Postoperative use of radioiodine (131-I): review of recommendations and guidelines

In the management of large number of patients with differentiated thyroid cancer, the radioactive iodine (131-I) administration plays an important role. The guidelines of numerous international and national medical societies regarding the issue of postoperative 131-I administration have been published and updated in the last few years. The guidelines differ in the shape and content, and contain some specific features. The different methods for evaluation and analysis of clinical evidence level and resulting grades of recommendations have been used in line with the very guidelines. The postoperative 131-I administration refers to the radioiodine ablation as a form of adjuvant treatment and radioiodine therapy in the management of patients with recurrent cancer, persistent disease and regional or distant metastases. According to the indications for the postoperative 131-I administration, the patients could be divided into the three risk groups: the very low risk group in which there is no indication for the postoperative 131-I administration, the low risk group in which the indication could be considered, and the high risk group in which there is a clear indication for the 131-I administration. The different criteria for distribution of patients into these three groups are expressed in a certain guidelines. There are different opinions about the necessary dosage of 131-I for the efficient ablation in the low risk group. Moreover, the opinions are also divided regarding the conduction of postoperative (preablative or pretherapeutic) scintigraphy with 131-I. As regards the instructions on preparation of patients for the radioiodine ablation and therapy, all the guidelines recommend the low iodine diet and endogenous or exogenous stimulation of TSH. The endogenous stimulation is accomplished by the withdrawal of thyroid hormones, whereas the recombinant human TSH (rhTSH) is used for exogenous stimulation. For conducting the therapy with 131-I the level of TSH has to be > 25-30 mU/L.     

Basidiomycete Clitocybe nebularis is rich in lectins with insecticidal activities

Basidiomycete mushrooms are a rich source of unique substances, including lectins, that could potentially be useful in biotechnology or biomedical applications. Lectins are a group of carbohydrate-binding proteins with diverse biological activities and functions. Here, we demonstrate the presence of a number of lectins in the basidiomycete mushroom Clitocybe nebularis. Glucose-, galactose-, sucrose-, lactose-, and Sepharose-binding lectins were isolated from fruiting bodies using affinity chromatography on Sepharose-immobilized sugars or on Sepharose. The lectins were characterized biochemically and their binding specificities examined by agglutination and agglutination inhibition assays. In addition, insecticidal and anti-nutritional properties of the lectins were studied against a model organism, fruit fly (Drosophila melanogaster), and Colorado potato beetle (Leptinotarsa decemlineata). Of the several basidiomycete mushrooms screened, C. nebularis extract showed the most potent insecticidal activity. Sucrose-binding lectin showed the strongest activity against D. melanogaster, followed by lactose- and galactose-binding lectins. Feeding bioassays with Colorado potato beetle revealed that C. nebularis extract exhibited high anti-nutritional activity against the insect; and of those tested, only lactose-binding lectin, named CNL showed the effect. Mushroom C. nebularis is shown to be rich in a variety of lectins with versatile biological activities, including insecticidal and anti-nutritional effects. C. nebularis lectins could thus have potential for use as natural insecticides.     

Cytochrome P450 Monooxygenase CYP53 Family in Fungi: Comparative Structural and Evolutionary Analysis and Its Role as a Common Alternative Anti-Fungal Drug Target

Cytochrome P450 monooxygenases (CYPs/P450s) are heme-thiolate proteins whose role as a drug target against pathogenic microbes has been explored because of their stereo- and regio-specific oxidation activity. We aimed to assess the CYP53 family''s role as a common alternative drug target against animal (including human) and plant pathogenic fungi and its role in fungal-mediated wood degradation. Genome-wide analysis of fungal species revealed the presence of CYP53 members in ascomycetes and basidiomycetes. Basidiomycetes had a higher number of CYP53 members in their genomes than ascomycetes. Only two CYP53 subfamilies were found in ascomycetes and six subfamilies in basidiomycetes, suggesting that during the divergence of phyla ascomycetes lost CYP53 P450s. According to phylogenetic and gene-structure analysis, enrichment of CYP53 P450s in basidiomycetes occurred due to the extensive duplication of CYP53 P450s in their genomes. Numerous amino acids (103) were found to be conserved in the ascomycetes CYP53 P450s, against only seven in basidiomycetes CYP53 P450s. 3D-modelling and active-site cavity mapping data revealed that the ascomycetes CYP53 P450s have a highly conserved protein structure whereby 78% amino acids in the active-site cavity were found to be conserved. Because of this rigid nature of ascomycetes CYP53 P450s'' active site cavity, any inhibitor directed against this P450 family can serve as a common anti-fungal drug target, particularly toward pathogenic ascomycetes. The dynamic nature of basidiomycetes CYP53 P450s at a gene and protein level indicates that these P450s are destined to acquire novel functions. Functional analysis of CYP53 P450s strongly supported our hypothesis that the ascomycetes CYP53 P450s ability is limited for detoxification of toxic molecules, whereas basidiomycetes CYP53 P450s play an additional role, i.e. involvement in degradation of wood and its derived components. This study is the first report on genome-wide comparative structural (gene and protein structure-level) and evolutionary analysis of a fungal P450 family.     

Genome sequences and description of novel exopolysaccharides producing species Komagataeibacter pomaceti sp. nov. and reclassification of Komagataeibacter kombuchae (Dutta and Gachhui 2007) Yamada et al., 2013 as a later heterotypic synonym of Komagataeibacter hansenii (Gosselé et al. 1983) Yamada et al., 2013

Strains T5K1 and AV446 isolated from apple cider vinegars during a submerged vinegar production in two separate vinegar facilities showed 94% 16S rRNA gene similarity to its closest neighbors Komagataeibacter maltaceti LMG 1529^T and Gluconacetobacter entanii LTH 4560^T. Further phylogenetic and phenotypic characterizations indicated that the isolates belonged to a novel species of the Komagataeibacter genus. Comparison based on 16S–23S rRNA gene ITS sequences and concatenated partial sequences of the housekeeping genes dnaK, groEL and rpoB, grouped both strains to a single phylogenetic cluster well separated from the other species of the Komagataeibacter genus. Average nucleotide identity of T5K1 and AV446 draft genome sequences compared to other Komagataeibacter type strains was below 94% and at the same time, in-silico DNA–DNA hybridization was below 70%. Both strains on the other hand showed approximately 98% (average nucleotide identity) and 87% (in silico DNA–DNA hybridization) similarity to each other. Strains T5K1 and AV446 can be differentiated from other Komagataeibacter type strains based on their ability to produce 2-keto-d-gluconic acid and at the same time inability to produce 5-keto-d-gluconic acid. Furthermore, strains of the new species do not grow on Asai medium supplemented with d-glucose or d-mannitol. The growth is also absent (T5K1) or weak (AV446) on Hoyer–Frateur medium supplemented with afore mentioned sugars. Both strains produce cellulose. In addition, draft genome analysis revealed that strains T5K1 and AV446 possess genes involved in the synthesis of acetan-like extracellular heteropolysaccharide. We propose the name Komagataeibacter pomaceti sp. nov. for the new species with LMG 30150^T [= CCM 8723^T = ZIM B1029^T] as the type strain. Data collected in this study and in a previous study also revealed that Komagataeibacter kombuchae is a later heterotypic synonym of Komagataeibacter hansenii.     

A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V(max)/K(m)=0.78 U x mg(-1) x mm(-1)), but can also use GABA (V(max)/K(m)=0.42 U x mg(-1) x mm(-1)), while SkUga1p only uses GABA (V(max)/K(m)=4.01 U x mg(-1) x mm(-1)). SpUga1p and ScUga1p transaminate only GABA and not BAL. While mammals degrade BAL and GABA with only one enzyme, but in different tissues, S. kluyveri and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication approximately 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity.     

Curvature-driven lateral segregation of membrane constituents in Golgi cisternae

Lateral segregation of mobile membrane constituents (e.g. lipids, proteins or membrane domains) into the regions of their preferred curvature relaxes stresses in the membrane. The equilibrium distribution of the constituents in the membrane is thus a balance between the gains in the membrane elastic energy and the segregation-induced loss of entropy. The membrane in the Golgi cisternae is particularly susceptible to the curvature-driven segregation because it possesses two very different curvatures-the highly curved membrane in the cisternal rims and the flat membrane in the cisternal sides. In this work, we calculate the extent of lateral segregation in the Golgi cisternae in the case where the segregation is driven by the Helfrich bending energy. It is assumed that the membrane bending constant and spontaneous curvature depend on the local membrane composition. A simple analytical expression for the extent of the lateral segregation is derived. The results show that the segregation depends on the ratio between the bending constant and the thermal energy, the difference of the preferred curvatures of the constituents and the sizes of the constituents. Applying the model to a typical Golgi cisterna, it was found that entropy can effectively limit the extent of the curvature-driven lateral segregation.     

The first known fossil record of pygmy pipehorses (Teleostei: Syngnathidae: Hippocampinae) from the Miocene Coprolitic Horizon,Tunjice Hills,Slovenia

The first known fossil record of pygmy pipehorses is described. The fossils were collected in the Middle Miocene (Sarmatian) beds of the Coprolitic Horizon in the Tunjice Hills, Slovenia. They belong to a new genus and species Hippotropiscis frenki, which was similar to the extant representatives of Acentronura, Amphelikturus, Idiotropiscis, and Kyonemichthys genera. Hippotropiscis frenki lived among seagrasses and macroalgae and probably also on a mud and silt bottom in the temperate shallow coastal waters of the western part of the Central Paratethys Sea. The high coronet on the head, the ridge system and the high angle at which the head is angled ventrad indicate that Hippotropiscis is most related to Idiotropiscis and Hippocampus (seahorses) and probably separated from the main seahorse lineage later than Idiotropiscis.     

Equilibrium mechanics of monolayered epithelium

In order to fully understand the epithelial mechanics it is essential to integrate different levels of epithelial organization. In this work, we propose a theoretical approach for connecting the macroscopic mechanical properties of a monolayered epithelium to the mechanical properties at the cellular level. The analysis is based on the established mechanical models—at the macroscopic scale the epithelium is described within the mechanics of thin layers, while the cellular level is modeled in terms of the cellular surface (cortical) tension and the intercellular adhesion. The macroscopic elastic energy of the epithelium is linked to the energy of an average epithelial cell. The epithelial equilibrium state is determined by energy minimization and the macroscopic elastic moduli are calculated from deformations around the equilibrium. The results indicate that the epithelial equilibrium state is defined by the ratio between the adhesion strength and the cellular surface tension. The lower and the upper bounds for this ratio are estimated. If the ratio is small, the epithelium is cuboidal, if it is large, the epithelium becomes columnar. Importantly, it is found that the cellular cortical tension and the intercellular adhesion alone cannot produce the flattened squamous epithelium. Any difference in the surface tension between the apical and basal cellular sides bends the epithelium towards the side with the larger surface tension. Interestingly, the analysis shows that the epithelial area expansivity modulus and the shear modulus depend only on the cellular surface tension and not on the intercellular adhesion. The results are presented in a general analytical form, and are thus applicable to a variety of monolayered epithelia, without relying on the specifics of numerical finite-element methods. In addition, by using the standard theoretical tools for multi-laminar systems, the results can be applied to epithelia consisting of layers with different mechanical properties.