The Beneficial Effects of Antifreeze Proteins in the Vitrification of Immature Mouse Oocytes

Antifreeze proteins (AFPs) are a class of polypeptides that permit organismal survival in sub-freezing environments. The purpose of this study was to investigate the effect of AFP supplementation on immature mouse oocyte vitrification. Germinal vesicle-stage oocytes were vitrified using a two-step exposure to equilibrium and vitrification solution in the presence or absence of 500 ng/mL of AFP III. After warming, oocyte survival, in vitro maturation, fertilization, and embryonic development up to the blastocyst stage were assessed. Spindle and chromosome morphology, membrane integrity, and the expression levels of several genes were assessed in in vitro matured oocytes. The rate of blastocyst formation was significantly higher and the number of caspase-positive blastomeres was significantly lower in the AFP-treated group compared with the untreated group. The proportion of oocytes with intact spindles/chromosomes and stable membranes was also significantly higher in the AFP group. The AFP group showed increased Mad2, Hook-1, Zar1, Zp1, and Bcl2 expression and lower Eg5, Zp2, Caspase6, and Rbm3 expression compared with the untreated group. Supplementation of the vitrification medium with AFP has a protective effect on immature mouse oocytes, promoting their resistance to chilling injury. AFPs may preserve spindle forming ability and membrane integrity at GV stage. The fertilization and subsequent developmental competence of oocytes may be associated with the modulation of Zar1, Zp1/Zp2, Bcl2, Caspase6, and Rbm3

Directed Induction of Functional Motor Neuron-Like Cells from Genetically Engineered Human Mesenchymal Stem Cells

Cell replacement using stem cells is a promising therapeutic approach to treat degenerative motor neuron (MN) disorders, such as amyotrophic lateral sclerosis and spinal cord injury. Human bone marrow-derived mesenchymal stem cells (hMSCs) are a desirable cell source for autologous cell replacement therapy to treat nervous system injury due to their plasticity, low immunogenicity, and a lower risk of tumor formation than embryonic stem cells. However, hMSCs are inefficient with regards to differentiating into MN-like cells. To solve this limitation, we genetically engineered hMSCs to express MN-associated transcription factors, Olig2 and Hb9, and then treat the hMSCs expressing Olig2 and Hb9 with optimal MN induction medium (MNIM). This method of induction led to higher expression (>30% of total cells) of MN markers. Electrophysiological data revealed that the induced hMSCs had the excitable properties of neurons and were able to form functional connections with muscle fibers in vitro. Furthermore, when the induced hMSCs were transplanted into an injured organotypic rat spinal cord slice culture, an ex vivo model of spinal cord injury, they exhibited characteristics of MNs. The data strongly suggest that induced Olig2/Hb9-expressing hMSCs were clearly reprogrammed and directed toward a MN-like lineage. We propose that methods to induce Olig2 and Hb9, followed by further induction with MNIM have therapeutic potential for autologous cell replacement therapy to treat degenerative MN disorders

Magnetic Iron Oxide Nanoparticles: Synthesis and Surface Functionalization Strategies

Surface functionalized magnetic iron oxide nanoparticles (NPs) are a kind of novel functional materials, which have been widely used in the biotechnology and catalysis. This review focuses on the recent development and various strategies in preparation, structure, and magnetic properties of naked and surface functionalized iron oxide NPs and their corresponding application briefly. In order to implement the practical application, the particles must have combined properties of high magnetic saturation, stability, biocompatibility, and interactive functions at the surface. Moreover, the surface of iron oxide NPs could be modified by organic materials or inorganic materials, such as polymers, biomolecules, silica, metals, etc. The problems and major challenges, along with the directions for the synthesis and surface functionalization of iron oxide NPs, are considered. Finally, some future trends and prospective in these research areas are also discussed

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Probing optical-phonon propagation in GaAs/AlxGa1-xAs quantum-well samples via their nonequilibrium population

We develop a theoretical model to analyze a nonequilibrium optical- (LO-) phonon population by Raman scattering in GaAs/AlxGa1-xAs quantum webs. With the assumption of bulklike hot-electron relaxation, the effect of LO-phonon confinement on a nonequilibrium optical-phonon population (NOP) is isolated. Our analysis shows that the decrease in spatial extent or coherence length of LO phonons is reflected by a decrease in NOP. This is because the contributions from large q wave vectors with small occupation numbers dominate as the spatial extent decreases. Our method is applied to explain picosecond Raman-scattering experiments on GaAs/AlxGa1-xAs. The increasing NOP with decreasing x is interpreted as the result of an increase in the coherence length of LO phonons, since for smaller x, the AlxGa1-xAs barrier is no longer effective in localizing GaAs LO phonons within the well. Using this model, we also deduce coherence length of LO phonons as a function of x. Our results show that for values of x between 0.2 and 0.4, the GaAs LO phonon in GaAs/AlxGa1-xAs quantum wells changes from a bulklike propagating mode to one localized within the wells