A generalised framework for super-resolution track-weighted imaging

Track-density imaging (TDI) was recently introduced as a method to achieve super-resolution imaging using whole-brain fibre-tracking data (the so called tractogram). A similar approach to achieve super-resolution was later applied for average pathlength mapping (APM). These two methods have in common that the tractogram information is used to create an image with novel contrast and super-resolution properties. In this study, we present a generalised framework for creating super-resolution track-weighted imaging (TWI), where the intensity of the map can be made dependent on any specific property of the streamlines or their set of spatial coordinates. Furthermore, each contrast can be determined by a number of characteristics that are under user control. It is shown that TDI and APM represent specific cases of this generalised framework, and that this framework opens up the possibility of generating a large range of images with novel image contrasts. Finally, it is shown that the same super-resolution principles as those introduced in the original TDI method are also applicable to any of these new images.     

Patenting 3D protein structures

The sequencing of entire genomes of living organisms has resulted in new potential inventions in the field of bioinformatics. Such sequence information will revolutionise the field of structural genomics by allowing for the identification of biological molecules, such as DNA, RNA and proteins, involved in disease. The information may also lead to the identification of protein families and mutations in proteins that are potentially related to disease and the determination of the 3D structure of such protein families and mutated proteins. Such 3D structural information has great therapeutic potential. It is useful, inter alia, for understanding the mechanism of action of proteins with respect to disease that, in turn, can lead to new therapies. In addition, the information is useful in rational drug design, for example, the 3D structure of mutated proteins known to have lost a particular desired activity associated with the wild type protein can lead to the identification of a small molecule capable of re-establishing wild type activity; alternatively, it may be desirable to design an inhibitory molecule that binds to the mutated protein and inhibits an undesirable activity associated with the mutated protein. Although such information has great therapeutic potential, there are few issued patents relating to the 3D structural information of proteins. However, under appropriate circumstances, it should be possible to obtain commercially significant patent protection relating to such structure information.     

Folding energy landscape and network dynamics of small globular proteins

The folding energy landscape of proteins has been suggested to be funnel-like with some degree of ruggedness on the slope. How complex the landscape, however, is still rather unclear. Many experiments for globular proteins suggested relative simplicity, whereas molecular simulations of shorter peptides implied more complexity. Here, by using complete conformational sampling of 2 globular proteins, protein G and src SH3 domain and 2 related random peptides, we investigated their energy landscapes, topological properties of folding networks, and folding dynamics. The projected energy surfaces of globular proteins were funneled in the vicinity of the native but also have other quite deep, accessible minima, whereas the randomized peptides have many local basins, including some leading to seriously misfolded forms. Dynamics in the denatured part of the network exhibited basin-hopping itinerancy among many conformations, whereas the protein reached relatively well-defined final stages that led to their native states. We also found that the folding network has the hierarchic nature characterized by the scale-free and the small-world properties.     

基于PubMed数据库的糖尿病肾病的共词分析研究

目的为了解近年来糖尿病肾病研究的热点及趋势,对文献资料进行共词分析。方法利用文本挖掘系统(BICOMB)统计分析2014年4月～2019年3月PubMed收录的糖尿病肾病的文献,将累积频次达到50的主题词进行聚类分析,形成战略坐标。结果累计收录糖尿病肾病文献3972篇,统计出高频主题词40个。聚类分析显示高频主题词聚类于6个类别:2型糖尿病肾病血糖与尿检之间的联系、糖尿病肾病的流行病学、病因学及病理生理学的研究、2型糖尿病肾病引起的慢性肾衰竭透析治疗的死亡率、糖尿病肾病的病理学及代谢的研究、糖尿病肾病的药物治疗、2型糖尿病肾病遗传学的多态性。利用共词矩阵和聚类分析的结果,得出6个热点的密度和向心度及战略坐标。结论糖尿病肾病作为代谢性疾病糖尿病的并发症,其药物治疗、防治以及遗传学仍是目前研究的热点问题。同时总结了糖尿病肾病研究的6个热点及发展趋势。位于战略坐标第四象限的糖尿病肾病的流行病学、病因学及病理生理学的研究,糖尿病肾病的病理学及代谢的研究,糖尿病肾病的药物治疗研究具有潜在的研究价值。     

Pig brain stereotaxic standard space: mapping of cerebral blood flow normative values and effect of MPTP-lesioning

The analysis of physiological processes in brain by position emission tomography (PET) is facilitated when images are spatially normalized to a standard coordinate system. Thus, PET activation studies of human brain frequently employ the common stereotaxic coordinates of Talairach. We have developed an analogous stereotaxic coordinate system for the brain of the Gottingen miniature pig, based on automatic co-registration of magnetic resonance (MR) images obtained in 22 male pigs. The origin of the pig brain stereotaxic space (0, 0, 0) was arbitrarily placed in the centroid of the pineal gland as identified on the average MRI template. The orthogonal planes were imposed using the line between stereotaxic zero and the optic chiasm. A series of mean MR images in the coronal, sagittal and horizontal planes were generated. To test the utility of the common coordinate system for functional imaging studies of minipig brain, we calculated cerebral blood flow (CBF) maps from normal minipigs and from minipigs with a syndrome of parkisonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-poisoning. These maps were transformed from the native space into the common stereotaxic space. After global normalization of these maps, an undirected search for differences between the groups was then performed using statistical parametric mapping. Using this method, we detected a statistically significant focal increase in CBF in the left cerebellum of the MPTP-lesioned group. We expect the present approach to be of general use in the statistical parametric mapping of CBF and other physiological parameters in living pig brain.     

Dissociating visual and kinesthetic coordinates during pointing movements

Goal-directed movements imply that the visual coordinates in which the localisation of the goal is coded are transformed into proprioceptive coordinates in which the arm movement is coded. The two systems of coordinates are normally superimposed. Using a virtual reality device attached to the subject's head, we have created a situation where these systems were dissociated from each other. The virtual environment involved virtual visual targets and an image of the subject's hand reconstructed from the output of a data glove wore by the subject's right hand. When the subject's head was rotated, the visual targets and the image of the hand rotated by the same amount. Movements of the real hand were thus in conflict with those of the reconstructed hand, which appeared to err in the direction of head rotation. Pointing movements directed at five targets (0°, 26° and 52° on each side) were studied for five different head positions (0°, 45° and 80° to the right and to the left). The results showed a significant pointing bias towards head position, except for the left-most targets in the right head rotations. Constant errors in azimuth were proportional to the amount of head rotation. When the head was rotated to the right, constant errors in azimuth were greater during pointing towards right than left targets. Similarly, they were greater for left than for right stimuli when the head was rotated to the left. Errors in amplitude were not influenced by the direction nor the amount of head rotation. Finally, a decrease in the directional bias took place within blocks of trials. These results indicate that head position signals are used during the process of transforming motor coordinates from the visual to the pro-prioceptive system of reference.     

Microbiome-based body fluid identification of samples exposed to indoor conditions

In the forensic reconstruction of crime scene activities, the identification of biological traces and their bodily origin are valuable evidence that can be presented in court. While several presumptive and confirmatory tests are currently available, the limitations in specificity and sensitivity have instigated a search for alternative methods. Bacterial markers have been proposed as a novel approach for forensic body fluid/tissue identification. Bacteria are not only ubiquitous throughout the human body, but also, as shown by recent microbiome sequencing studies of the 16S rRNA gene, bacterial community structures are distinct across body sites. Traces and stains at crime scenes are, however, often exposed to the environment outside the human body for variable periods of time before laboratory processing. Thus, it is not clear whether exposed samples continue to harbor microbial signatures characteristic of their body site of origin. In this proof-of-concept study we collected samples from six different body sites: saliva, skin, peripheral blood, vaginal fluid, menstrual blood and semen. We exposed a subset of these samples to indoor conditions for 30 days while the remaining samples were processed directly after extraction. Our analyses of 16S rRNA gene sequence data for a total of 46 control and exposed samples show that both types of samples group by body site, although a few outliers are observed. Based on our results, vaginal and menstrual samples share their microbial signatures, and cannot be distinguished using bacterial markers. Overall, our findings indicate that bacterial markers are a promising avenue for forensic body fluid/tissue identification.     

基于“色如漆，甘如饴”的砂仁陈皮制熟地黄炮制过程质量评价

目的:研究砂仁陈皮制熟地黄炮制过程样品表观颜色、综合甜度与苷类成分含量变化的关联性,为揭示地黄炮制原理奠定基础。方法:采用全自动色差计测量熟地黄样品粉末颜色;采用高效液相色谱法测定不同加热时间点样品中14个活性成分的含量(5-羟甲基糠醛、梓醇、益母草苷、毛蕊花糖苷、异类叶升麻苷、橙皮苷、地黄苷D共7个苷类成分和D-果糖、葡萄糖、蔗糖、蜜二糖、棉子糖、甘露三糖、水苏糖共7个糖类成分),流动相乙腈-水梯度洗脱。以糖类成分甜度计算样品综合甜度变化,运用SPSS 21.0软件对砂仁陈皮制熟地黄炮制样品色度值、综合甜度与苷类成分含量进行关联分析,以三角形面积法建立熟地黄炮制样品质量综合评价指数。结果:在炮制过程中,样品粉末色度值增加,样品表观颜色变深。含量测定结果显示,随加热时间增加,熟地黄样品的苷类成分含量减少,单糖成分含量增加,样品综合甜度增加。关联性分析结果表明色度值、综合甜度与环烯醚萜苷含量呈显著负相关(P<0.01),色度值与呋喃醛衍生物含量、苯乙醇苷含量、黄酮类含量,以及综合甜度与呋喃醛衍生物含量、苯乙醇苷含量均呈显著正相关(P<0.01),综合甜度与黄酮类含量呈明显正相关(P<0.05)。炮制至52 h时样品综合评价指数最高,达0.99。结论:熟地黄样品粉末色度值聚类分析总体趋势与直观区分基本一致,结合样品粉末色度值、综合甜度与苷类成分含量3个指标可对砂仁陈皮制熟地黄进行综合质量评价。     

516例正常人舌色与唇色的可见反射光谱色度学调查

目的：通过检测正常人群舌色与唇色的可见反射光谱色度学数据,统计正常人群舌色与唇色的色度学参数分布特性。方法：于广东省高等院校学生中筛选516例在读学生作为研究对象,应用可见反射光谱法采集舌色与唇色数据,进行CIEXYZ的颜色匹配三刺激值的计算,获得CIE1964色品坐标、明度、主波长、色纯度色度学参数。结果：应用可见反射光谱数据反演于CIE1964色度图,正常舌色的色品坐标x10为0.3413±0.0085,y10为0.3326±0.0051;正常唇色的色品坐标x10为0.3577±0.0092,y10为0.3383±0.0057;正常舌色与唇色的明度Y值分别为17.96±3.78和19.78±3.72;正常舌色与唇色的主波长值分别为（626.3±51.6）和（600.4±18.2）nm;正常舌色与唇色的兴奋纯度值分别为0.083±0.031和0.144±0.036。结论：应用可见反射光谱法对色诊资料采集可提供一种标准的测色方法,对正常舌色与唇色的色坐标、主波长与色纯度数据的检测与归纳总结,可以为病理的舌色与唇色的病证诊断提供基本参照。