Structural insights into the Switching Off of the Interaction between the Archaeal Ribosomal Stalk and aEF1A by Nucleotide Exchange Factor aEF1B

The ribosomal stalk protein plays a crucial role in functional interactions with translational GTPase factors. It has been shown that the archaeal stalk aP1 binds to both GDP- and GTP-bound conformations of aEF1A through its C-terminal region in two different modes. To obtain an insight into how the aP1•aEF1A binding mode changes during the process of nucleotide exchange from GDP to GTP on aEF1A, we have analyzed structural changes in aEF1A upon binding of the nucleotide exchange factor aEF1B. The isolated archaeal aEF1B has nucleotide exchange ability in the presence of aa-tRNA but not deacylated tRNA, and increases activity of polyphenylalanine synthesis 4-fold. The aEF1B mutation, R90A, results in loss of its original nucleotide exchange activity but retains a remarkable ability to enhance polyphenylalanine synthesis. These results suggest an additional functional role for aEF1B other than in nucleotide exchange. The crystal structure of the aEF1A•aEF1B complex, resolved at 2.0 Å resolution, shows marked rotational movement of domain 1 of aEF1A compared to the structure of aEF1A•GDP•aP1, and this conformational change results in disruption of the original aP1 binding site between domains 1 and 3 of aEF1A. The loss of aP1 binding to the aEF1A•aEF1B complex was confirmed by native gel analysis. The results suggest that aEF1B plays a role in switching off the interaction between aP1 and aEF1A•GDP, as well as in nucleotide exchange, and promote translation elongation.     

In-depth Profiling and Quantification of the Lysine Acetylome in Hepatocellular Carcinoma with a Trapped Ion Mobility Mass Spectrometer

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with limited therapeutic options. Comprehensive investigation of protein posttranslational modifications in HCC is still limited. Lysine acetylation is one of the most common types of posttranslational modification involved in many cellular processes and plays crucial roles in the regulation of cancer. In this study, we analyzed the proteome and K-acetylome in eight pairs of HCC tumors and normal adjacent tissues using a timsTOF Pro instrument. As a result, we identified 9219 K-acetylation sites in 2625 proteins, of which 1003 sites exhibited differential acetylation levels between tumors and normal adjacent tissues. Interestingly, many novel tumor-specific K-acetylation sites were characterized, for example, filamin A (K865), filamin B (K697), and cofilin (K19), suggesting altered activities of these cytoskeleton-modulating molecules, which may contribute to tumor metastasis. In addition, we observed an overall suppression of protein K-acetylation in HCC tumors, especially for enzymes from various metabolic pathways, for example, glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Moreover, the expression of deacetylase sirtuin 2 (SIRT2) was upregulated in HCC tumors, and its role of deacetylation in HCC cells was further explored by examining the impact of SIRT2 overexpression on the proteome and K-acetylome in Huh7 HCC cells. SIRT2 overexpression reduced K-acetylation of proteins involved in a wide range of cellular processes, including energy metabolism. Furthermore, cellular assays showed that overexpression of SIRT2 in HCC cells inhibited both glycolysis and oxidative phosphorylation. Taken together, our findings provide valuable information to better understand the roles of K-acetylation in HCC and to treat this disease by correcting the aberrant acetylation patterns.     

Intrinsically disordered proteins and biomolecular condensates as drug targets

Intrinsically disordered domains represent attractive therapeutic targets because they play key roles in cancer, as well as in neurodegenerative and infectious diseases. They are, however, considered undruggable because they do not form stable binding pockets for small molecules and, therefore, have not been prioritized in drug discovery. Under physiological solution conditions many biomedically relevant intrinsically disordered proteins undergo phase separation processes leading to the formation of mesoscopic highly dynamic assemblies, generally known as biomolecular condensates that define environments that can be quite different from the solutions surrounding them. In what follows, we review key recent findings in this area and show how biomolecular condensation can offer opportunities for modulating the activities of intrinsically disordered targets.     

Wood species utilization for timber constructions in the Czech lands over the period 1400–1900

Longstanding demographic growth accompanied by rising settlement activities and development of industry led to an increasing demand on utilization of wood. Tree species were selected for their specific properties. As a consequence of regional differences of forest species composition, wood has become an extremely important trade commodity. Therefore, the utilization of individual species could substantially change in space and time. In this study, we use 8´135 precisely dated timber constructions from a dendrochronological database to investigate spatio-temporal changes in wood utilization across the Czech lands from the 15th to the 19th century. Our results suggest that the utilization of individual species in historical timber constructions was primarily limited by their availability. Species selection was also based on wood properties and stem geometry. Most of historical constructions (99.7%), represented mainly by roofs and ceilings, are made of fir, spruce, pine, and oak. While fir constructions prevail in eastern Moravia and Silesia, spruce constructions are largely spread across the western and central part of the Czech Republic. Pine and oak constructions reflect natural occurrence of such forests in lower elevated central Bohemia and southern Moravia. Although fir prevailed in timber construction in the late-Medieval and post-Medieval times, planting of spruce monocultures resulted in its significantly increased utilization by the end of the 19th century. This study demonstrates the value of dendrochronological databases as an indicator of historical wood utilization.     

利用Ecopath模型评价鲢鳙放养对千岛湖生态系统的影响

“保水渔业”是中国控制"水华"暴发等生态灾变的措施之一，其结果存在较大的不确定性。在浙江省的新安江水库（千岛湖），"保水渔业"的实施带来了水质改善和渔业增产的双重效果。但在生态系统自组织层面，这种人工干预手段引起的生态系统结构化效应的研究，尚未真正展开。基于2008-2010年千岛湖的生态和渔业资源调查数据，应用EwE （V6.6）构建了2010年千岛湖生态系统的Ecopath模型，并将其与2004和2016年的模型进行对照，分析了千岛湖生态系统在鲢、鳙鱼放养下的变化。千岛湖生态系统在3个年份均为4个整合营养级，营养能流分布成典型的金字塔型，且营养流总量中流向碎屑的占比很大，营养级Ⅰ、Ⅱ的能量被利用得不够充分；除鲢、鳙鱼外大部分鱼类的生物量逐渐下降，浮游植物和碎屑的生物量增多；系统的初级生产力和规模得到了一定提升，但总体的能量转换效率有所降低。在一些和系统成熟度、复原力和稳定性密切相关的参数方面，总初级生产量/总呼吸量增加，Finn氏循环指数和Finn氏平均路径长度逐渐降低，3个年份的连接指数（CI）分别为0.223、0.219、0.263，系统杂食指数（SOI）分别为0.087、0.102和0.131。研究分析表明，长期的鲢、鳙鱼放养使千岛湖的食物网结构发生了较大的变动，生态系统的营养交互关系不够复杂，成熟度和稳定性有所下降。千岛湖作为一个由水库发展而来的淡水水体，食物网关系本身就较为简单。因此，未来需要避免过多的人为干扰，并基于生态学原理更系统地进行修复工作。     

县域城镇空间形态与居住建筑能耗关联性的连续尺度研究——以浙江长兴、福建连江为例

居住建筑能耗受建筑周边空间形态的直接影响，确定空间形态低碳效应及其最佳尺度将有助于实现县域城镇低碳转型。以浙江省长兴县、福建省连江县为例，共计选取49个具有代表性的居住建筑样本，采用GIS分析与数理统计相结合的方式，在居住建筑1800m半径范围内，以200m为间隔建立缓冲区，开展全年、最冷月份能耗期及最热月份能耗期建筑能耗与周边空间形态关联性的连续尺度研究。结果表明：(1)道路密度、开发密度、容积率均与建筑能耗呈正相关，但各指标对应的能耗时期、尺度范围有较大差异。(2)水面率、土地利用混合度是与建筑能耗相关的共性指标，但在不同地区的正负效应及尺度范围不同；(3)影响浙闽地区县域城镇最热月份能耗期能耗的关键形态因子为1000m-道路密度、800m-水面率、1600m-开放空间率；影响连江最冷月份能耗期能耗的关键形态因子为800m-水面率。(4)就控碳单元设置而言，长兴县可重点关注1000—1200m半径范围，连江县可重点关注800—1000m、1400m半径范围。(5)浙闽地区县域城镇特性指标为开放空间率，与最热月份能耗期建筑能呈负相关；长兴县特性指标为容积率、水岸密度，分别与全年、最冷...     

Contributions of animal nutrition research in rostock to energetic feed evaluation

The Rostock research in animal nutrition has underlain in continuation and progressive development of Kellner's starch value system, net energy fat as measuring unit for energetic feed evaluation. Net energy‐fat was used as an uniform unit of measure for all farm animals with different performances. The scientific basis for the net energy‐fat system was created by numerous studies on energy retention and utilisation efficiency of pure nutrients and nutrients of feedstuffs and rations. For the estimation the energy content of feedstuffs and rations, multiple regression equations were derived on the basis of experimental results of the energy research group. The regressions for the estimation of energy values are used directly and modified in feed evaluation systems for practical use. The Rostock research group in energy metabolism created also essential contributions to factorial derivations of energy requirement of farm animals. In the presented paper selected results on maintenance energy requirement in relation to partial energy requirement values and utilisation efficiencies in growing, pregnant and lactating animals, especially cattle and pigs, are comprised. The Rostock results are compared to those from literature.