Genetic resources offer efficient tools for rice functional genomics research

Rice is an important crop and major model plant for monocot functional genomics studies. With the establishment of various genetic resources for rice genomics, the next challenge is to systematically assign functions to predicted genes in the rice genome. Compared with the robustness of genome sequencing and bioinformatics techniques, progress in understanding the function of rice genes has lagged, hampering the utilization of rice genes for cereal crop improvement. The use of transfer DNA (T‐DNA) insertional mutagenesis offers the advantage of uniform distribution throughout the rice genome, but preferentially in gene‐rich regions, resulting in direct gene knockout or activation of genes within 20–30 kb up‐ and downstream of the T‐DNA insertion site and high gene tagging efficiency. Here, we summarize the recent progress in functional genomics using the T‐DNA‐tagged rice mutant population. We also discuss important features of T‐DNA activation‐ and knockout‐tagging and promoter‐trapping of the rice genome in relation to mutant and candidate gene characterizations and how to more efficiently utilize rice mutant populations and datasets for high‐throughput functional genomics and phenomics studies by forward and reverse genetics approaches. These studies may facilitate the translation of rice functional genomics research to improvements of rice and other cereal crops.     

Chemiluminescence analysis of antioxidant capacity for serum albumin isolated from healthy or uremic volunteers

Regular hemodialysis treatment induces an elevation in oxidative stress in patients with end‐stage renal failure, resulting in oxidative damage of the most abundant serum protein, albumin. Oxidation of serum albumin causes depletion of albumin reactive thiols, leading to oxidative modification of serum albumin. The aim of this study was to screen the antioxidant capacity of albumins isolated from uremic patients (HD‐ALB) or healthy volunteers (N‐ALB). From high‐performance liquid chromatography spectra, we observed that one uremic solute binds to HD‐ALB via the formation of disulfide bonds between HD‐ALB and the uremic solute. Furthermore, we found using chemiluminescent analysis that the antioxidant capacities for N‐ALB to scavenge reactive oxygen species including singlet oxygen, hypochlorite and hydrogen peroxide were higher than HD‐ALB. Our results suggest that protein‐bound uremic solute binds to albumin via formation of disulfide bonds, resulting in the depletion of albumin reactive thiols. The depletion of albumin reactive thiols leads to a reduced antioxidant capacity of HD‐ALB, implying postmodification of albumin. This situation may reduce the antioxidant capacity of albumin and increase oxidative stress, resulting in increase in complications related to oxidative damage in uremic patients. Copyright © 2016 John Wiley & Sons, Ltd.     

Colchicine modulates calcium homeostasis and electrical property of HL‐1 cells

Colchicine is a microtubule disruptor that reduces the occurrence of atrial fibrillation (AF) after an operation or ablation. However, knowledge of the effects of colchicine on atrial myocytes is limited. The aim of this study was to determine if colchicine can regulate calcium (Ca²⁺) homeostasis and attenuate the electrical effects of the extracellular matrix on atrial myocytes. Whole‐cell clamp, confocal microscopy with fluorescence, and western blotting were used to evaluate the action potential and ionic currents of HL‐1 cells treated with and without (control) colchicine (3 nM) for 24 hrs. Compared with control cells, colchicine‐treated HL‐1 cells had a longer action potential duration with smaller intracellular Ca²⁺ transients and sarcoplasmic reticulum (SR) Ca²⁺ content by 10% and 47%, respectively. Colchicine‐treated HL‐1 cells showed a smaller L‐type Ca²⁺ current, reverse mode sodium–calcium exchanger (NCX) current and transient outward potassium current than control cells, but had a similar ultra‐rapid activating outward potassium current and apamin‐sensitive small‐conductance Ca²⁺‐activated potassium current compared with control cells. Colchicine‐treated HL‐1 cells expressed less SERCA2a, total, Thr17‐phosphorylated phospholamban, Cav1.2, CaMKII, NCX, Kv1.4 and Kv1.5, but they expressed similar levels of the ryanodine receptor, Ser16‐phosphorylated phospholamban and Kv4.2. Colchicine attenuated the shortening of the collagen‐induced action potential duration in HL‐1 cells. These findings suggest that colchicine modulates the atrial electrical activity and Ca²⁺ regulation and attenuates the electrical effects of collagen, which may contribute to its anti‐AF activity.     

Role of electroencephalogram and oxygen saturation in the induction mechanism of arousal for obstructive sleep apnea-hypopnea syndrome patients

Arousal concomitant with obstructive sleep apnea-hypopnea syndrome (OSAHS) is known to result in sleep fragmentation and excessive daytime sleepiness. The cause of arousal is multifarious, and the mechanism is not yet clear. The aim of this study was to further research the induction mechanism of arousal by investigating the variation of electroencephalogram (EEG) and oxygen saturation (SaO₂). This study enrolled 20 subjects with a clinical diagnosis of OSAHS who underwent overnight polysomnography. Respiratory events and arousals were scored, and individuals with insufficient samples (<30) were excluded. Thus, 13 subjects mostly with severe OSAHS were analyzed in this study. The wavelet coefficients, spectral power of EEG (C4-M1 and C3-M2) before arousal or airway reopening, and the maximum desaturations of SaO₂ during respiratory events were analyzed. For most subjects, EEG (in stages N1 and N2) during respiratory events with arousals exhibited significantly lower values of wavelet coefficients and spectral power (p < 0.05). The maximum desaturations of SaO₂ during respiratory events with arousals are larger than those without among individual. In binary logistic regression analysis, the P values of EEG features and SaO₂ desaturation were both less than 0.001. Our results demonstrate that in light NREM stage, less activity in EEG during respiratory events and larger SaO₂ drop both independently were related to the occurrence of arousal. These significant differences come from major subjects based on the statistical analysis, and help supplement the induction mechanism of arousal.     

Ni‐Metalloid (B,Si, P,As, and Te) Alloys as Water Oxidation Electrocatalysts

Breakthroughs toward effective water‐splitting electrocatalysts for mass hydrogen production will necessitate material design strategies based on unexplored material chemistries. Herein, Ni‐metalloid (B, Si, P, As, Te) alloys are reported as an emergent class of highly promising electrocatalysts for the oxygen evolution reaction (OER) and insight is offered into the origin of activity enhancement on the premise of the surface electronic structure, the OER activation energy, influence of the guest metalloid elements on the lattice structure of the host metal (Ni), and surface‐oxidized metalloid oxoanions. The metalloids modify the lattice structure of Ni, causing changes in the nearest Ni–Ni interatomic distance (d_Ni–Ni). The activation energy E_a scales with d_Ni–Ni indicating an apparent dependence of the OER activity on lattice properties. During the OER, surface Ni atoms are oxidized to nickel oxyhydroxide, which is the active state of the catalyst, meanwhile, the surface metalloids are oxidized to the corresponding oxoanions that affect the interfacial electrode/electrolyte properties and hence the adsorption/desorption interaction energies of the reacting species.     

State-dependent Lipid Interactions with the A2a Receptor Revealed by MD Simulations Using In Vivo-Mimetic Membranes

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Combinatorial computational approaches to identify tetracycline derivatives as flavivirus inhibitors

Limited structural information of drug targets, cellular toxicity possessed by lead compounds, and large amounts of potential leads are the major issues facing the design-oriented approach of discovering new leads. In an attempt to tackle these issues, we have developed a process of virtual screening based on the observation that conformational rearrangements of the dengue virus envelope protein are essential for the mediation of viral entry into host cells via membrane fusion. Screening was based solely on the structural information of the Dengue virus envelope protein and was focused on a target site that is presumably important for the conformational rearrangements necessary for viral entry. To circumvent the issue of lead compound toxicity, we performed screening based on molecular docking using structural databases of medical compounds. To enhance the identification of hits, we further categorized and selected candidates according to their novel structural characteristics. Finally, the selected candidates were subjected to a biological validation assay to assess inhibition of Dengue virus propagation in mammalian host cells using a plaque formation assay. Among the 10 compounds examined, rolitetracycline and doxycycline significantly inhibited plaque formation, demonstrating their inhibitory effect on dengue virus propagation. Both compounds were tetracycline derivatives with IC(50)s estimated to be 67.1 microM and 55.6 microM, respectively. Their docked conformations displayed common hydrophobic interactions with critical residues that affected membrane fusion during viral entry. These interactions will therefore position the tetracyclic ring moieties of both inhibitors to bind firmly to the target and, subsequently, disrupt conformational rearrangement and block viral entry. This process can be applied to other drug targets in which conformational rearrangement is critical to function.     

Ethnobotany in the Cumbres de Monterrey National Park, Nuevo León, México

The archives of Flora Medicinal, an ancient pharmaceutical laboratory that supported ethnomedical research in Brazil for more than 30 years, were searched for plants with antimalarial use. Forty plant species indicated to treat malaria were described by Dr. J. Monteiro da Silva (Flora Medicinal leader) and his co-workers. Eight species, Bathysa cuspidata, Cosmos sulphureus, Cecropia hololeuca, Erisma calcaratum, Gomphrena arborescens, Musa paradisiaca, Ocotea odorifera, and Pradosia lactescens, are related as antimalarial for the first time in ethnobotanical studies. Some species, including Mikania glomerata, Melampodium divaricatum, Galipea multiflora, Aspidosperma polyneuron, and Coutarea hexandra, were reported to have activity in malaria patients under clinical observation. In the information obtained, also, there were many details about the appropriate indication of each plant. For example, some plants are indicated to increase others' potency. There are also plants that are traditionally employed for specific symptoms or conditions that often accompany malaria, such as weakness, renal failure or cerebral malaria. Many plants that have been considered to lack activity against malaria due to absence of in vitro activity against Plasmodium can have other mechanisms of action. Thus researchers should observe ethnomedical information before deciding which kind of screening should be used in the search of antimalarial drugs.