Inhibition of the nuclear factor-κB pathway prevents beta cell failure and diet induced diabetes in Psammomys obesus

Background

High doses of anti-inflammatory drugs, such as aspirin and salicylates, improve glucose metabolism in insulin resistant and type 2 diabetic patients. It has also been shown that the glucose lowering effect is related to the unspecific ability of these drugs to inhibit inhibitor kinaseβ (IKKβ). In this study we have investigated the effect of a selective IKKβ-inhibitor on beta cell survival and the prevention of diet induced type 2 diabetes in the gerbil Psammomys obesus (P. obesus).

Methodology/Principal Findings

P. obesus were fed a diabetes inducing high energy diet for one month in the absence or presence of the IKKβ-inhibitor. Body mass, blood glucose, HbA_1C, insulin production and pancreatic insulin stores were measured. The effects on beta cell survival were also studied in INS-1 cells and primary islets. The cells were exposed to IL-1β and subsequently reactive oxygen species, insulin release and cell death were measured in the absence or presence of the IKKβ-inhibitor. In primary islets and beta cells, IL-1β induced the production of reactive oxygen species, reduced insulin production and increased beta cell death, which were all reversed by pre-treatment with the IKKβ-inhibitor. In P. obesus the IKKβ-inhibitor prevented the development of hyperglycaemia and hyperinsulinaemia, and maintained pancreatic insulin stores with no effect on body weight.

Conclusions/Significance

Inhibition of IKKβ activity prevents diet-induced diabetes in P. obesus and inhibits IL-1β induced reactive oxygen species, loss of insulin production and beta cell death in vitro.     

The four hexamerin genes in the honey bee: structure,molecular evolution and function deduced from expression patterns in queens,workers and drones

Background  

Hexamerins are hemocyanin-derived proteins that have lost the ability to bind copper ions and transport oxygen; instead, they became storage proteins. The current study aimed to broaden our knowledge on the hexamerin genes found in the honey bee genome by exploring their structural characteristics, expression profiles, evolution, and functions in the life cycle of workers, drones and queens.     

Mitochondrial control-region sequences in two shorebird species, the turnstone and the dunlin, and their utility in population genetic studies

We determined the mitochondrial control-region sequences of five turnstones (Arenaria interpres) and three dunlins (Calidris alpina). Comparisons revealed that the central part (part II) is conserved relative to much more variable parts at the beginning (part I) and the end (part III). This pattern of sequence conservation is also found in the control regions of other vertebrates. The average sequence divergence between turnstone and dunlin was 21.8% for part I, 7.5% for part II, and 29.5% for part III. Within-species sequence divergence over the entire control region was much lower, at 0.9% for turnstones and 2.0% for dunlins. In both shorebird species, part III contains a repetitive sequence composed only of A and C nucleotides, which has not been found in the control regions of other birds. A survey of the part I sequences of 25 turnstones and 25 dunlins sampled around the world revealed that these species have very different population genetic structures. Dunlins are not only much more differentiated in their sequences but also have a strongly subdivided population genetic structure. Pleistocene vicariant events combined with strong natal philopatry and high mutation rates of the sequences are likely responsible for this population genetic subdivision. Conversely, part I sequences of turnstones are weakly differentiated and are geographically unstructured. We argue that this is not the result of global gene flow but that, instead turnstones have recently expanded from a refugial population that was bottlenecked.      

Molecular characteristics of diverse populations are consistent with the hypothesis of a recent invasion of Drosophila melanogaster by mobile P elements

Approximately 100 strains derived from natural populations of Drosophila melanogaster were tested for the presence or absence of P- element sequences by using two molecular probes derived from internal regions of a full-sized P element. Strains that had been collected from several continents at varying times during the past 60 years were examined. The oldest available strains, representing most major geographical regions of the world, exhibited no detectable hybridization to the P-element probes. In contrast, all recently collected natural populations that were tested carried P-element sequences. The earliest appearance of P elements occurred in collections made during the 1950s and early 1960s in the Americas and during the late 1960s on other continents. The youngest strains that were completely devoid of P elements originated in populations sampled during the mid-1960s in America, but as late as 1974 in populations from the USSR. There are differences in the patterns of hybridization to the two P-element probes between populations from different geographical regions. These differences are consistent with the varying P-M phenotypic properties of these populations. Taken together with the results of phenotypic tests reported in earlier studies, the available evidence is consistent with the hypothesis of a worldwide P-element invasion of D. melanogaster during the past 30 years and suggests that the putative invasion of the Americas possibly preceded by approximately a decade that in Europe, Africa, and the rest of the world.      

Resting CD4+ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell function

Background

Previously we described a system whereby human peripheral blood T cells stimulated for 8 days in a cytokine cocktail acquired effector function for contact-dependent induction of proinflammatory cytokines from monocytes. We termed these cells cytokine-activated (Tck) cells and found that the signalling pathways elicited in the responding monocytes were identical whether they were placed in contact with Tck cells or with T cells isolated from rheumatoid arthritis (RA) synovial tissue.

Methods

Here, using magnetic beads and fluorescence-activated cell sorting, we extensively phenotype the Tck effector cells and conclude that effector function resides within the CD4⁺CD45RO⁺, CCR7^-, CD49d^high population, and that these cells are derived from the effector memory CD4⁺ T cells in resting blood.

Results

After stimulation in culture, these cells produce a wide range of T-cell cytokines, undergo proliferation and differentiate to acquire an extensively activated phenotype resembling RA synovial T cells. Blocking antibodies against CD69, CD18, or CD49d resulted in a reduction of tumour necrosis factor-α production from monocytes stimulated with CD4⁺CD45RO⁺ Tck cells in the co-culture assay. Moreover, blockade of these ligands also resulted in inhibition of spontaneous tumour necrosis factor-α production in RA synovial mononuclear cell cultures.

Conclusion

Taken together, these data strengthen our understanding of T-cell effector function, highlight the multiple involvement of different cell surface ligands in cell-cell contact and, provide novel insights into the pathogenesis of inflammatory RA disease.     

叶绿素b聚集体和它的能化态的性质

叶绿素b由单体聚合成多聚体后吸收光谱明显红移。叶绿素b聚集体膜在光下产生150 mV的光电位,停止照光后此电位消失速度比叶绿素a聚集体膜的慢。叶绿素b聚集体吸收光能后形成相当稳定的能化态,半生命期约几分钟。当聚集体解聚时所吸收的光能又以光的形式辐射出来。叶绿素b聚集体能化态的能量可快速而有效地传给叶绿素a聚集体,以叶绿素a的延迟发光形式释放出来。     

Pig Reticulocytes. III. Glucose permeability in naturally occurring reticulocytes and red cells from newborn piglets

The loss of facilitated glucose transport of red cells occurring in the newborn pig was monitored in 11 density-separated cells from birth to a 4 wk of age. At birth there was a threefold increase in glucose permeability from the lightest cells to the most dense, suggesting that cells having progressively less glucose permeability are released into the circulation as gestation proceeds. Because of extraordinary stimulation of erythropoietic activity, the uppermost top fraction constituting 2-3 percent of the total cells is composed purely of reticulocytes in the growing animal. The glucose permeability of these reticulocytes which at birth has a slow but significant rate of 3.7 μmol/ml cell x min at 25 degrees C is rapidly decreased within 3-4 days to the level of reticulocytes produced in the adult in response to phenylhydrazine assault. Moreover, reticulocytes themselves discard their membrane permeability to glucose in the course of maturation to red cells. Thus, even though reticulocytes at birth are permeable to glucose, they will become red cells practically impervious to glucose within a few days. These findings suggest that the transition from a glucose- permeable fetal state to a glucose-impermeable postnatal state is brought about by two mechanisms: (a) dilution of fetal cells by glucose-impervious cells produced coincidentally with or shortly after birth; and (b) elimination of fetal cells, which have a shorter half-life, from the circulation.     

Molecular evolution of P transposable elements in the genus Drosophila. I. The saltans and willistoni species groups

A phylogenetic survey using the polymerase chain reaction (PCR) has identified four major P element subfamilies in the saltans and willistoni species groups of Drosophila. One subfamily, containing about half of the sequences studied, consists of elements that are very similar to the canonical (and active) P element from D. melanogaster. Within this subfamily, nucleotide sequence differentiation among different copies from the same species and among elements from different species is relatively low. This observation suggests that the canonical elements are relatively recent additions to the genome or, less likely, are evolving slowly relative to the other subfamilies. Elements belonging to the three noncanonical lineages are distinct from the canonical elements and from one another. Furthermore, there is considerably more sequence variation, on the average, within the noncanonical subfamilies compared to the canonical elements. Horizontal transfer and the coexistence of multiple, independently evolving element subfamilies in the same genome may explain the distribution of P elements in the saltans and willistoni species groups. Such explanations are not mutually exclusive, and each may be involved to varying degrees in the maintenance of P elements in natural populations of Drosophila.