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  This is an Open Access Journal Open Access journal
ISSN (Online) 2050-2966
Published by Pensoft Homepage  [26 journals]
  • Antibacterial activity of thin films TiO2 doped with Ag and Cu on
           Gracilicutes and Firmicutes bacteria

    • Abstract: BioDiscovery 20: e21596
      DOI : 10.3897/biodiscovery.20.e21596
      Authors : Dragomira Stoyanova, Iliana Ivanova, Orlin Angelov, Todorka Vladkova : This article aims to explore the antibacterial activity of thin films of TiO2 doped with Ag and Cu using two types of Gram-negative and Gram-positive test bacteria with clinical significance (Gracilicutes and Firmcutes bacteria). The thin films (thickness of about 60 nm) were deposited on glass substrates by radio frequency magnetron co-sputtering (r.f. power of 50 W) of TiO2 target with Ag and Cu pieces on its surface in an Ar atmosphere (0.8 Pa) without heating during the deposition. The total surface area of the Ag was 60 mm2 and that of the Cu was 100 mm2. Bacillus cereus, Staphylococcus epidermidis, Salmonella enterica, Escherichia coli and Pseudomonas sp. were used as test strains. The antibacterial actvity of the films was evaluated by the classical Koch's method and optical density measurements. The bactericidal effect was established at different time points between 30 min and 90 min for Pseudomonas sp. and S. enterica. The Firmicutes bacteria B. cereus and S. epidermidis were killed at the 4th and 8th hour of the treatment, respectively. The effect on E. coli was bacteriostatic until the 10th hour. The results were confirmed by assessment of the bacterial dehydrogenase activity. The studied thin films of TiO2 co-doped with Ag and Cu have a potential for application as antibacterial coatings. HTML XML PDF
      PubDate: Fri, 15 Dec 2017 15:27:23 +020
  • Identification of the gene complexes that determine some individual
           characteristics of a person

    • Abstract: BioDiscovery 20: e21998
      DOI : 10.3897/biodiscovery.20.e21998
      Authors : Irma Mosse, Alexander Kilchevsky, Alexander Gonchar, Maxim Ameliyanovich, Nikita Sedlyar : There are some data about genes associated with certain traits of a person in the scientific literature, but these data are often contradictory. It is evident that complexes of genes that affect the manifestation of the trait can be more informative. We have investigated genotypes of 9000 people, using the PCR method, in order to determine their athletic abilities or predisposition to different diseases and pathologies. In particular, we tested about 3000 women with unknown causes of miscarriages for 14 genes associated with the pregnancy development. 1,5 years later we interviewed 700 women and have identified a high genetic risk of pregnancy loss due to hereditary thrombophilia. In most of the cases, doctors took into account our data and applied for these women treatment with anticoagulant drugs such as fragmin in the subsequent pregnancies. So 86.6% of pregnant women have successfully conceived and given birth, and we have received over 500 touching letters of gratitude. Thus, genetic testing allows to identify individual human properties in order to prevent some pathologies or to chose the most suitable kind of sport. HTML XML PDF
      PubDate: Mon, 6 Nov 2017 15:36:24 +0200
  • Innovative sterilization technology - bacterial inactivation by cold argon

    • Abstract: BioDiscovery 20: e21977
      DOI : 10.3897/biodiscovery.20.e21977
      Authors : Yovana Todorova, Ivaylo Yotinov, Yana Topalova, Plamena Marinova, Evgenia Benova, Mariana Atanasova, Todor Bogdanov : Non-thermal (cold) plasma is subject of intensive scientific interest as an alternative sterilization technique for advanced control of microbial quality and safety in food biotechnology. The cold plasma is a flow of weakly ionized gas at atmospheric pressure that includes radicals, H2O2, O3, ultraviolet radiation, charged particles, exited metastable atoms, electric fields. One of the major benefits of plasma-based technologies is the synergy between the strong effects of these highly active components that provides a high bactericidal efficiency at low costs, time-saving and non-toxicity. The aim of this study is to assess the bactericidal effect of cold argon plasma in liquids and surfaces, contaminated with Gram-negative and Gram-positive spore-forming bacteria. The used plasma source is surface-wave-sustained discharge (SWD) operating at 2.45 GHz in argon (plasma torch) produced by an electromagnetic wave launcher surfatron type. The bactericidal effect was studied by direct contact treatment of contaminated liquids and agar plates with Pseudomonas aureofaciens AP-9 and Brevibacillus laterosporus BT-271. The results show that the cold argon plasma is able to inactivate bacteria at short exposure time (under 1 min). The clear sterilization zones on treated surfaces with diameter depending on exposure time and initial bacterial density were obtained. In bacteria-contaminated liquids the partial disinfection was observed at least. The potential of plasma based technologies as innovative sterilization approach is high and can be used for various purposes related to microbial control and food safety. HTML XML PDF
      PubDate: Fri, 3 Nov 2017 20:47:28 +0200
  • Participation of NO-synthase in Control of Nitric Oxide Level in Rat
           Hippocampus after Modelling of Ischaemic and Haemorrhagic Insult

    • Abstract: BioDiscovery 20: e14810
      DOI : 10.3897/biodiscovery.20.e14810
      Authors : Khalil L. Gainutdinov, Svetlana G. Pashkevich, Vyatcheslav V. Andrianov, Guzel G. Yafarova, Margarita O. Dosina, Tatiana Kh. Bogodvid, Julia P. Stukach, Dinara I. Silant'eva, Aleksandra S. Zamaro , Timur V. Sushko, Vladimir Kulchitsky : Electron paramagnetic resonance (EPR) was used as a method for recording the content of the nitric oxide (NO) in hippocampal tissues of intact rats and rats after modelling of ischaemic and haemorrhagic stroke. Based on direct measurements of NO by EPR spectroscopy, it was shown that, within 5 hours after the onset of symptoms of ischaemic and haemorrhagic stroke, the formation of NO in the hippocampus was reduced by a factor of 2-3 and this reduction was maintained for a period of between 24 and 72 hours. The results show that a systemic character of a decrease in the intensity of NO production during the modelling of ischaemic events in the brain reflects the effects of central dysregulation of the functions at the level of the whole organism such that it is appropriate to consider implementing the correction of the vital systems of the body in a stroke. It has indicated that non-selective NO-synthase blocker L-NAME reduced the low level of NO production by a factor of 3 by its administration within 72 hours after post-ischaemic and haemorrhagic stroke. It was discovered however that L-NAME returns the level of NO production to baseline (control) by its administration within 5 hours after ischaemia. HTML XML PDF
      PubDate: Wed, 18 Oct 2017 12:05:23 +030
  • Pilot assessment of cyanotoxins as potential risk factors for cancer in

    • Abstract: BioDiscovery 20: e20501
      DOI : 10.3897/biodiscovery.20.e20501
      Authors : Maya Stoyneva-Gärtner, Blagoy Uzunov, Petya Dimitrova : Cyanoprokaryotes (=cyanobacteria, blue-green algae) are the most ancient oxygen-producing phototrophic microorganisms, spread all over the Globe, which form the important basis of different food chains in aquatic and terrestrial habitats. However, due to strong anthropogenic pressure during the last decades they are also responsible for causing nuisance algal blooms in different water bodies with deleterious effects on the mankind and ecosystems mainly due to production of toxic substances (cyanotoxins). Amongst them are the microcystins, nodularins, lyngbyatoxins and aplysiatoxins, known as tumor-promotors with increase of exposure routes through which humans and animals can be placed at risk (Meriluoto et al. 2017). However, the investigations on the relations between the occurrence and development of such diseases with the cyanotoxins and their producers are extremely scarce at a global scale (Yu and Chen 1994, Ueno et al. 1996, Fleming et al. 2002, Svircev et al. 2009, Drobac et al. 2011, Labine et al. 2015). During the last 15 years cyanoblooms and microcystins, nodularins and saxitoxins were detected in 16 different Bulgarian freshwater bodies, including some drinking-water reservoirs (Stoyneva-Gärtner et al. 2017). Amongst the detected toxins some new forms were recognized by their characteristic spectra (Pavlova 2007, Pavlova et al. 2007), and, more recently, a new potential producer of lyngbyatoxin was found in the Black Sea (Stoyneva et al. 2015). The poster shows a pilot assessment of the spread of cancer distribution and mortality vs. spread of cyanoblooms and cyanotoxins in Bulgaria. The pilot assessment is made on the basis of comparison of the general regions of spread of cyanotoxins in Bulgarian water bodies and toxin-producing cyanospecies during the period 2000-2017 (Stoyneva-Gärtner et al. 2017) with the spread of cancer in Bulgaria (e.g. Valerianova et al. 2015). The comparison shows general conformities between the spread of the “most dangerous” water bodies and main regions of cancer diseases in the country. The results obtained served as a basis for a new project proposal which aims at a deepening of the studies for improvement of prevention of cancer in the country. HTML XML PDF
      PubDate: Thu, 24 Aug 2017 15:09:52 +030
  • Osteogenic, adipogenic and neurogenic differentiation of human
           adipose-derived mesenchymal stem cells before and after cryopreservation

    • Abstract: BioDiscovery 20: e20272
      DOI : 10.3897/biodiscovery.20.e20272
      Authors : Marina Hristova, Elena Hristova, Plamen Todorov : Mesenchymal stem cells (MSCs) represent a promising tool for the regeneration of damaged tissues in cell therapy. They are characterized as undifferentiated progenitors, which have the ability for self-renewal and multilineage differentiation potential. The development of effective protocols for long-term storage, with the aim of subsequent clinical usage, is essential for their application as cellular therapeutics. In our experiments, we aimed to investigate fresh and cryopreserved human adipose tissue-derived MSCs (AT-MSCs) and their osteogenic, adipogenic and neurogenic differentiation potential. The obtained results pointed out that the cells possess spindle-like shape and form characteristic wave-like layers when reaching confluency. The immunophenotypic analysis shows that they express CD73, CD90 and CD105 and lack the hematopoiеtic lineage markers CD34 and CD45. Both cryopreserved and fresh hAT-MSCs maintain similar ability to specialize towards osteogenic, adipogenic and neural lineage. In conclusion, the present study indicates that the isolated cells are cryotolerant and are able to retain their morphological and immunophenotypical characteristics  after freezing, as well as their multilineage differentiation potential. HTML XML PDF
      PubDate: Mon, 21 Aug 2017 23:16:27 +030
  • Two candidate genes for recurrent pregnancy loss and infertility: Could
           ZP3 and UPK3B give us new diagnostic and therapeutic approach'

    • Abstract: BioDiscovery 20: e20113
      DOI : 10.3897/biodiscovery.20.e20113
      Authors : Fatma Sılan, Baris Paksoy, Taner Karakaya, Onur Yildiz, Mine Urfali, Ozturk Ozdemir : Introduction: Chromosomal indels are relatively common cytogenetic abnormalities. Nonetheless, clinical outcomes depend on the location, size and genes in deletion or duplication regions. The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by ZP3(Zona pellucida3) gene is a structural component of the zona pellucida and functions in primary binding and induction of the sperm acrosome reaction. UPK3B(Uroplakin 3B), a minor component of the apical plaques of mammalian urothelium that binds and dimerizes with uroplakin-1b(UPK1B), one of the major conserved urothelium membrane proteins. We herein report two cases presenting with the deletions encompassing POMZP3, UPK3B, ZP3, POM121 and POM121C genes. Case1: 25-year-old female presented to our clinic with recurrent pregnancy loss. After clinical and cytogenetic evaluation, which all of them do not feature, she was diagnosed as the deletion of POMZP3 and UPK3B genes with the array-CGH platform. (Agilent SurePrintG3 HumanCGH 60K) Case2: Ten-week embrio of 34-year-old female, infertile for ten years before and this is her first pregnancy after IVF, revealed the deletion of POM121,POM121C and ZP3 genes with the same array-CGH platform. Conclusion: We have evaluated the deletion of two consecutive genes -UPK3B and ZP3- in the genome by array-CGH analysis. Early abortion or infertility due to triploidic, tetraploidic embryos or uniparental disomy, resulting in a change in the structure of the zona pellucida with the mutations of ZP3 gene, may occur. Also mutations of UPK3B gene may cause abortion or infertility due to endometrial origin with defective function of the urothelium membrane proteins. ICSI could be a good choice for ZP3 deficient infertile woman and if PGS choosen without ICSI, uniparental disomia should be excluded. HTML XML PDF
      PubDate: Thu, 10 Aug 2017 14:04:33 +030
  • Comet assay - a sensitive tool for genotoxicity assessment of
           environmental stress in Mytilus galloprovincialis from the Bulgarian Black
           Sea coast

    • Abstract: BioDiscovery 20: e19265
      DOI : 10.3897/biodiscovery.20.e19265
      Authors : Bela Vasileva, Lachezar Yakimov, Borislava Kukurina, Milena Georgieva, George Miloshev, Nesho Chipev : Assessment of DNA damage is of primary concern when the pollution-related stress in living organisms has to be determined. The reason for this concern comes from the evidence that damages in DNA often lead to mutations which are potential threat for the sustainability of organisms and ecological systems. To monitor genotoxicity of the marine environment we have developed a special procedure for application of the method of Comet assay (CA) on the native populations of Mytilus galloprovincialis. Samples were collected from areas with different anthropogenic load along the Bulgarian South Black Sea coast. As the first organ to encounter marine pollutants the gills of the mussels turned-out to be the most appropriate tissue for obtaining a single-cell suspension. Comet assay tests were performed and DNA damage was quantified using several different methods including percentage of DNA in the tail, Comet head and tail area, Comet number, Tail moment, Comet shape, etc. The method allowed us to monitor and predict the genetic risk of marine environmental stressors, particularly persistent pollutants. It proved to be convenient for precise quantification of the on-site loads of genotoxic stress on coastal ecosystems. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 22:58:49 +0300
  • Genetic changes in natural Taraxacum officinale populations obtained under
           pollution stress

    • Abstract: BioDiscovery 20: e18712
      DOI : 10.3897/biodiscovery.20.e18712
      Authors : Borislava Kukurina, George Miloshev : Plant populations under stress undergo genotypic alterations which can drive the species towards extinction or adaptation. Defining a suitable plant model and the respective genetic markers for studying the perturbations in the population’s genetic diversity is of crucial importance for the needs of bioconservation and proper ecosystem management. In the current study we prove the usefulness of Taraxacum officinale (common dandelion) as a suitable model plant for genetic biomonitoring. We compared the genotype composition of four specific dandelion populations: 1) a population from the area around the closed “Kremikovtzi” metallurgical plant; 2) a population from the still working “Stomana”-Pernik metallurgical facility; 3) a population from a rural, but naturally rich in heavy metals region close to Bosnek village; 4) a control population from a clean site next to Lokorsko village. Four genetic markers of tree different kinds (a microsatellite, a ribosomal DNA marker and two chloroplastic DNA markers) were tested in order to reveal the genotype diversity in the chosen populations. Our results showed strong quantitative and qualitative genotypic differentiation between pollution-impacted and clean populations. The most interesting observation was that the unique genotypes, considered as result of mutations, were predominantly detected in the plants from the heavy metal polluted regions. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 22:55:33 +0300
  • Basal and PGF2α-stimulated secretion of pro-inflammatory cytokines from
           3T3-L1 adipocyte-like cells

    • Abstract: BioDiscovery 20: e17757
      DOI : 10.3897/biodiscovery.20.e17757
      Authors : Bilyana Ilieva, Elena Marinova, Hristo Gagov, Rossitza Konakchieva : Adipocytes were recently identified as an important source of endocrine and paracrine mediators, regulating the metabolism and activity of various cell types and body functions. 3T3-L1 preadipocytes are useful model for physiological, pharmacological and cell signaling studies. Differentiation of 3T3-L1 murine fibroblasts into adipocyte-like cells was conducted in presence of IBMX, dexamethasone and insulin and demonstrated by Oil Red O staining of accumulated lipid droplets. Using Inflammatory Multi- Analyte Cytokines ELISArray Kit we investigated the release of cytokines under basal conditions, after PGF2α treatment for 24 hours to induce pro-inflammatory phenotype, and after PGF2α treatment and incubation in the presence of L-C-Propargylglycine (PGG, 1 mmol/l), a selective inhibitor of cystathionine-gamma-lyase (CSE). The last combination was used to explore the role of H2S, released from CSE, for cytokine and H2O2 release. We found that PGF2α strongly increased TNFα secretion from differentiated adipocytes, the latter effect being antagonized by PGG. The CSE inhibitor enhanced IL-6 production and suppressed IL-10 secretion. PGG enhanced H2O2 production of in PGF2α-treated cells. It is concluded that pro-inflammatory phenotype of differentiated 3T3-L1 adipocyte-like cells, induced by PGF2α is characterized by enhanced TNFα production which critically depends on the ability of CSE to produce H2S.  HTML XML PDF
      PubDate: Tue, 1 Aug 2017 19:14:03 +0300
  • Perivascular adipose tissue as regulator of the force of artery
           contractions in health and disease

    • Abstract: BioDiscovery 20: e19831
      DOI : 10.3897/biodiscovery.20.e19831
      Authors : Hristo Gagov, Radoslava Emilova, Daniela Dimitrova, Mitko Mladenov, Rudolf Schubert : During the last two decades, perivascular adipose tissue (PVAT) has been revealed as an important regulator of vascular processes such as proliferation of smooth muscle cells, pro- and anti-oxidant reactions in the vascular wall, angiogenesis, inflammation, apoptosis of neutrophils, migration of monocytes and others. PVAT derived mediators either increase or decrease the amplitudes of the force of artery contraction measured using isometric small vessel myography. In healthy animals and humans predominates the relaxing effect while in diseases the contractile influence of PVAT is common. In aging and pathological conditions like atherosclerosis and diabetes, or with environmental factors like tobacco smoke and high-fat diet, the phenotype of perivascular adipocytes is changed from anti-inflammatory to pro-inflammatory. This change is accompanied by a significant rearrangement of mediators released from PVAT. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 16:21:23 +0300
  • Ultrananocrystalline diamond coated implants for enhanced osseointegration

    • Abstract: BioDiscovery 20: e19830
      DOI : 10.3897/biodiscovery.20.e19830
      Authors : Silviya Stateva, Daniel Merker, Cyril Popov, Margarita Apostolova : Osteoporosis causes bones to become weak and brittle. It is known that the alterations in bone metabolism associated to osteoporosis can impair bone healing around implants and affect their osseointegration. The main objective of this study was the development of new nanostructured implant materials based on ultrananocrystalline diamond (UNCD) coatings for enhancing osseointegration. The films were deposited on Ti substrates by microwave plasma CVD from 17% CH4/N2 gas mixtures and modified by O2 or NH3/N2 plasmas. The modifications rendered the H-terminated hydrophobic as-grown films hydrophilic. The interaction of endothelial (EA.hy926) and osteosarcoma (MG63) cells with differently modified UNCD surfaces was investigated by proteome analyses. It revealed the identification of over 19 000 proteins (extracellular and cytosolic). They correspond to 508 (Ti), 634 (UNCD), 651 (O-UNCD), and 668 (NH2-UNCD) protein groups. The interaction network analysis showed differences in the connectivity of inferred protein networks between the ECM niches, which suggests the presence of specific cell microenvironments on O- and NH2-terminated UNCD surfaces. Our results show that due to a favorable combination of surface chemical and topological properties the UNCD films, as-grown and especially after their plasma modifications, may serve as superior scaffolding for promoting the cell attachment and growth during osseointegration. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 15:43:01 +0300
  • Testosterone as Diamine Oxidase Activity Regulator

    • Abstract: BioDiscovery 20: e17372
      DOI : 10.3897/biodiscovery.20.e17372
      Authors : Milena Mishonova, Hristo Gagov : Diamine oxidase (DAO) is a key enzyme of the metabolism of polyamines. Its activity was assayed in homogenate of male immature rat liver and kidney.  The androgens are important regulators of polyamines’ metabolism. It was known that testosterone (T) activates DAO in murine kidney, an effect that might depend on the intracellular level of polyamines. The aim of this research was to study the participation of androgen receptor and ornithine decarboxylase (ODC) in DAO testosterone regulation. The rats were treated i.p. 4 hours before measurements with T, T + Hydroxyflutamide (HF), an androgen receptor antagonist or T + difluoromethylornithine (DFMO), an inhibitor of ODC. It was observed that i) T significantly increased DAO activity of rat liver and kidney; ii) the presence of HF abolished the effect of T ; iii) the presence of DFMO slowly reduced the effect of T on DAO activity. It is concluded that T activates DAO mainly by a mechanism, which includes androgen receptor binding and ODC stimulation. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 11:07:33 +0300
  • New Mechanisms of Perinatal Hypoxia and Perspectives of
           Pathogenesis-oriented Treatment

    • Abstract: BioDiscovery 20: e14945
      DOI : 10.3897/biodiscovery.20.e14945
      Authors : Larisa A. Balykova, Ludmila V. Ledyajkina, Vladimir A. Trofimov, Alexei P. Vlasov, Irina S. Nazarova, Victor V. Revin : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 23:16:45 +030
  • Change in morphometric and oxygen-binding properties of erythrocytes in
           vascular diseases patients

    • Abstract: BioDiscovery 20: e15079
      DOI : 10.3897/biodiscovery.20.e15079
      Authors : Natalia Gromova, Victor Revin, Nadezhda Revina, Anastasiya Kukina, Elvira Revina, Anastasiya Samonova , Ilya Solomadin, Alexander Tychkov, Inessa Moiseeva : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 20:57:38 +030
  • Antibacterial activity of thin films TiO2 doped with Ag and Cu on
           Gracilicutes and Firmicutes bacteria

    • Abstract: BioDiscovery 20: e15076
      DOI : 10.3897/biodiscovery.20.e15076
      Authors : Dragomira Stoyanova, Iliana Ivanova, Orlin Angelov, Todorka Vladkova : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 20:24:58 +030
  • Application of safe-by-design approach for curing osteoporosis – a
           lock at the future

    • Abstract: BioDiscovery 20: e15099
      DOI : 10.3897/biodiscovery.20.e15099
      Authors : Armine Grigoryan, Iliyan Kolev, Anelia Dimitrova, Margarita Apostolova : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 20:00:32 +030
  • Antiviral activity of Stachys Thracica Dav. extracts against Human Herpes
           virus type 1 and 2

    • Abstract: BioDiscovery 20: e15022
      DOI : 10.3897/biodiscovery.20.e15022
      Authors : Petya Angelova, Venelin Tsvetkov, Anton Hinkov, Daniel Todorov, Kalina Shishkova, Zhenya Yordanova, Veneta Kapchina-Toteva, Stoyan Shishkov : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 16:38:18 +030
  • Synthesis of a drug discovery library for the identification of sigma
           receptors modulators

    • Abstract: BioDiscovery 20: e14958
      DOI : 10.3897/biodiscovery.20.e14958
      Authors : Giacomo Rossino, Marta Rui, Marcello Di Giacomo, Daniela Rossi, Simona Collina : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 13:24:10 +030
  • Recent advances in the structure-guided research and development of
           antimicrobial therapeutics

    • Abstract: BioDiscovery 20: e14952
      DOI : 10.3897/biodiscovery.20.e14952
      Authors : Dimitar Trifonov, Tom Evers : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 10:24:41 +030
  • Validation of a novel HPLC-based serum thymidine kinase assay for breast
           cancer detection

    • Abstract: BioDiscovery 20: e14563
      DOI : 10.3897/biodiscovery.20.e14563
      Authors : Elena Kuzmanova, Marilena Spanou, Emma Leckie, Nikolai Zhelev : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 5:44:23 +0300
  • A step forward in the identification of compounds interfering with the
           Embryonic Lethal Abnormal Vision (ELAV) protein - RNA complexes

    • Abstract: BioDiscovery 20: e14670
      DOI : 10.3897/biodiscovery.20.e14670
      Authors : Serena Della Volpe, Daniela Rossi, Francesca Vasile, Donatella Potenza, Marialaura Amadio, Alessia Pascale, Simona Collina : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 4:44:08 +0300
  • Sigma 1 receptor modulators as a new weapon against multiple sclerosis

    • Abstract: BioDiscovery 20: e14565
      DOI : 10.3897/biodiscovery.20.e14565
      Authors : Simona Collina, Marta Rui, Giacomo Rossino, Serena Della Volpe, Daniela Rossi, Arianna Scuteri, Alessio Malacrida, Guido Cavaletti : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 3:40:56 +0300
  • Cryogenic pretreatment of keratinous waste for enhanced methane production

    • Abstract: BioDiscovery 20: e14096
      DOI : 10.3897/biodiscovery.20.e14096
      Authors : Elena Kuzmanova, Joseph Akunna, Nikolai Zhelev : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 2:40:27 +0300
  • The effects of changes in composition and state of the lipids on
           erythrocytes’ oxygen-transport function in pathological conditions
           associated with the development of hypoxia

    • Abstract: BioDiscovery 20: e14701
      DOI : 10.3897/biodiscovery.20.e14701
      Authors : Victor V. Revin, Natalia V. Gromova, Elvira S. Revina, Ilya N. Solomadin, Alexander Yu. Tychkov : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 1:39:59 +0300
  • Phosphorylase Kinase Inhibition Therapy in Burns and Scalds

    • Abstract: BioDiscovery 20: e11207
      DOI : 10.3897/biodiscovery.20.e11207
      Authors : Madalene Heng : Severe burns and scalds almost always result in unsightly hypertrophic scarring. Among the important processes involved in scarring are fibroblast formation and transformation of fibroblasts into myofibroblasts. Myofibroblasts contain α-smooth muscle actin which has contractile properties and can lead to wound contraction and hypertrophic scarring. Phosphorylase kinase (PhK), expressed within 5 mins of injury, is among the earliest enzymes released after tissue damage. It is responsible for activation of NF-kB, which in turn activates over 200 different genes related to inflammation, fibroblastic proliferation, myofibroblast conversion, and eventual scar tissue formation. The sequence and approximate timing of events following injury include the following: activation of PhK (5 mins), followed by appearance of neutrophils (30 mins), macrophages (hours to days), fibroblasts (1 week) and myofibroblasts (2 weeks). Cytokines and growth factors secreted by macrophages include fibroblast growth factor (FGF) and transforming growth factors α and β (TGFα and TGFβ). Fibroblast growth factor is responsible for fibroblastic proliferation, and TGFβ1 for conversion of fibroblasts into myofibroblasts. After thermal injury, the use of topical curcumin, a non-competitive, selective PhK inhibitor that blocks PhK activity upstream of NF-kB activation, was found to be associated with more rapid and improved skin healing, as well as less severe or absent scarring. HTML XML PDF
      PubDate: Fri, 24 Feb 2017 10:49:14 +020
  • Drug resistance of cancer cells is crucially affected by expression levels
           of ABC-transporters

    • Abstract: BioDiscovery 20: e11211
      DOI : 10.3897/biodiscovery.20.e11211
      Authors : Petr Mlejnek, Petr Dolezel, Eliska Ruzickova : Dasatinib (DAS), a second generation of tyrosine kinase inhibitor (TKI), represents excellent choice for the treatment of chronic myeloid leukemia resistant to imatinib. Unfortunately, recent laboratory studies suggested that antiproliferative effect of DAS might be significantly reduced due to the overexpression of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2. However, whether these drug transporters might compromise therapeutic effect of DAS in clinic is unclear. We believe that the drug transporter expression level is a crucial factor that affects the results and its consideration may help to explain the existing controversy. In addition, clinically relevant concentrations of drug must be used. In our study, human leukemia K562 cells with high and low expression levels of ABCB1 or ABCG2 were used. DAS was applied at nanomolar concentrations. We observed that K562 cells expressing high levels of ABCB1 and ABCG2 contained significantly reduced intracellular levels of DAS and these cells exhibited significantly increased resistance to this drug. Importantly, cells with the low expression of ABCB1 or ABCG2 effluxed DAS less efficiently, however, still significantly. Accordingly, the observed resistance was lower but significant. Conclusions: The antiproliferative effects of DAS might be reduced by ABCB1 or ABCG2. However, the actual effect of these ABC transporters on DAS efficiency depends on their expression levels. The lower expression levels of ABC transporters mediate lower resistance. Considering the fact that expression levels of ABCB1 and ABCG2 transporters are usually low in clinical samples, their contribution to the overall resistance to DAS is probably low but significant. HTML XML PDF
      PubDate: Wed, 8 Feb 2017 10:52:09 +0200
  • Screening an Archetypal Collection of Microorganisms for the Presence of
           Unexplored Antimicrobial Compounds

    • Abstract: BioDiscovery 20: e10763
      DOI : 10.3897/biodiscovery.20.e10763
      Authors : Lucia Cimarelli, Anna Maria Giuliodori, Anna Brandi, Karolina Adamkiewicz, Roberto Spurio, Attilio Fabbretti : HTML XML PDF
      PubDate: Wed, 8 Feb 2017 9:26:49 +0200
  • From Roscovitine to CYC202 to Seliciclib – from bench to bedside:
           discovery and development

    • Abstract: BioDiscovery 10: e8956
      DOI : 10.7750/BioDiscovery.2013.10.1
      Authors : Nikolai Zhelev, Dimitar Trifonov, Shudong Wang, Moustapha Hassan, Ibrahim El Serafi : This monograph reviews the discovery and development of the cyclin-dependent kinase inhibitor roscovitine (R-roscovitine, CYC202, Seliciclib). The authors summarise the in vitro and in vivo data that have formed the basis for clinical investigation of Seliciclib as an anti-cancer drug. Kinase selectivity, cellular effects and the pharmacological properties of the drug are discussed in addition to the clinical results of Seliciclib being reviewed. Novel results on the effect of the drug in cardiac hypertrophy are summarized and potential applications of Seliciclib in other therapeutic areas, including, inflammation, virology, glomerulonephritis and polycystic kidney disease, are discussed. Finally the authors argue that optimisation of the therapeutic effect of kinase inhibitors such as Seliciclib can be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. HTML XML PDF
      PubDate: Mon, 30 Dec 2013 0:00:00 +0200
  • Reverse engineering of drug induced DNA damage response signalling pathway
           reveals dual outcomes of ATM kinase inhibition

    • Abstract: BioDiscovery 9: e8954
      DOI : 10.7750/BioDiscovery.2013.9.4
      Authors : Michael A. Idowu, Hilal S Khalil, James L. Bown, Nikolai Zhelev : The DNA Damage Response (DDR) pathway represents a signalling mechanism that is activated in eukaryotic cells following DNA damage and comprises of proteins involved in DNA damage detection, DNA repair, cell cycle arrest and apoptosis. This pathway consists of an intricate network of signalling interactions driving the cellular ability to recognise DNA damage and recruit specialised proteins to take decisions between DNA repair or apoptosis. ATM and ATR are central components of the DDR pathway. The activities of these kinases are vital in DNA damage induced phosphorylational induction of DDR substrates. Here, firstly we have experimentally determined DDR signalling network surrounding the ATM/ATR pathway induced following double stranded DNA damage by monitoring and quantifying time dependent inductions of their phosphorylated forms and their key substrates. We next involved an automated inference of unsupervised predictive models of time series data to generate <em>in silico</em> (molecular) interaction maps. We characterized the complex signalling network through system analysis and gradual utilisation of small time series measurements of key substrates through a novel network inference algorithm. Furthermore, we demonstrate an application of an assumption-free reverse engineering of the intricate signalling network of the activated ATM/ATR pathway. We next studied the consequences of such drug induced inductions as well as of time dependent ATM kinase inhibition on cell survival through further biological experiments. Intermediate and temporal modelling outcomes revealed the distinct signaling profile associated with ATM kinase activity and inhibition and explained the underlying signalling mechanism for dual ATM functionality in cytotoxic and cytoprotective pathways. HTML XML PDF
      PubDate: Wed, 11 Dec 2013 0:00:00 +0200
  • Progesterone significantly enhances the mobility of boar spermatozoa

    • Abstract: BioDiscovery 9: e8955
      DOI : 10.7750/BioDiscovery.2013.9.5
      Authors : Johan M. Campbell, Anne L. Savage, Oladipo Madamidola, Kshitij Tamhane, Renalyn Soriano, Ashok K. Adya, Sean G. Brown : Progesterone released from the cumulus cells of the oocyte causes a number of physiological responses in human sperm cells including hyperactivation, acrosome reaction and chemotaxis. We employed a validated sperm mobility assay, which involves measuring the ability of sperm to penetrate an inert cell separation solution over time, to assess the ability of progesterone to enhance the mobility of boar spermatozoa. Cells maximally penetrate the solution over 50 minutes. 100nM progesterone significantly (P = 0.01) increased the mobility of non-capacitated sperm cells causing a doubling in the rate at which the cells penetrated through the cell separation solution (control half maximal penetration rate [Km] = 18.0±2.2; +100nM progesterone Km = 8.8±0.8min). Similarly, capacitated cells penetrated at a rate (Km = 19.2±3.0 min) not significantly different from non-capacitated cells and 100nM progesterone also significantly increased the rate of penetration of capacitated cells (Km = 9.5±1.0 min, P&lt;0.05). The T-type voltage gated calcium channel blocker mibefradil (30mM) significantly inhibited both the control and progesterone enhanced mobility in non-capacitated and capacitated sperm. Only capacitated cells showed a significant increase in the acrosome reaction in response to 100nM progesterone (control non-reacted = 75±4%, +100nM progesterone non-reacted = 47±10%). Western blot analysis confirmed that there was an increase in the total protein tyrosine phosphorylation levels in capacitated cells. In conclusion, we have demonstrated that 100nM progesterone accelerates the mobility of boar sperm cells through an inert cell separation solution in an extracellular calcium dependent manner. HTML XML PDF
      PubDate: Wed, 11 Dec 2013 0:00:00 +0200
  • The alternate GNB3 splice variant, Gβ3s, exhibits an altered signalling
           response to EGF stimulation, which leads to enhanced cell migration

    • Abstract: BioDiscovery 9: e8953
      DOI : 10.7750/BioDiscovery.2013.9.3
      Authors : Hemanth Tummala, Hilal S Khalil, Mohammad R. Islam, Sarah J. Jones, Ian R. Ellis, Isabella D’Ascanio, Nikolai Zhelev, Douglas H. Lester : It has recently been reported that the duplication of the GNB3 gene has been shown to be directly linked to an obesity phenotype, both in humans and also in a humanised mouse model. Moreover, the common human GNB3 c.825C&gt;T polymorphism (rs5443) causes this ubiquitously expressed gene to be aberrantly spliced approximately 50% of the time leading to the production of both a normal Gβ3 protein and a truncated, possibly less stable subunit, known as Gβ3s. The presence of the GNB3 825T allele has previously been shown to be associated with predisposition to hypertension, obesity, various cancers, Alzheimers, age related cognitive function, erectile dysfunction as well as a marker for pharmacogenetic drug action. Great controversy, however, currently exists as to whether these phenotypes associated with the 825T allele are a) mainly due to the presence of the smaller, possibly more active, Gβ3s subunit or b) merely down to the haploinsufficiency of the normal GNB3 transcript, due to its frequent aberrant splicing. In order to try and address these two conflicting hypothesis, we report on the identification and characterisation of signalling alterations unique to the presence of Gβ3s protein subunit. Moreover we also show the physiological consequences associated with altered signalling, directly induced by the Gβ3s subunit. For this, we used both an EBV transformed lymphoblast cell line homozygote for GNB3 825T/825T (TT) and a stable Gβ3s expressing recombinant COS-7 clone. In both of these cell lines that express the Gβ3s subunit, we found enhanced cytosolic calcium influx upon stimulation with EGF, TGFα and VEGF ligands, as compared to "normal" GNB3 controls with the 825C/825C (CC) genotype. This aberrant calcium influx also led to an increase in ERK, but not AKT1, phosphorylation. Despite the lack of AKT1 activation, we paradoxically observed a significant increase in phosphorylation of its downstream substrates, namely mTOR and p70<sup>S6k</sup> (KS6B2). Moreover we observed a decrease in phospho FoxO3a only in Gβ3s expressing cells, but not in the "normal" GNB3 (CC) control cell line. The presence of the Gβ3s subunit also appeared to alter the distinct localisation patterns of both Foxo3a and AKT1, while also increasing the colocalisation of mTOR and p70<sup>S6K</sup>. Subsequent growth factor stimulation studies revealed that EGF treatment, of Gβ3s expressing cells, appeared to cause a significant decrease in cAMP levels, which, in turn resulted in both enhanced caveolin-1a phosphorylation, and an increase in actin stress fibre formation. The identification of these distinct Gβ3s specific signalling alterations were indicative of a more aggressive migratory phenotype. This led us to further investigate and confirm that the presence of the Gβ3s subunit also appears to cause significantly enhanced migration and robust scratch wound healing kinetics, as compared to cells harbouring only the normal copy of the gene. These data therefore present convincing evidence that the Gβ3s subunit is stable, functional and its presence can significantly alter signalling pathways, in different cell types. HTML XML PDF
      PubDate: Sat, 30 Nov 2013 0:00:00 +0200
  • Evolution of Conformational Disorder & Diversity of the P53

    • Abstract: BioDiscovery 8: e8952
      DOI : 10.7750/BioDiscovery.2013.8.5
      Authors : Anne-Sophie Huart, Ted R. Hupp : The tumour suppressor p53 is now known to be an ancient transcription factor that had already evolved interaction sites with its partner protein MDM2 at the dawn of multi-cellular eukaryotic animal life. The billion-year life history of the p53-MDM2 axis has permitted significant time for the proteins to integrate into a distinct range of cellular pathways including binding to hundreds of genomic promoters and regulatory protein-protein interactions with hundreds of distinct functions. This long age of p53 allows us to understand how the protein can regulate a range of functions such as energy generation of the cell, cell motility, genome integrity, virus infection, immune cell response, ageing, and oxidative stress. Due to this deep integration of p53 into the core of eukaryotic life, it is not surprising that the p53 pathway requires inactivation in order for human cancer cells to evade the normal growth controlling processes that have been shaped through evolution by natural selection. This review will focus on the emerging concepts in the protein science field that shed light on p53 protein evolution and function including the nature of thermodynamically unstable regulatory proteins and the growing realisation that the majority of protein-protein interactions in complex eukaryotic cells are driven by intrinsically unstructured and weakly interacting peptide motifs. These concepts help to explain how the vast number of dynamic and specific protein-protein interactions in the p53 pathway evolved, suggest how amino acid modifications like phosphorylation or acetylation in turn evolved to regulate dynamically the p53 interactome, and finally reveal therapeutic strategies for targeting the p53 interactome in human cancers. HTML XML PDF
      PubDate: Wed, 14 Aug 2013 0:00:00 +0300
  • Changes in the connective tissue element of the thyroid gland in normal
           and recurrent euthyroid goiter

    • Abstract: BioDiscovery 9: e8951
      DOI : 10.7750/BioDiscovery.2013.9.1
      Authors : Kalin Vidinov, Nikolay Vidinov, Manol Kalniev, Dimo Krastev : Goitre recurrence is a common problem following subtotal thyroid gland resection for multinodular goitre disease. The aim of our study was to trace out the ultrastructure of the thyroid gland of man after primary and redo operations for struma nodosa. We undertook the task to study the fine ultrastructural changes taking place in the stromal part of the gland. For ultrastructural examination we used routine transmission electron microscopy. The electron microscopy has been made on Hitachi H-500 microscope Our main goal was to compare the ultrastructural characteristics of the thyroid gland in two different groups - patients with primary disease and patients with recurrence.The results from our research showed that in the first group the stroma was presented by one or two rows of cells in the septum or in small groups in the interfolicular space. Studies by electron microscopically showed that the cells of the stroma had the ultrastructural characteristics of fibroblasts, but there was an increased number cisterne of Granular endoplasmic reticulum, well developed Goldgi complex, as well as relatively small amount of vesicles and vacuoles. The examination of the specimens from the second group showed a much thicker stroma between the follicles. There was an increased amount of stromal cells and collagen bundles in the interfolicular space. The proteoglycan complexes in the extracellular matrix were rarely situated.Our results suggest that the connective tissue of the thyroid gland reacts faster to the changes of the structure of the gland than the epithelial cells of the follicles. HTML XML PDF
      PubDate: Sat, 27 Jul 2013 0:00:00 +0300
  • Small Molecule Inhibitors of MDM2-p53 and MDMX-p53 Interactions as New
           Cancer Therapeutics

    • Abstract: BioDiscovery 8: e8950
      DOI : 10.7750/BioDiscovery.2013.8.4
      Authors : Yujun Zhao, Denzil Bernard, Shaomeng Wang : Inactivation of the function of tumor suppressor p53 is common in human cancers. In approximately half of human cancers, the tumor suppressor function of p53 is inactivated by deletion or mutation of TP53, the gene encoding p53 protein. In the remaining 50% of human cancers, p53 tumor suppressor function can be effectively inhibited by oncoprotein MDM2 or its homolog MDMX. Since inhibition of p53 by MDM2 or MDMX protein is mediated by their direct interaction with p53, small-molecule inhibitors designed to block the MDM2-p53 or MDMX-p53 protein-protein interaction (MDM2 or MDMX inhibitors) can activate p53 in tumor cells retaining wild-type p53. In the last few years, several classes of potent, selective, and efficacious small molecule MDM2 inhibitors have been designed and developed, and six such compounds are being evaluated in clinical trials as new anticancer drugs. Additionally, non-peptide, small-molecule MDMX inhibitors have been reported. We review herein the design and development of potent small-molecule MDM2 and MDMX inhibitors. HTML XML PDF
      PubDate: Mon, 8 Jul 2013 0:00:00 +0300
  • Distinct target genes and effector processes appear to be critical for
           p53-activated responses to acute DNA damage versus p53-mediated tumour

    • Abstract: BioDiscovery 8: e8948
      DOI : 10.7750/BioDiscovery.2013.8.3
      Authors : Liz J Valente, Andreas Strasser : The p53 tumour suppressor is the most frequently mutated gene in human cancer. This transcription factor can be activated by diverse cellular stresses, including DNA damage and oncogene activation. Through transcriptional induction of appropriate target genes, p53 can stimulate activity in a broad range of effector pathways, most notably cell cycle arrest, cellular senescence and apoptotic cell death. Insensitivity to cell death-inducing signals and deregulated proliferation are two key hallmarks of cancer cells. Given that p53 inhibits proliferation and induces apoptosis, it was widely believed that these processes are the most critical ones for p53-mediated tumour suppression. However, this dogma has been challenged. In striking contrast to p53-deficient mice, which all develop tumours before 250 days of age, mutant mice in which expression of the p53 target genes that are critical for induction of cell cycle arrest and apoptosis is impaired or abrogated are not cancer-prone. This demonstrates that distinct effector processes are critical for the p53-mediated acute response to DNA damage versus p53-mediated tumour suppression. The discovery that cell cycle arrest, senescence and apoptosis are not essential for p53-mediated tumour suppression re-launches the search for the p53 target genes and effector processes that are critical to prevent tumour development, with coordination of DNA repair being a leading contender. HTML XML PDF
      PubDate: Sun, 30 Jun 2013 0:00:00 +0300
  • Modulation of immune responses by the tumor suppressor p53

    • Abstract: BioDiscovery 8: e8947
      DOI : 10.7750/BioDiscovery.2013.8.2
      Authors : Julie Lowe, Maria Shatz, Michael A. Resnick, Daniel Menendez : The commonly held view of the tumor suppressor p53 as a regulator of cell proliferation, apoptosis and senescence has expanded greatly in recent years to cover many biological processes as well as external and internal stress responses. Since the discovery over 30 years ago of p53 as a cellular protein that co-precipitates with the large T antigen of Simian Virus SV40, there has been an intertwining of p53 activities with immune-related processes, especially as relates to cancer. A variety of interactions between the p53 and the immune stress systems are currently being addressed that suggest opportunities to utilize p53 in modulating immunological activities. Here, we discuss those interactions along with implications for human disease. HTML XML PDF
      PubDate: Fri, 31 May 2013 0:00:00 +0300
  • Switching on p53: an essential role for protein phosphorylation'

    • Abstract: BioDiscovery 8: e8946
      DOI : 10.7750/BioDiscovery.2013.8.1
      Authors : Jayne Loughery, David Meek : The p53 tumour suppressor protein coordinates widespread changes in gene expression in response to a range of stress stimuli. p53 is regulated primarily through ubiquitylation and protein turnover mediated by its transcriptional target, MDM2. Induction and activation of p53 is achieved largely through uncoupling the p53/MDM2 interaction, with various stress stimuli employing different but overlapping mechanisms to achieve this. p53 undergoes a range of post-translational modifications including multi-site phosphorylation, acetylation, methylation and ubiquitylation. DNA damage pathways in particular engender a large number of phosphorylation events, both in p53 itself and in regulatory partners including MDM2 and MDM4; these modifications mediate both the induction of p53 and stimulation of its activity. Surprisingly, other p53-activating stimuli do not promote multi-site phosphorylation. Moreover, simply uncoupling p53 and MDM2 pharmacologically can induce a robust p53 response. Various lines of evidence propose that activation of p53 via the DNA damage pathways is dispensable for p53-mediated tumour suppression and, by implication, that phosphorylation is not required. In contrast to this view, however, emerging evidence from animal models indicates that phosphorylation may indeed impact on tumour suppression, albeit in a possibly selective manner. Here we review the role of phosphorylation in regulating the p53 response in comparison to mechanisms employed by other stress signalling pathways. We consider its effects on biological outcome and reflect on issues that have yet to be addressed. HTML XML PDF
      PubDate: Mon, 29 Apr 2013 0:00:00 +0300
  • Modelling c-Abl Signalling in Activated Neutrophils: The Anti-inflammatory
           Effect of Seliciclib

    • Abstract: BioDiscovery 7: e8945
      DOI : 10.7750/BioDiscovery.2013.7.4
      Authors : Robert C. Jackson, Tomas Radivoyevitch : When mammalian tissues are infected by bacteria or fungi, inflammatory cytokines are released that cause circulating neutrophils to invade the infected tissue. The cytosolic tyrosine kinase, c-Abl, in these tissue neutrophils is activated by TNFα. c-Abl then phosphorylates STAT transcription factors, which results in production of the antiapoptotic protein Mcl-1. The normally short-lived tissue neutrophils are then unable to enter apoptosis. c-Abl also causes release of reactive oxygen species (ROS) from the mitochondria of the activated neutrophils. These ROS, and ROS generated by NADPH oxidase, are bactericidal agents of the innate immune system. In some inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), the invading neutrophils become permanently activated, and the resulting ROS overproduction causes severe tissue damage. The cyclin-dependent kinase inhibitor, seliciclib, blocks transcription through inhibition of cdk9. This results in a relatively rapid decline of antiapoptotic Mcl-1 transcripts in activated neutrophils, an increase in neutrophil apoptosis, and less ROS leakage and oxidative damage. We present here a model of neutrophil kinetics that simulates the principal pathways of c-Abl signalling and use it to explore possible treatment options for inflammatory lung disease. HTML XML PDF
      PubDate: Sun, 31 Mar 2013 0:00:00 +0200
  • Herpetofauna in the city of Blagoevgrad, south-western Bulgaria

    • Abstract: BioDiscovery 7: e8943
      DOI : 10.7750/BioDiscovery.2013.7.3
      Authors : Alexander Pulev, Lidia Sakelarieva : The city of Blagoevgrad and its surroundings (about 16.4 km<sup>2</sup>) were researched in order to establish the diversity, distribution and level of synanthropy of the amphibian and reptile species. Data about the herpetofauna were obtained in the period 1988–2012. Totally 25 species were registered – 10 amphibians and 15 reptiles. The number of species, discovered around the city, was 23, and 6 of them were not found within the administrative boundaries of the city. The different urban zones are inhabited by 19 species. They represent 37% of the amphibians and 31% of the reptiles, found in Bulgaria, and 64% of the amphibians and 60% of the reptiles, distributed in the Blagoevgrad municipality, which is very high species richness. The herpetofauna has found quite favourable conditions in the territory of the city as a whole, and especially in the sparsely populated and built up areas and city periphery. The presence of great variety of urban habitats and the pattern of situation of the city residential districts are very important for the successful adaptation of herpetofauna for inhabiting in urban environment. The high species richness could be explained also by the fact, that comparatively great number of amphibians and reptiles are hemerodiaphoric species, which easily exist in landscapes, transformed by man. The results from the case study of the herpetofauna in Blagoevgrad show that the urban areas could provide good conditions for the wild animals and could be places of substantial biological diversity. HTML XML PDF
      PubDate: Thu, 28 Mar 2013 0:00:00 +0200
  • Skeletal muscle: novel and intriguing characteristics as a secretory organ

    • Abstract: BioDiscovery 7: e8942
      DOI : 10.7750/BioDiscovery.2013.7.2
      Authors : Wataru Aoi, Kunihiro Sakuma : Growing evidence has shown that skeletal muscle secretes several bioactive proteins from within the cell into extracellular fluid. The secretion of several proteins, whose levels increase in response to exercise, can regulate the functions of several organs via autocrine and paracrine actions, and mediate exercise-induced benefits such as metabolic improvement, anti-inflammation, and muscle building; this is known as the myokine theory. In addition, we found a novel muscle-secreted protein, secreted protein acidic and rich in cysteine (SPARC), a secreted matricellular glycoprotein. The muscle-secreted protein SPARC can support underlying mechanisms of epidemiological studies that suggest that regular exercise can prevent the incidence of colon cancer. Many different types of studies have suggested that many other proteins secreted from muscle have yet to be identified. In addition to the proteins, non-coding small RNA in exosome and metabolites which generate in process of nutrients metabolism with muscle contraction are also suggested to be secretory bioactive factors. These secretory factors may be biomarkers that reflect muscular function and beneficial adaptation achieved by exercise training, and could estimate adequate condition of exercise to obtain its beneficial effects. HTML XML PDF
      PubDate: Sat, 2 Mar 2013 0:00:00 +0200
  • Chromosome rearrangements in sublines of human embryonic stem cell lines
           hESM01 and hESM03

    • Abstract: BioDiscovery 7: e8941
      DOI : 10.7750/BioDiscovery.2013.7.1
      Authors : T.V. Karamysheva, Мaria А. Prokhorovich, Maria A. Lagarkova, Sergey L. Kiselev, Thomas Liehr, Nicolay Rubtsov : Due to possible proliferative effects of karyotypic reorganization of human embryonic stem cell (hESC) lines detailed genetic analysis are indicated prior to any application of hESCs. Molecular cytogenetic analysis of two different hESC sublines was performed and revealed aberrant chromosomes in both of them, i.e. in hESM01r18 (46,ХХ,-18,+mar) and hESM0309 (46,ХХ,del(4),dup(9)). This study shows that microdissection and multicolor fluorescence <em>in situ</em> hybridization (mFISH) can be used to detect the chromosomal changes precisely of the derivative chromosomes that are difficult to identify by conventional G-banded chromosome analysis. In the present study chromosome microdissection and reverse FISH were applied using multicolor fluorescence <em>in situ</em> hybridization (mFISH) for detailed characterization of the derivative chromosomes. The karyotypes of hESC lines were described as: 46,ХХ,r(18)(::p11.31→q21.2::q21.2→p11.31::) and 46,XX,del(4)(q25q31.1),dup(9)(q12q33), respectively. The potential role of the chromosomal regions involved in rearrangements for cell proliferation is discussed. HTML XML PDF
      PubDate: Fri, 25 Jan 2013 0:00:00 +0200
  • Advocating the need of a systems biology approach for personalised
           prognosis and treatment of B-CLL patients

    • Abstract: BioDiscovery 6: e8939
      DOI : 10.7750/BioDiscovery.2012.6.4
      Authors : Hemanth Tummala, Alexey Goltsov, Hilal S Khalil, Anne Sproul, Fiona Scott, Vanio Mitev, Nikolai Zhelev : The clinical course of B-CLL is heterogeneous. This heterogeneity leads to a clinical dilemma: can we identify those patients who will benefit from early treatment and predict the survival' In recent years, mathematical modelling has contributed significantly in understanding the complexity of diseases. In order to build a mathematical model for determining prognosis of B-CLL one has to identify, characterise and quantify key molecules involved in the disease. Here we discuss the need and role of mathematical modelling in predicting B-CLL disease pathogenesis and suggest a new systems biology approach for a personalised therapy of B-CLL patients. HTML XML PDF
      PubDate: Sun, 30 Dec 2012 0:00:00 +0200
  • The aromatase inhibitor letrozole enhances the effect of doxorubicin and
           docetaxel in an MCF7 cell line model

    • Abstract: BioDiscovery 6: e8940
      DOI : 10.7750/BioDiscovery.2012.6.2
      Authors : Mary O’Neill, Fiona E.M. Paulin, Julie Vendrell, Clinton W. Ali, Alastair M. Thompson : <p>Introduction: Post-menopausal women with estrogen receptor (ER) positive breast cancer receive adjuvant chemotherapy and endocrine therapy sequentially since tamoxifen may antagonise the cytotoxicity of chemotherapy drugs. With increased use of aromatase inhibitors (AIs) in place of tamoxifen, the potential use of concomitant chemo-endocrine treatments with the AI letrozole, before clinical trials are undertaken, requires evaluation. </p><p>Methods: MCF7-aro cells expressing the aromatase gene were treated with letrozole, doxorubicin and docetaxel. The effects of different drug concentrations, drug combinations and scheduling on cytotoxicity and aromatase activity were investigated. Key receptor, cell cycle regulation and apoptosis proteins were examined by immunoblotting.</p><p>Results: Administration of letrozole with either doxorubicin or docetaxel resulted in increased levels of cytotoxicity under all treatment schedules (add in, sequential or simultaneous drug administration) with the greatest anti-proliferative effect observed using concomitant treatment (letrozole first with chemotherapy added in). The inhibitory effect of letrozole on aromatase activity was unchanged by the addition of doxorubicin or docetaxel. Letrozole treatment resulted in decreased HER2 expression and addition of doxorubicin and docetaxel to letrozole led to elevated ER-ß levels.</p><p>Conclusions: <em>In vitro</em>, letrozole, unlike tamoxifen, enhances the cytotoxicity of both doxorubicin and docetaxel. This supports the prospect of trials using letrozole with chemotherapy in postmenopausal women with ER positive breast cancer. </p> HTML XML PDF
      PubDate: Wed, 19 Dec 2012 0:00:00 +0200
  • Primed for the kill: occupying Bcl-2 to target death in acute myeloid

    • Abstract: BioDiscovery 6: e8938
      DOI : 10.7750/BioDiscovery.2012.6.1
      Authors : Andrew Wei, Tse-Chieh Teh : ss="articleHead"> HTML XML PDF
      PubDate: Fri, 7 Dec 2012 0:00:00 +0200
  • Bringing together all aspects of cancer research, prevention and
           treatment. A report from the 8th NCRI Cancer Conference

    • Abstract: BioDiscovery 6: e8937
      DOI : 10.7750/BioDiscovery.2012.6.3
      Authors : Dimitar Trifonov : The 8<sup>th</sup> NCRI Cancer Conference took place from 4<sup>th</sup> until 7<sup>th</sup> of November 2012 in the BT Convention Centre, Liverpool, UK. This scientific event has established itself as the leading international oncology meeting in the UK and this year attracted more than 2,000 delegates: from researchers and data managers to clinicians, nurses and policy makers. The conference covered six main topics: 1) Diagnosis and therapy 2) Epidemiology and prevention 3) Information, patients and the public 4) Survivorship and end-of-life care 4) The cancer cell and model systems 6) Tumour specific research. This report presents the highlights of the conference. HTML XML PDF
      PubDate: Sat, 1 Dec 2012 0:00:00 +0200
  • ATM in focus: A damage sensor and cancer target

    • Abstract: BioDiscovery 5: e8936
      DOI : 10.7750/BioDiscovery.2012.5.1
      Authors : Hilal S Khalil, Hemanth Tummala, Nikolai Zhelev : The ability of a cell to conserve and maintain its native DNA sequence is fundamental for the survival and normal functioning of the whole organism and protection from cancer development. Here we review recently obtained results and current topics concerning the role of the ataxia-telangiectasia mutated (ATM) protein kinase as a damage sensor and its potential as therapeutic target for treating cancer. This monograph discusses DNA repair mechanisms activated after DNA double-strand breaks (DSBs), i.e. non-homologous end joining, homologous recombination and single strand annealing and the role of ATM in the above types of repair. In addition to DNA repair, ATM participates in a diverse set of physiological processes involving metabolic regulation, oxidative stress, transcriptional modulation, protein degradation and cell proliferation. Full understanding of the complexity of ATM functions and the design of therapeutics that modulate its activity to combat diseases such as cancer necessitates parallel theoretical and experimental efforts. This could be best addressed by employing a systems biology approach, involving mathematical modelling of cell signalling pathways. HTML XML PDF
      PubDate: Fri, 30 Nov 2012 0:00:00 +0200
  • To see an interphase chromosome or: How a disease can be associated with
           specific nuclear genome organization

    • Abstract: BioDiscovery 4: e8932
      DOI : 10.7750/BioDiscovery.2012.4.5
      Authors : Ivan Y. Iourov : The last hierarchical level of cellular genome organization is the spatial arrangement of chromosomes within the nuclear space. Despite of high regulatory potential and functional implications, issues concerning nuclear organization at chromosomal level are rarely addressed because of limitations in visualizing interphase chromosomes. The problem is especially seen when an attempt to associate specific patterns of nuclear genome organization with a pathological condition is made. Fortunately, advances in molecular cytogenetics have provided for a solution to visualize chromosomes in interphase nuclei at molecular resolution. A study in this issue of <em>BioDiscovery</em> shows the way of how to identify interphase chromosome architecture at molecular resolutions and demonstrates the involvement of specific nuclear genome organization in generating a cancer-causing chromosomal aberration (translocation between chromosomes 8 and 21 in acute myelogenous leukemia).
      Authors ’ findings suggest interphase molecular cytogenetic techniques (i.e. interphase chromosome-specific multicolor banding or ICS-MCB) to be required to perform studies regarding nuclear genome organization at chromosomal level and its role in disease pathogenesis. HTML XML PDF
      PubDate: Wed, 31 Oct 2012 0:00:00 +0200
  • What can systems pharmacology contribute to drug development' Disease
           modelling as a predictive tool

    • Abstract: BioDiscovery 4: e8933
      DOI : 10.7750/BioDiscovery.2012.4.4
      Authors : Robert C. Jackson : ss="articleHead"> HTML XML PDF
      PubDate: Wed, 31 Oct 2012 0:00:00 +0200
  • Prevalence of oral lesions in HIV infected adult population of Mangalore,
           Karnataka, India

    • Abstract: BioDiscovery 4: e8935
      DOI : 10.7750/BioDiscovery.2012.4.3
      Authors : Mithra N. Hegde, Nidarsh D. Hegde, Amit Malhotra : The aim of this study was to find the prevalence of oral lesions in human immunodeficiency virus (HIV) positive patients and investigate if there was a relationship between oral manifestations and the level of immunosuppression. 125 patients infected with HIV in the age group of 20-40 years were examined for the presence of different oral lesions according to the EEC criterion. The CD4 count, as well as any therapy being instituted was recorded and correlated with the oral manifestations seen. Comparison of common oral lesions present to absent was done by chi square test using linear by linear association. The prevalence of oral lesions among the investigated HIV patients was found to be 71%, with periodontitis – 52% and erythematous candidiasis – 48% being the most prevalent oral lesions; as well, periodontitis and oral hairy leukoplakia were found to be significantly associated with the immunosuppression in the disease. Thus, oral lesions have been found to be associated with the early manifestation of HIV and a measure of disease severity. HTML XML PDF
      PubDate: Tue, 23 Oct 2012 0:00:00 +0300
  • Does positioning of chromosomes 8 and 21 in interphase drive t(8;21) in
           acute myelogenous leukemia'

    • Abstract: BioDiscovery 4: e8934
      DOI : 10.7750/BioDiscovery.2012.4.2
      Authors : Moneeb A.K. Othman, Amelie Lier, Susann Junker, Philipp Kempf, Franziska Dorka, Erich Gebhart, Frenny J. Sheth, Beata Grygalewicz, Samarth Bhatt, Anja Weise, Kristin Mrasek, Thomas Liehr, Marina Manvelyan : The impact of chromosome architecture in the formation of chromosome aberrations is a recent finding of interphase directed molecular cytogenetic studies. There evidence was provided that disease specific chromosomal translocations could be due to tissue specific genomic organization. In a recent small pilot study using three-dimensional interphase fluorescence in situ hybridization, we showed that there might be a specific chromosome positioning in myeloid bone marrow cells, i.e. a co-localization of chromosomes 8 and 21. Here we could substantiate this finding in overall 21 studied cases with acute myeloid leukemia (AML) that there is even a co-localization of the genes AML1 and ETO. This finding led to the suggestion that a specific interphase architecture of myeloid bone marrow cells might promote the typical t(8;21)(q22;q22) leading to AML-M2. HTML XML PDF
      PubDate: Tue, 23 Oct 2012 0:00:00 +0300
  • In vitro assessment of the cytotoxic effects of novel RGD analogues

    • Abstract: BioDiscovery 4: e8931
      DOI : 10.7750/BioDiscovery.2012.4.1
      Authors : Anelia Balacheva, Ivan Iliev, Roumyana Detcheva, Tatyana Dzimbova, Tamara Pajpanova, Evgeny Golovinsky : The RGD sequence is present in many extracellular matrix proteins and intracellular proteins, including caspases. Synthetic RGD peptides may affect adhesion, migration and tumour metastasis, or directly induce apoptosis. Several RGD peptides were synthesized, and their anti-adhesive and cytotoxic properties were analyzed in vitro. Here we present the cytotoxic activities of RGD, R(NO2)GD, CavGD and RGD-OMe on non-tumour 3T3 cells and tumour cell lines HepG2 and MCF-7. The cell growth inhibitory effects of RGD-OMe are significantly higher than those of RGD on the cell lines used. Evidently the modification in the carboxylic group of RGD with simple esterification increases the cell growth inhibitory effects of the parent compound. HTML XML PDF
      PubDate: Tue, 16 Oct 2012 0:00:00 +0300
  • Lifestyle characteristics and dietary impact on plasma concentrations of
           beta-carotene and retinol

    • Abstract: BioDiscovery 3: e8928
      DOI : 10.7750/BioDiscovery.2012.3.3
      Authors : Rabindra Nath Das, Pradip K. Sarkar : Mechanisms of dietary micronutrients and personal characteristics of the human body are intricately complicated. These mechanisms, however, can be easily interpreted through appropriate mathematical relationships. The present study aims to detect the statistically significant impact of personal characteristics and diet on plasma concentrations of retinol and beta-carotene using statistical modeling. The present analyses indicate that age, sex, smoking habit, quetelet, vitamin use, consumed calories, fiber, and dietary beta-carotene are statistically significant factors on plasma beta-carotene levels. On the other hand age, sex, smoking status, consumed fat, and dietary beta-carotene are significant factors on plasma retinol. These analyses indicate that changes in the variances of plasma beta-carotene and retinol are non-constant. Impacts of personal characteristics and dietary factors on human plasma concentrations of retinol and beta-carotene are explained based on mathematical relationships. These analyses support many earlier researches findings. However, the analyses also identify many additional casual factors that explain the means and variances of plasma beta-carotene and retinol, which earlier researches have not reported. HTML XML PDF
      PubDate: Sun, 30 Sep 2012 0:00:00 +0300
  • The dark side of light. Light pollution kills leatherback turtle

    • Abstract: BioDiscovery 3: e8930
      DOI : 10.7750/BioDiscovery.2012.3.4
      Authors : Marina Zheleva : The leatherback turtle is the largest and most migratory of all sea turtles and deepest diving air-breathing animal. It has unique physiology which allows it to adapt to various habitats ranging from sub-polar to equatorial during its migrations. The leatherback turtle is also the only sea turtle where no cases of tumours have been diagnosed. These unique features add to the arguments for preservation of this endangered species. Here we discuss the effect of light pollution on leatherback turtle hatchlings in Tobago and the measures for their protection. HTML XML PDF
      PubDate: Sun, 30 Sep 2012 0:00:00 +0300
  • The Apoe-/- Mouse PhysioLab® Platform: A Validated Physiologically-based
           Mathematical Model of Atherosclerotic Plaque Progression in the Apoe-/-

    • Abstract: BioDiscovery 3: e8929
      DOI : 10.7750/BioDiscovery.2012.3.2
      Authors : Jason R Chan, Gregory Vuillaume, Caitlin Bever, Stefan Lebrun, Michael Lietz, Yvonne Steffen, Katrin Stolle, Karim Wahba, Xiao Wang, Shonna Moodie, Julia Hoeng, Manuel C Peitsch, Lyn M Powell : <em>Motivation:</em>Atherosclerosis is a complex multi-pathway inflammatory disease where accumulation of oxidatively modified lipids and leukocytes in the arterial intima leads to plaque formation over time. Translating Apoe<sup>-/-</sup> mouse results to the clinical setting is complicated by uncertainty around (a) mechanisms underlying disease etiology, (b) relative importance of these mechanisms as drivers of progression, and (c) how these roles change in response to perturbation by therapeutic intervention or lifestyle changes. <br><em>Results: </em>We describe a large-scale mechanistic, mathematical model of atherosclerosis in the Apoe<sup>-/-</sup> mouse and its validation with <em>in vivo</em> Apoe <sup>-/-</sup> data. Major physiological components include cholesterol/macrophage trafficking, inflammation, endothelial function, oxidative stress, and thrombosis. Heterogeneity in disease progression, observed despite genetic uniformity and experimentally controlled conditions, was captured through “virtual mice”. This model may be used to optimize <em>in vivo</em> experiments and paves the way for a similar modeling approach for human disease.<br><em>Availability: </em>The model is available by remote desktop client at HTML XML PDF
      PubDate: Sun, 30 Sep 2012 0:00:00 +0300
  • Of mice and men – differential mechanisms of maintaining the
           undifferentiated state in mESC and hESC

    • Abstract: BioDiscovery 3: e8927
      DOI : 10.7750/BioDiscovery.2012.3.1
      Authors : Borislav Arabadjiev, Rumena Petkova, Albena Momchilova, Stoyan Chakarov, Rumen Pankov : The persistence of the defining characteristics of undifferentiated cells in vivo and in vitro is maintained via a complex interplay of several mechanisms, employing molecular events internal to the cell as well as signals originating outside the cell. The exogenous and the endogenous mechanisms maintaining stemness qualities of the cell are intricately interwoven with one another and susceptible to cross-interference. Mice and rats as animal models are almost universally considered to be close enough to humans so as to be used in research and applications eventually intended for use in human biology and medicine, at the same time being related distantly enough from primates so as not to overstep ethical boundaries. Studying the specific molecular features of both species in the context of maintenance of the undifferentiated state of mESC and hESC can provide researchers with an unique opportunity to unravel the network of interactions which take part in the decision about cell fate under different conditions; to glean interesting insights into the parallel evolution of the two species and to observe how different variants of basic cellular processes have been tried and tested in the evolutionary process. The present paper reviews the basic signalling pathways responsible for the maintenance of the undifferentiated state in mESC and hESC and analyses some specific aspects of the molecular physiology that are unique to the particular species. HTML XML PDF
      PubDate: Thu, 20 Sep 2012 0:00:00 +0300
  • Parallel Researching with Online Collaboration (PROC), a new cost
           effective model for multicentre multinational research

    • Abstract: BioDiscovery 2: e8926
      DOI : 10.7750/BioDiscovery.2012.2.3
      Authors : Chaturaka Rodrigo, Senaka Rajapakse : The traditional model of multicentre multinational studies is a costly exercise that limits its feasibility for resource limited settings. We propose an alternate model for such studies named Parallel Researching with Online Collaboration (PROC). If implemented, this hypothetical model will make multicentre trials feasible in many resource limited settings. PROC can be summarized in five phases; phase I – academics using free access social networking sites to collaborate and develop research questions, phase II – further consolidation of an idea and expansion of it with online contributions from experts, identification of key persons to carry out the study in parallel at different centres, phase III – drawing up a common research protocol and study tools, phase IV – each satellite centre functioning independently to carry out the common protocol, Phase V – pooling of data in a common summarized format and writing up the findings. HTML XML PDF
      PubDate: Sun, 26 Aug 2012 0:00:00 +0300
  • Viability of unstimulated lymphocytes exposed to extremely low frequency
           electromagnetic fields is dependent on intensity

    • Abstract: BioDiscovery 2: e8925
      DOI : 10.7750/BioDiscovery.2012.2.2
      Authors : P Rajendra, HN Sujatha, RB Sashidhar, C Subramanyam, D Devendranath, RSS Aradhya : The cell viability and DNA damage in unstimulated sheep primary lymphocytes subjected to different extremely low electromagnetic field intensities (5, 50 and 100 µT; 50 Hz) were studied with special emphasis on apoptosis. Sheep primary lymphocytes cultured in RPMI, supplemented with 10% FBS in the absence of mitogens, were exposed till 16 h. The cell viability assessment by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay showed a dose dependent enhancement of viability at 16 h. Further, quantitative DNA laddering and flow cytometric analysis showed a significant decrease in apoptosis of the cells subjected to 100 (p HTML XML PDF
      PubDate: Wed, 22 Aug 2012 0:00:00 +0300
  • Up-regulation of Gr1 + CD11b + cell population in the spleen of
           NaClO-administered mice works to repair skin wounds

    • Abstract: BioDiscovery 2: e8924
      DOI : 10.7750/BioDiscovery.2012.2.1
      Authors : Mayu Hara, Naomi Nishio, Sachiko Ito, Masashi Akiyama : In wound healing, early infiltration of neutrophils followed by macrophage infiltration are important defense mechanisms for repair of tissue damage. Here we examined the effects of neutrophils on wound healing. Administration of sodium hypochlorite (NaClO) to mouse skin induces neutrophil recruitment to the wound site and repeated administration of NaClO was shown to prolong wound healing. Examination of the spleens of mice whose wounds were repeatedly treated with NaClO, showed that GR-1<sup>+</sup>CD11b<sup>+</sup> cells were up regulated in the recovery phase of wounding. Many of the GR-1<sup>+</sup>CD11b <sup>+</sup> cells in the mouse bone marrow were neutrophils, as indicated by a ring-shaped nucleus, and some of the cells were immature myeloid-lineage cells. GR-1<sup>+</sup>CD11b<sup>+</sup> cells from bone marrow were sorted and injected intravenously to syngeneic Imprinting Control Region (ICR) mice. The mice that received GR-1<sup>+</sup>CD11b<sup>+</sup> cells recovered faster than the mice injected with the control, phosphate buffer saline (PBS). HTML XML PDF
      PubDate: Mon, 6 Aug 2012 0:00:00 +0300
  • Targeting ATM pathway for therapeutic intervention in cancer

    • Abstract: BioDiscovery 1: e8920
      DOI : 10.7750/BioDiscovery.2012.1.3
      Authors : Hilal S Khalil, Hemanth Tummala, Stoyan Chakarov, Nikolai Zhelev, David P. Lane : The Ataxia Telangiectasia Mutated gene encodes the ATM protein, a key element in the DNA damage response (DDR) signalling pathway responsible for maintaining genomic integrity within the cell. The ATM protein belongs to a family of large protein kinases containing the phosphatidylinositol-3 catalytic domain, including ATM, ATR and PI3K. ATM provides the crucial link between DNA damage, cell cycle progression and cell death by first sensing double stranded DNA breaks and subsequently phosphorylating and activating other downstream proteins functioning in DNA damage repair, cell cycle arrest and apoptotic pathways,. Mammalian cells are constantly challenged by genotoxic agents from a variety of sources and therefore require a robust sensing and repair mechanism to maintain DNA integrity or activate alternative cell fate pathways. This review covers the role of ATM in DDR signalling and describes the interaction of the ATM kinase with other proteins in order to fulfil its various functions. Special emphasis is given to how the growing knowledge of the DDR can help identify drug targets for cancer therapy, thus providing a rationale for exploiting the ATM pathway in anticancer drug development. Moreover, we discuss how a network modelling approach can be used to identify and characterise ATM inhibitors and predict their therapeutic potential. HTML XML PDF
      PubDate: Sun, 29 Jul 2012 0:00:00 +0300
  • Identification of a novel deletion mutant strain in Saccharomyces
           cerevisiae that results in a microsatellite instability phenotype

    • Abstract: BioDiscovery 1: e8918
      DOI : 10.7750/BioDiscovery.2012.1.4
      Authors : Hanlee P. Ji, Shannon Morales, Katrina Welch, Cam Yuen, Kyle Farnam, James M Ford : The DNA mismatch repair (MMR) pathway corrects specific types of DNA replication errors that affect microsatellites and thus is critical for maintaining genomic integrity. The genes of the MMR pathway are highly conserved across different organisms. Likewise, defective MMR function universally results in microsatellite instability (MSI) which is a hallmark of certain types of cancer associated with the Mendelian disorder hereditary nonpolyposis colorectal cancer. (Lynch syndrome). To identify previously unrecognized deleted genes or loci that can lead to MSI, we developed a functional genomics screen utilizing a plasmid containing a microsatellite sequence that is a host spot for MSI mutations and the comprehensive homozygous diploid deletion mutant resource for Saccharomyces cerevisiae. This pool represents a collection of non-essential homozygous yeast diploid (2N) mutants in which there are deletions for over four thousand yeast open reading frames (ORFs). From this screen, we identified a deletion mutant strain of the <i>PAU24</i> gene that leads to MSI. In a series of validation experiments, we determined that this <i>PAU24</i> mutant strain had an increased MSI-specific mutation rate in comparison to the original background wildtype strain, other deletion mutants and comparable to a MMR mutant involving the MLH1 gene. Likewise, in yeast strains with a deletion of <i>PAU24</i>, we identified specific de novo indel mutations that occurred within the targeted microsatellite used for this screen. HTML XML PDF
      PubDate: Mon, 23 Jul 2012 0:00:00 +0300
  • Bisphosphonate-related osteonecrosis of the jaws: Report of two cases with
           breast cancer, a dental concern and review of the literature

    • Abstract: BioDiscovery 1: e8917
      DOI : 10.7750/BioDiscovery.2012.1.2
      Authors : Ahmet Ercan Şekerci, Halil Sahman, Murat Ulu, Osman A Etoz, Yıldıray Sisman : Bisphosphonates are becoming increasingly important in the treatment of metabolic and oncological diseases involving the skeleton. In recent years, several cases of necrosis of the jaws associated with long-term use of bisphoshponates have been reported. The management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is emerging as a significant problem in the field of dentistry. In this article, we report two new cases of patients with osteonecrosis induced by bisphosphonates. Two unrelated female patients undergoing treatment with bisphosphonates for metastatic breast cancer were referred to the department of oral surgery due to non-healing extraction sockets and intraoral exposed bone after dental extraction. The treatment modality of case 1 included antibiotic therapy, sequestrectomy, periodontal flap, and chlorhexidine mouthwashes. After an eleven-month follow-up period the affected area has healed totally. The other patient refused any surgical intervention. In addition, this article reviews the current literature describing the dental procedures for patients with BRONJ. HTML XML PDF
      PubDate: Sun, 15 Jul 2012 0:00:00 +0300
  • Modelling malignant progression with a finite state machine supports a two
           checkpoint theory of cancer

    • Abstract: BioDiscovery 1: e8916
      DOI : 10.7750/BioDiscovery.2012.1.1
      Authors : Robert C. Jackson : We postulate the two checkpoints theory of cancer, a model of cancer development suggesting that malignant transformation of cells requires loss of function of both the G1 checkpoint and the mitotic spindle checkpoint. Malignant progression can be described as a process analogous to a genetic algorithm, which we term the malignant progression algorithm. There are two prerequisites for this process: first, there must be competition for reproductive resources, and this is driven by loss of the G1 checkpoint; second, there must be a source of genetic variation, and this is provided by loss of the mitotic spindle checkpoint, resulting in aneuploidy. These two factors then trigger a process of Darwinian selection, driving the emergence of cells with the various abnormalities that have been termed the “hallmarks of cancer”. Malignant progression is iterative, autocatalytic, and irreversible. The process can be modelled mathematically by describing the system as a finite state machine. The model indicates that loss of the two checkpoints is necessary and sufficient for tumour progression. The order of loss of the two checkpoints appears to be important: loss of the G1 checkpoint results in premalignant cells that replicate independently of physiological growth signals, but which remain diploid. Loss of the mitotic spindle checkpoint then results in aneuploid, malignant cells with highly error-prone replication, which rapidly progress to invasive, metastatic, hypoxia-tolerant, immortalised cells. This model of malignant progression has implications for the selection of anticancer drug targets and for tumour prevention strategies. HTML XML PDF
      PubDate: Thu, 5 Jul 2012 0:00:00 +0300
  • Man of Science: Celebrating Professor Sir David Lane’s 60th

    • Abstract: BioDiscovery 1: e8921
      DOI : 10.7750/BioDiscovery.2012.1.5
      Authors : Nikolai Zhelev : This article is devoted to the 60th anniversary of Professor Sir David Lane and summarises his renowned research career and scientific and business achievements to date. Professor Lane is one of the world’s foremost cancer biologists with more than 350 publications in the world leading science journals and was the second most highly cited UK-based scientist in the 1990’s. Sir David is best known for the discovery of the p53 protein which he termed “the guardian of the genome” due to its vital role in the defence against cancer. A decade later p53 was named “molecule of the year” by the scientific journal Science. Professor Lane has won many international prizes and awards for his outstanding work in the field of cancer research and drug development. HTML XML PDF
      PubDate: Sun, 1 Jul 2012 0:00:00 +0300
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