The role of Islet-1 in cell specification,differentiation,and maintenance of phenotypes in the vertebrate neural retina

Many blinding diseases,such as retinitis pigmentosa,age-related macular degeneration,and glaucoma involve the permanent loss of retinal neurons,especially photoreceptors or the centrally projecting retinal ganglion cells.Stem cells have been proposed as a potential source of cells for neuronal transplantation.

P2X receptors in maintenance and differentiation of neural progenitor cells

Purinergic receptors are among the first cell surface receptors expressed during embryonic development （Burnstock and Ulrich, 2011）. These are characterized based on their pharmacological properties of being activated by adenosine or purine/pyrimidine nucleotides as P1 and P2 receptors. P2 receptors are further classified by their structure as P2Y metabotropic and P2X ionotropic receptors.

Effect of etoposide plus thalidomide as maintenance therapy on progression-free survival of elderly patients with advanced non-small cell lung cancer

Objective The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer（NSCLC） without disease progression after first-line chemotherapy.Methods After four to six cycles of platinum-based first-line therapy, 64 elderly patients with advanced NSCLC without disease progression who were treated in the General Hospital of Shenyang Military Region（China） from 2014 to 2016 were enrolled in this study. According to the different maintenance treatment methods, patients were divided as having received etoposide plus thalidomide therapy（treatment group, n = 32） and best supportive care（control group, n = 32）. Disease control and progression-free survival（PFS） were compared between the two groups. Results The recent curative effect objective response rates of the treatment group and the control group were 31.3% and 3.1%, respectively, and the disease control rates were 71.9% and 31.3%, respectively. The Kaplan-Meier survival curves of the two groups were significantly different（χ2 = 26.532, P = 0.001）. The median PFS for the treatment group and control group was 6.0 months [95% confidence interval（CI） = 4.3–7.9 months] and 3.2 months（95% CI = 2.6–3.8 months）, respectively. The side effects in the treatment group included hematologic abnormalities, gastrointestinal toxicity, and impaired liver function, which were relieved after symptomatic support therapy and drug withdrawal.Conclusion Etoposide plus thalidomide as maintenance therapy is associated with a significantly longer PFS with tolerable toxicity for elderly patients with advanced NSCLC.AcknowledgementThe authors would like to thank Liu Zhongzheng for his technical assistance.

Contributions of Individual Amino Acid Residues to the Endogenous CLV3 Function in Shoot Apical Meristem Maintenance in Arabidopsis

As a peptide hormone, CLV3 restricts the stem cell number in shoot apical meristem （SAM） by interacting with CLV1/CLV2/CRN/RPK2 receptor complexes. To elucidate how the function of the CLV3 peptide in SAM maintenance is established at the amino acid （AA） level, alanine substitutions were performed by introducing point mutations to individual residues in the peptide-coding region of CLV3 and its flanking sequences. Constructs carrying such substitutions, expressed under the control of CLV3 regulatory elements, were transformed to the clv3-2 null mutant to evaluate their efficiencies in complementing its defects in SAMs in vivo. These studies showed that aspartate-8, histidine-11, glycine-6, proline-4, arginine-1, and proline-9, arranged in an order of importance, were critical, while threonine-2, valine-3, serine-5, and the previously assigned hydroxylation and arabinosylation residue proline-7 were trivial for the endogenous CLV3 function in SAM maintenance. In contrast, substitutions of flanking residues did not impose much damage on CLV3. Complementation of different alanine-substituted constructs was confirmed by measurements of the sizes of SAMs and the WUS expression levels in transgenic plants. These studies established a complete contribution map of individual residues in the peptide-coding region of CLV3 for its function in SAM, which may help to understand peptide hormones in general.

Alternative splicing switching in stem cell lineages

The application of stem cells to regenerative medicine depends on a thorough understanding of the molecular mechanisms underlying their pluripotency. Many studies have identified key transcription factor-regulated transcriptional networks and chromatin landscapes of embryonic and a number of adult stem cells. In addition, recent publications have revealed another interesting molecular feature of stem cells-- a distinct alternative splicing pattern. Thus, it is possible that both the identity and activity of stem cells are maintained by stem cell-specific mRNA isoforms, while switching to different isoforms ensures proper differentiation. In this review, we will discuss the generality of mRNA isoform switching and its interaction with other molecular mechanisms to regulate stem cell pluripotency, as well as the reprogramming process in which differentiated cells are induced to become pluripotent stem cell-like cells （iPSCs）.