A new look towards BAC-based array CGH through a comprehensive comparison with oligo-based array CGH

Background

Natural populations of the teleost fish Fundulus heteroclitus tolerate a broad range of environmental conditions including temperature, salinity, hypoxia and chemical pollutants. Strikingly, populations of Fundulus inhabit and have adapted to highly polluted Superfund sites that are contaminated with persistent toxic chemicals. These natural populations provide a foundation to discover critical gene pathways that have evolved in a complex natural environment in response to environmental stressors.

Results

We used Fundulus cDNA arrays to compare metabolic gene expression patterns in the brains of individuals among nine populations: three independent, polluted Superfund populations and two genetically similar, reference populations for each Superfund population. We found that up to 17% of metabolic genes have evolved adaptive changes in gene expression in these Superfund populations. Among these genes, two (1.2%) show a conserved response among three polluted populations, suggesting common, independently evolved mechanisms for adaptation to environmental pollution in these natural populations.

Conclusion

Significant differences among individuals between polluted and reference populations, statistical analyses indicating shared adaptive changes among the Superfund populations, and lack of reduction in gene expression variation suggest that common mechanisms of adaptive resistance to anthropogenic pollutants have evolved independently in multiple Fundulus populations. Among three independent, Superfund populations, two genes have a common response indicating that high selective pressures may favor specific responses.     

Conformational diversity of single‐stranded DNA from bacterial repetitive extragenic palindromes: Implications for the DNA recognition elements of transposases

Repetitive extragenic palindrome (REP)—associated tyrosine transposase enzymes (RAYTs) bind REP DNA domains and catalyze their cleavage. Genomic sequence analyses identify potential noncoding REP sequences associated with RAYT‐encoding genes. To probe the conformational space of potential RAYT DNA binding domains, we report here spectroscopic and calorimetric measurements that detect and partially characterize the solution conformational heterogeneity of REP oligonucleotides from six bacterial species. Our data reveal most of these REP oligonucleotides adopt multiple conformations, suggesting that RAYTs confront a landscape of potential DNA substrates in dynamic equilibrium that could be selected, enriched, and/or induced via differential binding. Thus, the transposase‐bound DNA motif may not be the predominant conformation of the isolated REP domain. Intriguingly, for several REPs, the circular dichroism spectra suggest guanine tetraplexes as potential alternative or additional RAYT recognition elements, an observation consistent with these REP domains being highly nonrandom, with tetraplex‐favoring 5′‐G and 3′‐C‐rich segments. In fact, the conformational heterogeneity of REP domains detected and reported here, including the formation of noncanonical DNA secondary structures, may reflect a general feature required for recognition by RAYT transposases. Based on our biophysical data, we propose guanine tetraplexes as an additional DNA recognition element for binding by RAYT transposase enzymes. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 585–596, 2015.     

5-Fluoro-4-thiouridine phosphoramidite: new synthon for introducing photoaffinity label into oligodeoxynucleotides

The synthesis of phosphoramidite of 5-fluoro-4-thio-2'-O-methyluridine is described. An appropriate set of protecting groups was optimized including the 4-thio function introduced via 4-triazolyl as the 4-(2-cyanoethyl)thio derivative, and the t-butyldimethyl silyl for 2' and 3' hydroxyl protection, enabling efficient synthesis of the phosphoramidite. These protecting groups prevented unwanted side reactions during oligonucleotide synthesis. The utility of the proposed synthetic route was proven by the preparation of several oligonucleotides via automated synthesis. Photochemical experiments confirmed the utility of the synthon.     

Sodium orthovanadate exerts influence on liver Golgi complexes from control and streptozotocin-diabetic rats

The paper presents the effect of one-week 3mM sodium orthovanadate (Na3VO4) oral treatment of control and streptozotocin[STZ]-diabetic rats. The body weight decreased as compared with untreated control (C group) in both vanadate treated groups (C + V and D + V) and in diabetic untreated rats (D group)--in all cases p < 0.01. A similar tendency was demonstrated by the weight of the livers, which was statistically significant lower than in the controls (p < 0.01). The fluid and food intake were lower in comparison with control vanadium treated groups, in D + V as compared with D it was limited, however, not achieved control level. A high mortality rate, approx. 67%, after the administration of streptozotocin and vanadate (D + V group) was noted; such result had never been previously found within all study groups of rats. But the surviving rats show very good decreased (60%) free blood sugar levels, however euglycaemia was not achieved. The activity of galactosyltransferase, the Golgi complex marker enzyme in group D, was statistically lower than the controls (p < 0.001). Treatment of STZ-diabetic rats with orthovanadate did not increase the enzyme activity toward control level, in both diabetic groups (treated and untreated with Na3VO4) similar dispersion of individual results was found. Morphological study demonstrated, for the first time, no larger cellular lesion in C + V group. The Golgi complex was well developed; showed several cisterns at the trans side, which were grossly distended and contained electron-lucid floccular material. In D + V group typical, cylindrical forms of Golgi complexes predominated. These structures consisted of 3-4 almost practically non-distended cisterns. Also in this case, large, electron-dense vesicles were noted in the vicinity. In this group, small in size, myelin-like structures were also found. These structures might indicate a relatively small, but nevertheless clear damage of the internal membrane system. The external cistern of the cylindrical forms of Golgi complexes, which corresponded the trans side, was often markedly distended and formed a vacuole-like structure filled with electron lucent material; the structure itself sometimes looked empty. Multi-vesicular structures were observed also in this case, but they were seen much more rarely.     

Bacterial transglycosylase inhibitors

The spread of bacterial resistance to known antibiotics has inspired interest in previously under-exploited drug targets. The transglycosylation reaction remains a 'black box' in the generally well-studied process of bacterial peptidoglycan biosynthesis, which is a very attractive target for chemotherapeutic intervention. Here, we summarize recent progress in the study of bacterial transglycosylases and the compounds that inhibit them. The transglycosylation reaction is readily targeted by several different classes of natural products, implying that it should be possible to develop drugs that inhibit this process once efficient high-throughput screens and appropriate compound libraries have been developed.     

A special case of thyroid associated ophthalmopathy in the course of Graves-Basedow disease

INTRODUCTION: The exact pathogenesis of Graves' ophthalmopathy and the possibility of causal treatment of this disease still remain unclear. Currently no standard treatment guidelines have been accepted. While treatment procedures have been established in specialized centres, management of complicated and long-lasting cases is always individual. We present an unusual case of Graves' ophthalmopathy accompanied by other autoimmune diseases. CASE REPORT: Our patient, MB, female, born in 1961, was diagnosed with Graves' disease 13 years ago. Recurrent hyperthyroidism and large goitre qualified her for strumectomy (performed twice) and long-term antithyroid treatment. Four years after her initial diagnosis, relapsing severe (ophthalmopathy index: 9 points, CAS: 7 points) occurred which persisted despite continuous administration of glucocorticoids. Due to imminent blindness, orbital decompression had to be performed, three times since. Concurrent autoimmune diseases: ulcerative colitis and seronegative rheumatoid arthritis were also stated. Two years ago, due to loss of vision acuity, rapid progression of exophthalmos and recurrence of hyperthyroidism, immunosuppressive treatment with azathioprine was undertaken over a period of 12 months. The present condition of the patient is satisfactory. CONCLUSION: Judging from the discussed course of treatment, in rare and difficult cases of proliferative ophthalmopathy, early immunosuppressive treatment other than glucocorticoids, should be considered.     

Structural diversity of neutral bis-(β-iminoaldehyde) complexes of nickel(II)

Series of Ni^II and Cu^II complexes with dianionic [N₂O₂] ligands were synthesized and characterised applying spectroscopic and X-ray diffraction techniques. The ligands were obtained by 1:2 condensation of ethylene- and propylenediamine with malonic aldehyde derivatives (R² = H, R¹ = H or OCH₃). Although the molecular formulae of the complexes are quite similar, the X-ray investigations have proved a significant structural diversity in the solid state. Among others, we found some simple nearly planar molecules stacked in the crystal lattice with electron density of six-membered rings delocalised over the chelate rings as well as some very complex polymeric or nickel acetate bridged trinuclear complexes. The coordination of the nickel ion by surrounding oxygen and nitrogen atoms is square-planar in the simplest case and octahedral in the most complex one. Small topological differences in similar molecules generate completely different crystal structures.From magnetic studies, a small, negative value of J obtained confirms the occurrence of weak antiferromagnetic interactions between the Ni^II ions in polymeric chain of the propylenediamine dialdehyde substituted derivative.