We present efficient syntheses of serofendic acids A and B (SA-A and SA-B), novel neuroprotective substances isolated from fetal calf serum. Biological and pharmacological evaluation showed that SA-A and SA-B have potent protective action against glutamate-induced neurotoxicity, but do not interact directly with glutamate receptors. A pharmacokinetic study showed that they have good oral bioavailability in rats. The results indicate that SA-A and SA-B are potential lead compounds for candidate drugs to treat various neurological disorders. 相似文献
The phenylboronic acids substituted with an azo group on the ortho-position show a significant change in UV-vis spectra upon sugar binding. A new mechanism for the spectral change of the dyes is proposed based on the formation and cleavage of B-N dative bond between boronic acid group and azo group. 相似文献
We established a new plant defense response assay using a transient expression system in rice protoplasts. The assay system sensitively detected defense induction by flagellin, which had previously been assigned to a specific elicitor. Our assay system provides a rapid and efficient way to dissect rice defense mechanisms. 相似文献
Proper neutrophil migration into inflammatory sites ensures host defense without tissue damage. Phosphoinositide 3-kinase (PI(3)K) and its lipid product phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) regulate cell migration, but the role of PtdIns(3,4,5)P(3)-degrading enzymes in this process is poorly understood. Here, we show that Src homology 2 (SH2) domain-containing inositol-5-phosphatase 1 (SHIP1), a PtdIns(3,4,5)P(3) phosphatase, is a key regulator of neutrophil migration. Genetic inactivation of SHIP1 led to severe defects in neutrophil polarization and motility. In contrast, loss of the PtdIns(3,4,5)P(3) phosphatase PTEN had no impact on neutrophil chemotaxis. To study PtdIns(3,4,5)P(3) metabolism in living primary cells, we generated a novel transgenic mouse (AktPH-GFP Tg) expressing a bioprobe for PtdIns(3,4,5)P(3.) Time-lapse footage showed rapid, localized binding of AktPH-GFP to the leading edge membrane of chemotaxing ship1(+/+)AktPH-GFP Tg neutrophils, but only diffuse localization in ship1(-/-)AktPH-GFP Tg neutrophils. By directing where PtdIns(3,4,5)P(3) accumulates, SHIP1 governs the formation of the leading edge and polarization required for chemotaxis. 相似文献
The recent increase of COVID-19-associated mucormycosis (CAM) has been commanding global attention. However, basic epidemiologic characteristics have not firmly been established. In this systematic review and meta-analysis, we sought to determine the clinical manifestations, potential risk factors, and outcomes of CAM. Observational studies reporting CAM were searched with PubMed and EMBASE databases in January 2022. We collected data on comorbidities and treatment for COVID-19, and performed a one-group meta-analysis on the frequency of orbital exenteration procedure and mortality of CAM using a random-effect model. Fifty-one observational studies, including a total of 2,312 patients with proven CAM, were identified. Among the 51 studies, 37 were conducted in India, 8 in Egypt, and 6 in other countries. The most common comorbidity was diabetes mellitus (82%). While 57% required oxygenation, 77% received systemic corticosteroids. Among CAM, 97% were rhino-orbital-cerebral (ROCM), and 2.7% were pulmonary mucormycosis. Usual presentations were headache (54%), periorbital swelling/pain (53%), facial swelling/pain (43%), ophthalmoplegia (42%), proptosis (41%), and nasal discharge/congestion (36%). Regarding the outcomes, orbital exenteration was performed in 17% (95% CI: 12–21%, I2?=?83%) of the COVID-19-associated ROCM patients. The mortality of CAM was 29% (95% CI; 22–36%, I2?=?92%). In conclusion, this systematic review and meta-analysis indicated that the most prevalent type of CAM was ROCM, and most CAM patients had diabetes mellitus and received systemic glucocorticoids. Clinicians in the endemic areas should have a high index of suspicion for this invasive fungal complication of COVID-19 when a diabetic patient who received high-dose systemic glucocorticoids developed rhino-orbital symptoms.
UDP‐glucose: anthocyanidin 3‐O‐glucosyltransferase (UGT78K6) from Clitoria ternatea catalyzes the transfer of glucose from UDP‐glucose to anthocyanidins such as delphinidin. After the acylation of the 3‐O‐glucosyl residue, the 3′‐ and 5′‐hydroxyl groups of the product are further glucosylated by a glucosyltransferase in the biosynthesis of ternatins, which are anthocyanin pigments. To understand the acceptor‐recognition scheme of UGT78K6, the crystal structure of UGT78K6 and its complex forms with anthocyanidin delphinidin and petunidin, and flavonol kaempferol were determined to resolutions of 1.85 Å, 2.55 Å, 2.70 Å, and 1.75 Å, respectively. The enzyme recognition of unstable anthocyanidin aglycones was initially observed in this structural determination. The anthocyanidin‐ and flavonol‐acceptor binding details are almost identical in each complex structure, although the glucosylation activities against each acceptor were significantly different. The 3‐hydroxyl groups of the acceptor substrates were located at hydrogen‐bonding distances to the Nε2 atom of the His17 catalytic residue, supporting a role for glucosyl transfer to the 3‐hydroxyl groups of anthocyanidins and flavonols. However, the molecular orientations of these three acceptors are different from those of the known flavonoid glycosyltransferases, VvGT1 and UGT78G1. The acceptor substrates in UGT78K6 are reversely bound to its binding site by a 180° rotation about the O1–O3 axis of the flavonoid backbones observed in VvGT1 and UGT78G1; consequently, the 5‐ and 7‐hydroxyl groups are protected from glucosylation. These substrate recognition schemes are useful to understand the unique reaction mechanism of UGT78K6 for the ternatin biosynthesis, and suggest the potential for controlled synthesis of natural pigments. 相似文献
In the vertebrate retina, neurites from distinct neuronal cell types are constrained within the plexiform layers, allowing for establishment of retinal lamination. However, the mechanisms by which retinal neurites are segregated within the inner or outer plexiform layers are not known. We find that the transmembrane semaphorins Sema5A and Sema5B constrain neurites from multiple retinal neuron subtypes within the inner plexiform layer (IPL). In Sema5A?/?; Sema5B?/? mice, retinal ganglion cells (RGCs) and amacrine and bipolar cells exhibit severe defects leading to neurite mistargeting into the outer portions of the retina. These targeting abnormalities are more prominent in the outer (OFF) layers of the IPL and result in functional defects in select RGC response properties. Sema5A and Sema5B inhibit retinal neurite outgrowth through PlexinA1 and PlexinA3 receptors both in vitro and in vivo. These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function. 相似文献
Three holocelluloses (i.e., cellulose and hemicellulose fractions) are prepared from softwood and hardwood by the Wise method. These holocelluloses completely dissolve in 8% lithium chloride/1,3-dimethyl-2-imidazolidinone (LiCl/DMI) after an ethylenediamine (EDA) pretreatment. After diluting the holocellulose solutions to 1% LiCl/DMI, they are subjected to size-exclusion chromatography/multiangle laser-light scattering/photodiode array (SEC-MALLS-PDA) analysis. All holocelluloses exhibit bimodal molecular weight distributions primarily due to high-molecular-weight (HMW) cellulose and low-molecular-weight hemicellulose fractions. Plots of molecular weight vs root-mean-square radius obtained by SEC-MALLS analysis revealed that all the wood celluloses comprise dense conformations in 1% LiCl/DMI. In contrast, bacterial cellulose, which was used as a pure cellulose model, has a random coil conformation as a linear polymer. These results show that both softwood and hardwood HMW celluloses contain branched structures, which are probably present on crystalline cellulose microfibril surfaces. These results are consistent with those obtained by permethylation analysis of wood celluloses. 相似文献
Plant phytohormone, Indole-3-acetic acid (IAA ), is synthesized by tryptophan (trp) dependent and independent pathway. Here we report that tryptophan auxotroph mutants completely suppressed the abnormalities of auxin over production mutant, superroot2. SUR2 is considered to modulate Trp dependent pathway, resulting IAA accumulation in Arabidopsis. Tryptophan auxotroph mutants showed hyper-sensitivity to the auxin polar transport inhibitor, NPA, on the phenotype of reduced gravitropism. These results together with the results of histochemical analyses, tryptophan auxotroph mutants seem to have a complete defect in Trp dependent IAA biosynthesis pathway, and it is also suggested that the Trp dependent pathway is responsible for the normal root gravitropism.Key words: Auxin, Trp dependent pathway, trp mutants, sur2, arabidopsis相似文献
The tripeptide Asn-d-Trp-Phe-NH(2) (NdWFamide) is a D-amino acid-containing cardioexcitatory peptide initially isolated from Aplysia. Previously we detected NdWFamide immunoreactivity in the visceral giant cells, the largest neurons in the brain of the terrestrial slug Limax located at the dorsal surface of the visceral ganglia. In the present study, we further analyzed the morphological features of these neurons by an intracellular injection of Lucifer yellow, and found that these neurons extend neurites out of the brain through at least 5 nerve bundles. We then isolated a gene and a cDNA clone potentially encoding a NdWFamide precursor, and investigated expression at the levels of mRNA and protein in Limax. The NdWFamide gene consists of 5 exons spanning at least 17 kb of the genome, and its open reading frame extends over 3 exons. The spatial expression pattern of NdWFamide mRNA was almost identical to that of the NdWFamide peptide, with some minor discrepancies in between. Although the most remarkable expression was evident in the visceral giant cells, we also found the expression of NdWFamide mRNA and peptide in the cerebral and pedal ganglia. These results suggest the involvement of NdWFamide in the regulation of a broad area of the slug's body. 相似文献