Fumonisin B(1) alters sphingolipid metabolism and tumor necrosis factor alpha expression in heart and lung of mice

Fumonisin B(1) (FB(1)), produced by Fusarium verticillioides, is a common contaminant in foods and feeds. Increase in tissue free sphingoid bases resulting from the inhibition of ceramide synthase is a biomarker of fumonisin exposure. Tumor necrosis factor alpha (TNFalpha) is induced in liver in response to FB(1) treatment. This study determined whether fumonisin B(1) caused increases in free sphingoid bases and altered the expression of TNFalpha in heart and lung, organs that are not targets of FB(1) toxicity, of male and female mice treated with 5-daily subcutaneous injection of 2.25 mg/kg FB(1). A significant increase in free sphingoid bases was observed in both heart and lung of FB(1)-exposed mice. The magnitude of increases in free sphingoid bases in both organs of female mice was much higher than that in males. The expression of TNFalpha was increased by FB(1) treatment in the lung of male mice and in the heart of female mice, whereas the expression of interferon gamma was unaltered. Results suggest that both sphingolipid accumulation and TNFalpha induction are observed in the tissues of mice that are not associated with FB(1) toxicity.     

Biochemical characterization of the intracellular domain of the human guanylyl cyclase C receptor provides evidence for a catalytically active homotrimer

Guanylyl cyclase C (GCC) is the receptor for the family of guanylin peptides and bacterial heat-stable enterotoxins (ST). The receptor is composed of an extracellular, ligand-binding domain and an intracellular domain with a region of homology to protein kinases and a guanylyl cyclase catalytic domain. We have expressed the entire intracellular domain of GCC in insect cells and purified the recombinant protein, GCC-IDbac, to study its catalytic activity and regulation. Kinetic properties of the purified protein were similar to that of full-length GCC, and high activity was observed when MnGTP was used as the substrate. Nonionic detergents, which stimulate the guanylyl cyclase activity of membrane-associated GCC, did not appreciably increase the activity of GCC-IDbac, indicating that activation of the receptor by Lubrol involved conformational changes that required the transmembrane and/or the extracellular domain. The guanylyl cyclase activity of GCC-IDbac was inhibited by Zn(2+), at concentrations shown to inhibit adenylyl cyclase, suggesting a structural homology between the two enzymes. Covalent cross-linking of GCC-IDbac indicated that the protein could associate as a dimer, but a large fraction was present as a trimer. Gel filtration analysis also showed that the major fraction of the protein eluted at a molecular size of a trimer, suggesting that the dimer detected by cross-linking represented subtle differences in the juxtaposition of the individual polypeptide chains. We therefore provide evidence that the trimeric state of GCC is catalytically active, and sequences required to generate the trimer are present in the intracellular domain of GCC.     

IGSF1: A novel oncogene regulates the thyroid cancer progression

Thyroid cancer has been continuously increasing and extraordinarily prevalent worldwide. The genetic diagnosis has been widely used in fine needle aspiration. IGSF1, an immunoglobulin superfamily member 1, has been shown to be associated with the regulation of thyroid hormone. But the function of IGSF1 in thyroid cancer has not been explored yet. In this article, we will illuminate the correlation between IGSF1 expression and thyroid cancer. We analysed the level of IGSF1 expression in 55 pairs of tissue samples by real‐time polymerase chain reaction (PCR) and The Cancer Genome Atlas (TCGA) data portal. After that, we transfected small interfering RNA to silence IGSF1 in thyroid cancer cell lines (KTC‐1 and BCPAP) and confirmed the function of IGSF1 by performed colony formation, migration, invasion, cell counting kit‐8, and apoptosis assays. IGSF1 was upregulated in thyroid cancer tissues compared with the adjacent normal tissues (t = 5.783, df = 54; P < .0001) and TCGA (T: N = 65.91 ± 3.998, n = 501: 2.824 ± 0.273, n = 58; P < .0001). In thyroid cell lines, experiments showed that downregulated IGSF1 inhibited proliferation, metastasis, and promoted cell apoptosis. Meanwhile, inhibited IGSF1 expression could downregulate N‐cadherin, vimentin, and EZH2, which is associated with metastasis. Thyroid cancer cells IGSF1 expression levels are a correlation with its ability to growth, metastasis, and apoptosis.     

Are rare species less shade tolerant than common species in fire-prone environments? A test with seven <Emphasis Type="Italic">Amorpha</Emphasis> (Fabaceae) species

Increases in tree density resulting from fire suppression have contributed considerably to the loss of savanna and grassland habitats in North America. Inability to tolerate shade is likely an important cause of species loss in areas that have not maintained historical burning regimes. We conducted an experiment to test whether differences in shade tolerance can explain rarity within the genus Amorpha. Four common and three rare species of Amorpha were grown in a greenhouse for 100 days in direct sun or under 90% shade. Overall, shading significantly reduced growth and survival and affected allocation among species, but these differences did not differ consistently between common and rare species. Ability to tolerate shade was best explained by phenotypic plasticity, with greater shade survival being exhibited by species with the largest changes in leaf area ratio. Furthermore, this study demonstrated that all three of the rare species can be readily cultivated under greenhouse conditions.     

MCTR1 alleviates lipopolysaccharide-induced acute lung injury by protecting lung endothelial glycocalyx

Endothelial glycocalyx degradation, critical for increased pulmonary vascular permeability, is thought to facilitate the development of sepsis into the multiple organ failure. Maresin conjugates in tissue regeneration 1 (MCTR1), a macrophage-derived lipid mediator, which exhibits potentially beneficial effects via the regulation of bacterial phagocytosis, promotion of inflammation resolution, and regeneration of tissue. In this study, we show that MCTR1 (100 ng/mouse) enhances the survival of mice with lipopolysaccharide (LPS)-induced (15 mg/kg) sepsis. MCTR1 alleviates LPS (10 mg/kg)-induced lung dysfunction and lung tissue inflammatory response by decreasing inflammatory cytokines (tumor necrosis factor-α, interleukin-1β [IL-1β], and IL-6) expression in serum and reducing the serum levels of heparan sulfate (HS) and syndecan-1. In human umbilical vein endothelial cells (HUVECs) experiments, MCTR1 (100 nM) was added to the culture medium with LPS for 6 hr. MCTR1 treatment markedly inhibited HS degradation by downregulating heparanase (HPA) protein expression in vivo and in vitro. Further analyses indicated that MCTR1 upregulates sirtuin 1 (SIRT1) expression and decreases NF-κB p65 phosphorylation. In the presence of BOC-2 or EX527, the above effects of MCTR1 were abolished. These results suggest that MCTR1 protects against LPS-induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF-κB/HPA pathway.     

Gluten quality of bread wheat is associated with activity of RabD GTPases

In the developing endosperm of bread wheat (Triticum aestivum), seed storage proteins are produced on the rough endoplasmic reticulum (ER) and transported to protein bodies, specialized vacuoles for the storage of protein. The functionally important gluten proteins of wheat are transported by two distinct routes to the protein bodies where they are stored: vesicles that bud directly off the ER and transport through the Golgi. However, little is known about the processing of glutenin and gliadin proteins during these steps or the possible impact on their properties. In plants, the RabD GTPases mediate ER‐to‐Golgi vesicle transport. Available sequence information for Rab GTPases in Arabidopsis, rice, Brachypodium and bread wheat was compiled and compared to identify wheat RabD orthologs. Partial genetic sequences were assembled using the first draft of the Chinese Spring wheat genome. A suitable candidate gene from the RabD clade (TaRabD2a) was chosen for down‐regulation by RNA interference (RNAi), and an RNAi construct was used to transform wheat plants. All four available RabD genes were shown by qRT‐PCR to be down‐regulated in the transgenic developing endosperm. The transgenic grain was found to produce flour with significantly altered processing properties when measured by farinograph and extensograph. SE‐HPLC found that a smaller proportion of HMW‐GS and large proportion of LMW‐GS are incorporated into the glutenin macropolymer in the transgenic dough. Lower protein content but a similar protein profile on SDS‐PAGE was seen in the transgenic grain.     

Chk2 and P53 Regulate the Transmission of Healed Chromosomes in the Drosophila Male Germline

When a dicentric chromosome breaks in mitosis, the broken ends cannot be repaired by normal mechanisms that join two broken ends since each end is in a separate daughter cell. However, in the male germline of Drosophila melanogaster, a broken end may be healed by de novo telomere addition. We find that Chk2 (encoded by lok) and P53, major mediators of the DNA damage response, have strong and opposite influences on the transmission of broken-and-healed chromosomes: lok mutants exhibit a large increase in the recovery of healed chromosomes relative to wildtype control males, but p53 mutants show a strong reduction. This contrasts with the soma, where mutations in lok and p53 have the nearly identical effect of allowing survival and proliferation of cells with irreparable DNA damage. Examination of testes revealed a transient depletion of germline cells after dicentric chromosome induction in the wildtype controls, and further showed that P53 is required for the germline to recover. Although lok mutant males transmit healed chromosomes at a high rate, broken chromosome ends can also persist through spermatogonial divisions without healing in lok mutants, giving rise to frequent dicentric bridges in Meiosis II. Cytological and genetic analyses show that spermatid nuclei derived from such meiotic divisions are eliminated during spermiogenesis, resulting in strong meiotic drive. We conclude that the primary responsibility for maintaining genome integrity in the male germline lies with Chk2, and that P53 is required to reconstitute the germline when cells are eliminated owing to unrepaired DNA damage.     

Cadmium toxicity in crop plants and its alleviation by arbuscular mycorrhizal (AM) fungi: An overview

Cadmium (Cd), a toxic metal released into agricultural settings induces numerous changes in plant growth and physiology. The main known mechanisms of Cd toxicity include its affinity for sulfhydryl groups in proteins and its ability to replace some essential metals in active sites of enzymes, thus causing inhibition of enzyme activities and protein denaturation. This article reviews detrimental effects of Cd toxicity on the functional biology of plants and summarizes the mechanisms that are activated by plants to prevent the absorption or to detoxify Cd ions such as synthesis of antioxidants, osmolytes, phytochelatins, metallothioneins, etc. Arbuscular mycorrhizal (AM) fungi are reported to be present on the roots of plants growing in metal-contaminated soils and play an important role in metal tolerance. Through mycorrhizal symbiosis, heavy metals are immobilized in the rhizosphere through precipitation in the soil matrix, adsorption onto the root surface or accumulation within roots, and compartmentalized in aboveground parts of the plant. This article unfolds the potential role of AM fungi in enhancing Cd tolerance of plants.