Effects of sunitinib on immunoreactivity of vimentin,E-cadherin and S100 in kidneys of streptozotocin induced diabetic mice

Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM.     

Effects of nitrogen enrichment on zooplankton biomass and N:P recycling ratios across a DOC gradient in northern-latitude lakes

We used data from whole-lake studies to assess how changes in food quantity (phytoplankton biomass) and quality (phytoplankton community composition, seston C:P and N:P) with N fertilization affect zooplankton biomass, community composition and C:N:P stoichiometry, and their N:P recycling ratio along a gradient in lake DOC concentrations. We found that despite major differences in phytoplankton biomass with DOC (unimodal distributions, especially with N fertilization), no major differences in zooplankton biomass were detectable. Instead, phytoplankton to zooplankton biomass ratios were high, especially at intermediate DOC and after N fertilization, implying low trophic transfer efficiencies. An explanation for the observed low phytoplankton resource use, and biomass responses in zooplankton, was dominance of colony forming chlorophytes of reduced edibility at intermediate lake DOC, combined with reduced phytoplankton mineral quality (enhanced seston N:P) with N fertilization. N fertilization, however, increased zooplankton N:P recycling ratios, with largest impact at low DOC where phytoplankton benefitted from light sufficiently to cause enhanced seston N:P. Our results suggest that although N enrichment and increased phytoplankton biomass do not necessarily increase zooplankton biomass, bottom-up effects may still impact zooplankton and their N:P recycling ratio through promotion of phytoplankton species of low edibility and altered mineral quality.

     

<Emphasis Type="Italic">Alu</Emphasis> elements: know the SINEs

Alu elements are primate-specific repeats and comprise 11% of the human genome. They have wide-ranging influences on gene expression. Their contribution to genome evolution, gene regulation and disease is reviewed.     

Characterization and population diversity of interspersed repeat sequence variants (IRS-morphs).

Inter-Alu PCR is increasingly useful in human genome mapping studies. One use is the generation of alumorphs, polymorphisms resulting from the presence or absence of inter-Alu PCR products. In this study, we have increased the proportion of the genome that can be analyzed by this technique with the use of long interspersed elements (LINEs). The set of polymorphisms detected by both Alu and LINE primers are referred to as interspersed repetitive sequence variants or IRS-morphs. Since a presence-absence variant may have been the result of a recent Alu or LINE insertion, we analyzed 7 isolated IRS-morphs that were generated, in part, with a primer derived from either a consensus LINE or a young Alu subfamily specific sequence, and observed by Southern blot analysis that these variants resulted from other types of genomic alterations. The use of these primers, however, reduces background from the numerous LINEs and Alu elements in the genome, providing sharp DNA fingerprint profiles. We have demonstrated the potential usefulness of these IRS-morph profiles in human population studies. We compared 12 IRS-morphs from a single amplification reaction from five distinct population groups (Caucasian (northern European descent), Hispanic (Mexican-American), Hindu-Indian, Papua New Guinean, and Greenland Eskimo) and observed that most have variable allelic frequencies among populations. The utilization of additional IRS-morph profiles will perpetuate this technique as a tool for DNA fingerprinting and for the analysis of human populations. Key words : Alu elements, DNA fingerprint, human populations, LINEs, SINEs.     

金黄地鼠视皮层通过胼胝体顺行和逆行激活的神经元的电活动和分布

用细胞外记录技术研究了金黄地鼠一侧视皮层神经元对电刺激另一侧相应部位的反应及其对视觉刺激反应的特点。(1)在17—18a 交界区大多数(78%)细胞能被电刺激对侧相应点所驱动。在17区内部,被驱动细胞数随离开17—18a 交界距离增加而减少。(2)按对电刺激的反应形式,记录的细胞可分为四类:a.逆行驱动细胞,占17—18a 交界区记录细胞数的20%;b.顺行驱动细胞,占52%中;c.自发发放因电刺激而减少或完全停止的细胞,占6%,d.其余细胞(22%)对电刺激没有可察觉的反应。(3)在17—18a 交界,除了Ⅰ层以外的各层都可记录到顺行驱动细胞,而逆行驱动细胞则主要集中在Ⅲ及Ⅴ层。(4)17—18a 交界细胞感受野(RF)多位于垂直中线附近的对侧视野内,有些 RF 跨越中线,其边界延伸到同侧约10°处。(5)逆行驱动细胞包括刁和 Blakemore 以前在视皮层中记录到的所有细胞类型和各种程度的眼优势,但单眼细胞的比例增加,非对称式 RF 和中心对称式的给-撤型 RF 的比例有所减少。     

A new restriction-site polymorphism in exon 18 of the low density lipoprotein receptor (LDLR) gene

A new restriction fragment length polymorphism (RFLP) in exon 18 of the low density lipoprotein receptor (LDLR) gene is described. It should be a useful marker in linkage to familial hypercholesterolemia.     

Clenbuterol-Induced Insulin Resistance in Calves Measured by Hyperinsulinemic,Euglycemic Clamp Technique

Hyperinsulinemic, euglycemic clamp tests were performed on calves before and after clenbuterol treatment. Clenbuterol was given as 2 intramuscular injections with an interval of about 12 h. The dose used was 1 μg/kg b.w. The treatment resulted in increased plasma levels of insulin and glucose. The results of the clamp tests showed that clenbuterol induced a transient decrease in insulin sensitivity. Both insulin mediated glucose disposal (M), expressed as μmol/kg live b.w./min. and the M/I-index (M divided by the average insulin concentration at steady state) were significantly reduced after treatment. The effect of clenbuterol on carbohydrate metabolism seemed to be rather short-lived, since significant changes occurred only in animals treated 5-6 h prior to the test. According to the literature, the metabolic effects of clenbuterol have been studied only after the high doses used for growth promoting purposes. The results from the present study showed that similar changes occur also after doses at the therapeutic level. The hyperinsulinemic, euglycemic clamp test was considered to be a valuable tool for the study of insulin sensitivity in cattle.     

The role and amplification of the HS Alu subfamily founder gene

A recently identified Alu element (Leeflang et al. J. Mol. Evol. 1993, 37:559–565), referred to as the putative founder of the HS (PV) subfamily, was found to be present at orthologous loci in the human, chimpanzee, gorilla, and gibbon lineages. The evolution of this Alu suggested that it is a source gene in the evolution of Alu family repeats for one of the most recent subfamilies, HS. We have determined that this putative founder of the HS subfamily was not present at the orthologous loci in older primates, including old world and new world monkeys. Thus, this particular Alu locus has only been responsible for the establishment of a very small subfamily of Alu sequences. We have further demonstrated that this putative founder Alu was not responsible for the de novo Alu insertion into the neurofibromatosis-1 gene of an individual causing neurofibromatosis. Our data demonstrate that although the putative founder of the HS subfamily found by Leeflang et al. (1993) probably gave rise to one of the most recent subfamilies of Alu sequences, it has not been very active in retroposition. Correspondence to: T.H. Shaikh     

Sporadic amplification of ID elements in rodents

ID sequences are members of a short interspersed element (SINE) repetitive DNA family within the rodent genome. The copy number of individual ID elements varies by up to three orders of magnitude between species. This amplification has been highly sporadic in the order Rodentia and does not follow any phylogenetic trend. Using library screening and dot-blot analysis, we estimate there are 25,000 copies of ID elements in the deer mouse, 1,500 copies in the gerbil (both cricetid rodents), and 60,000 copies of either ID or ID-like elements in a sciurid rodent (squirrel). By dot-blot analysis, we estimate there are 150,000, 4,000, 1,000, and 200 copies of ID elements in the rat, mouse, hamster, and guinea pig, respectively (which is consistent with previous reports) and 200 copies in the hystricognath rodent, nutria. Therefore, a rapid amplification took place not only after the divergence of rat and mouse but also following the deer mouse (Peromyscus) and hamster split, with no evidence of increased amplifications in hystricognath rodents. No notable variations of sequences from the BC1 genes of several myomorphic rodents were observed that would possibly explain the varied levels of ID amplification. We did observe subgenera and species-group-specific variation in the ID core sequence of the BC1 gene within the genus Peromyscus. Sequence analysis of cloned ID elements in Peromyscus show most ID elements in this genus arose prior to Peromyscus subgenus divergence. Correspondence of the consensus sequence of individual ID elements in gerbil and deer mouse further confirms BC1 as a master gene in ID amplification. Several possible mechanisms responsible for the quantitative variations are explored.The nucleotide sequences reported in this paper have been submitted to the GenBank/EMBL Data Bank with accession numbers: U33850, U33851, U33852 (BC1 sequences); and U33853, U33854, U33855, U33856, U33857, U33858, U33859, U33860, U33861, U33862, U33863, U33864, U33865, U33866, U33867 (ID sequences) Correspondence to: D.H. Kass