The magic of four： induction of pluripotent stem cells from somatic cells by Oct4, Sox2, Myc and Klf4

The developmental process from a fertilized egg to agrown adult is programmed with remarkable accuracy.While the genetic information of the fertilized egg and itsdescendent somatic cells are the same, it is the selectiveexpressions of the same genome that give rise to the 200or so different cell types in an adult. The differentiatedstates of these adult cells are maintained epigenetically,presumably through the modification of chromatins and theassociated histones. In higher mammals, it was thought thatthe differentiation process is irreversible until the successfulcloning of Dolly [1]. By transferring a nucleus from a fullydifferentiated cell in the mammary gland, Wilmut and col-leagues were able to generate an exact replica of a highermammal, the Doily [1]. This work not only demonstratedthat the genome of differentiated cells can be reprogrammedinto an embryonic state and then to resume a full-fledgeddevelopmental process to generate a normal adult, but alsorejuvenated the field of animal cloning. The prospect thata somatic cell from a patient may be reprogrammed to the     

EGF receptor—mediated intracellular calcium increase in human hepatoma BEL—7404 cells

Epidermal growth factor(EGF) induced intracellular free calcium ([Ca^2 ]i) response was studied in fura-2- or fluo-3-loaded human hepatoma cells of BEL-7404 cell line.Single cell[Ca^2 ]i analysis and [Ca^2 ]i measurement in cell populations revealed that EGF triggered a rapid[Ca^2 ]i increase in the dose-dependent and time-dependent manner.Pretreatment of cells with an endoplasmic reticulum(ER) Ca^2 -ATPase inhibitor,thapsigargin(TG) at 100nM concentration for 20 min,completely abolished EGF-induced [Ca^2 ]i increase,and chelating extracellular calcium by excess EGTA partially inhibited the increase.Furthermore,the expression of antisense EGF receptor sequence in BEL-7404 cells suppressed the [Ca^2 ]i response to EGF.The results suggest that EGF receptor-mediated [Ca^2 ]i increase in the human hepatoma cells is essentially dependent on the Ca^2 storage in ER.     

Paradoxal pharmacologic effects observed withβ-blocker agents on cardiac cells in culture

Summary The direct effects of propranolol and metoprolol were studied on cultured neonatal rat ventricular myocytes by recording cellular contraction with a video signal analyzer of cells movements. The experiments were performed on 3-d-old cultures forming a synchronously beating monolayer. The spontaneous beating frequency of preparations depended on cultures and varied from 100 to 330 beats/min with a peak for the interval 140 to 149 beats/min. Propranolol and metoprolol were tested at 1, 5, 10μM and 10, 50, 100μM, respectively. At these doses the twoβ-blockers induced chronotropic and inotropic effects in the same range. The two agents induced rapid and short-lasting negative inotropic effects, which were dose-dependent and delayed negative chronotropic effects even with the lowest doses. In some preparations paradoxal effects were evidenced: an increase of the amplitude or frequency of the contractions was observed. The results obtained with 5μM propranolol or 50μM metoprolol could be separated in two groups depending on the basal beating rate (〈 or 〉 to 150 beats/min). In cultures with a rapid frequency, the drugs had a marked negative chronotropic effect and, surprisingly, a positive inotropic effect was observed. These findings confirm the interdependence of the two parameters frequency and amplitude of contraction on this model, and evidence the interest of taking into account the control parameters before any interpretation.     

Differentiation profile of brain tumor stem cells： a comparative study with neural stem cells

Understanding of the differentiation profile of brain tumor stem cells （BTSCs）, the key ones among tumor cell population, through comparison with neural stem cells （NSCs） would lend insight into the origin of glioma and ultimately yield new approaches to fight this intractable disease. Here, we cultured and purified BTSCs from surgical glioma specimens and NSCs from human fetal brain tissue, and further analyzed their cellular biological behaviors, especially their differentiation property. As expected, NSCs differentiated into mature neural phenotypes. In the same differentiation condition, however, BTSCs exhibited distinguished differences. Morphologically, cells grew flattened and attached for the first week, but gradually aggregated and reformed floating tumor sphere thereafter. During the corresponding period, the expression rate of undifferentiated cell marker CD 133 and nestin in BTSCs kept decreasing, but 1 week later, they regained ascending tendency. Interestingly, the differentiated cell markers GFAP and β-tubulinlII showed an expression change inverse to that of undifferentiated cell markers. Taken together, BTSCs were revealed to possess a capacity to resist differentiation, which actually represents the malignant behaviors of glioma.     

How do resident stem cells repair the damaged myocardium?

It has been a decade since the monumental discovery of resident stem cells in the mammalian heart, and the following studies witnessed the continuous turnover of cardiomyocytes and vascular cells, maintaining the homeostasis of the organ. Recently, the autologous administration of c-kit-positive cardiac stem cells in patients with ischemic heart failure has led to an incredible outcome; the left ventricular ejection fraction of the celltreated group improved from 30% at the baseline to 38% after one year and to 42% after two years of cell injection. The potential underlying mechanisms, before and after cell infusion, are explored and discussed in this article. Some of them are related to the intrinsic property of the resident stem cells, such as direct differentiation, paracrine action, and immunomodulatory function, whereas others involve environmental factors, leading to cellular reverse remodeling and to the natural selection of "juvenile" cells. It has now been demonstrated that cardiac stem cells for therapeutic purposes can be prepared from tiny biopsied specimens of the failing heart as well as from frozen tissues, which may remarkably expand the repertoire of the strategy against various cardiovascular disorders, including non-ischemic cardiomyopathy and congenital heart diseases. Further translational investigations are needed to explore these possibilities.     

Blockage of IGF－1R signaling sensitizes urinary bladder cancer cells to mitomycin－mediated cytotoxicity

INTRODUCTIONtransitional cell carcinoma (TCC) of the bladder represents the fifth most preValent malignancy inwestern population. A major problem in the management of TCC is the low sensitivity to chemotherapy and the high recu-rrence after transurethral resection, which occupies a large proportion (approximately 40%) among bladder cancer patients[1, 21. Sodrug resistance remains a major and difficult problem to resolye in TCC chemotherapy. This phenomenon has often been ascribed to so…     

Beyond tumorigenesis： cancer stem cells in metastasis

The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.     

Say “NO” to ABA signaling in guard cells by S-nitrosylation of OST1

<正>Nitric oxide(NO),a gaseous compound,plays important roles in plant immunity,abiotic stress response and plant development[1].In plants,NO is synthesized through either oxidative or reductive route that is dependent on the nitrate reductases(NADH)1(NIA1)and NIA2.NO bioactivity is realized through redox-based post-translational protein     

TOTAL SYNTHESIS OF CRYSTALLINE BOVINE INSULIN

<正>We should like to communicate,as a result of our combined efforts for the past five years,this preliminary report on the total synthesis of crystalline bovine insulin,the structure of which was first elucidated by Sanger and coworkers[1]ten years ago.A number of papers on the synthetic work concerning insulin has been published during the past two years.Katsoyannis and coworkers[2,3].synthesized both the A and B chains of sheep insulin and,by combining them together according to the procedure of Dixon and Wardlow[4],observed only traces of insulin activity.Zahn,Meienhofer and co-     

Selective proliferation of human γδ T cells in vitro

The effect of monoethylphosphate (MEP,commercial available or synthesized) together with IL-2 on the selective proliferation of human γδT cells in vitro from peripheral blood mononuclear cells (PBMC) of healthy donors and of cancer patients was investigated.The γδT cells were stimulated by MEP to proliferate in a dose-dependent manner.The effect of synthesized MEP was 10 times greater than that of commercial MEP.When the PBMCs of healthy donors were cultured for 25 d in the medium containing different concentrations of MEP,the total cell number increased about 1000-3000 fold;and the ratio of γδT cells reached to 70-80%.The selective expansion of γδT cells depended on the synergic action of MEP and IL-2.The bulk cultured γδT cells exhibited obvious cytotoxic activities against allogenic tumor cell lines (SQ-5,K562 and Daudi) and autologous tumor cells.The culture system described here not only offers a simple method for obtaining a large number of γδT cells which may become a new effector in the adoptive immunotherapy,but also provides a useful model for the further studies of the structure and function of γδT cells in vitro.     

Altered expression of nuclear matrix proteins in etoposide induced apoptosis in HL－60 cells

INTRODUCTIIONThe nuclear matrix is an essential component ofthe nucleus which is important for the nuclear structural integrity and specific genomic functions[1, 2].Several articles have reported that the nuclear matrix, as a higher order framework structures, mightbe disassembled du-ring the apoptotic process[3-5].Accordingly3 nuclear lamins A/C or B have beenfound to decrease in apoptotic thymocytes[6], Tcells[7], and carcinoma cell line[8, 9]. The nucleolar protein B23, an obscure ma…     

The impact of atmospheric CO2 concentration enrichment on rice quality – A research review

Global atmospheric carbon dioxide concentration ([CO₂]) is increasing rapidly. The Intergovernmental Panel on Climate Change estimated that atmospheric [CO₂] has risen from approximately 280 μmol mol^?1 in pre-industrial times to approximately 381 μmol mol^?1 at present and will reach 550 μmol mol^?1 by 2050. In the absence of strict emission controls, atmospheric [CO₂] is likely to reach 730–1020 μmol mol^?1 by 2100. Rising atmospheric [CO₂] is the primary driver of global warming, but as the principal substrate for photosynthesis it also directly affects the yield and quality of crops. Food quality is receiving much more attentions recently, however, compared with grain yield, our understanding in the response of grain quality to elevated [CO₂] is very limited. Rice (Oryza sativa L.) is one of the most important crops in the world and the first staple food in Asia, providing nutrition to a large proportion of the world’s population. Elevated [CO₂] leads to numerous physiological changes in rice crops, such as changes in the photosynthesis and assimilate translocation, nutrient uptake and translocation, water relation, and altered gene expression and enzyme activity. These altered processes are very likely to affect the chemical and physical characteristics of rice grains. In this review, we first describe main characteristics of rice grain quality, and then summarize findings in literature related to the impact of elevated [CO₂] on grain quality falling into four categories: processing quality, appearance, cooking and eating quality, and nutritional quality, as well as the possible mechanisms responsible for the observed impacts. Elevated [CO₂] caused serious deterioration of processing suitability, in particular, head rice percentage was significantly decreased. In most cases, elevated [CO₂] increased chalkiness of rice grains. The evaluation of physicochemical characteristics together with starch Rapid Visco Analyser (RVA) properties indicated no change or small changes in cooking and eating quality under elevated [CO₂], and these changes could not be detected by sensory taste panel evaluation. Elevated [CO₂] significantly decreased nitrogen or protein concentration in rice grains, while in most cases other macro- and micro-nutrients showed no change or decrease in concentration. In addition, the responses of rice quality to elevated [CO₂] might be modified by varieties, applied fertilizer rates or gas fumigation methodologies. The available information in the literature indicates a clear tendency of quality deterioration and thus lower commercial value for rice grains grown under a projected high CO₂ environment. Understanding the factors causing quality deterioration in rice and the related biological mechanisms might be the utmost important scientific theme in future research. Here we also discuss the necessity of formulating adaptation strategies for rice production in future atmospheric environments, nevertheless, the increase in yield, the improvement in quality and stress resistance of rice should be combined and integrated into the adaptation approaches. Compared with enclosure studies, the field experiments using Free-Air CO₂ Enrichment (FACE) system provide sufficient experimental space and the most realistic mimic of a future high CO₂ atmosphere, and give scientists perhaps the best opportunity to achieve multiple goals.     

The impact of atmospheric CO2 concentration enrichment on rice quality – A research review

Global atmospheric carbon dioxide concentration ([CO₂]) is increasing rapidly. The Intergovernmental Panel on Climate Change estimated that atmospheric [CO₂] has risen from approximately 280 μmol mol^?1 in pre-industrial times to approximately 381 μmol mol^?1 at present and will reach 550 μmol mol^?1 by 2050. In the absence of strict emission controls, atmospheric [CO₂] is likely to reach 730–1020 μmol mol^?1 by 2100. Rising atmospheric [CO₂] is the primary driver of global warming, but as the principal substrate for photosynthesis it also directly affects the yield and quality of crops. Food quality is receiving much more attentions recently, however, compared with grain yield, our understanding in the response of grain quality to elevated [CO₂] is very limited. Rice (Oryza sativa L.) is one of the most important crops in the world and the first staple food in Asia, providing nutrition to a large proportion of the world’s population. Elevated [CO₂] leads to numerous physiological changes in rice crops, such as changes in the photosynthesis and assimilate translocation, nutrient uptake and translocation, water relation, and altered gene expression and enzyme activity. These altered processes are very likely to affect the chemical and physical characteristics of rice grains. In this review, we first describe main characteristics of rice grain quality, and then summarize findings in literature related to the impact of elevated [CO₂] on grain quality falling into four categories: processing quality, appearance, cooking and eating quality, and nutritional quality, as well as the possible mechanisms responsible for the observed impacts. Elevated [CO₂] caused serious deterioration of processing suitability, in particular, head rice percentage was significantly decreased. In most cases, elevated [CO₂] increased chalkiness of rice grains. The evaluation of physicochemical characteristics together with starch Rapid Visco Analyser (RVA) properties indicated no change or small changes in cooking and eating quality under elevated [CO₂], and these changes could not be detected by sensory taste panel evaluation. Elevated [CO₂] significantly decreased nitrogen or protein concentration in rice grains, while in most cases other macro- and micro-nutrients showed no change or decrease in concentration. In addition, the responses of rice quality to elevated [CO₂] might be modified by varieties, applied fertilizer rates or gas fumigation methodologies. The available information in the literature indicates a clear tendency of quality deterioration and thus lower commercial value for rice grains grown under a projected high CO₂ environment. Understanding the factors causing quality deterioration in rice and the related biological mechanisms might be the utmost important scientific theme in future research. Here we also discuss the necessity of formulating adaptation strategies for rice production in future atmospheric environments, nevertheless, the increase in yield, the improvement in quality and stress resistance of rice should be combined and integrated into the adaptation approaches. Compared with enclosure studies, the field experiments using Free-Air CO₂ Enrichment (FACE) system provide sufficient experimental space and the most realistic mimic of a future high CO₂ atmosphere, and give scientists perhaps the best opportunity to achieve multiple goals.     

A multi-omics integrated study deciphers biology of the rumen and lipid metabolism

<正>Sheep(Ovis aries),as one of the earliest domesticated ruminant livestock,can effectively make use of plant fibers via the rumen,and provide multiple products such as meat,milk and wool for human.However,molecular mechanism of the digestion and lipid metabolism for ruminants has been largely unexplored.The publishing of the complete genomes of cattle(Bos taurus)in 2009[1]and later two other ruminant livestock,i.e.,yak[2]and goat[3],have     

Cilia containing 9 ＋ 2 structures grown from immortalized cells

Cilia depend on their highly differentiated structure, a 9 ＋ 2 arrangement, to remove particles from the lung and to transport reproductive cells. Immortalized cells could potentially be of great use in cilia research. Immortalization of cells with cilia structure containing the 9 ＋ 2 arrangement might be able to generate cell lines with such cilia structure. How- ever, whether immortalized cells can retain such a highly differentiated structure remains unclear. Here we demonstrate that （1） using Ela gene transfection, tracheal cells are immortalized; （2） interestingly, in a gel culture the immortalized cells form spherical aggregations within which a lumen is developed; and （3） surprisingly, inside the aggregation, cilia containing a 9 ＋ 2 arrangement grow from the cell＇s apical pole and protrude into the lumen. These results may influence future research in many areas such as understanding the mechanisms of cilia differentiation, cilia generation in other existing cell lines, cilia disorders, generation of other highly differentiated structures besides cilia using the gel culture, immortalization of other ciliated cells with the Ela gene, development of cilia motile function, and establishment of a research model to provide uniform ciliated cells.     

Immunoelectron microscopic localization of calmodulin in corn root cells

Methods for the localization of plant calmodulin by immuno-gold and immuno-peroxidase electron microscopy have been developed. In both corn root-cap cells and meristematic cells, calmodulin was found to be localized in the nucleus, cytoplasm, mitochondria as well as in the cell wall, In the meristematic cells, calmodulin was distinctly localized on the plasma membrane, cytoplasmic face of rough endoplasmic rcticulum and polyribosomes. Characteristically, calmodulin was present in the amyloplasts of root-cap cells. The widespread distribution of calmodulin may reflect its plciotropic functions in plant cellular activities.     

Search for nave human pluripotent stem cells

Normal mouse pluripotent stem cells were originally derived from the inner cell mass(ICM) of blastocysts and shown to be the in vitro equivalent of those pre-implantation embryonic cells, and thus were called embryonic stem cells(ESCs). More than a decade later, pluripotent cells were isolated from the ICM of human blastocysts. Despite being called human ESCs, these cells differ significantly from mouse ESCs, including different morphology and mechanisms of control of pluripotency, suggesting distinct embryonic origins of ESCs from the two species. Subsequently, mouse pluripotent stem cells were established from the ICMderived epiblast of post-implantation embryos. These mouse epiblast stem cells(Epi SCs) are morphological and epigenetically more similar to human ESCs. This raised the question of whether cells from the human ICM are in a more advanced differentiation stage than their murine counterpart, or whether the available culture conditions were not adequate to maintain those human cells in their in vivo state, leading to a transition into Epi SC-like cells in vitro. More recently, novel culture conditions allowed the conversion of human ESCs into mouse ESC-like cells called nave(or ground state) human ESCs, and the derivation of nave human ESCs from blastocysts. Here we will review the characteristics of each type of pluripotent stem cells, how(and whether) these relate to different stages of embryonic development, and discuss the potential implications of nave human ESCs in research and therapy.