RESUMO
Recent genome-wide association studies have suggested novel risk loci associated with periodontitis, which is initiated by dysbiosis in subgingival plaque and leads to destruction of teeth-supporting structures. One such genetic locus was the tumor necrosis factor receptor-associated factor 3 interacting protein 2 (TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)-17 receptor adaptor. In this study, we first determined that carriers of the lead exonic variant rs13190932 within the TRAF3IP2 locus combined with a high plaque microbial burden was associated with more severe periodontitis than noncarriers. We then demonstrated that TRAF3IP2 is essential in the IL-17-mediated CCL2 and IL-8 chemokine production in primary gingival epithelial cells. Further analysis suggested that rs13190932 may serve a surrogate variant for a genuine loss-of-function variant rs33980500 within the same gene. Traf3ip2 null mice (Traf3ip2-/-) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis-induced periodontal alveolar bone loss. Such bone loss was associated with a delayed P. gingivalis clearance and an attenuated neutrophil recruitment in the gingiva of Traf3ip2-/- mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2-/- mouse gingiva in comparison to WT mice prior to or upon P. gingivalis oral challenge. Further 16S ribosomal RNA sequencing analysis identified a distinct microbial community in the Traf3ip2-/- mouse oral plaque, which was featured by a reduced microbial diversity and an overabundance of Streptococcus genus bacteria. More P. gingivalis was observed in the Traf3ip2-/- mouse gingiva than WT control animals in a ligature-promoted P. gingivalis invasion model. In agreement, neutrophil depletion resulted in more local gingival tissue invasion by P. gingivalis. Thus, we identified a homeostatic IL-17-TRAF3IP2-neutrophil axis underpinning host defense against a keystone periodontal pathogen.
Assuntos
Perda do Osso Alveolar , Periodontite , Camundongos , Animais , Gengiva/metabolismo , Interleucina-17/metabolismo , Estudo de Associação Genômica Ampla , Periodontite/microbiologia , Perda do Osso Alveolar/metabolismo , Porphyromonas gingivalis , Camundongos Knockout , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
In the exceedingly rare event of nuclear reactor core meltdown, uranium dioxide fuel reacts with Zircaloy cladding to produce eutectic melts which can subsequently be oxidized by coolant/moderator water. Oxidized corium liquids in the xUO2·(100 - x)ZrO2 system were produced via laser melting of UO2-ZrO2 mixtures to temperatures in excess of 3000 K. Contamination was avoided by floating the droplets on a gas stream within an aerodynamic levitator and in-situ high-energy x-ray diffraction experiments allowed structural details to be elucidated. Molecular dynamics simulations well reproduced diffraction and density data, and show less compositional variation in thermal expansion and viscosity than suggested by existing measurements. As such, corium liquids maintain their highly penetrating nature irrespective of the amount of oxidized cladding dissolved in the molten fuel. Metal-oxygen coordination numbers vary with both composition and temperature. The former is due to mismatch in native values, nUO(x = 100) ≈ 7 and nZrO(x = 0) ≈ 6, and the requirement for oxygen site stabilization. The latter provides a thermal expansion mechanism.
RESUMO
This study investigated the involvement of estrogen receptors alpha and beta in estradiol-induced enhancement of hippocampal neurogenesis in the adult female rat. Subtype selective estrogen receptor agonists, propyl-pyrazole triol (estrogen receptor alpha agonist) and diarylpropionitrile (estrogen receptor beta agonist) were examined for each receptor's contribution, individual and cooperative, for estradiol-enhanced hippocampal cell proliferation. Estradiol increases hippocampal cell proliferation within 4 h [Ormerod BK, Lee TT, Galea LA (2003) Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats. J Neurobiol 55:247-260]. Therefore, animals received s.c. injections of estradiol (10 microg), propyl-pyrazole triol and diarylpropionitrile alone (1.25, 2.5, 5.0 mg/0.1 ml dimethylsulfoxide) or in combination (2.5 mg propyl-pyrazole triol+2.5 mg diarylpropionitrile/0.1 ml dimethylsulfoxide) and 4 h later received an i.p. injection of the cell synthesis marker, bromodeoxyuridine (200 mg/kg). Diarylpropionitrile enhanced cell proliferation at all three administered doses (1.25 mg, P<0.008; 2.5 mg, P<0.003; 5 mg, P<0.005), whereas propyl-pyrazole triol significantly increased cell proliferation (P<0.0002) only at the dose of 2.5 mg. Our results demonstrate both estrogen receptor alpha and estrogen receptor beta are individually involved in estradiol-enhanced cell proliferation. Furthermore both estrogen receptor alpha and estrogen receptor beta mRNA was found co-localized with Ki-67 expression in the hippocampus albeit at low levels, indicating a potential direct influence of each receptor subtype on progenitor cells and their progeny. Dual receptor activation resulted in reduced levels of cell proliferation, supporting previous studies suggesting that estrogen receptor alpha and estrogen receptor beta may modulate each other's activity. Our results also suggest that a component of estrogen receptor-regulated cell proliferation may take place through alternative ligand and/or cell-signaling mechanisms.
Assuntos
Proliferação de Células/efeitos dos fármacos , Giro Denteado/citologia , Receptor alfa de Estrogênio/agonistas , Receptor beta de Estrogênio/agonistas , Nitrilas/farmacologia , Propionatos/farmacologia , Pirazóis/farmacologia , Análise de Variância , Animais , Bromodesoxiuridina/metabolismo , Contagem de Células/métodos , Relação Dose-Resposta a Droga , Proteínas do Domínio Duplacortina , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Antígeno Ki-67/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropeptídeos/metabolismo , Fenóis , RatosRESUMO
A quick and reproducible microgel plate assay was adapted to screen bacteria from cattle gastrointestinal tracts for production of compounds inhibitory to the growth of three enterohemorrhagic Escherichia coli (EHEC) serotypes: O157:H7, O111:H-, and O26:H11. The inhibitory activity of 309 bacteria, isolated on several agar media, was assessed by a microgel assay performed in 96-well microtiter plates. Fifty-three isolates secreted inhibitory compounds with a molecular weight of less than 1,000. In 12 isolates, the inhibitory activity was attributable to compounds other than lactic or acetic acid. These compounds were highly heat tolerant, with varying sensitivity to digestion by proteolytic enzymes. The inhibitory isolates were identified as lactic acid-producing bacteria on the basis of a combination of analyses, including 16S-rDNA restriction fragment length polymorphisms, 16S-rDNA gene sequences, and fermentation end products. The lactic acid bacteria of ruminants may contain antibacterial compounds not yet described. Naturally occurring populations of lactic acid bacteria may have potential as probiotics, to reduce the carriage of EHEC in the gastrointestinal tract of ruminants.
Assuntos
Bovinos/microbiologia , Escherichia coli O157/crescimento & desenvolvimento , Escherichia coli/crescimento & desenvolvimento , Lactobacillus/fisiologia , Animais , Antibiose , Bifidobacterium/fisiologia , Contagem de Colônia Microbiana , DNA Bacteriano/análise , Enterococcus/fisiologia , Escherichia coli/isolamento & purificação , Escherichia coli O157/isolamento & purificação , Testes de Sensibilidade Microbiana , Peso Molecular , Selenomonas/fisiologia , Sorotipagem , Streptococcus/fisiologiaRESUMO
A Pindo palm tree (Butia capitata) declined in a commercial landscape setting in Georgetown, SC during June of 2005. In the spring, after looking healthy the previous year, the entire canopy collapsed with leaves attached. The canopy defoliated shortly thereafter. A cross section through primary and secondary roots of the wilting plant revealed necrotic areas with the presence of white mycelial fans. Diseased roots containing mycelial fans were collected and small sections were transferred to benomyl dichloran streptomycin (BDS) selective medium. Fungal cultures grew approximately 1 mm in diameter per day and developed aeriel mycelium first. Later, cultures developed mainly crustose mycelium with some parts being aerial. Ribosomal internal transcribed spacer (ITS) regions 1 and 2 were polymerase chain reaction amplified with universal primers ITS1-F and ITS4 and sequenced (GenBank Accession No. DQ109806). A BLAST search in GenBank of the ITS1-5.8S-ITS2 region identified the pathogen as Armillaria tabescens (Scop.) Emel (synonym Clitocybe tabescens (Fr.) Bres) with 98% sequence homology to A. tabescens single-spore isolate ss23 from South Carolina (Accession No. AY695408). The diploid culture from the roots of the Pindo palm was compatible with haploid tester strains of A. tabescens as indicated by diploidization of the haploid mycelium. The disease has been reported on Pindo palm in Florida (1), but to our knowledge, this is the first report of A. tabescens causing disease on Butia species in South Carolina. Our findings indicate that Pindo palm trees could be at risk for infection and should not be cultivated in soils containing pathogenic Armillaria species. Reference: (1) S. A. Alfieri, Jr. et al. Index of Plant Diseases in Florida (Revised). Fla. Dep. Agric. Consum. Serv. Div. Plant Ind. Bull. 11:389, 1984.
RESUMO
An aerodynamic levitator with carbon dioxide laser beam heating was integrated with a hermetically sealed controlled atmosphere chamber and sample handling mechanism. The system enabled containment of radioactive samples and control of the process atmosphere chemistry. The chamber was typically operated at a pressure of approximately 0.9 bars to ensure containment of the materials being processed. Samples 2.5-3 mm in diameter were levitated in flowing gas to achieve containerless conditions. Levitated samples were heated to temperatures of up to 3500 °C with a partially focused carbon dioxide laser beam. Sample temperature was measured using an optical pyrometer. The sample environment was integrated with a high energy (100 keV) x-ray synchrotron beamline to enable in situ structure measurements to be made on levitated samples as they were heated, melted, and supercooled. The system was controlled from outside the x-ray beamline hutch by using a LabVIEW program. Measurements have been made on hot solid and molten uranium dioxide and binary uranium dioxide-zirconium dioxide compositions.
RESUMO
Our laboratory was asked to help with the rehydration of mummified human fingertips that had been removed from a recently deceased, unidentified female. Using a solution that was found in the archeological literature, we were able to successfully rehydrate dermal tissues to the extent that fingerprints could be taken. We believe that this solution, which until now has not been described in the forensic literature, is effective, affordable, and relatively easy to produce and use.
Assuntos
Dermatoglifia , Antropologia Forense/métodos , Múmias , Autopsia , Feminino , Hidratação , Medicina Legal/métodos , Humanos , Soluções para ReidrataçãoRESUMO
Uranium dioxide (UO2) is the major nuclear fuel component of fission power reactors. A key concern during severe accidents is the melting and leakage of radioactive UO2 as it corrodes through its zirconium cladding and steel containment. Yet, the very high temperatures (>3140 kelvin) and chemical reactivity of molten UO2 have prevented structural studies. In this work, we combine laser heating, sample levitation, and synchrotron x-rays to obtain pair distribution function measurements of hot solid and molten UO2. The hot solid shows a substantial increase in oxygen disorder around the lambda transition (2670 K) but negligible U-O coordination change. On melting, the average U-O coordination drops from 8 to 6.7 ± 0.5. Molecular dynamics models refined to this structure predict higher U-U mobility than 8-coordinated melts.