Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients

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Alternative Lengthening of Telomeres through Two Distinct Break-Induced Replication Pathways

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基于CRISPR/Cas9的基因编辑技术研究进展及其在植物中的应用

CRISPR/Cas9技术是利用RNA靶向引导Cas9核酸酶对基因组中的目标基因进行编辑的生物技术。近年来, 该技术的多种新型基因编辑器更新迅猛, 编辑效果愈加精细和高效, 在作物定向分子设计育种中展现出巨大的应用前景。该文对CRISPR/Cas9及其相关编辑器的技术原理、编辑效果和应用情况进行综述, 并探讨了该技术在应用中面临的问题、应对措施和发展前景, 旨在为相关领域的科研工作者提供参考。     

碳酸酐酶在红细胞分化发育过程中的功能研究

目前红系分化调控相关的研究主要集中在细胞因子、转录因子、lncRNA及表观遗传方面,为了对红系分化调控机制进行更加深入的解析,研究了碳酸酐酶在红系分化中的功能。碳酸酐酶可以高效催化二氧化碳的水合,但它在红细胞发育过程中的功能尚不清楚。利用脐带血来源的CD34⁺细胞在体外进行红细胞诱导分化,在分化过程中通过慢病毒介导的基因敲降的方法能够降低碳酸酐酶1和碳酸酐酶2的表达,并使用流式细胞仪检测红细胞的生成和分化效率。研究结果表明,与对照组相比,碳酸酐酶1的表达缺陷使红细胞的晚期分化明显受阻,而碳酸酐酶2的表达缺陷则将红细胞的分化阻滞在早期阶段。研究结果表明,虽然作用窗口不同,但碳酸酐酶1和碳酸酐酶2在红系分化的过程中均发挥着重要的调控作用,这一发现对将来在体外红细胞生成具有指导意义。     

Engineered blood and lymphatic capillaries in 3-D VEGF-fibrin-collagen matrices with interstitial flow

In vitro endothelial cell organization into capillaries is a long standing challenge of tissue engineering. We recently showed the utility of low level interstitial flow in guiding the organization of endothelial cells through a 3-D fibrin matrix-containing covalently bound vascular endothelial growth factor (VEGF). Here this synergistic phenomenon was extended to explore the effects of matrix composition on in vitro capillary morphogenesis of human blood versus lymphatic endothelial cells (BECs and LECs). Different mixtures of fibrin and collagen were used in conjunction with constant concentrations of matrix-bound VEGF and slow interstitial flow over 10 days. Interestingly, the BECs and LECs each showed a distinct preference in terms of organization for matrix composition: LECs organized the most extensively in a fibrin-only matrix, while BEC organization was optimized in the compliant collagen-containing matrices. Furthermore, the BECs and LECs produced architecturally different structures; while BECs organized in thick, branched networks containing wide lumen, the LECs were elongated into slender, overlapping networks with fine lumen. These data demonstrate the importance of the 3-D matrix composition in facilitating and coordinating BEC and LEC capillary morphogenesis, which is important for in vitro vascularization of engineered tissues.     

Dipolar relaxation in a lipid bilayer detected by a fluorescent probe, 4'-dimethylaminochalcone

The dynamic behavior of polar molecules in egg phosphatidylcholine (PC) bilayers has been studied using a membrane fluorescent probe, 4'-dimethylaminochalcone (DMAC). Time and spectrally resolved fluorescence spectroscopy of DMAC incorporated in PC liposomes, as compared to studies of the probe in organic solvents, shows the existence of two independent populations, associated with different extent and speed of dipolar solvent relaxation. The first DMAC population represents approximately 69% of the fluorescence-emitting molecules, has a short fluorescence decay time (0.32 ns) and undergoes Stokes shift of 80 nm. The remaining 31% fraction of DMAC molecules has a decay time of 0.74 ns and undergoes a high (106 nm) Stokes shift. A fraction of the shift, ca. 24 nm for the first and 46 nm for the second population, is attributed to the fast (<0.1 ns) rotational relaxation of nearby dipolar molecules, which might be water. This two-state model accounts well for the detailed fluorescence properties of DMAC in egg PC, i.e. its broadened steady-state spectrum, its average fluorescence quantum yield and its complex wavelength-dependent fluorescence decays.     

Hepatocytes--the choice to investigate drug metabolism and toxicity in man: in vitro variability as a reflection of in vivo

The pharmaceutical industry is committed to marketing safer drugs with fewer side effects, predictable pharmacokinetic properties and quantifiable drug-drug interactions. Drug metabolism is a major determinant of drug clearance and interindividual pharmacokinetic differences, and an indirect determinant of the clinical efficacy and toxicity of drugs. Progressive advances in the knowledge of metabolic routes and enzymes responsible for drug biotransformation have contributed to understanding the great metabolic variations existing in human beings. Phenotypic as well genotypic differences in the expression of the enzymes involved in drug metabolism are the main causes of this variability. However, only a minor part of phenotypic variability in man is attributable to gene polymorphisms, thus making the definition of a normal liver complex. At present, the use of human in vitro hepatic models at early preclinical stages means that the process of selecting drug candidates is becoming much more rational. Cultured human hepatocytes are considered to be the closest model to human liver. However, the fact that hepatocytes are located in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism variability observed in vitro actually reflect that of the liver in vivo? By comparing the metabolism of a model compound both in vitro and in vivo in the same individual, a good correlation between the in vitro and in vivo relative abundance of oxidized metabolites and the hydrolysis of the compound was observed. Thus, it is reasonable to consider that the variability observed in human hepatocytes reflects the existing phenotypic heterogeneity of the P450 expression in human liver.     

The pivotal role of hepatocytes in drug discovery

This review promotes the value of isolated hepatocytes in modern Drug Discovery programmes and outlines how increased understanding, particularly in the area of in vitro-in vivo extrapolation (IVIVE), has led to more widespread use. The importance of in vitro metabolic intrinsic clearance data for predicting in vivo clearance has been acknowledged for several years and the greater utility of hepatocytes, compared with hepatic microsomes and liver slices, for this application is discussed. The application of hepatocytes in predicting drug-drug interactions (DDIs) resulting from reversible and irreversible (time-dependent) inhibition is relatively novel but affords the potential to study both phase I and phase II processes together with any impact of drug efflux and/or uptake (cellular accumulation). Progress in this area is reviewed along with current opinions on the comparative use of primary hepatocytes and higher throughput reporter gene-based systems for studying cytochrome P450 (CYP) induction. The appreciation of the role of transporter proteins in drug disposition continues to evolve. The study of hepatic uptake using isolated hepatocytes and the interplay between drug transport and metabolism with respect to both clearance and DDIs and subsequent IVIVE is also considered.     

Describing maize (Zea Mays L.) landrace persistence in the Bajío of Mexico: A survey of 1940s and 1950s collection locations

Passport data for Mexico’s Guanajuato State were used to locate the sites where maize was collected in the 1940s and 1950s in an effort to document and conserve diversity. A map presenting survey points illustrates that collections have occurred repeatedly in the same locations. Observations of these locations reveal that urbanization and industrialization, not high yielding varieties, are displacing traditional varieties. Non-linear principal components analysis was used to assess associations between variables in areas where maize persists. Landraces appear to be associated with mountains and mesas, mixed cropping, little or no access to irrigation and areas classified as having low agricultural capacity; conversely, landraces have more commonly been replaced in areas of high agricultural capacity. The areas of high agriculture capacity, located in the riparian areas and plains, also have been the easiest to develop for urban and industrial use. Increasingly high rates of urbanization and development in areas of high agriculture capacity will impede the conservation of crop diversity in these areas.     

The motility and dynamic properties of intermediate filaments and their constituent proteins

Intermediate filament (IF) proteins exist in multiple structural forms within cells including mature IF, short filaments or 'squiggles', and non-filamentous precursors called particles. These forms are interconvertible and their relative abundance is IF type, cell type- and cell cycle stage-dependent. These structures are often associated with molecular motors, such as kinesin and dynein, and are therefore capable of translocating through the cytoplasm along microtubules. The assembly of mature IF from their precursor particles is also coupled to translation. These dynamic properties of IF provide mechanisms for regulating their reorganization and assembly in response to the functional requirements of cells. The recent findings that IF and their precursors are frequently associated with signaling molecules have revealed new functions for IF beyond their more traditional roles as mechanical integrators of cells and tissues.