Observations on the centromere area of human chromosomes

Zusammenfassung Das dem Centromer der menschlichen Chromosomen (ebenfalls bei andern Arten) anliegende Gebiet erscheint hell, klar und rund. Dies wurde in einigen Zellen bei fast jedem Centromer, bei andern Zellen nur selten oder überhaupt nicht beobachtet. Eine ähnliche Erscheinung trat auch in Form von Streifen auf, die sich manchmal vom Centromer aus zu anliegenden Chromosomen erstreckten oder sich ins Cytoplasma ausbreiteten. Die mögliche Deutung dieser Beobachtung wurde besprochen.

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This project was supported in part by Public Health Service Career Development Award No. K3-CA-19, 745 from the National Cancer Institute, Research Grant No. GM 11078 from the General Medical Science Branch, and the John A. Hartford Foundation.     

Shock effects on the growth of radish seedlings: the effect of the pressure duration

Résumé Des semis de radis furent soumis à la pression produite par un choc atmosphérique. La pression engendrée par une pulsation augmentant rapidement durait de 0, 1 à 14 sec. La durée de la pression servit de critère pour évaluer les effets des niveaux élevés du choc atmosphérique.     

Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages

The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for cardiac cell lineage formation, and their links to forms of congenital and adult cardiac diseases. Until now there has been little evidence for native cardiac precursor cells in the postnatal heart. Herein, we report the identification of isl1+ cardiac progenitors in postnatal rat, mouse and human myocardium. A cardiac mesenchymal feeder layer allows renewal of the isolated progenitor cells with maintenance of their capability to adopt a fully differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Co-culture studies with neonatal myocytes indicate that isl1+ cells represent authentic, endogenous cardiac progenitors (cardioblasts) that display highly efficient conversion to a mature cardiac phenotype with stable expression of myocytic markers (25%) in the absence of cell fusion, intact Ca2+-cycling, and the generation of action potentials. The discovery of native cardioblasts represents a genetically based system to identify steps in cardiac cell lineage formation and maturation in development and disease.     

Effects of breakfast with different calorigenic amounts on blood glucose, insulin and glucagon levels

This study was aimed to investigate the relationship between breakfast and serum glucose, insulin and glucagon concentrations in order to establish a model breakfast appropriate for Chinese. Twenty-four volunteers were randomly assigned to four study groups: high carbohydrate breakfast, high fat and protein breakfast, the typical breakfast and fasting. Each subject had serum and urine samples collected while fasting and at 1,2 and 3.5 hours following the meal. The concentration of serum glucose, insulin and glucagon was measured. The levels of serum glucose in group A, B and C differed significantly at 1 and 2 hour after meal compared to those at fasting (P<0.05). The serum glucose in group A increased insignificantly after meal. The serum insulin levels were in group A, B and C significant different compared with control group(P<0.05).Those peaked at 1 hour after meal, with group C rising the furthest. Compared with the fasting group, the serum glucagons rose and maintained the increase after breakfast in group A, B and C (P<0.05). The data suggested that various diets with different calorigenic amounts increased hormone concentration to various extents. We found that a breakfast rich in carbohydrates could maintain proper blood glucose level.     

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages.     

Innovations for a changing and challenging world

We live in a rapidly changing world. Firstly, emerging and developing countries＇ research and innovation capabilities are increasing rapidly. China is the most impressive example, having dramatically increased its expenditure on research and development （R＆D） and its human resources for science and technology. As a result, China＇ s share of global knowledge resources has grown dramatically in the past 30 years. Secondly, the nature of innovation is changing. Innovation used to be very much defined and dominated by large companies in Europe, North America and Japan, characterized by a strongly science driven and linear process in which knowledge was generated in academia and then commercialized by industry.     

Vascular normalization in Rgs5-deficient tumours promotes immune destruction

The vasculature of solid tumours is morphologically aberrant and characterized by dilated and fragile vessels, intensive vessel sprouting and loss of hierarchical architecture. Constant vessel remodelling leads to spontaneous haemorrhages and increased interstitial fluid pressure in the tumour environment. Tumour-related angiogenesis supports tumour growth and is also a major obstacle for successful immune therapy as it prevents migration of immune effector cells into established tumour parenchyma. The molecular mechanisms for these angiogenic alterations are largely unknown. Here we identify regulator of G-protein signalling 5 (Rgs5) as a master gene responsible for the abnormal tumour vascular morphology in mice. Loss of Rgs5 results in pericyte maturation, vascular normalization and consequent marked reductions in tumour hypoxia and vessel leakiness. These vascular and intratumoral changes enhance influx of immune effector cells into tumour parenchyma and markedly prolong survival of tumour-bearing mice. This is the first demonstration, to our knowledge, of reduced tumour angiogenesis and improved immune therapeutic outcome on loss of a vascular gene function and establishes a previously unrecognized role of G-protein signalling in tumour angiogenesis.     

LNA-mediated microRNA silencing in non-human primates

microRNAs (miRNAs) are small regulatory RNAs that are important in development and disease and therefore represent a potential new class of targets for therapeutic intervention. Despite recent progress in silencing of miRNAs in rodents, the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS-formulated locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) effectively antagonizes the liver-expressed miR-122 in non-human primates. Acute administration by intravenous injections of 3 or 10 mg kg(-1) LNA-antimiR to African green monkeys resulted in uptake of the LNA-antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg(-1) LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA-antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.