Assessing strategies for improved superfamily recognition

There are more than 200 completed genomes and over 1 million nonredundant sequences in public repositories. Although the structural data are more sparse (approximately 13,000 nonredundant structures solved to date), several powerful sequence-based methodologies now allow these structures to be mapped onto related regions in a significant proportion of genome sequences. We review a number of publicly available strategies for providing structural annotations for genome sequences, and we describe the protocol adopted to provide CATH structural annotations for completed genomes. In particular, we assess the performance of several sequence-based protocols employing Hidden Markov model (HMM) technologies for superfamily recognition, including a new approach (SAMOSA [sequence augmented models of structure alignments]) that exploits multiple structural alignments from the CATH domain structure database when building the models. Using a data set of remote homologs detected by structure comparison and manually validated in CATH, a single-seed HMM library was able to recognize 76% of the data set. Including the SAMOSA models in the HMM library showed little gain in homolog recognition, although a slight improvement in alignment quality was observed for very remote homologs. However, using an expanded 1D-HMM library, CATH-ISL increased the coverage to 86%. The single-seed HMM library has been used to annotate the protein sequences of 120 genomes from all three major kingdoms, allowing up to 70% of the genes or partial genes to be assigned to CATH superfamilies. It has also been used to recruit sequences from Swiss-Prot and TrEMBL into CATH domain superfamilies, expanding the CATH database eightfold.     

线粒体与多潜能干细胞功能

线粒体是细胞内重要的细胞器,主要功能是通过氧化磷酸化为细胞生命活动提供能量。近年来,研究表明,在多潜能干细胞（Pluripotent stem cells, PSCs）中线粒体表现出独有的特征,即在多能性状态下,PSCs主要依靠糖酵解提供能量,其分化期间线粒体氧化磷酸化代谢能力逐渐增强。相反,体细胞重编程为多潜能干细胞期间,线粒体氧化磷酸化向糖酵解途径的转变是其成功重编程必需的代谢过程。另外,线粒体通过生物合成和形态结构的动态重塑维持了PSCs多能性、诱导分化及诱导多能干细胞（Induced pluripotent stem cells, iPSCs）的重编程。因此,本文综述了PSCs线粒体形态结构及其在调控PSCs多能性、合成代谢、氧化还原状态的平衡、分化及重新编程中的作用,为深入了解线粒体调控PSCs功能的作用提供理论基础。     

Effect of cultural conditions on the protein and lipopolysaccharide profiles of Haemophilus ducreyi analysed by SDS-PAGE

Abstract A comparative study of the protein and lipopolysaccharide (LPS) profiles of 8 strains of Haemophilus ducreyi revealed that protein patterns remained unaffected by changes in medium composition, atmospheric conditions and temperature. In contrast, the LPS patterns exhibited marked variations under the different cultural conditions.     

The evolution of Queensland spiny mountain crayfish of the genus Euastacus. I. Testing vicariance and dispersal with interspecific mitochondrial DNA

The upland mesic rainforests of eastern Australia have been described as a "mesothermal archipelago" where a chain of cool mountain "islands" arise from a warm "sea" of tropical and subtropical lowlands. An endemic freshwater crayfish belonging to the genus Euastacus is found on each of these mountain "islands." The Euastacus are particularly suitable for the study of evolution because each mountain harbors a unique species, there are many taxa present providing replication within the group and, most importantly, their distribution is linear, extending along a south-north axis. This group could have evolved by "simultaneous vicariance" where there was one vicariant separation event of a widespread ancestor, or by "south to north stepping stone dispersal" where there were long distance dispersal events from neighboring mountain islands, starting in the south and proceeding north in a dispersal-colonization wave. We used pairwise genetic distances between nearest geographic neighbors as a novel way to test the two hypotheses. If diversification was due to "south to north stepping stone dispersal," then pairwise genetic distances between nearest geographic neighbors should decrease progressively the farther north the taxon pairs are found, reflecting the decreasing periods of isolation. In this case there should be a negative correlation between the south to north rank order of nearest neighbors and pairwise genetic distances. A Spearman's correlation on 16S mtDNA pairwise genetic distances and geographic rank order was not significant, indicating there was no support for the south to north stepping stone dispersal hypothesis. If simultaneous vicariance was responsible for diversification then all nearest geographic neighbor taxon pairs should have similar genetic distances and, therefore, the variance in nearest neighbor distances should be zero, or close to it. To test if the observed variance was tending towards zero we developed a randomization test where nearest neighbor taxon pairs were assigned random genetic distances and the variances calculated. The observed variance lay in the < 0.05 range of the simulated variances, providing support for the simultaneous vicariance hypothesis. The data also suggest there was simultaneous vicariance of at least two ancestral Queensland lineages. The timing of this vicariant event was probably in the Pliocene, which is consistent with the divergence times reported for other Australian mesic rainforest restricted taxa.     

腕踝针联合耳穴压豆治疗肝癌癌痛的疗效及对心理状态和血清疼痛介质的影响

摘要 目的：观察腕踝针联合耳穴压豆治疗原发性肝癌（PHC）癌痛的疗效及对心理状态和血清疼痛介质的影响。方法：选取湖南中医药大学第一附属医院2020年3月~2022年12月期间收治的PHC癌痛患者117例,按随机数字表法分为对照组和联合组,例数分别为58例和59例。两组患者均接受常规疼痛处理,对照组患者接受耳穴压豆治疗,联合组在对照组的基础上接受腕踝针治疗。对比两组疼痛缓解率、临床指标、心理状态和疼痛介质水平。结果：联合组的疼痛缓解率高于对照组（P<0.05）。联合组的数字疼痛法（NRS）评分低于对照组,止痛起效时间、每次疼痛持续时间短于对照组,爆发痛次少于对照组（P<0.05）。治疗后,两组焦虑自评量表（SAS）、抑郁自评量表（SDS）评分下降,且联合组低于对照组（P<0.05）。治疗后,两组5-羟色胺（5-HT）、P物质（SP）、前列腺素E₂（PGE₂）下降,且联合组低于对照组（P<0.05）。结论：腕踝针联合耳穴压豆治疗PHC癌痛,可有效减轻疼痛症状,降低血清疼痛介质水平,同时还可有效调节患者的心理状态,应用价值较好。     

针灸联合逍遥散合半夏厚朴汤治疗肝郁脾虚型抑郁症患者伴胃肠功能紊乱的临床疗效

摘要 目的：探讨针灸联合逍遥散合半夏厚朴汤治疗肝郁脾虚型抑郁症患者伴胃肠功能紊乱的临床疗效。方法：选取我院2020年5月到2023年5月收治的80例抑郁症伴胃肠功能紊乱患者作为研究对象,中医证型均为肝郁脾虚型,分为观察组与对照组,40例。对照组患者采取逍遥散合半夏厚朴汤治疗,观察组在对照组基础上增加针灸治疗,对比两组患者临床疗效,分别在治疗前后应用汉密尔顿抑郁量表（HAMD）、负性认知加工偏向问卷（NCPBQ）评价抑郁症状和负性认知情况,并对比治疗前后肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、白细胞介素-6（IL-6）表达水平和胃动素（motilin,MTL）、生长抑素（SS）、胃泌素（GAS）相关血清肠胃激素表达水平,并采用世界卫生组织生活质量-100量表（WHOQOL-100）评估生活质量。结果：观察组治疗总有效率较对照组高（P＜0.05）;治疗前两组患者HAMD、NCPBQ评分对比无差异（P＞0.05）,治疗后两组患者均降低,且观察组较对照组低（P＜0.05）;治疗前两组患者TNF-α、CRP、IL-6相关炎症因子和MTL、SS、GAS相关胃肠激素水平对比无明显差异（P＞0.05）,治疗后两组患者TNF-α、CRP、IL-6、SS、GAS水平均降低,且观察组较对照组低,MTL水平升高,观察组较对照组高（P＜0.05）;两组患者治疗后生活质量相关评分均升高,且观察组较对照组高（P＜0.05）。结论：针灸联合逍遥散合半夏厚朴汤治疗肝郁脾虚型抑郁症伴胃肠功能紊乱疗效显著,可减轻患者抑郁情绪和负性认知,降低炎症反应,改善胃肠激素水平,提升患者生活质量。     

Psychosine-induced alterations in peroxisomes of twitcher mouse liver

Krabbe disease is a neuroinflammatory disorder in which galactosylsphingosine (psychosine) accumulates in nervous tissue. To gain insight into whether the psychosine-induced effects in nervous tissue extend to peripheral organs, we investigated the expression of cytokines and their effects on peroxisomal structure/functions in twitcher mouse liver (animal model of Krabbe disease). Immunofluorescence analysis demonstrated TNF-α and IL-6 expression, which was confirmed by mRNAs quantitation. Despite the presence of TNF-α, lipidomic analysis did not indicate a significant decrease in sphingomyelin or an increase in ceramide fractions. Ultrastructural analysis of catalase-dependent staining of liver sections showed reduced reactivity without significant changes in peroxisomal contents. This observation was confirmed by assaying catalase activity and quantitation of its mRNA, both of which were found significantly decreased in twitcher mouse liver. Western blot analysis demonstrated a generalized reduction of peroxisomal matrix and membrane proteins. These observations indicate that twitcher mouse pathobiology extends to the liver, where psychosine-induced TNF-α and IL-6 compromise peroxisomal structure and functions.     

Evidence for long-distance dispersal in a sedentary passerine, Gymnorhina tibicen (Artamidae)

Australian magpies (Gymnorhina tibicen) are group-living birds found across much of mainland Australia. Adults commonly remain in a breeding territory until death. Young of the year either remain on the natal (birth) site or are forced by their parents to disperse. Observational studies in south-eastern Australia suggest that most dispersing juveniles settle within 7 km of their natal territory. Therefore, despite potential for considerable gene flow (via flight), social organization predisposes magpies towards local population structuring. In this study, we measured genetic variation at both nuclear (allozyme) and mitochondrial loci and found evidence of substantial gene flow over very large distances (up to 1599 km). Thus, some juvenile magpies may disperse much greater distances than was previously thought. For mtDNA, geographic and genetic distance were strongly correlated, consistent with a pattern of isolation by distance. Therefore, although female gene flow is substantial it is apparently geographically restricted over large distances, in approximately a stepping-stone fashion. We conclude that a strong relationship between gene flow and geographic distance can develop even over large distances if populations have experienced no major historical disturbances to gene flow.