Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.

Autism spectrum disorder:difficulties in diagnosis and microRNA biomarkers

We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.

局域性和de Broglie方程

非局域性具体表现在三个方面:(1)不承认物质粒子的质量和能量(全部或大部分)局限于一小范围内,即粒子是“不成形”的;(2)允许信号传播速度可以超过光速,因而有时将“超光速”作为非局域性的一种狭义表述;(3)空间分离事件具有相关性,这种相关性包含了Bohr“整体性”的全部内容.在这三方面中,“相关性”是最主要的特点。

刺葡萄VdERD6L15基因克隆及功能分析

【目的】探究VdERD6L15在刺葡萄果实生长发育中的功能,从湘刺1号中克隆VdERD6L15基因及其启动子,进行基因功能研究和启动子活性分析。【方法】克隆VdERD6L15基因CDS序列,并对CDS进行生物信息学分析;构建VdERD6L15表达载体,并通过瞬时转化烟草确定VdERD6L15基因编码蛋白的亚细胞定位;同时,通过在己糖缺陷型酵母菌株EBY.VW4000中异源表达VdERD6L15探究其功能;此外,通过启动子截短试验确定VdERD6L15启动子的核心区域。【结果】成功克隆刺葡萄VdERD6L15基因编码序列,该编码序列长1461 bp,可编码486个氨基酸,具有膜蛋白特征,属于单糖转运蛋白家族。亚细胞定位试验确认VdERD6L15蛋白主要定位于液泡膜上。通过在酵母菌株EBY.VW4000中进行异源表达,验证了VdERD6L15具有转运葡萄糖的能力。利用PlantCARE数据库对VdERD6L15启动子顺式作用元件进行分析,发现其主要包含光响应元件、干旱胁迫和激素响应元件。通过GUS染色分析,进一步确定候选基因VdERD6L15启动子的关键调控区域位于-500 bp到-1000 bp之间。【结论】VdERD6L15是一个定位在液泡膜上的糖转运蛋白,具有转运葡萄糖的功能;VdERD6L15启动子的核心元件位于ATG上游500~1000 bp之间。

De Broglie波的相速与群速

ＤｅＢｒｏｇｌｉｅ波的相速和群速是两类不同的速率，相速等于单色波传播速率，群速等于粒子运动速率．文中给出了相速与群速的一般关系．

De Broglie Wave的相速度和群速度

De Broglie Wave是可以按照几率解释的,在几率解释的基础上研究De Broglie Wave的相速度、群速度等速度特性,并建立了它们的关系。

L形冷弯薄壁型钢组合钢管混凝土柱轴压性能

为解决异形钢管混凝土柱阴角对其承载力的影响,提出了用1个冷弯薄壁方钢管和2个U形钢管焊接成L形钢管,内填充混凝土形成L形冷弯薄壁型钢组合钢管混凝土柱形式。设计了5组共10根试件的轴压试验,并开展了有限元参数分析,研究了钢管厚度、U形管外伸长度和钢材强度等参数对构件承载力和延性等力学性能的影响。结果表明:该类试件的主要破坏形态为中上部局部鼓曲破坏,适量增大U形管外伸长度可以提高承载力,但增大到一定程度之后易发生弯扭破坏;承载力和延性随着钢管厚度和钢材强度增大而增加;混凝土强度对构件的初始刚度和峰值荷载的影响都很小,但对曲线下降段的影响较大;试件端部和中部截面阴角处的混凝土应力值比各边中部更大,说明采用U形钢管与方钢管组合的方式改善了阴角处钢管对混凝土约束普遍较弱的问题。基于“统一理论”,给出了两种承载力建议计算公式,与试验结果吻合较好,两种计算方法在0.44~1.94的约束效应系数范围内具有良好的适用性。

de Broglie波的四维张量形式

由于de Broglie物质波具有相对论协变性,故de Broglie物质波的波矢可以写为四维形式,在四维形式下,德布罗意波的波矢可以用四维动量来表示。通过引入波矢张量,还得到了de Broglie波的四维张量形式,这种形式下de Broglie波的波矢由物质的能量-动量张量表示。

基于L-DeepLabv3+的轻量化光学遥感图像道路提取

针对DeepLabv3+在进行光学遥感图像道路提取任务时,存在模型参数量大、细节提取效果差等问题,提出一种改进DeepLabv3+的轻量化道路提取模型L-DeepLabv3+。首先通过将主干网络替换为MobileNetv2来减少模型参数量;其次,在编码层中设计一个改进的空洞空间卷积池化金字塔模块。该模块通过嵌入一个通道空间并联注意力模块和YOLOF模块来增强模型特征表达能力,并且将普通卷积替换为深度可分离卷积进一步减少模型参数量;最后组合采用Dice_loss和Focal_loss作为损失函数来解决正负样本不均衡问题。实验结果表明:L-DeepLabv3+在DeepGlobe Road数据集上进行道路提取的交并比达到68.40%,像素准确率达到82.67%,且模型参数量仅为5.63 MB,FPS达到72.3,与其他模型相比具有明显提升,实现了模型精度与轻量化之间更好的平衡。

粒子超非线性的总能和de Broglie波的理论

用Ｌｏｕｒｅｎｔ级数对高速运动粒子的速度（～ｃ）展开并取得总能量表达式·总能包含静能和动能二项·由能量＿动量的关系得到了ｄｅＢｒｏｇｌｉｅ波的理论。

基于de Broglie-Bohm解释的量子史瓦西解

利用正则量子化方法以及deBroglie-Bohm解释求解得一个球对称量子黑洞解,该解满足量子力学的对应原理,在普朗克常数趋于零时退化为史瓦西解。

Ecological Analysis of Leontice L. Species Distributed in the Navoi Region, Kyzyl-Kum Desert (Uzbekistan)

Leontice L. is a perennial herbaceous plant belonging to the Berberidaceae family. Our research was conducted in Navoi region. The article presents an ecological analysis of Leontice L. species in the Navoi region. The genus Leontice grows mainly in mountainous areas and some are distributed in arid climates. According to the information that 2 species have been identified in Navoi region, these species are plants with flavanoids healing properties. Leontice species have been used in traditional medicine since ancient times in ethnobotany. The presence of this species was discovered during the research and Leontice has identified numerous unique compounds, such as alkaloids, flavonoids, and phenolic acids, with potential medicinal properties such as anti-inflammatory, antitumor, and antiviral effects. According to ecological analysis, the Leontice genus thrives on stony, gravelly, and fine-grained mountain slopes and ridges, foothills, mountains, rocks, colorful rock outcrops, rocky slopes, and sandy, clay, and gravel deserts.

ON DE FINETTI'S OPTIMAL IMPULSE DIVIDEND CONTROL PROBLEM UNDER CHAPTER 11 BANKRUPTCY

Motivated by recent advances made in the study of dividend control and risk management problems involving the U.S.bankruptcy code,in this paper we follow[44]to revisit the De Finetti dividend control problem under the reorganization process and the regulator's intervention documented in U.S.Chapter 11 bankruptcy.We do this by further accommodating the fixed transaction costs on dividends to imitate the real-world procedure of dividend payments.Incorporating the fixed transaction costs transforms the targeting optimal dividend problem into an impulse control problem rather than a singular control problem,and hence computations and proofs that are distinct from[44]are needed.To account for the financial stress that is due to the more subtle concept of Chapter 11 bankruptcy,the surplus process after dividends is driven by a piece-wise spectrally negative Lévy process with endogenous regime switching.Some explicit expressions of the expected net present values under a double barrier dividend strategy,new to the literature,are established in terms of scale functions.With the help of these expressions,we are able to characterize the optimal strategy among the set of admissible double barrier dividend strategies.When the tail of the Lévy measure is log-convex,this optimal double barrier dividend strategy is then verified as the optimal dividend strategy,solving our optimal impulse control problem.

Ultrafine ordered L1_(2)-Pt-Co-Mn ternary intermetallic nanoparticles as high-performance oxygen-reduction electrocatalysts for practical fuel cells

The long-range periodically ordered atomic structures in intermetallic nanoparticles(INPs)can significantly enhance both the electrocatalytic activity and electrochemical stability toward the oxygen reduction reaction(ORR)compared to the disordered atomic structures in ordinary solid-solution alloy NPs.Accordingly,through a facile and scalable synthetic method,a series of carbon-supported ultrafine Pt_3Co_(x)Mn_(1-x)ternary INPs are prepared in this work,which possess the"skin-like"ultrathin Pt shells,the ordered L1_(2) atomic structure,and the high-even dispersion on supports(L1_(2)-Pt_3Co_(x)Mn_(1-x)/~SPt INPs/C).Electrochemical results present that the composition-optimized L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C exhibits the highest electrocata lytic activity among the series,which are also much better than those of the pristine ultrafine Pt/C.Besides,it also has a greatly enhanced electrochemical stability.In addition,the effects of annealing temperature and time are further investigated.More importantly,such superior ORR electrocatalytic performance of L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C are also well demonstrated in practical fuel cells.Physicochemical characterization analyses further reveal the major origins of the greatly enhanced ORR electrocata lytic performance:the Pt-Co-Mn alloy-induced geometric and ligand effects as well as the extremely high L1_(2) atomic-ordering degree.This work not only successfully develops a highly active and stable ordered ternary intermetallic ORR electrocatalyst,but also elucidates the corresponding"structure-function"relationship,which can be further applied in designing other intermetallic(electro)catalysts.

Phytochemical Screening and Assays of Phenolic Compounds in Senna occidentalis L. Leaf and Seed Extracts

Phytochemical screening and assay of secondary metabolites, crude extracts with distilled water, aqueous methanol, aqueous acetone and aqueous ethanol of leaves and seeds of Senna occidentalis L. were studied in this work. The aim was to verify the distribution of secondary metabolites according to S. occidentalis organs. Four leaf samples from four different localities (South, East, West and Central Senegal) and a mixed sample of seeds were used. Functional molecules such as polyphenols, flavonoids and tannins were then assessed in the leaves and seeds using various standard methods. The results show that Senna occidentalis L. leaf and seed samples display an identical and homogeneous profile, regardless of locality. They contain secondary metabolites and the polyphenol content of extracts from southern, eastern, western and central leaves is: 0.620 - 0.539 - 0.811 - 0.573 g GAE/100 g DM;flavonoids: 0.064 - 0.074 - 0.130 - 0.101 g CE/100 g DM and tannins: 0.326 - 0.264 - 0.269 - 0.494 g TAE/100 g DM. The efficacy of S. occidentalis L. infusions in therapy is thus justified by the presence of these metabolites, whose biological properties are well known. It is then possible to explore isolation of active principles of Senna occidentalis L. leaves and even seeds for producing medicines.

Evaluation of the Potential of Araucaria angustifolia Seeds as Source of Oligosaccharides, Resistant Starch and Growth of Probiotic Bacteria

“Pinhão”, the seed of Araucaria angustifolia, is an important food, being part of the eating habits of Indigenous communities. In this study, we evaluated the oligosaccharide content, resistant starch and the growth of probiotic bacteria. GF4 (1-fructofuranosylnystose) was the main fructo-oligosaccharides found, in higher contents compared to other food sources. Maltooligosaccharides (MOS) represented the main part of the oligosaccharides profile of Brazilian pine seeds. In descending order of importance was maltoheptaose (G7), maltohexose (G6) and maltotriose (G3). The starches from the variety Sanct josephi presented the highest amount of resistant starch that could stimulate probiotic strains, mainly B. breve and L. plantarum, and may have a prebiotic effect, potentially promoting health benefits. This study advances the understanding of the chemical composition of the main portion of the “pinhão” enhancing awareness of its potential as a healthy food source, contributing to different uses and indirectly with the species preservation.

Wave-Particle Duality in Einstein-de Broglie Programs

The standard model of particle physics forms a consistent system for universe description. After following quantum mechanics, it derives particles from relativistic quantum fields. Since it does not include gravitation, it describes only one aspect of the universe. In extension of general relativity, Einstein had proposed a symmetrical and complementary approach of physics. In his program, he privileged a relativist field based on representations for physical phenomena, before a precise mathematical description. It allows completing and unifying the universe description, like both eyes for relief vision, and both ears for stereophonic audition. We propose to show it with many simple examples.

Phenotypic Characterization and QTL/Gene Identification for Internode Number and Length Related Traits in Maize

Internode number and length are the foundation to constitute plant height, ear height and the above-ground spatial structure of maize plant. In this study, segregating populations were constructed between EHel with extremely low ear height and B73. Through the SNP-based genotyping and phenotypic characterization, 13 QTL distributed on the chromosomes (Chrs) of Chr1, Chr2, Chr5-Chr8 were detected for four traits of internode no. above ear (INa), average internode length above ear (ILaa), internode no. below ear (INb), and average internode length below ear (ILab). Phenotypic variation explained (PVE) by a single QTL ranged from 6.82% (qILab2-2) to 12.99% (qILaa5). Zm00001d016823 within the physical region of qILaa5, the major QTL for ILaa with the largest PVE was determined as the candidate through the genomic annotation and sequence alignment between EHel and B73. Product of Zm00001d016823 was annotated as a WEB family protein homogenous to At1g75720. qRT-PCR assay showed that Zm00001d016823 highly expressed within the tissue of internode, exhibiting statistically higher expression levels among internodes of IN4 to IN7 in EHel than those in B73 (P Zm00001d016823 might provide novel insight into molecular mechanism beyond phytohormones controlling internode development in maize.

Saffron(Crocus sativus L.) stigmas as a potential natural additive to improve oxidative stability attributes of sunflower(Helianthus annuus L.) oil stored under different conditions

The aim of our study was to explore the antioxidant potential of Moroccan saffron stigmas(SS) and examine their performance as a natural antioxidant in enhancing the stability and quality properties of edible sunflower oil(SO), with a focus on understanding the critical importance of edible oil stability for predicting quality deterioration during storage. Bearing this in mind, our research was designed to compare the efficacy of three concentrations of dried SS(at 0.2%, 0.3%, and 0.6%) against tocobiol(a synthetic antioxidant) as a positive control(at 0.3% concentration). This comparison was conducted under three distinct storage conditions namely accelerated ageing(60 ℃), exposure to light at ambient temperature, and darkness, to evaluate their impact on preventing severe oxidation and extending oil shelf-life. Oxidation state evolution was evaluated through peroxide value(PV), free fatty acid(FFA), anisidine value(p-AV), K_(270)value(conjugated trienes), total oxidation index(TOTOX), iodine value(IV), and fatty acid composition(FA). Our results revealed notable differences in stability tracking parameters. Specifically, these parameters were higher in samples stored under accelerated conditions, followed by the samples stored in ambient light, while those stored in darkness showed the highest stability among the three storage conditions. Supplementation of sunflower oil with SS and tocobiol significantly enhanced its oxidation stability. Notably, SS exhibited exceptional effectiveness in stabilizing sunflower oil regardless of SS dose, with the highest efficacy observed at 0.6%. This was evidenced by the slower rate of oxidation parameters under various storage conditions, highlighting a superior antioxidant activity compared to both the non-enriched oil and tocobiol-enriched oil. Furthermore, saffron stigmas, used as a natural supplement,contributed to the preservation of polyunsaturated fatty acids, indicating its potential as a robust source of natural antioxidants in sunflower oil. These attributes position SS as a promising alternative to synthetic antioxidants, offering opportunities to enhance the nutritional quality and extend edible oil shelf-life.

Mutation in a non-force-bearing region of protein L influences force-dependent unfolding behavior

Single-molecule magnetic tweezers(MTs) have revealed multiple transition barriers along the unfolding pathway of several two-state proteins, such as GB1 and Csp. In this study, we utilized MTs to measure the force-dependent folding and unfolding rates of both protein L(PLWT) and its Y47W mutant(PLY47W) where the mutation point is not at the force-bearing β-strands. The measurements were conducted within a force range of 3–120 pN. Notably, the unfolding rates of both PLWT and PWY47W exhibit distinct force sensitivities below 50 pN and above 60 pN, implying a two-barrier free energy landscape. Both PLWT and PLY47W share the same force-dependent folding rate and the same transition barriers,but the unfolding rate of PLY47W is faster than that of PLWT. Our finding demonstrates that the residue outside of the force-bearing region will also affect the force-induced unfolding dynamics.