Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals

Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D₁-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a timescale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illumination-dependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.     

Structural Characteristics of the 5′-Terminal Region of Mouse p53 mRNA and Identification of Proteins That Bind to This mRNA Region

A mouse model has often been used in studies of p53 gene expression. Detailed interpretation of functional studies is, however, hampered by insufficient knowledge of the impact of mouse p53 mRNA’s structure and its interactions with proteins in the translation process. In particular, the 5′-terminal region of mouse p53 mRNA is an important region which takes part in the regulation of the synthesis of p53 protein and its N-truncated isoform Δ41p53. In this work, the spatial folding of the 5′-terminal region of mouse p53 mRNA and its selected sub-fragments was proposed based on the results of the SAXS method and the RNAComposer program. Subsequently, RNA-assisted affinity chromatography was used to identify proteins present in mouse fibroblast cell lysates that are able to bind the RNA oligomer, which corresponds to the 5′-terminal region of mouse p53 mRNA. Possible sites to which the selected, identified proteins can bind were proposed. Interestingly, most of these binding sites coincide with the sites determined as accessible to hybridization of complementary oligonucleotides. Finally, the high binding affinity of hnRNP K and PCBP2 to the 5′-terminal region of mouse p53 mRNA was confirmed and their possible binding sites were proposed.     

Plasmids as Key Players in Acinetobacter Adaptation

This review briefly summarizes the data on the mechanisms of development of the adaptability of Acinetobacters to various living conditions in the environment and in the clinic. A comparative analysis of the genomes of free-living and clinical strains of A. lwoffii, as well as the genomes of A. lwoffii and A. baumannii, has been carried out. It has been shown that plasmids, both large and small, play a key role in the formation of the adaptability of Acinetobacter to their living conditions. In particular, it has been demonstrated that the plasmids of various strains of Acinetobacter differ from each other in their structure and gene composition depending on the lifestyle of their host bacteria. Plasmids of modern strains are enriched with antibiotic-resistant genes, while the content of genes involved in resistance to heavy metals and arsenic is comparable to plasmids from modern and ancient strains. It is concluded that Acinetobacter plasmids may ensure the survival of host bacteria under conditions of various types of environmental and clinical stresses. A brief overview of the main mechanisms of horizontal gene transfer on plasmids inherent in Acinetobacter strains is also given.     

Metabolic Adaptation as Potential Target in Papillary Renal Cell Carcinomas Based on Their In Situ Metabolic Characteristics

Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clear cell renal cell carcinoma (CCRCC) studies. Moreover, the bioenergetic perturbances that affect metabolic adaptation possibilities of papillary renal cell carcinoma (PRCC) have not yet been detailed. Therefore, our study aimed to analyze the in situ metabolic features of PRCC vs. CCRCC tissues and compared the metabolic characteristics of PRCC, CCRCC, and normal tubular epithelial cell lines. The protein and mRNA expressions of the molecular elements in mammalian target of rapamycin (mTOR) and additional metabolic pathways were analyzed in human PRCC cases compared to CCRCC. The metabolic protein expression pattern, metabolite content, mTOR, and metabolic inhibitor sensitivity of renal carcinoma cell lines were also studied and compared with tubular epithelial cells, as “normal” control. We observed higher protein expressions of the “alternative bioenergetic pathway” elements, in correlation with the possible higher glutamine and acetate consumption in PRCC cells instead of higher glycolytic and mTOR activity in CCRCCs. Increased expression of certain metabolic pathway markers correlates with the detected differences in metabolite ratios, as well. The lower lactate/pyruvate, lactate/malate, and higher pyruvate/citrate intracellular metabolite ratios in PRCC compared to CCRCC cell lines suggest that ACHN (PRCC) have lower Warburg glycolytic capacity, less pronounced pyruvate to lactate producing activity and shifted OXPHOS phenotype. However, both studied renal carcinoma cell lines showed higher mTOR activity than tubular epithelial cells cultured in vitro, the metabolite ratio, the enzyme expression profiles, and the higher mitochondrial content also suggest increased importance of mitochondrial functions, including mitochondrial OXPHOS in PRCCs. Additionally, PRCC cells showed significant mTOR inhibitor sensitivity and the used metabolic inhibitors increased the effect of rapamycin in combined treatments. Our study revealed in situ metabolic differences in mTOR and metabolic protein expression patterns of human PRCC and CCRCC tissues as well as in cell lines. These underline the importance in the development of specific new treatment strategies, new mTOR inhibitors, and other anti-metabolic drug combinations in PRCC therapy.     

濮城油田沙三中6-10油藏活性纳米粉体降压增注技术研究

濮城油田沙三中6-10油藏为低渗油藏,因注入水质差,造成对地层的伤害,注水压力不断上升。通过分析造成地层伤害的主要因素,为控制注水压力的上升,提出了活性纳米降压增注技术,并在室内进行了研究,从活性材料选择、表面修饰剂选择、分散介质选择以及纳米粉体水分散最佳浓度进行了室内筛选,指出了纳米酸化技术的可行性。在室内研究的基础上,在现场开展了10口井活性纳米技术的应用,取得了良好的效果。     

Various Approaches to Studying the Phase Transition in an Octamethylcyclotetrasiloxane Crystal: From X-ray Structural Analysis to Metadynamics

The structure, thermodynamic parameters, and the character of thermal motion in octamethylcyclotetrasiloxane (D4) were investigated using the combination of experimental (single-crystal X-ray diffraction, thermochemistry) and theoretical (density functional theory calculations, ab initio molecular dynamics and metadynamics) methods. Single crystals of D4 were grown in a glass capillary in situ and the structures of high- (238–270 K) and low-temperature (100–230 K) phases were studied in detail. In the temperature interval 230–238 K, a phase transition with rather low enthalpy (−1.04(7) kcal/mol) was detected. It was found that phase transition is accompanied by change of conformation of cyclosiloxane moiety from boat-saddle (cradle) to chair. According to PBE0/6-311G(d,p) calculation of isolated D4, such conformation changes are characterized by a low barrier (0.07 kcal/mol). The character of molecular thermal motion and the path of phase transition were established with combination of periodic DFT calculations, including molecular dynamics and metadynamics. The effect of crystal field led to an increase in the calculated phase transition barrier (4.27 kcal/mol from low- to high-temperature phase and 3.20 kcal/mol in opposite direction).     

塔河油田底水砂岩油藏水平井剩余油主控因素分析

针对塔河油田一区、九区等强底水砂岩油藏高含水期油水关系复杂、影响因素多、剩余油认识不清造成措施难度大的特点,分析了不同主控因素下水淹模式及剩余油的形成和分布特征。从水平井轨迹与夹层不同的配置关系入手,将轨迹与夹层的配置关系分为全遮挡型、穿行夹层型、穿过夹层型和半遮挡型4种配置关系。根据渗透率组合形态将水平段渗透率组合分为4种形态:两段式、锯齿式、台阶式和均匀式,并结合油井生产动态研究了不同配置关系及渗透率形态所对应的水平段水淹模式,描述其对剩余油不同控制作用,并结合矿场试验给出各种剩余油赋存方式适合的挖潜手段,为底水油藏剩余油精细挖潜提供依据。     

排土场粒度分布与干涉区的分形特征研究

运用分形统计技术手段分析了排土场的物料分异规律,并对料堆间的干涉作用进行了研究。研究表明排土场料堆粒度分布具有良好的分形结构,从底部到顶部分形维度逐渐增大,岩石粒径逐渐变细;水平方向上具有粗细交替的现象;由外向内具有粗粒含量降低,细粒含量增高的特征。受干涉作用影响,干扰区呈二重分形特征,且岩石长轴方向均向水平低角度方向靠拢。对排土场分形特征的分析为研究其变形、破坏、滑坡、泥石流、滚石等灾害提了重要的理论依据。     

SephadexLH-20纯化红松松球鳞片多酚及其体外抗氧化研究

为了得到高纯度红松松球鳞片多酚样品和初步评价其抗氧化活性,采用葡萄糖凝胶LH-20对红松松球鳞片多酚的初级纯化物进行二次精制,得到了纯度为95.86%的多酚样品。该多酚样品对DPPH自由基、ABTS自由基和羟自由基具有良好的清除作用,IC50分别为20.48、86.59μg/mL和0.45mg/mL;对铁离子（Fe3+）和铜离子（Cu2+）具有很强的还原能力,其还原铁离子（Fe3+）能力与V C相近,还原铜离子（Cu2+）能力略低于V C;对亚铁离子具有一定的螯合作用,其IC50为2.14mg/mL;对卵黄脂质过氧化具有明显的抑制作用,其IC50为0.33mg/mL。      

塔河油田AT1区块T2a3凝析气藏综合治理研究

砂岩凝析气藏见水后开发效果迅速变差,见水后治理成本高、难度大.塔河油田AT1区块T₂a³凝析气藏存在井网分布不均导致局部采速过高、储层非均质性严重、开发初期采气强度偏大、前期认识存在局限性等问题,通过捕捉生产动态中的异常信号,认为气藏存在底油,并据此形成了以油基堵剂堵水等为代表的改善开发效果的针对性技术手段.通过利用隔夹层和平面非均质性进行剩余油气挖潜,取得了较好的治理效果.