Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer's disease

Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (Abeta). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 microm was achieved. FTIRM results showed that the amyloid plaques have elevated beta-sheet content, as demonstrated by a strong amide I absorbance at 1625cm(-1). Using SXRF microprobe, we find that AD tissue also contains "hot spots" of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The "hot spots" of accumulated Zn and Cu were co-localized with beta-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated beta-sheet content in Abeta plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD.     

Language Differences in the Brain Network for Reading in Naturalistic Story Reading and Lexical Decision

Differences in how writing systems represent language raise important questions about whether there could be a universal functional architecture for reading across languages. In order to study potential language differences in the neural networks that support reading skill, we collected fMRI data from readers of alphabetic (English) and morpho-syllabic (Chinese) writing systems during two reading tasks. In one, participants read short stories under conditions that approximate natural reading, and in the other, participants decided whether individual stimuli were real words or not. Prior work comparing these two writing systems has overwhelmingly used meta-linguistic tasks, generally supporting the conclusion that the reading system is organized differently for skilled readers of Chinese and English. We observed that language differences in the reading network were greatly dependent on task. In lexical decision, a pattern consistent with prior research was observed in which the Middle Frontal Gyrus (MFG) and right Fusiform Gyrus (rFFG) were more active for Chinese than for English, whereas the posterior temporal sulcus was more active for English than for Chinese. We found a very different pattern of language effects in a naturalistic reading paradigm, during which significant differences were only observed in visual regions not typically considered specific to the reading network, and the middle temporal gyrus, which is thought to be important for direct mapping of orthography to semantics. Indeed, in areas that are often discussed as supporting distinct cognitive or linguistic functions between the two languages, we observed interaction. Specifically, language differences were most pronounced in MFG and rFFG during the lexical decision task, whereas no language differences were observed in these areas during silent reading of text for comprehension.     

Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency

Glycosylation, an important post-translation modification, could alter biological activity or influence the clearance rates of glycoproteins. We report here the first example of a heterozygous protein deficiency leading to metabolic alteration of N-glycan structures in residual secreted protein. Analysis of C1 esterase inhibitor (C1INH) glycans from normal individuals and patients with hereditary deficiency of C1INH demonstrated identical O-glycan structures but the N-glycans of patients with a heterozygous genetic deficiency were small, highly charged and lacked sialidase releasable N-acetylneuraminic acid. Structural studies indicate that the charge character of these aberrant N-glycan structures may result from the presence of mannose-6-phosphate residues. These residues might facilitate secretion of C1INH through an alternate lysosomal pathway, possibly serving as a compensatory mechanism to enhance plasma levels of C1INH in these deficient patients.     

Topological constraints in nucleic acid hybridization kinetics

A theoretical examination of kinetic mechanisms for forming knots and links in nucleic acid structures suggests that molecules involving base pairs between loops are likely to become topologically trapped in persistent frustrated states through the mechanism of ‘helix-driven wrapping’. Augmentation of the state space to include both secondary structure and topology in describing the free energy landscape illustrates the potential for topological effects to influence the kinetics and function of nucleic acid strands. An experimental study of metastable complementary ‘kissing hairpins’ demonstrates that the topological constraint of zero linking number between the loops effectively prevents conversion to the minimum free energy helical state. Introduction of short catalyst strands that break the topological constraint causes rapid conversion to full duplex.     

利用假型反转录病毒对大部分胰腺切除后再生细胞的世系追踪

胰腺是一个重要的内外分泌混合腺, 胰腺发生损伤后能够再生。为了探讨胰腺活体细胞世系追踪的方法和胰腺损伤后再生细胞的来源,分别通过胰腺伤口涂抹并胰内注射、尾静脉注射及腹腔注射三种方法, 利用假型反转录病毒对成体小鼠大部分切除后胰腺的细胞进行世系追踪。结果发现在活体条件下, 与尾静脉注射及腹腔注射法相比, 胰腺伤口涂抹并胰腺内注射反转录病毒的方法能够更有效的标记胰腺细胞; 而且, 通过对标记细胞的世系追踪研究证明, 在胰腺损伤后, 胰腺腺泡细胞能够接受损伤信号刺激发生再生。为今后进一步利用反转录假病毒对活体胰腺进行细胞命运追踪研究奠定基础, 为利用反转录病毒载体进行胰腺疾病的基因治疗提供线索。     

DISTRIBUTION,MORPHOLOGICAL DIVERSITY AND EVIDENCE FOR POLYPLOIDY IN NORTH AMERICAN ZYGNEMATACEAE (CHLOROPHYTA)1

Large-scale collections of Zygnemataceae in the continental United States of America were made between March and August in 1982, 1983, and 1984. Collections were made on a 31000-km transect through 35 states. Zygnemataceae were found at 318 sites was inspected. Temperature average 19°C and p^H averaged 6.1 over all sites. Algal strains in collections were identified to genus, characterized for filament width, chloroplast number, and end wall type, then photographed and isolated into unialgal culture. Spirogyra was the most common genus collected(632 strains), followed in abundance by Zygnema (174 Strains) and Mougeotia (135 strains). These three genera contained 95% of the strains collected and were equally widely distributed. Strains of the three genera frequently occurred together; no genus displayed evidence of habitat specialization among the three habitat types: flowing water, permanent ponds or lakes, and temporary pools. In Spirogyra, strains with plane (flat) end walls were four times more abundant than those with replicate (interlocking) end walls. Spirogyra with plane end walls showed more variation in filament width than Zygnema, Mougeotia, or Spirogyra with replicate end walls. In Spirogyra with plane end walls, filament width was correlted with nuclear DNA content and number of strains found per collection site was twice that of other genera or Spirogyra, with replicate end walls. Spirogyra strains wider than 70 μm were more frequent on the northern part of the transect. It is proposed that polyploidy may be of widespread occurrence in Spirogyra with plane end walls and that associated morphological plasticity may account for the high apparent specied diversity and survival of the genus in a wider variety of microhabitats than occupied by other Zygnemataceae.     

小RNA病毒和小DNA病毒的三维结构模型

本文综述了小RNA病毒和小DNA病毒的主要结构特征,绘制出了它们的三维结构模型,从中找出了两者间的共同点和差异,为进一步研究两种病毒提供了依据。     

玉米转录因子zmCBF1的凝胶阻滞分析

凝胶阻滞试验是分析核酸与蛋白质相互作用的有效方法,在转录因子的功能分析中得到了广泛应用。以玉米转录因子zmCBF1与顺式元件CRT的结合为例,建立了用于转录因子分析的GRA/EMSA实验体系,并对其在应用中可能出现的问题进行了分析。     

Fe- and S-Metabolizing Microbial Communities Dominate an AMD-Contaminated River Ecosystem and Play Important Roles in Fe and S Cycling

Indigenous Fe- and S-metabolizing bacteria play important roles both in the formation and the natural attenuation of acid mine drainage (AMD). Due to its low pH and Fe-S-rich waters, a river located in the Dabaoshan Mine area provides an ideal opportunity to study indigenous Fe- and S-metabolizing microbial communities and their roles in biogeochemical Fe and S cycling. In this work, water and sediment samples were collected from the river for physicochemical, mineralogical, and microbiological analyses. Illumina MiSeq sequencing indicated higher species richness in the sediment than in the water. Sequencing also found that Fe- and S-metabolizing bacteria were the dominant microorganisms in the heavily and moderately contaminated areas. Fe- and S-metabolizing bacteria found in the water were aerobes or facultative anaerobes, including Acidithiobacillus, Acidiphilium, Thiomonas, Gallionella, and Leptospirillum. Fe- and S-metabolizing bacteria found in the sediment belong to microaerobes, facultative anaerobes, or obligatory anaerobes, including Acidithiobacillus, Sulfobacillus, Thiomonas, Gallionella, Geobacter, Geothrix, and Clostridium. Among the dominant genera in the sediment, Geobacter and Geothrix were rarely detected in AMD-contaminated natural environments. Canonical correspondence analysis indicated that pH, S, and Fe concentration gradients were the most important factors in structuring the river microbial community. Moreover, a scheme explaining the biogeochemical Fe and S cycling is advanced in light of the Fe and S species distribution and the identified Fe- and S-metabolizing bacteria.