Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis

Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1(G93A)). Treating symptomatic SOD1(G93A) mice with ASC-CM significantly increased post-onset survival time and lifespan. Moreover, SOD1(G93A) mice given ASC-CM treatment showed high motor neuron counts, less activation of microglia and astrocytes at an early symptomatic stage in the spinal cords under immunohistochemical analysis. SOD1(G93A) mice treated with ASC-CM for 7 days showed reduced levels of phosphorylated p38 (pp38) in the spinal cord, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death. Additionally, the levels of α-II spectrin in spinal cords were also inhibited in SOD1(G93A) mice treated with ASC-CM for 3 days. Interestingly, nerve growth factor (NGF), a neurotrophic factor found in ASC-CM, played a significant role in the protection of neurodegeneration inSOD1(G93A) mouse. These results indicate that ASC-CM has the potential to develop into a novel and effective therapeutic treatment for ALS

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

Polarimetric Imaging of Large Cavity Structures in the Pre-transitional Protoplanetary Disk around PDS 70: Observations of the disk

We present high resolution H-band polarized intensity (PI; FWHM = 0."1: 14 AU) and L'-band imaging data (FWHM = 0."11: 15 AU) of the circumstellar disk around the weak-lined T Tauri star PDS 70 in Centaurus at a radial distance of 28 AU (0."2) up to 210 AU (1."5). In both images, a giant inner gap is clearly resolved for the first time, and the radius of the gap is ~70 AU. Our data show that the geometric center of the disk shifts by ~6 AU toward the minor axis. We confirm that the brown dwarf companion candidate to the north of PDS 70 is a background star based on its proper motion. As a result of SED fitting by Monte Carlo radiative transfer modeling, we infer the existence of an optically thick inner disk at a few AU. Combining our observations and modeling, we classify the disk of PDS 70 as a pre-transitional disk. Furthermore, based on the analysis of L'-band imaging data, we put an upper limit mass of companions at ~30 to ~50MJ within the gap. Taking account of the presence of the large and sharp gap, we suggest that the gap could be formed by dynamical interactions of sub-stellar companions or multiple unseen giant planets in the gap.Comment: accepted by APJ

Timing of uplift and evolution of the Lüliang Mountains, North China Craton

This study analyses evidence for reformed basin development and basin-mountain coupling associated with development of the Ordos Basin and the Lüliang Mountains, China. Gaining an improved understanding of the timing and nature of uplift and evolution of the Lüliang Mountains is important for the reconstruction of the eastern sedimentary boundary of the Ordos Basin (a major petroliferous basin) as well as for providing insight into the evolution and breakup of the North China Craton (NCC). Based on systematic sampling for fission track analysis, it is suggested that the main phase of uplift of the Lüliang Mountains occurred since later part of the Early Cretaceous. Three evolutionary stages of uplift and development are identified: slow initial uplift (120–65 Ma), accelerated uplift (65–23 Ma), and intensive uplift (23 Ma to present), with the majority of the uplift activity having occurred during the Cenozoic. The history of uplift is non-equilibrium and exhibits complexity in temporal and spatial aspects. The middle and northern parts of the Lüliang Mountains were uplifted earlier than the southern part. The most intensive episode of uplift activity commenced in the Miocene and was associated with a genetic coupling relationship with the eastern neighboring Cenozoic Shanxi Grabens. The uplifting and evolutionary processes of the Lüliang Mountains area since later part of the Early Cretaceous share a unified regional geodynamic setting, which was accompanied by uplift of the Mesozoic Ordos Basin and development of the neighboring Cenozoic Shanxi Grabens. Collectively, this regional orogenic activity is related principally to the far-field effects of both the compression sourced from the southwestern Tibet Plateau and westward subduction of the Pacific Plate in Cenozoic

Comparison of phase structures and surface free energy values for the coatings synthesised from linear polyurethanes and from waterborne polyurethane cationomers

WAXS, DSC and AFM methods were employed to compare phase structures of the coatings obtained from waterborne polyurethane cationomers which had been synthesised in the reaction of some diisocyanates (MDI, IPDI, TDI and HDI) with polyoxyethylene glycols (M = 600 and 2,000) and butane1,4-diol or N-methyl- or N-butyldiethanolamine and 2,2,3,3-tetrafluoro-1,4-butanediol. The structures were also analysed of the coatings derived from linear polyurethanes which had been synthesised on the basis of similar raw materials. Better rigidity was found for generally amorphous cationomer coats. Changes were discussed in the surface free energy (SFE) values and in their components, as calculated independently with the use of the van Oss–Good and Owens–Wendt methods. Polyurethane coats turned out more hydrophobic as compared to cationomer ones. In both coat types, fluorine incorporated into cationomers contributed to lower SFE values: from 50 down to about 30 mJ/m2

Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10

9月20日，《科学》子刊《科学•进展》（Science Advances）刊出了我校夏宁邵教授团队发表的题为“Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10”的研究论文。该研究首次发现手足口病重要病原体柯萨奇病毒A组10型（CVA10）不同类型病毒颗粒共有的优势中和表位，揭示了病毒颗粒及其与优势中和抗体复合物的精确三维结构，阐明了中和抗体的功能与作用机制，为新型疫苗和治疗药物的研制提供了重要的理论基础。 该研究首次揭示并描绘了CVA10的病毒颗粒及其优势中和表位的精确特征，发现了具有良好应用潜能的治疗性中和抗体，为新型疫苗和特异性治疗药物的研究提供了关键基础。 我校夏宁邵教授、程通副教授和美国加州大学洛杉矶分校纳米系统研究所Z. Hong Zhou（周正洪）教授、美国加州大学圣地亚哥分校颜晓东博士为该论文的共同通讯作者。我校博士生朱瑞、徐龙发博士后、郑清炳工程师、李少伟教授和美国加州大学洛杉矶分校崔彦祥博士后为该论文共同第一作者。【Abstract】Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has made therapeutic antibody identification a public health priority. By targeting a local isolate, CVA10-FJ-01, we obtained a potent antibody, 2G8, against all three capsid forms of CVA10. We show that 2G8 exhibited both 100% preventive and 100% therapeutic efficacy against CVA10 infection in mice. Comparisons of the near-atomic cryo–electron microscopy structures of the three forms of CVA10 capsid and their complexes with 2G8 Fab reveal that a single Fab binds a border region across the three capsid proteins (VP1 to VP3) and explain 2G8’s remarkable cross-reactivities against all three capsid forms. The atomic structures of this first neutralizing antibody of CVA10 should inform strategies for designing vaccines and therapeutics against CVA10 infections.This work was supported by grants from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (2017ZX10304402-002-003), the National Natural Science Foundation of China (31670933 and 81801646), and the National Institutes of Health (R37-GM33050, GM071940, DE025567, and AI094386). We acknowledge the use of instruments at the Electron Imaging Center for Nanomachines supported by the University of California, Los Angeles and by instrumentation grants from NIH (1S10RR23057 and 1U24GM116792) and NSF (DBI-1338135 and DMR-1548924). 该研究获得了国家自然科学基金、新药创制国家科技重大专项、传染病防治国家科技重大专项和美国国立卫生研究院基金的资助

Unique Neoproterozoic carbon isotope excursions sustained by coupled evaporite dissolution and pyrite burial

The Neoproterozoic era witnessed a succession of biological innovations that culminated in diverse animal body plans and behaviours during the Ediacaran–Cambrian radiations. Intriguingly, this interval is also marked by perturbations to the global carbon cycle, as evidenced by extreme fluctuations in climate and carbon isotopes. The Neoproterozoic isotope record has defied parsimonious explanation because sustained 12C-enrichment (low δ13C) in seawater seems to imply that substantially more oxygen was consumed by organic carbon oxidation than could possibly have been available. We propose a solution to this problem, in which carbon and oxygen cycles can maintain dynamic equilibrium during negative δ13C excursions when surplus oxidant is generated through bacterial reduction of sulfate that originates from evaporite weathering. Coupling of evaporite dissolution with pyrite burial drives a positive feedback loop whereby net oxidation of marine organic carbon can sustain greenhouse forcing of chemical weathering, nutrient input and ocean margin euxinia. Our proposed framework is particularly applicable to the late Ediacaran ‘Shuram’ isotope excursion that directly preceded the emergence of energetic metazoan metabolisms during the Ediacaran–Cambrian transition. Here we show that non-steady-state sulfate dynamics contributed to climate change, episodic ocean oxygenation and opportunistic radiations of aerobic life during the Neoproterozoic era

Structural Analysis of a Repetitive Protein Sequence Motif in Strepsirrhine Primate Amelogenin

Strepsirrhines are members of a primate suborder that has a distinctive set of features associated with the development of the dentition. Amelogenin (AMEL), the better known of the enamel matrix proteins, forms 90% of the secreted organic matrix during amelogenesis. Although AMEL has been sequenced in numerous mammalian lineages, the only reported strepsirrhine AMEL sequences are those of the ring-tailed lemur and galago, which contain a set of additional proline-rich tandem repeats absent in all other primates species analyzed to date, but present in some non-primate mammals. Here, we first determined that these repeats are present in AMEL from three additional lemur species and thus are likely to be widespread throughout this group. To evaluate the functional relevance of these repeats in strepsirrhines, we engineered a mutated murine amelogenin sequence containing a similar proline-rich sequence to that of Lemur catta. In the monomeric form, the MQP insertions had no influence on the secondary structure or refolding properties, whereas in the assembled form, the insertions increased the hydrodynamic radii. We speculate that increased AMEL nanosphere size may influence enamel formation in strepsirrhine primates

Transcript Annotation in FANTOM3: Mouse Gene Catalog Based on Physical cDNAs

The international FANTOM consortium aims to produce a comprehensive picture of the mammalian transcriptome, based upon an extensive cDNA collection and functional annotation of full-length enriched cDNAs. The previous dataset, FANTOM2, comprised 60,770 full-length enriched cDNAs. Functional annotation revealed that this cDNA dataset contained only about half of the estimated number of mouse protein-coding genes, indicating that a number of cDNAs still remained to be collected and identified. To pursue the complete gene catalog that covers all predicted mouse genes, cloning and sequencing of full-length enriched cDNAs has been continued since FANTOM2. In FANTOM3, 42,031 newly isolated cDNAs were subjected to functional annotation, and the annotation of 4,347 FANTOM2 cDNAs was updated. To accomplish accurate functional annotation, we improved our automated annotation pipeline by introducing new coding sequence prediction programs and developed a Web-based annotation interface for simplifying the annotation procedures to reduce manual annotation errors. Automated coding sequence and function prediction was followed with manual curation and review by expert curators. A total of 102,801 full-length enriched mouse cDNAs were annotated. Out of 102,801 transcripts, 56,722 were functionally annotated as protein coding (including partial or truncated transcripts), providing to our knowledge the greatest current coverage of the mouse proteome by full-length cDNAs. The total number of distinct non-protein-coding transcripts increased to 34,030. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species