The cyclooxygenases

Cyclooxygenases (COXs) catalyze the rate-limiting step in the production of prostaglandins, bioactive compounds involved in processes such as fever and sensitivity to pain, and are the target of aspirin-like drugs. COX genes have been cloned from coral, tunicates and vertebrates, and in all the phyla where they are found, there are two genes encoding two COX isoenzymes; it is unclear whether these genes arose from an early single duplication event or from multiple independent duplications in evolution. The intron-exon arrangement of COX genes is completely conserved in vertebrates and mostly conserved in all species. Exon boundaries largely define the four functional domains of the encoded protein: the amino-terminal hydrophobic signal peptide, the dimerization domain, the membrane-binding domain, and the catalytic domain. The catalytic domain of each enzyme contains distinct peroxidase and cyclooxygenase active sites; COXs are classified as members of the myeloperoxidase family. All COXs are homodimers and monotopic membrane proteins (inserted into only one leaflet of the membrane), and they appear to be targeted to the lumenal membrane of the endoplasmic reticulum, where they are N-glycosylated. In mammals, the two COX genes encode a constitutive isoenzyme (COX-1) and an inducible isoenzyme (COX-2); both are of significant pharmacological importance.     

Membrane lipids and cytosol carbohydrates in <Emphasis Type="Italic">Aspergillus niger</Emphasis> under osmotic,oxidative, and cold impact

The composition of the membrane lipids and cytosol soluble carbohydrates under three kinds of unfavorable impacts (osmotic, oxidative, and cold) was studied. Changes in the composition of the membrane lipids, specifically, increasing content of phosphatidic acids and decreasing levels of phosphatidylcholines and phosphatidylethanolamines, were the general response to the impacts. The degree of fatty acid unsaturation increased in all dominant phospholipids under osmotic shock, only in cardiolipins and phosphatidic acids under oxidative stress, and only in phosphatidylcholines under cold shock. Increased sterol content was observed only under cold and osmotic treatments. No general pattern was revealed in the composition of cytosol carbohydrates in response to stresses. Oxidative stress had almost no effect on the carbohydrate composition, while osmotic and cold treatments resulted in increased glycerol content and decreased total carbohydrate content. The mechanisms of fungal response to various stress impacts are discussed.     

Biosynthesis of chlorophyll P-680 of photosystem II in greening leaves of plants adapted to heat shock

In etiolated pea and maize leaves illuminated after incubation at 38 degreesC, a new dark reaction was shown manifested in the bathochromic shift of spectral bands and accompanied by esterification of the product of protochlorophyllide photochemical reduction--Chld 684/676: Chld 684/676 --> Chl 688/680. After completion of the reaction a rapid (20-30 sec) quenching of the fluorescence of the reaction product (Chl 688/680) was observed. The reaction Chld 684/676 --> Chl 688/680 is inhibited under anaerobic conditions and in the presence of cyanide; the reaction accompanied by Chl 688/680 fluorescence quenching is not observed in pea mutants with impaired function of photosystem II reaction centers. The spectral properties of the formed Chl form with the absorption maximum at 680 nm, fluorescence quenching, and simultaneous synthesis of pheophytin suggest that the reaction is connected with the chlorophyll of photosystem II reaction center--P-680.     

Late thrombotic occlusion of a malapposed stent 10 months after intracoronary brachytherapy

We report a patient who received a stent following intracoronary 3-irradiation. Despite a good initial angiographic result, the stent appeared to be not fully expanded on intravascular ultrasound imaging at 6-month follow-up. Four months later, sudden thrombotic occlusion occurred shortly after aspirin cessation.     

Generation of Silver Standard Concept Annotations from Biomedical Texts with Special Relevance to Phenotypes

Electronic health records and scientific articles possess differing linguistic characteristics that may impact the performance of natural language processing tools developed for one or the other. In this paper, we investigate the performance of four extant concept recognition tools: the clinical Text Analysis and Knowledge Extraction System (cTAKES), the National Center for Biomedical Ontology (NCBO) Annotator, the Biomedical Concept Annotation System (BeCAS) and MetaMap. Each of the four concept recognition systems is applied to four different corpora: the i2b2 corpus of clinical documents, a PubMed corpus of Medline abstracts, a clinical trails corpus and the ShARe/CLEF corpus. In addition, we assess the individual system performances with respect to one gold standard annotation set, available for the ShARe/CLEF corpus. Furthermore, we built a silver standard annotation set from the individual systems’ output and assess the quality as well as the contribution of individual systems to the quality of the silver standard. Our results demonstrate that mainly the NCBO annotator and cTAKES contribute to the silver standard corpora (F1-measures in the range of 21% to 74%) and their quality (best F1-measure of 33%), independent from the type of text investigated. While BeCAS and MetaMap can contribute to the precision of silver standard annotations (precision of up to 42%), the F1-measure drops when combined with NCBO Annotator and cTAKES due to a low recall. In conclusion, the performances of individual systems need to be improved independently from the text types, and the leveraging strategies to best take advantage of individual systems’ annotations need to be revised. The textual content of the PubMed corpus, accession numbers for the clinical trials corpus, and assigned annotations of the four concept recognition systems as well as the generated silver standard annotation sets are available from http://purl.org/phenotype/resources. The textual content of the ShARe/CLEF (https://sites.google.com/site/shareclefehealth/data) and i2b2 (https://i2b2.org/NLP/DataSets/) corpora needs to be requested with the individual corpus providers.     

Decision Support Methods for Finding Phenotype — Disorder Associations in the Bone Dysplasia Domain

A lack of mature domain knowledge and well established guidelines makes the medical diagnosis of skeletal dysplasias (a group of rare genetic disorders) a very complex process. Machine learning techniques can facilitate objective interpretation of medical observations for the purposes of decision support. However, building decision support models using such techniques is highly problematic in the context of rare genetic disorders, because it depends on access to mature domain knowledge. This paper describes an approach for developing a decision support model in medical domains that are underpinned by relatively sparse knowledge bases. We propose a solution that combines association rule mining with the Dempster-Shafer theory (DST) to compute probabilistic associations between sets of clinical features and disorders, which can then serve as support for medical decision making (e.g., diagnosis). We show, via experimental results, that our approach is able to provide meaningful outcomes even on small datasets with sparse distributions, in addition to outperforming other Machine Learning techniques and behaving slightly better than an initial diagnosis by a clinician.     

Lectin histochemistry for detecting cadmium-induced changes in the glycosylation pattern of rat placenta

Cadmium (Cd) is an industrial and environmental pollutant that produces toxic effects on gametogenesis, pre- and post-implantation embryos, and the placenta. Because the effects of acute Cd intoxication on the placenta are not well understood, we investigated changes in its glycosylated components in Cd treated dams at days 4, 7, 10 and 15 of gestation using lectin histochemistry. CdCl₂ was administered to pregnant rats; control animals received sterile normal saline. Placentas were processed for DBA, Con A, SBA, PNA, UEA-I, RCA-I and WGA lectin histochemistry to evaluate changes in the carbohydrate pattern of the placenta that might modify cell interactions and contribute to embryonic alterations. Lectin binding was analyzed in the yolk sac; trophoblast giant cells; trophoblast I, II and III; spongiotrophoblast cells and endovascular trophoblast cells in the chorioallantoic placenta. Our lectin binding patterns showed that Cd caused alteration of SBA and DBA labeling of trophoblast-derived cells, which suggested increased expressions of α and β GalNAc. Cd also caused decreased UEA-1 binding affinity, which indicated fewer α-L-Fuc residues in placentas of Cd treated dams. The nonreactivity in trophoblast I of the control placentas incubated with Con-A contrasted with the labeling in placentas of experimental dams, which indicated increased expression of terminal α-D-Man, and α-D-Glc residues. We found that Cd altered the reactivity of placenta to several lectins, which indicated modification of the glycotype presented by the fetal component of the placenta. We report that Cd exerts a deleterious effect on the glycosylation pattern of the placenta.     

The effects of Sambucus nigra polyphenols on oxidative stress and metabolic disorders in experimental diabetes mellitus

The paper focuses on certain natural polyphenolic extracts from common elder fruit (Sambucus nigra), and also on their effects in diabetes mellitus. The results reveal that the glycosylated hemoglobin values are much higher in the diabetic group and they are significantly lower in the group protected by polyphenols. The natural polyphenol compounds reduce the lipids peroxides, neutralize the lipid peroxil radicals and inhibit the LDL oxidation. Following the perturbation of the lipid metabolism in the diabetic rats, atherogen risk has significantly increased values in comparison to the rats from the witness groups. It is found that due to the polyphenolic protection of the rats from the diabetic group treated with polyphenols, the atherogen risk is preserved at normal limits. The serum activity of glutathione-peroxidase and superoxide-dismutase has significantly lower values in the diabetic group as compared to the group protected by polyphenols. Through the hypoglycemiant, hypolipemiant and antioxidant effects,Sambucus nigra represents a possible dietary adjunct for the treatment of diabetes and a potential source for the discovery of new orally active agent(s) for future diabetes therapy. Understanding the mechanism through which the natural polyphenols have effects on the functionality of the endothelium cells, including on the membrane sensitivity and intracellular signalling, could represent a new way of therapeutically approaching chronic metabolic diseases and cardiovascular illnesses.     

Cytochrome P450-dependent metabolism of arachidonic acid.

The cytochrome P450-dependent metabolism of arachidonic acid, the mechanisms of regulation of stereo- and regiospecificity by cytochrome P450 isoenzymes, and the biological relevance of metabolites of the arachidonic acid cascade is discussed in this review.