Meta-analysis of iron metabolism markers levels of Parkinson’s disease patients determined by fluid and MRI measurements

BackgroundParkinson’ s disease (PD) is a progressive neurodegenerative disease featured neuropathologically by the loss of dopaminergic neurons of the substantia nigra (SN). Iron overload in the SN is mainly relative to the pathology and pathogenesis of PD. Postmortem samples of PD has indicated the increased levels of brain iron. However, there is no consensus on iron content through iron-sensitive magnetic resonance imaging (MRI) techniques and the alteration of iron and iron related metabolism markers levels in blood and cerebrospinal fluids (CSF) are still unclear based on the current studies. In this study, we performed a meta-analysis to explore the iron concentration and iron metabolism markers levels through iron-sensitive MRI quantification and body fluid.MethodsA comprehensive literature search was performed in PubMed, EMBASE and Cochrane Library databases for relevant published studies that analyzed iron load in the SN of PD patients using quantitative susceptibility mapping (QSM) or susceptibility weighting imaging (SWI), and iron metabolism markers, iron, ferritin, transferrin, total iron-binding capacity（TIBC）in CSF sample or serum/plasma sample (from Jan 2010 to Sep 2022 to filter these inaccurate researches attributed to unadvanced equipment, inaccurate analytical methods). Standardized mean differences (SMD) or mean differences (MD) and 95% confidence intervals (CI) with random or fixed effect model was used to estimate the results.ResultsForty-two articles fulfilled the inclusion criteria including 19 for QSM, 6 for SWI, and 17 for serum/plasma/CSF sample including 2874 PD patients and 2821 healthy controls (HCs). Our meta-analysis results founded a notable difference for QSM values increase (19.67, 95% CI=18.69–20.64) and for SWI measurements (−1.99, 95% CI= −3.52 to −0.46) in the SN in PD patients. However, the serum/plasma/CSF iron levels and serum/plasma ferritin, transferrin, total iron-binding capacity (TIBC) did not differ significantly between PD patients and HCs.ConclusionsOur meta-analysis showed the consistent increase in the SN in PD patients using QSM and SWI techniques of iron-sensitive MRI measures while no significant differences were observed in other iron metabolism markers levels.     

Protein structure dynamics by crosslinking mass spectrometry

Crosslinking mass spectrometry captures protein structures in solution. The crosslinks reveal spatial proximities as distance restraints, but do not easily reveal which of these restraints derive from the same protein conformation. This superposition can be reduced by photo-crosslinking, and adding information from protein structure models, or quantitative crosslinking reveals conformation-specific crosslinks. As a consequence, crosslinking MS has proven useful already in the context of multiple dynamic protein systems. We foresee a breakthrough in the resolution and scale of studying protein dynamics when crosslinks are used to guide deep-learning-based protein modelling. Advances in crosslinking MS, such as photoactivatable crosslinking and in-situ crosslinking, will then reveal protein conformation dynamics in the cellular context, at a pseudo-atomic resolution, and plausibly in a time-resolved manner.     

洞庭平原褐家鼠年龄分组及种群年龄动态分析

本文采用1986年10月—1989年12月在洞庭平原收集的褐家鼠(Rattus norvegicus)标本,以胴体重作指标,参考繁殖特征,将褐家鼠划分5个年龄组:Ⅰ.幼体组,雌鼠<60克,雄鼠<70克;Ⅱ.亚成体组,雌鼠60—99克,雄鼠70—119克;Ⅲ.成体Ⅰ组,雌鼠100—139克,雄鼠120—169克;Ⅳ.成体Ⅱ组,雌鼠140—189克,雄鼠170—219克;Ⅴ.老体组,雌鼠>190克,雄鼠>220克。种群年龄结构的季节动态特征是:开春时以Ⅲ、Ⅳ组占优势,初夏时Ⅰ、Ⅱ组明显增加,7、8、9月各年龄组比例较均匀,冬季以Ⅱ、Ⅲ组为主。还探讨了年龄与体重、体长、尾长及繁殖率的相互关系。     

AGE, GROWTH, AND REPRODUCTION OF THE FINLESS PORPOISE, NEOPHOCAENA PHOCAENOIDES, IN THE COASTAL WATERS OF WESTERN KYUSHU, JAPAN

Abstract: In the coastal waters of western Kyushu, Japan, a total of 97 incidentally taken or stranded finless porpoises, Neophocaena phocaenoides , was collected for studying age, growth and reproduction. An additional 17 specimens from the Inland Sea were used for a comparison of life history. Mean neonatal body length was 78.2 cm. Both males and females grew to around 140 cm by 5 yr of age. The maximum body lengths of males and females in western Kyushu were 174.5 cm and 165.0 cm, respectively, which were smaller than those recorded in other Japanese waters. Females probably attain sexual maturity at ages of 6–9 yr and at body lengths of 135–145 cm. Males probably mature sexually at ages of 4–6 yr, at body lengths of 135–140 cm and at weight of testis of 40–150 g. The lack of females aged 5–6 yr and males aged 4–5 yr precluded firm conclusions on ages at sexual maturity. Parturition in western Kyushu was estimated to be prolonged from autumn to spring, whereas in the Inland Sea and Pacific waters it was restricted from spring to summer with a peak in April. These geographical differences and available information on distribution implies that the finless porpoises in western Kyushu constitute a local population.     

Recognition of errors in three-dimensional structures of proteins

A major problem in the determination of the three-dimensional structure of proteins concerns the quality of the structural models obtained from the interpretation of experimental data. New developments in X-ray crystallography and nuclear magnetic resonance spectroscopy have acceleratedd the process of structure determination and the biological community is confronted with a steadily increasing number of experimentally determined protein folds. However, in the recent past several experimentally determined protein structures have been proven to contain major errors, indicating that in some cases the interpretation of experimental data is difficult and may yield incorrect models. Such problems can be avoided when computational methods are employed which complement experimental structure determinations. A prerequisite of such computational tools is that they are independent of the parameters obtained from a particular experiment. In addition such techniques are able to support and accelerate experimental structure determinations. Here we present techniques based on knowledge based mean fields which can be used to judge the quality of protein folds. The methods can be used to identify misfolded structures as well as faulty parts of structural models. The techniques are even applicable in cases where only the C_α trace of a protein conformation is available. The capabilities of the technique are demonstrated using correct and incorrect protein folds. © 1993 Wiley-Liss, Inc.     

Synthesis of (+)-(R)- and (−)-(S)-5-hydroxy-2-methyl-2-dipropylaminotetralin: Effects on rat hippocampal output of 5-HT, 5-HIAA,and DOPAC as determined by in vivo microdialysis

Racemic 5-methoxy-2-methyl-2-dipropylaminotetralin ( 3 ) has been prepared by a short synthetic route, in which the N,N-dipropyliminium perchlorate of 5-methoxy-2-tetralone ( 4 ) is a key intermediate. Racemic 3 was resolved by crystallization of the corresponding diastereomeric di-p-toluoyltartrates. The enantiomeric excess (%ee) of the phenolic derivatives of (+)-(R)- and (?)-(S)-3 [(+)-(R)- and (?)-(S)-2] was determined by ¹HNMR spectroscopic analysis of the corresponding diastereomeric (?)-(R)-1,1′-binaphthyl-2,2′-diylphosphoric acid salts utilizing ¹³C satellites. X-ray crystallography established the absolute configuration of (?)-(S)-2 · HCl. The enantiomers of 2 were tested for hippocampal output of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, and dihydroxyphenylacetic acid in rats by use of in vivo microdialysis. The (?)-(S)-enantiomer appeared to affect 5-HT-turnover, whereas (+)-(R)- 2 was inactive. Results obtained provide support for the previously reported hypothesis that the inactivity of (?)-(S)- 2 at central DA receptors is caused by the steric bulk of the C(2)-methyl group. This makes it possible to define a “DA D2 receptor essential volume.” © 1993 Wiley-Liss, Inc.     

Identification of a genomic region linked with sex determination of Undaria pinnatifida (Alariaceae) through genomic resequencing and genetic linkage analyses of a segregating gametophyte family

Different from the traditional knowledge about kelp, three sexual phenotypes (female, male, and monoecious) exist in the haploid gametophytes of Undaria pinnatifida. However, the sex-determining mechanisms remain unknown. Genetic linkage mapping is an efficient tool to identify sex-linked regions. In the present study, we resequenced a segregating gametophyte family based on the male genome of U. pinnatifida. A high-density genetic linkage map was constructed using 9887 SNPs, with an average distance of 0.41 cM between adjacent SNPs. On the basis of this genetic map and using the composite interval mapping method, we identified 62 SNPs significantly linked with the sexual phenotype. They were located at a position of 67.67 cM on the linkage group 23, corresponding to a physical range of 14.67 Mbp on the HiC_Scaffold_23 of the genome. Reanalysis of the previous specific length amplified fragment sequencing data according to the reference genome led to the identification of a sex-linked genomic region that encompassed the above-mentioned 14.67 Mbp region. Hence, this overlapped genomic range was likely the sex-determining region. Within this region, 129 genes were retrieved and 39 of them were annotated with explicit function, including the potential male sex-determining gene-encoding high mobility group (HMG) domain protein. Relative expression analysis of the HMG gene showed that its expression was higher in male gametophytes during the vegetative phase and monoecious gametophytes during both the vegetative and gametogenesis phases, but significantly lower in male gametophytes during the gametogenesis phase. These results provide a foundation for deciphering the sex-determining mechanism of U. pinnatifida.     

Structural and dynamic studies of two antigenic loops from haemagglutinin: A relaxation matrix approach

Summary We have investigated the dynamics and structural behaviour of two antigenic peptides using ¹H NMR. The two cyclic peptides mimic the antigenic site A of influenza haemagglutinin protein; they only differ in the way they were cyclized and in the size of their respective linkers. Homonuclear relaxation parameters extracted from a complete NOE matrix were interpreted in terms of local dynamics. A set of distance constraints was deduced from these parameters which allowed 3D models to be constructed using distance geometry. NOE back-calculation was used to check the validity of the final models. Strong variations of internal motion amplitude have been found in both peptides along their backbone. Motions with high amplitudes have been localized in the Gly-Pro-Gly sequence which forms a -turn in both structures.Abbreviations DSS 3-(trimethylsilyl)-1-propanesulfonic acid - D-loop aspartic acid loop - ELISA enzyme-linked immunoabsorbent assay - f.i.d free induction decay - HOHAHA homonuclear Hartmann-Hahn spectroscopy - HPLC high pressure liquid chromatography - K-loop lysine loop - NMR nuclear magnetic resonance - NOE nuclear Overhauser enhancement - NOESY nuclear Overhauser enhancement spectroscopy - r.m.s.d. root-mean-square deviation of atomic positions     

A chromosome-level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex-determining gene in the flatfish Solea senegalensis

Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis.     

乳腺良恶肿瘤患者超声弹性成像定量参数与临床分期、病理分子分型的相关性分析

摘要 目的：探讨乳腺良恶肿瘤患者超声弹性成像定量参数与临床分期、病理分子分型的相关性。方法：选择2020年1月至2022年12月来我院诊治的乳腺肿块患者85例,均行超声弹性成像检查,分析85例乳腺肿块患者的病理检查结果,对比良恶性肿瘤患者的弹性成像参数,对弹性应变率、直径变化率、面积比及三者联合绘制ROC曲线,分析不同乳腺肿瘤患者临床分期的弹性成像参数,分析乳腺肿瘤患者病理分子分型的弹性成像参数。结果：85例乳腺肿块患者中,良性肿块35例,恶性肿块50例。恶性组的弹性应变率、肿块直径、直径变化率、肿块面积、面积比明显较良性组低（P<0.05）。面积比ROC曲线AUC为0.580,以1.73为临界值,乳腺恶性肿瘤的诊断灵敏度为73.5 %,特异度为38.5 %;直径变化率ROC曲线AUC为0.630,以0.28为临界值,诊断灵敏度为75.5 %,特异度为47.5 %;弹性应变率ROC曲线AUC为0.790,以15.2 cm²为临界值,诊断灵敏度为64.5 %,特异度为83.5 %,以三者联合绘制ROC曲线,AUC为0.920,诊断灵敏度为82.5 %,特异度为92.5 %。乳腺恶性肿瘤患者TNM分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期者的弹性应变率、肿块直径、直径变化率、肿块面积、面积比对比有统计学意义（P<0.05）;其中Ⅳ期者的弹性应变率、肿块直径、直径变化率、肿块面积、面积比明显较Ⅲ、Ⅱ、Ⅰ期者高,Ⅲ期者明显较Ⅱ、Ⅰ期者高,Ⅱ期者明显较Ⅰ期高。乳腺恶性肿瘤患者Luminal A型者、Liminal B型者、Her2过表达型者、基底样型者的弹性应变率、肿块直径、直径变化率、肿块面积、面积比对比有统计学意义（P<0.05）;其中Liminal B型者的弹性应变率、肿块直径、直径变化率、肿块面积、面积比明显较Luminal A型者、Her2过表达型者、基底样型者高,Her2过表达型者明显较Luminal A型者、基底样型者高（P均<0.05）,Luminal A型者与基底样型者对比无统计学意义（P>0.05）。结论：超声弹性成像可用于乳腺良恶肿瘤的诊断,超声弹性成像定量参数可用于恶性乳腺肿瘤临床分期、Liminal B型、Her2过表达型的判断。