The analogs of oxytocin and D-homoarginine vasopressin with bulky substituted phenylalanine in position 2

Summary Solid phase technique on p-methylbenzhydrylamine resin was used for the synthesis of eight analogs of oxytocin and 8-D-homoarginine vasopressin with the non-coded amino acids L- or D-2,3,4,5,6-pentamethylphenylalanine and L- or D-4-phenylphenylalanine in position 2. The preparation of the above mentioned non-coded amino acids is described as well. All eight analogs were found to be potent inhibitors of oxytocin activity in the uterotonicin vitro test in the absence of Mg²⁺ ions. In the uterotonic testin vitro in the presence of Mg²⁺ and in the testin vivo, their potency is strongly decreased or completely abolished. The substances are also weak pressor inhibitors. The L or D configuration does not seem to influence the activity significantly. Abbreviations: All the chiral amino acids unless otherwise stated are of the L-series. Phe(4-Ph) denotes the 4-phenylphenylalanine, Phe(pentaMe) the 2,3,4,5,6-pentamethylphenylalanine, Har the homoarginine, DMF dimethylformamide, OHBT 1-hydroxybenzotriazole and DCC dicylohexyl-carbodiimitz. The Nomenclature and symbols of the amino acids and peptides obey the published recommendations: IUPAC-IUB Joint Commission on Biochemical Nomenclature: Eur. J. Biochem., 138 (1984) 9.     

Supramolecular organization of fucoxanthin–chlorophyll proteins in centric and pennate diatoms

Fucoxanthin–chlorophyll proteins (FCP) are the major light-harvesting proteins of diatom algae, a major contributor to marine carbon fixation. FCP complexes from representatives of centric (Cyclotella meneghiniana) and pennate (Phaeodactylum tricornutum) diatoms were prepared by sucrose gradient centrifugation and studied by means of electron microscopy followed by single particle analysis. The oligomeric FCP from a centric diatom were observed to take the form of unusual chain-like or circular shapes, a very unique supramolecular assembly for such antennas. The existence of the often disputed oligomeric form of FCP in pennate diatoms has been confirmed. Contrary to the centric diatom FCP, pennate diatom FCP oligomers are very similar to oligomeric antennas from related heterokont (Stramenopila) algae. Evolutionary aspects of the presence of novel light-harvesting protein arrangement in centric diatoms are discussed.     

Dynamic imbalance between cancer cell subpopulations induced by Transforming Growth Factor Beta (TGF-β) is associated with a DNA methylome switch

Background

Distinct subpopulations of neoplastic cells within tumors, including hepatocellular carcinoma (HCC), display pronounced ability to initiate new tumors and induce metastasis. Recent evidence suggests that signals from transforming growth factor beta (TGF-β) may increase the survival of these so called tumor initiating cells leading to poor HCC prognosis. However, how TGF-β establishes and modifies the key features of these cell subpopulations is not fully understood.

Results

In the present report we describe the differential DNA methylome of CD133-negative and CD133-expressing liver cancer cells. Next, we show that TGF-β is able to increase the proportion of CD133+ cells in liver cancer cell lines in a way that is stable and persistent across cell division. This process is associated with stable genome-wide changes in DNA methylation that persist through cell division. Differential methylation in response to TGF-β is under-represented at promoter CpG islands and enriched at gene bodies, including a locus in the body of the de novo DNA methyl-transferase DNMT3B gene. Moreover, phenotypic changes induced by TGF-β, including the induction of CD133, are impaired by siRNA silencing of de novo DNA methyl-transferases.

Conclusions

Our study reveals a self-perpetuating crosstalk between TGF-β signaling and the DNA methylation machinery, which can be relevant in the establishment of cellular phenotypes. This is the first indication of the ability of TGF-β to induce genome-wide changes in DNA methylation, resulting in a stable change in the proportion of liver cancer cell subpopulations.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-435) contains supplementary material, which is available to authorized users.     

Acute coronary syndrome frequency in western Herzegovina over the fifteen year period (1987-2001)

All patients who suffered from the acute coronary syndrome in western Herzegovina over the fifteen year period (1987-2001) are included in this retrospective epidemiological study. The population that was undertaken by the study is relative stabile and did not emigrate during the war period. The study compared the time before the war (1987-1991), during the war (1992-1996) and after the war (1997-2001). The data were acquired from the archives of the patients of the Mostar hospital and Clinical hospital Split during the war period. A total of 2022 acute coronary syndrome patients were found, 1305 men and 717 women. More patients were treated during the war compared to the time before the war for both male and female patients (p<0.0005). During the after-war period the number of treated patients was greater (p< 0.0005) compared to the war-time for both sexes. The comparison of the after-war period and the pre-war period reveals a statistically significant difference as the number of treated patients (male and female) is larger in the after-war period. The number of patient who are 65 years old and older than that is greater, and that is statistically significant (p= 0.0005.). We can conclude that the stress caused by the war and other factors have influenced a larger number of treated patients of acute coronary syndrome. Therefore, further epidemiological researches of acute coronary syndrome with the accent on prevention and treatment are needed.     

Pregnancy outcome after treatment with radioiodine for differentiated thyroid carcinoma

The aim of the study was to investigate the influence of radioiodine (RAI) therapy on pregnancies and the health status of children born to mothers who had received therapeutic doses of I-131 for differentiated thyroid carcinoma (DTC). Gestational histories of 76 women treated for DTC from 1971-2005 were retrospectively analyzed. The outcome of 49 pregnancies after RAI was: 35 children (72%), 5 (10%) miscarriages and 9 (18%) induced abortions. RAI did not adversely affect the rate of successful delivery and live birth demographics. Congenital malformation and first year mortality were not observed. The children's ages range from 1 month to 29 years (chi+/-SD=8.0+/-8.4). A higher therapeutic dose (>100 mCi) did not significantly alter the pregnancy outcome. There is no reason to discourage females treated with 1-131 from becoming pregnant. Patients should avoid pregnancy after RAI administration for 1 year.     

Seawater Stress Differentially Affects Germination, Growth, Photosynthesis, and Ion Concentration in Genotypes of Jerusalem Artichoke (Helianthus tuberosus L.)

Two Jerusalem artichoke (Helianthus tuberosus L.) genotypes, NY-1 and NY-7, were subjected to different seawater concentrations (0, 10, 20, 30, 40, and 50%) for various periods of time to determine the effects on seedling growth, ion content, and photosynthetic productivity in a greenhouse. Under different seawater concentrations, sprouting rates varied greatly among the genotypes. The differences in relative growth rate (RGR), leaf chlorophyll content, total leaf area (TLA), plant dry weight (PDW), photosynthetic rate (A), stomatal conductance (g _s), and efficiency of the light harvesting of photosystem II (F _v^′/F _m^′) were significant between NY-1 and NY-7 after 12 days of stress at 40 and 50% seawater. Seawater treatments resulted in the reduction of almost all the growth parameters and coincident increases of Na⁺ and Ca²⁺ concentrations in plant tissues. Our results indicate that there is great variability for seawater tolerance among H. tuberosus varieties, and that greater photosynthesis capacity, higher RGR, and relatively higher tissue Na⁺ accumulation at high seawater concentrations appears to be associated with seawater tolerance in H. tuberosus varieties.     

Chromatin structure in double strand break repair

Cells are under constant assault by endogenous and environmental DNA damaging agents. DNA double strand breaks (DSBs) sever entire chromosomes and pose a major threat to genome integrity as a result of chromosomal fragment loss or chromosomal rearrangements. Exogenous factors such as ionizing radiation, crosslinking agents, and topoisomerase poisons, contribute to break formation. DSBs are associated with oxidative metabolism, form during the normal S phase, when replication forks collapse and are generated during physiological processes such as V(D)J recombination, yeast mating type switching and meiosis. It is estimated that in mammalian cells ∼10 DSBs per cell are formed daily. If left unrepaired DSBs can lead to cell death or deregulated growth, and cancer development. Cellular response to DSB damage includes mechanisms to halt the progression of the cell cycle and to restore the structure of the broken chromosome. Changes in chromatin adjacent to DNA break sites are instrumental to the DNA damage response (DDR) with two apparent ends: to control compaction and to bind repair and signaling molecules to the lesion. Here, we review the key findings related to each of these functions and examine their cross-talk.     

Comparisons of microRNA Patterns in Plasma before and after Tumor Removal Reveal New Biomarkers of Lung Squamous Cell Carcinoma

Lung cancer is the major human malignancy, accounting for 30% of all cancer-related deaths worldwide. Poor survival of lung cancer patients, together with late diagnosis and resistance to classic chemotherapy, highlights the need for identification of new biomarkers for early detection. Among different cancer biomarkers, small non-coding RNAs called microRNAs (miRNAs) are considered the most promising, owing to their remarkable stability, their cancer-type specificity, and their presence in body fluids. However, results of multiple previous attempts to identify circulating miRNAs specific for lung cancer are inconsistent, likely due to two main reasons: prominent variability in blood miRNA content among individuals and difficulties in distinguishing tumor-relevant miRNAs in the blood from their non-tumor counterparts. To overcome these impediments, we compared circulating miRNA profiles in patients with lung squamous cell carcinoma (SCC) before and after tumor removal, assuming that the levels of all tumor-relevant miRNAs would drop after the surgery. Our results revealed a specific panel of the miRNAs (miR-205, -19a, -19b, -30b, and -20a) whose levels decreased strikingly in the blood of patients after lung SCC surgery. Interestingly, miRNA profiling of plasma fractions of lung SCC patients revealed high levels of these miRNA species in tumor-specific exosomes; additionally, some of these miRNAs were also found to be selectively secreted to the medium by cultivated lung cancer cells. These results strengthen the notion that tumor cells secrete miRNA-containing exosomes into circulation, and that miRNA profiling of the exosomal plasma fraction may reveal powerful cancer biomarkers.