Ranking the affinity of aromatic residues for carbon nanotubes by using designed surfactant peptides.

A series of surfactant peptides were created to evaluate the affinity of aromatic AAs for single-walled carbon nanotubes in the absence of complications from peptide folding or self-association. Each surfactant peptide has a lipidlike architecture, with two Lys residues at the C-terminus as a hydrophilic head, five Val residues to form a hydrophobic tail, and the testing AA at the N-terminus. Raman and CD spectroscopic studies reveal that the surfactant peptides have a large unordered structural component which is independent of peptide concentration, suggesting that the peptides undergo minimal association under experimental conditions, thus removing this interference from interpretation of the peptide/carbon nanotube interactions. A lack of peptide self-association is also indicated by sedimentation equilibrium ultracentrifugation results. Optical spectroscopy of the peptide/carbon nanotube dispersions indicate that among the three aromatic AAs, tryptophan has the highest affinity for carbon nanotubes (both bundled and individual states) when incorporated into a surfactant peptide, while the Tyr-containing peptide is more selective for individual carbon nanotubes. Phe has the lowest overall affinity for carbon nanotubes. Raman spectra of dispersions made with SPF, SPY and SPW display similar types of nanotubes dispersed, although differences in the relative nanotube populations are observed by optical spectroscopy.     

The Wilms Tumor Gene,Wt1, Is Critical for Mouse Spermatogenesis via Regulation of Sertoli Cell Polarity and Is Associated with Non-Obstructive Azoospermia in Humans

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1^flox and Cre-ER^TM mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood–testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.     

Pharmacophore-based design and discovery of (−)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis

Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer’s disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (?)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC₅₀ 31.6?nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-β (Aβ) lowering effects (51.9% decrease of Aβ₄₂) superior to phenserine (31% decrease of total Aβ) in SH-SY5Y-APP₆₉₅ cells at 50?µM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents.     

Generation and analysis of ESTs from the grass carp, Ctenopharyngodon idellus

Grass carp, Ctenopharyngodon idellus (Valenciennes, 1844), is an economically important species widely cultured in the world, but its genome research resources are largely lacking. The objectives of this study were to construct normalized cDNA libraries for efficient EST analysis, to generate ESTs from these libraries, and to identify EST-related molecular markers such as microsatellites and single nucleotide polymorphisms (SNPs) for genetic analysis of this species. A total of 6,269 ESTs were generated representing 4,815 unique sequences, from which 105 putative microsatellites and 5,228 SNPs were identified. These genome resources provide the material basis for future genetic and functional analyses in this species.     

AI辅助识别的鸟类被动声学监测在城市湿地公园中的应用

为了探究基于AI识别的鸟类被动声学监测手段在城市湿地公园中的应用效果, 同时对比其与传统人工样线调查结果的差别, 本研究于2023年3-5月在广州市湾咀头湿地公园开展了为期3个月的同期监测。样线法为每月调查两次; 声学监测法通过安装两台声纹监测仪, 全天开启触发录制模式, 通过4G网络回传音频文件并使用以珠三角鸟类名录构建的AI识别模型进行鸟种识别, 再对结果进行置信度筛选和人工复核。样线法累计记录鸟类2,200只次; 声学监测法共采集音频96,848条, 筛选验证获得有效记录34,117条。两种方法共记录鸟类70种, 其中样线调查记录鸟类48种, 声学监测记录49种, 两种调查方法都记录到的鸟类有27种。两种调查方法重叠的物种比例不足总物种数的一半, 说明在此类湿地公园生境下这两种方法尚无法互相取代。样线调查结果相对准确、便于估算种群密度, 但对调查者的认鸟水平和工作量要求较高; 声学监测可自动化运行, 便于扩大监测规模, 但后期数据处理难度较大, 结合AI物种识别和人工校正可以提高数据处理效率。综上, 基于机器学习的AI识别技术的鸟类被动声学监测方法大大提高了数据处理效率, 但仍需要结合传统的样线调查方法, 两者结合将有更高的准确率和更广阔的应用前景。     

Protein transfer through polyacrylamide hydrogel membranes polymerized in lyotropic phases

A way to control the average pore size in cross-linked polyacrylamide-based membranes is by altering the ratio of cross-linker to acylamide monomer. Larger pore sizes are prepared with a minimum amount of cross-linker, resulting in membranes that are mechanically weak and have short lifetimes. The aim of this study was to prepare cross-linked polyacrylamide membranes with large pore sizes and with good mechanical integrity. The methodology was to carry out the polymerization in a template, formed from the self-aggregation of surfactant. Two surfactant templates were used, and their pore size was examined with proteins of different sizes. The surfactants chosen for this study were sodium dodecyl sulfate (SDS, ionic surfactant) and TERIC BL8 (nonionic surfactant), both of which have very different aggregation properties. The data showed that at 10% and greater of TERIC BL8, a very different and open gel structure is formed, in which the pore size was significantly increased. SDS seemed to have little effect on the pore size. The data suggests that the gel structures for both surfactants up to 4% (w/v) are similar and micellular, because SDS is known to favor a micelle structure. Above 4% (w/v), TERIC BL8 then goes through a change in its lyotropic phase, thus, producing membranes of a large pore size. In conclusion, the pore size and gel structure of polyacrylamide hydrogel membranes can be significantly increased using TERIC BL8 (nonionic) surfactant. This allows large-pore-size membranes with a high cross-link density and consequently high mechanical strength to be prepared for the separation of large biomolecules.     

Transport of Intranasally Instilled Fine Fe2O3 Particles into the Brain: Micro-distribution, Chemical States, and Histopathological Observation

It has been demonstrated that inhaled fine (d < 2.5 μm) and ultrafine (d < 100 nm) particles produce more severe toxicity than coarse particles. Some recent data support the concept that the central nervous system (CNS) may be a target for the inhaled fine particulates. This work describes initial observation of the transport of intranasally instilled fine ferric oxide (Fe₂O₃) particles in animal brain. The iron micro-distribution and chemical state in the mice olfactory bulb and brain stem on day 14 after intranasal instillation of fine Fe₂O₃ particle (280 ± 80 nm) suspension at a single dose of 40 mg/kg body weight were analyzed by synchrotron radiation x-ray fluorescence and x-ray absorption near-edge structure (XANES). The micro-distribution map of iron in the olfactory bulb and brain stem shows an obvious increase of Fe contents in the olfactory nerve and the trigeminus of brain stem, suggesting that Fe₂O₃ particles were possibly transported via uptake by sensory nerve endings of the olfactory nerve and trigeminus. The XANES results indicate that the ratios of Fe (III)/Fe (II) were increased in the olfactory bulb and brain stem. The further histopathological observation showed that the neuron fatty degeneration occurred in the CA3 area of hippocampus. Such results imply an adverse impact of inhalation of fine Fe₂O₃ particles on CNS.     

Catalytic reduction of carbonyl groups in oxidized PAPC by Kvβ2 (AKR6)

The β-subunits of the voltage-gated potassium channel (Kvβ) belong to the aldo-keto reductase superfamily. The Kvβ-subunits dock with the pore-forming Kv α-subunits and impart or accelerate the rate of inactivation in Kv channels. Inactivation of Kv currents by Kvβ is differentially regulated by oxidized and reduced pyridine nucleotides. In mammals, AKR6 family is comprised of 3 different genes Kvβ1-3. We have shown previously that Kvβ2 catalyzes the reduction of a broad range of carbonyls including aromatic carbonyls, electrophilic aldehydes and prostaglandins. However, the endogenous substrates for Kvβ have not been identified. To determine whether products of lipid oxidation are substrates of Kvβs, we tested the enzymatic activity of Kvβ2 with oxidized phospholipids generated during the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC). Electrospray ionization mass spectrometric analysis showed that Kvβ2 catalyzed the NADPH-dependent reduction of several products of oxPAPC, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC), 1-palmitoyl-2-(epoxycyclopentenone)-sn-glycero-3-phosphorylcholine (PECPC), 1-palmitoyl-2-(5,6)- epoxyisoprostane E2-sn-glycero-3-phosphocholine (PEIPC). These results were validated using high resolution mass spectrometric analysis. Time course analysis revealed that the reduced products reached significant levels for ions at m/z 594/596 (POVPC/PHVPC), 810/812 (PECPC/2H-PECPC) and 828/830 (PEIPC/2H-PEIPC) in the oxPAPC+Kvβ2 mixture (p<0.01). These results suggest that Kvβ could serve as a sensor of lipid oxidation via its catalytic activity and thereby alter Kv currents under conditions of oxidative stress.