcription of Notch1, Notch2, Hes1, Maml1, Furin and c-Myc were all decreased following selenite treatment. We further showed that selenite can inhibit Notch1 expression in cultured MCF7 breast adenocarcinoma cells and HEPG2 liver carcinoma cells. In mice acutely treated with 2.5 mg/kg selenite via intraperitoneal injection, we found that Notch1 expression was drastically lowered in liver and kidney tissues by 90% and 70%, respectively. Combined, these results support selenite as a novel inhibitor of Notch signaling, and a plausible mechanism of inhibition has been proposed. This discovery highlights the potential value of selenite applied in a pathological context where Notch is a key drug target in diseases such as cancer, fibrosis, and neurodegenerative disorders

In utero gene expression in the Slc39a8(neo/neo) knockdown mouse

Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10–15% of wild-type ZIP8 mRNA and protein levels, and show pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed RNA-seq analysis of gestational day (GD)13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum,comparing Slc39a8(neo/neo) with Slc39a8(+/+) wild-type. Meta-data analysis of differentially- expressed genes revealed 29 unique genes from all tissues — having enriched GO categories associated with hematopoiesis and hypoxia and KEGG categories of complement, response to infection, and coagulation cascade — consistent with dysregulated hematopoietic stem cell fate. Based on transcription factor (TF) profiles in the JASPAR database, and searching for TF-binding sites enriched by Pscan, we identified numerous genes encoding zinc-finger and other TFs associated with hematopoietic stem cell functions. We conclude that, in this mouse model, deficient ZIP8-mediated divalent cation transport affects zinc-finger (e.g. GATA proteins) and other TFs interacting with GATA proteins (e.g. TAL1), predominantly in yolk sac. These data strongly support the phenotype of dysmorphogenesis and anemia seen in Slc39a8(neo/neo) mice in utero

Arsenic transport by zebrafish aquaglyceroporins

<p>Abstract</p> <p>Background</p> <p>Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (As^III) is one of the major species that exists environmentally. The transport of As^IIIhas been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct As^IIIand its organic metabolite, monomethylarsenite (MAs^III). However, the transport of As^IIIand MAs^IIIin in any fish species has not been characterized.</p> <p>Results</p> <p>In this study, five members of the aquaglyceroporin family from zebrafish (<it>Danio rerio</it>) were cloned, and their ability to transport water, glycerol, and trivalent arsenicals (As^IIIand MAs^III) and antimonite (Sb^III) was investigated. Genes for at least seven aquaglyceroporins have been annotated in the zebrafish genome project. Here, five genes which are close homologues to human AQP3, AQP9 and AQP10 were cloned from a zebrafish cDNA preparation. These genes were named <it>aqp3, aqp3l, aqp9a, aqp9b </it>and <it>aqp10 </it>according to their similarities to the corresponding human AQPs. Expression of <it>aqp9a, aqp9b</it>, <it>aqp3, aqp3l </it>and <it>aqp10 </it>in multiple zebrafish organs were examined by RT-PCR. Our results demonstrated that these aquaglyceroporins exhibited different tissue expression. They are all detected in more than one tissue. The ability of these five aquaglyceroporins to transport water, glycerol and the metalloids arsenic and antimony was examined following expression in oocytes from <it>Xenopus leavis</it>. Each of these channels showed substantial glycerol transport at equivalent rates. These aquaglyceroporins also facilitate uptake of inorganic As^III, MAs^IIIand Sb^III. Arsenic accumulation in fish larvae and in different tissues from adult zebrafish was studied following short-term arsenic exposure. The results showed that liver is the major organ of arsenic accumulation; other tissues such as gill, eye, heart, intestine muscle and skin also exhibited significant ability to accumulate arsenic. The zebrafish larvae also accumulate considerable amounts of arsenic.</p> <p>Conclusion</p> <p>This is the first molecular identification of fish arsenite transport systems and we propose that the extensive expression of the fish aquaglyceroporins and their ability to transport metalloids suggests that aquaglyceroporins are the major pathways for arsenic accumulation in a variety of zebrafish tissues. Uptake is one important step of arsenic metabolism. Our results will contribute to a new understanding of aquatic arsenic metabolism and will support the use of zebrafish as a new model system to study arsenic associated human diseases.</p

Anatomical physiological and biochemical processes involved in grapevine rootstock drought tolerance

In order to explore the drought resistance mechanism of grape rootstocks, two grape rootstock species, '1103P' (a drought-tolerant rootstock) and '101-14M' (drought-sensitive), were treated with moderate water deficit (field capacity of 45-50 %). Throughout the experimental period, the leaves of '1103P' showed a higher stomatal conductance (gs), relative water content and photosynthetic rate (Pn) than '101-14M', indicating '1103P' was more resistant to tolerant than '101-14M'. We propose that '1103P' could prevent water loss from leaves under drought conditions based on the discoveries that '1103P' had higher leaf phytohormone abscisic acid (ABA) content and leaf cuticular wax content, and smaller stomata aperture than those of '101-14M'. Additionally, the activities of H2O2-scavenging enzymes in leaves of '1103P' were higher than those of '101-14M' under drought conditions, indicating the lipid peroxidation induced by H2O2 of '1103P' was less serious than that of '101-14M'. Therefore, better water-saving and higher reactive oxygen species (ROS) scavenging abilities contributed together to stronger drought resistance of '1103P' than '101-14M'

Chemically functionalised suspended-core fibre for ammonia gas detection

An optical fibre ammonia gas sensor utilising a functionalised four-leaf-clover-shaped suspended-core fibre (SCF) is demonstrated. The fibre is functionalised by depositing a thin layer of an ammonia sensitive dye (tetraphenylporphyrin tetrasulfonic acid hydrate) on the wall of the inner cavities of the SCF through capillary action. An in-line fibre sensing structure is designed for light transmission through the SCF and also allows gas exchange with the atmosphere through two porous polyethylene housings. The sensing structure exhibits a temperature-dependent transmission due to the thermal expansion of the housings. A ratiometric method is applied for signal processing which is demonstrated to reduce significantly the effect of temperature change in the tested range (20-30 C). The sensor is tested in ammonia concentration ranges from 0-10 ppm and demonstrates capability of detecting ammonia at ppb levels. The minimum tested concentration is 150 ppb in the experiment with a calculated limit of detection of 20 ppb. The sensor response time (T10-90%) is 160 s and it is demonstrated to be reusable after treatment with hydrogen chloride vapour. Numerical simulation of evanescent absorption features of such an SCF indicates that approximately 0.02% of the optical power exists in the air holes for the fundamental propagation mode. Distinctive absorption bands observed in the transmission spectrum of the fabricated sensor can also be observed in the simulated model after adding the TPPS absorption layer in the holes

Inositol transporters AtINT2 and AtINT4 regulate arsenic accumulation in Arabidopsis seeds

Arsenic is a global environmental contaminant that threatens tens of millions people world-wide via food and water. Understanding how arsenic is accumulated in crop seeds is of critical importance. To date, membrane transport proteins catalyzing arsenic uptake by roots and translocation through xylem to shoots have been characterized. However, no transporters responsible for loading arsenic from xylem into phloem and further unloading into plant seeds have been identified. In this study we demonstrate that expressing the gene for either Arabidopsis thaliana inositol transporter AtINT2 or AtINT4 in Saccharomyces cerevisiae leads to increased arsenic accumulation and elevated sensitivity to arsenite [As(III)], and Xenopus laevis oocytes expressing AtINT2 import As(III). When A. thaliana plants with disruptions in either AtINT2 or AtINT4 were supplemented with As(III) through roots, there was a substantial decrease in both the arsenic content in the phloem extrude and in total arsenic accumulation in siliques and seeds. Similarly, when As(III) is fed through the leaves, there was a very large decrease in arsenic accumulation in siliques and seeds compared with wild-type plants. These results clearly demonstrate that inositol transporters are responsible for As(III) loading into phloem, the key step regulating arsenic accumulation in seeds

Metal–organic frameworks and their derivatives for optimizing lithium metal anodes

Lithium metal anodes (LMAs) have been considered the ultimate anode materials for next-generation batteries. However, the uncontrollable lithium dendrite growth and huge volume expansion that can occur during charge and discharge seriously hinder the practical application of LMAs. Metal–organic framework (MOF) materials, which possess the merits of huge specific surface area, excellent porosity, and flexible composition/structure tunability, have demonstrated great potential for resolving both of these issues. This article first explores the mechanism of lithium dendrite formation as described by four influential models. Subsequently, based on an in-depth understanding of these models, we propose potential strategies for utilizing MOFs and their derivatives to suppress lithium dendrite growth. We then provide a comprehensive review of research progress with respect to various applications of MOFs and their derivatives to suppress lithium dendrites and inhibit volume expansion. The paper closes with a discussion of perspectives on future modifications of MOFs and their derivatives to achieve stable, dendrite-free lithium metal batteries

Effect of Oak Chip Aging on the Flavor of Persimmon Brandy

Mopan persimmon brandy with an alcohol content of 42% (V/V), prepared by fermentation and distillation, was aged after being added with 5–20 g/L of Chinese-made moderately roasted oak chips. The volatile and non-volatile components of persimmon brandy were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), the total phenol content and antioxidant activity were determined, and sensory evaluation was also performed. The results showed that a total of 33 volatile components were identified by GC-MS, among which the major components were ethyl acetate, ethyl decanoate, and ethyl laurate. The content of volatile components was the highest upon the addition of 10 g/L of oak chips. The results of LC-MS showed that the number of non-volatile substances increased by 183 after aging. The total phenol content and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity increased with increasing addition of oak chips, but was basically stable after 90 days of aging. In the sensory evaluation, persimmon brandy with 15 g/L of oak chip scored the highest (72.5 points)

Three-Dimensional Manganese Oxide@Carbon Networks as Free-Standing, High-Loading Cathodes for High-Performance Zinc-Ion Batteries

Zinc-ion batteries (ZIBs), which are inexpensive and environmentally friendly, have a lot of potential for use in grid-scale energy storage systems, but their use is constrained by the availability of suitable cathode materials. MnO2-based cathodes are emerging as a promising contenders, due to the great availability and safety, as well as the device's stable output voltage platform (1.5 V). Improving the slow kinetics of MnO2-based cathodes caused by low electrical conductivity and mass diffusion rate is a challenge for their future use in next-generation rapid charging devices. Herein, the aforementioned challenges are overcome by proposing a sodium-intercalated manganese oxide (NMO) with 3D varying thinness carbon nanotubes (VTCNTs) networks as appropriate free-standing, binder-free cathodes (NMO/VTCNTs) without any heat treatment. A network construction strategy based on CNTs of different diameters is proposed for the first time to provide high specific capacity while achieving high mass loading. The specific capacity of as-prepared cathodes is significantly increased. The resulting free-standing binder-free cathodes achieve excellent capacity (329 mAh g−1 after 120 cycles at 0.2 A g−1 and 225 mAh g−1 after 200 cycles at 1 A g−1) and long-term cycling stability (158 mAh g−1 at 2 A g−1 after 1000 cycles)