Physicochemical classification of organisms

The hypervariable residues that compose the major part of proteins’ surfaces are generally considered outside evolutionary control. Yet, these “nonconserved” residues determine the outcome of stochastic encounters in crowded cells. It has recently become apparent that these encounters are not as random as one might imagine, but carefully orchestrated by the intracellular electrostatics to optimize protein diffusion, interactivity, and partner search. The most influential factor here is the protein surface-charge density, which takes different optimal values across organisms with different intracellular conditions. In this study, we examine how far the net-charge density and other physicochemical properties of proteomes will take us in terms of distinguishing organisms in general. The results show that these global proteome properties not only follow the established taxonomical hierarchy, but also provide clues to functional adaptation. In many cases, the proteome–property divergence is even resolved at species level. Accordingly, the variable parts of the genes are not as free to drift as they seem in sequence alignment, but present a complementary tool for functional, taxonomic, and evolutionary assignment.

Recent studies of live cells reveal that cytosolic crowding imposes some unique functional challenges that have previously been unconsidered. Essentially, the cytosolic proteins are not just sterically obstructive, but also interact electrostatically with one another through repulsive and attractive forces (1). These diffusive interactions are commonly referred to as “quinary interactions” (2), and their effect on the proteins largely exceeds that predicted from simplistic hard-sphere crowding models (3). The most dramatic effect of altering the quinary interactions is observed for the protein motions. A protein that normally diffuses relatively freely in the cytosolic compartment can be changed to get stuck to the intracellular surrounding by a single surface mutation (4). The principal determinant behind this effect is the protein-surface charge (4, 5). To maintain the cytosolic components suitably fluid, most biological macromolecules, like proteins, nucleic acids, and membranes, carry repulsive net-negative charge, and complete loss of this repulsion will naturally promote aggregation and functional arrest (1). However, the role of the protein charge has turned out to be more subtle than that: It modulates in detail the functional protein–protein encounters (1, 5–8). Because the strength and duration of these dynamic encounters need to be kept within certain limits for the cell to function optimally, the protein-charge decoration itself has been suggested to be under biological control (1, 4, 9–11). This very idea challenges the notion that the composition of the variable protein surfaces drifts freely and adds another dimension to protein evolution and organism fitness (12). Attention then shifts from the relatively small and highly conserved binding interfaces and active sites visible in crystal structures to the least-conserved parts of the protein surfaces exposed to the cytosolic surrounding. Proteome-wide studies of Escherichia coli confirm that there is indeed a systematic bias toward negative charge density and show also that not any negative charge density is acceptable: Proteins distribute around a moderately negative value, away from which few deviations are observed (1, 13) (Fig. 1). Similar results are obtained from measurements of isoelectric points, leading to the conclusion that the majority of soluble proteins are acidic and that the degree of this acidity varies across organisms (14–17). Classical examples are the proteomes of some halophilic archaea, with net-charge densities 10 times more negative than observed for most other organisms (18–23). Together, these findings show that the variable protein surfaces contain previously unrecognized evolutionary cues, which can be captured in terms of specific sets of physicochemical properties. The question is then whether organism identity can be deduced from physicochemical observables alone. To explore this possibility, we map here the divergence of proteome properties across organisms against the established taxonomic classification and demonstrate that the resolving power is indeed remarkably high. The results show that distinct clustering and separations of proteome properties not only follow taxonomic divisions, but also reflect their adaptation to various biotopes and functional specializations. Given that the data cover ∼18,000 organisms in all kingdoms of life, we focus below on a few representative examples of divergent optimizations and refer the specialist readers to our proteome explorer website for more specific analysis (https://proteome-explorer.herokuapp.com/).Open in a separate windowFig. 1.Outline of approach. (A) The UniProt Proteomes of Archaea, Bacteria, and Eukaryota were sampled and the physicochemical properties of each of their proteins calculated (Methods). From this dataset, containing ∼10,000 proteomes, any species can be further analyzed with respect to its detailed protein properties. (B) The distributions of protein MW and protein NCD for the proteomes of H. salinarum, E. coli, and H. sapiens. (C) Plot of the average MW and NCD values, derived from the protein distributions in B. This two-dimensional representation shows clear separation of the three species. Corresponding plots can be obtained for all UniProt Proteomes and, similarly, for all NCBI Assemblies (Methods; SI Appendix, Fig. S1; and Fig. 2). (D–F) Generally, the protein-surface charge of individual proteins follows closely that of the proteome average (SI Appendix, Fig. S19). Shown are surface charge potentials in vacuum (red for negative and blue for positive) of ribonucleotide reductase orthologs in H. salinarum (UniProt {"type":"entrez-protein","attrs":{"text":"Q9HMU3","term_id":"74568776","term_text":"Q9HMU3"}}Q9HMU3 modeled on PDB 5im3), E. coli (PDB 2xap), and H. sapiens (PDB 3hnc).     

2005-2013年武汉市医疗资源配置公平性研究

目的：分析武汉市卫生资源配置的公平性,为优化区域卫生资源配置提供依据。方法采用基尼系数和泰尔指数分析2005年、2009年和2013年度武汉市各区床位、卫生技术人员等指标的公平性。结果武汉市卫生资源人口维度的基尼系数在0.3~0.4之间,且呈上升趋势;卫生资源的总泰尔指数在0.06~0.14之间,呈上升趋势且区域间泰尔指数远大于区域内泰尔指数。结论武汉市卫生资源配置的公平性出现一定程度的恶化,建议采取多种手段提高资源配置的公平性。     

2003-2012年全国新生儿遗传代谢病筛查室间质量评价结果分析

目的 总结并分析2003-2012年全国新生儿筛查实验室检测苯丙氨酸(phenylalanine,Phe)和促甲状腺素(thyroid stimulating hormone,TSH)室间质量评价(external quality assessment,EQA)结果,为进一步提高我国Phe和TSH检测水平提供有价值的参考。方法 参照美国疾病控制中心(CDC)新筛质量保证计划和中华人民共和国国家标准GB/T 20470-2006《临床实验室室间质量评价要求》。每年进行3次EQA,每次发放5个质控血片,要求各筛查实验室在规定时间内检测,回报Phe和TSH浓度水平结果及临床定性判断结果;组织者对所有回报的结果进行统计分析,作出实验室检测水平的评价。结果 2003-2012年测定Phe荧光分析法所占比例为54.9%~85.2%、定量酶法和细菌抑制法分别为12.6%~6.2%和35.4%~4.6%;测定TSH时间分辨荧光分析法(Tr-FIA)所占比例为44.8%~70.7%、酶联免疫分析法(ELISA)和荧光酶免疫分析法(FEIA)分别为36.0%~11.2%,17.5%~13.0%。十年来Phe 150个批号实验室间平均变异系数分别为12.13%(定量酶法)、17.15%(细菌抑制法)、12.14%~12.97%(荧光法);TSH 150个批号实验室间平均变异系数:Tr-FIA为14.14%,ELISA 为14.88%~27.20%,FEIA为17.07%~34.98% 。2003-2012年间Phe和TSH浓度水平检测的平均合格率分别为95.3%和89.4%,临床定性判断平均合格率分别97.8%和98.0%。 结论 目前Tr-FIA成为我国筛查实验室测定TSH的首选方法,荧光分析法明显优于细菌抑制法。开展全国新生儿遗传代谢病Phe和TSH室间质量评价工作,有助于筛查实验室发现检测中存在的问题,逐步提高国内新生儿遗传代谢病检测质量水平。     

死亡月分布离散程度对中国不同年龄性别人口终寿年成数的影响

目的 探讨中国不同年龄性别死亡人口月分布离散程度及终寿年成数的特点。方法 利用中国1989年全年按月死亡人口数据计算中国不同年龄性别死亡人口月分布变异系数（CV）和终寿年成数（a)。结果 CV随年龄和性别有较大变化，a较少受年龄性别的影响。结论 不同年龄性别死亡人口月分布偏离均匀分布状态的程度存在很大差异。但终寿年成数似乎不受死亡人口月分布离散程度的影响，表现出相当的稳定性。     

新生儿大脑纤维束观察值及其对侧化的影响

目的 探讨新生儿纤维束追踪参数改变对纤维束追踪稳定性及纤维侧化发育的影响。 方法 获取40例36.6~42.1周(中位数为40周)足月新生儿多球壳弥散张量数据(HARDI),使用MRtrix3软件,采用多感兴趣区(ROIs)协议追踪皮质脊髓束(CST)、扣带纤维(CGC)、胼胝体大钳(Fmajor)、胼胝体小钳(Fminor)、下纵束(ILF)、钩束(UNC)、额枕下束(IFO)等脑内主要纤维束,通过双因素重复方差分析及计算期望值的方法分析不同终止值域及最大转角对纤维束体积及稳定性的影响,采用裂区设计分析不同参数对侧化发育的影响。 结果 当最大转角为45°时纤维体积明显减少,当纤维终止值域为0.02时,纤维追踪的评分者内信度及评分者间信度减低且一致性离散度增大;不同的纤维追踪参数设定对双侧不同纤维的侧化存在影响,双侧皮质脊髓束、扣带纤维及钩束的侧化发育均有统计学意义(P<0.001,P=0.017,P=0.024)。在皮质脊髓束、扣带束的分数各向异性(FA)平均值测量中,终止值域和最大转角对双侧皮质脊髓束、扣带束的侧化影响的主效应均具有统计学意义。 结论 采用合适的追踪参数设定能够提高纤维追踪的稳定性,有助于分析新生儿大脑发育的普遍规律。     

Monitoring of Ion Mobility in the Cement Matrix to Establish Sensitivity to the ASR Caused by External Sources

The possibility of the formation of an alkali–silicate reaction (ASR) is a crucial issue for the service life of concrete. The coexistence of key parameters such as the presence of alkalis, reactive SiO₂, humidity, and temperature predetermine the possibility of its formation and application. When an ASR gel forms, it results in the concreting cracking and spalling as well as in the deterioration of its overall properties. The risk of ASR depends on the concentration of alkalis and their mobility, which influence their ability to penetrate the concrete. The objective of this study was to determine the ionic mobility of not only Na⁺ and K⁺, but Ca²⁺ as well, from external sources (0.5 and 1.0 mol/L solutions of Na/K carbonate, nitrate, and hydroxide) to a cementitious matrix as the precursor for ASR. The concentrations of ions in both the immersion solutions (ICP) and the cementitious matrix itself (SEM-EDX) were studied as a function of time, from 0 to 120 days, for leaching, and according to temperature (25 and 40 °C). The reaction products were characterized using SEM-EDX. Different diffusion rates and behavior were observed depending on the anion type of the external alkali source. Both sodium and potassium ions in all the three environments studied, namely carbonate, hydroxide, and nitrate, penetrated into the composite and further into its structure by different mechanisms. The action of hydroxides, in particular, transformed the original hydration products into calcium-silicate-hydrate (CASH) or ASR gel, while nitrates crystallized in pores and did not cause any changes in the hydration product. The driving force was the increased temperature of the experiment as well as the increased concentration of the solution to which the test specimen was exposed.     

基于变异系数评价重症医学科DRG分组效能研究

目的 评价重症医学科DRG分组的效能,发现存在的问题,为DRG付费或绩效考核提供建议.方法 采用DRG分组器获得样本医院2016-2019年出院患者的分组结果.在2555名重症医学科出院患者中选取病例数排名前5位的DRG组作为DRG研究组.在351148名全院出院患者中筛选出DRG研究组的所有病例.对入组同一个DRG组...     

Heritability of the limbic networks

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum (‘medial default-mode network’), the ventral cingulum and the fornix (‘hippocampal-diencephalic-retrosplenial network’) and the uncinate fasciculus (‘temporo-amygdala-orbitofrontal network’). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing.     

急性大脑中动脉栓塞的动静脉联合溶栓治疗的实验研究

目的:评价动静脉联合溶栓治疗实验兔急性脑梗死的疗效。方法:采用兔自体血栓栓塞大脑中动脉制成急性脑梗死模型,随机分为动、静脉联合溶栓组(IA+IV组)、静脉溶栓组(IV组)及对照组,分别给予以动脉+静脉、静脉内注射尿激酶及静脉内注射生理盐水。采用DSA观察血管再通率、核磁共振弥散成像观察相对表观系数(rADC)、改良Bederson评分法观察神经功能缺损。结果:IA+IV组血管再通率为83.3%、rADC值(0.918±0.144)及神经功能缺损评分(0.80±0.84)均优于IV组和对照组。结论:动静脉联合溶栓治疗急性脑梗死优于静脉内溶栓治疗。     

三维弥散张量成像在脑胶质瘤术前评价及术中神经导航中的应用

目的本文探讨以磁共振三维弥散张量成像(DTI)评价术前神经传导纤维情况及其在导航手术中的应用价值。方法对6例磁共振提示脑胶质瘤的病人进行两方面研究:1、术前对每例病人均以DTI评价神经传导纤维的完整性;2、DTI与神经导航序列影像融合进行术中导航。结果1、术前DTI提示2例神经纤维以推移为主、4例有不同程度神经纤维的破坏。2、本组术后弥散张量影像复查神经传导束未见进一步损伤,临床症状无加重。结论(1)DTI可以帮助医师在术前评价神经纤维损伤程度,借以估价预后。(2)DTI融合影像神经导航有助于术者设计合理的手术入路及指导手术的神经保护。