Deep-sea hydrothermal vent sediments reveal diverse fungi with antibacterial activities

Relatively little is known about the diversity of fungi in deep-sea, hydrothermal sediments. Less thoroughly explored environments are likely untapped reservoirs of unique biodiversity with the potential to augment our current arsenal of microbial compounds with biomedical and/or industrial applications. In this study, we applied traditional culture-based methods to examine a subset of the morphological and phylogenetic diversity of filamentous fungi and yeasts present in 11 hydrothermally influenced sediment samples collected from eight sites on the seafloor of Guaymas Basin, Mexico. A total of 12 unique isolates affiliating with Ascomycota and Basidiomycota were obtained and taxonomically identified on the basis of morphological features and analyses of marker genes including actin, β-tubulin, small subunit ribosomal DNA (18S rRNA), internal transcribed spacer (ITS) and large subunit ribosomal DNA (26S rRNA) D1/D2 domain sequences (depending on taxon). A total of 11 isolates possess congeners previously detected in, or recovered from, deep-sea environments. A total of seven isolates exhibited antibacterial activity against human bacterial pathogens Staphylococcus aureus ATCC-35556 and/or Escherichia coli ATCC-25922. This first investigation suggests that hydrothermal environments may serve as promising reservoirs of much greater fungal diversity, some of which may produce biomedically useful metabolites

Retroviral expression of a kinase-defective IGF-I receptor suppresses growth and causes apoptosis of CHO and U87 cells in-vivo

BACKGROUND: Phosphatidylinositol-3,4,5-triphosphate (PtdInsP3) signaling is elevated in many tumors due to loss of the tumor suppressor PTEN, and leads to constitutive activation of Akt, a kinase involved in cell survival. Reintroduction of PTEN in cells suppresses transformation and tumorigenicity. While this approach works in-vitro, it may prove difficult to achieve in-vivo. In this study, we investigated whether inhibition of growth factor signaling would have the same effect as re-expression of PTEN. METHODS: Dominant negative IGF-I receptors were expressed in CHO and U87 cells by retroviral infection. Cell proliferation, transformation and tumor formation in athymic nude mice were assessed. RESULTS: Inhibition of IGF-IR signaling in a CHO cell model system by expression of a kinase-defective IGF-IR impairs proliferation, transformation and tumor growth. Reduction in tumor growth is associated with an increase in apoptosis in-vivo. The dominant-negative IGF-IRs also prevented growth of U87 PTEN-negative glioblastoma cells when injected into nude mice. Injection of an IGF-IR blocking antibody αIR3 into mice harboring parental U87 tumors inhibits tumor growth and increases apoptosis. CONCLUSION: Inhibition of an upstream growth factor signal prevents tumor growth of the U87 PTEN-deficient glioma to the same extent as re-introduction of PTEN. This result suggests that growth factor receptor inhibition may be an effective alternative therapy for PTEN-deficient tumors

Secondary Metabolites of Marine Microbes: From Natural Products Chemistry to Chemical Ecology

Marine natural products (MNPs) exhibit a wide range of pharmaceutically relevant bioactivities, including antibiotic, antiviral, anticancer, or anti-inflammatory properties. Besides marine macroorganisms such as sponges, algae, or corals, specifically marine bacteria and fungi have shown to produce novel secondary metabolites (SMs) with unique and diverse chemical structures that may hold the key for the development of novel drugs or drug leads. Apart from highlighting their potential benefit to humankind, this review is focusing on the manifold functions of SMs in the marine ecosystem. For example, potent MNPs have the ability to exile predators and competing organisms, act as attractants for mating purposes, or serve as dye for the expulsion or attraction of other organisms. A large compilation of literature on the role of MNPs in marine ecology is available, and several reviews evaluated the function of MNPs for the aforementioned topics. Therefore, we focused the second part of this review on the importance of bioactive compounds from crustose coralline algae (CCA) and their role during coral settlement, a topic that has received less attention. It has been shown that certain SMs derived from CCA and their associated bacteria are able to induce attachment and/or metamorphosis of many benthic invertebrate larvae, including globally threatened reef-building scleractinian corals. This review provides an overview on bioactivities of MNPs from marine microbes and their potential use in medicine as well as on the latest findings of the chemical ecology and settlement process of scleractinian corals and other invertebrate larvae

Mechanical, Thermal, and Optical Properties of New Chloroantimonite Glasses in the Sb2O3-PbCl2 -Ag Cl System

International audienceNew chloroantimonite glasses were obtained in the Sb2O3 - PbCl2 -AgCl ternary system. Their thermal, optical, and mechanical properties are studied. The concentration of silver chloride increases at the expense of antimony oxide accordingtothe following composition rules: (80-x)Sb2O3 -20PbCl(2) -xAgCl and (70-x)Sb2O3 -30PbCl(2) -xAgCl. Depending on the AgCl content, Vickers microhardness varied between 110 MPa and 140 MPa. The elastic moduli were measured by ultrasonic velocity. The optical transmission range extended from 400 nm in the visible spectrum to 7 mu m in the infrared spectrum. The refractive index was close to 2. The glass transition temperature measured by the DSC ranged from 250 to 290A degrees C. It is shown that the glass transition temperature decreases as AgCl substitutes for Sb2O3 and a more stable system was with 20% PbCl2 in the (80-x)Sb2O3 -20PbCl(2) -xAgCl

Mechanical, thermal and optical properties of new chloroantimonite glasses in the Sb₂O₃–PbCl₂–AgCl system

New chloroantimonite glasses were obtained in the Sb₂O₃–PbCl₂–AgCl ternary system. Thermal, optical and mechanical properties were studied. The silver chloride concentration was increased at the expense of antimony oxide according to the following composition rules: (80–x)Sb₂O₃–20PbCl₂–xAgCl; (70–x)Sb₂O₃–30PbCl₂–xAgCl. Depending on AgCl content, Vickers micro-hardness varied between 110 MPa and 140 MPa. Elastic moduli were measured by ultrasonic velocity. The optical transmission range extended from 400 nm in the visible spectrum to 7 mm in the infrared spectrum. The refractive index was close to 2. Glass transition temperature measured by DSC ranged from 250 to 290°C. It was noticed that the glass transition temperature decreased as AgCl substitute for Sb₂O₃ and the more stable system was with 20% PbCl₂ in the (80–x)Sb₂O₃–20PbCl₂–xAgCl.Описано нові хлорантімонітові скла, отримані в потрійній системі Sb₂O₃–PbCl₂–AgCl. Подано результати дослідження їх теплових, оптичних і механічних властивостей. Вміст хлориду у складі цих матеріалів збільшено, що вплинуло на їх мікротвердість. Залежно від вмісту AgCl мікротвердість скла змінювалася в межах від 110 до 140 МРа. Оптичний діапазон пропускання збільшений з 400 nm у видимій області спектра до 7 mm в інфрачервоному спектрі. Показник заломлення ~2. Температура склування, виміряна методом диференційної сканівної калориметрії, коливалася в межах 250...290°С. Відмічено, що вона зменшується за заміни Sb₂O₃ AgCl і найстабільніша система з 20% PbCl₂ у склі (80–x)Sb₂O₃–20PbCl₂–xAgCl.Описаны новые хлорантимонитовые стекла, полученные в тройной системе Sb₂O₃–PbCl₂–AgCl. Представлены результаты исследований их тепловых, оптических и механических свойств. Содержание хлорида в составе этих материалов увеличено, что повлияло на их микротвердость. В зависимости от содержания AgCl микротвердость стекла изменялась в пределах от 110 до 140 МРа. Оптический диапазон пропускания увеличен от 400 nm в видимой области спектра до 7 mm в инфракрасном спектре. Показатель преломления ~2. Температура стеклования, измеренная методом дифференциальной сканирующей калориметрии, колебалась в пределах 250...290°С. Отмечено, что она уменьшается в меру замены Sb₂O₃ AgCl и наиболее стабильная система с 20% PbCl₂ в стекле (80–x)Sb₂O₃–20PbCl₂–xAgCl

Seawater-Based Biocatalytic Strategy : Stereoselective Reductions of Ketones with Marine Yeasts

The large consumption of freshwater in fermentations and bio-transformations is a matter of concern for the sustainability of many bio-processes. The use of seawater to perform bio-processes is a sustainable alternative. In this work, we used marine yeasts from deep-sub-seafloor sediments grown in seawater as bio-catalysts to perform the stereoselective reduction of different ketones, and the bio-transformations were accomplished in seawater as well. Strains of Meyerozyma guilliermondii and Rhodotorula mucilaginosa were able to reduce different aromatic ketones with high molar conversions and moderate-to-high enantioselectivity with no significant differences between bio-catalysis performed in seawater and freshwater. Finally, the selected marine yeasts were used for the reduction of key intermediates in seawater for the synthesis of molecules of pharmaceutical interest (desogestrel, norgestrel, gestodene, pramipexole)

Clinical Evaluation of a Novel Liquid Formulation of L-Thyroxine for Once Daily Treatment of Dogs with Hypothyroidism

peer reviewed[en] BACKGROUND: A liquid solution of levothyroxine (L-T4) is available for treatment of canine hypothyroidism. HYPOTHESIS: Once daily oral administration of a liquid L-T4 solution is effective and safe for controlling hypothyroidism in dogs. ANIMALS: Thirty-five dogs with naturally occurring hypothyroidism. METHODS: Dogs received L-T4 solution PO once daily at a starting dosage of 20 microg/kg body weight (BW). The dose was adjusted every 4 weeks, based on clinical signs and peak serum total T4 (tT4) concentrations. Target peak serum tT4 and thyroid stimulating hormone (TSH) concentrations, 4-6 hours posttreatment, were 35-95 nmol/L and < 0.68 ng/mL, respectively. Dogs were followed for up to 22 weeks after establishment of the maintenance dose. RESULTS: Clinical signs of hypothyroidism improved or resolved in 91% of dogs after 4 weeks of L-T4 treatment at 20 microg/kg once daily. The maintenance dose was established in 76, 94, and 100% of dogs after 4, 8, and 12 weeks of treatment, respectively. This was 20 microg L-T4/kg BW for 79% of the dogs, 30 microg/kg BW for 15%, and 10-15 microg/kg BW in the remaining 6%, once daily. Thereafter, median peak tT4 and TSH concentrations were 51 nmol/L and 0.18 ng/mL, respectively, and remained stable during the 22-week follow-up; clinical signs did not recur. CONCLUSIONS AND CLINICAL IMPORTANCE: All of the hypothyroid dogs had rapid clinical and hormonal responses to supplementation with the PO-administered L-T4 solution. The starting dosage of 20 microg L-T4/kg BW once daily was suitable for 79% of dogs