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1.
Cell ; 171(6): 1354-1367.e20, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-29103614

RESUMO

A number of bacterial cell processes are confined functional membrane microdomains (FMMs), structurally and functionally similar to lipid rafts of eukaryotic cells. How bacteria organize these intricate platforms and what their biological significance is remain important questions. Using the pathogen methicillin-resistant Staphylococcus aureus (MRSA), we show here that membrane-carotenoid interaction with the scaffold protein flotillin leads to FMM formation, which can be visualized using super-resolution array tomography. These membrane platforms accumulate multimeric protein complexes, for which flotillin facilitates efficient oligomerization. One of these proteins is PBP2a, responsible for penicillin resistance in MRSA. Flotillin mutants are defective in PBP2a oligomerization. Perturbation of FMM assembly using available drugs interferes with PBP2a oligomerization and disables MRSA penicillin resistance in vitro and in vivo, resulting in MRSA infections that are susceptible to penicillin treatment. Our study demonstrates that bacteria possess sophisticated cell organization programs and defines alternative therapies to fight multidrug-resistant pathogens using conventional antibiotics.


Assuntos
Microdomínios da Membrana/metabolismo , Staphylococcus aureus Resistente à Meticilina/fisiologia , Infecções Estafilocócicas/microbiologia , Animais , Proteínas de Bactérias/metabolismo , Carotenoides/metabolismo , Membrana Celular/metabolismo , Feminino , Microdomínios da Membrana/química , Proteínas de Membrana/metabolismo , Staphylococcus aureus Resistente à Meticilina/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Ligação às Penicilinas/metabolismo , Xantofilas/metabolismo
2.
PLoS Pathog ; 19(6): e1011454, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37363922

RESUMO

Gram-negative bacteria can antagonize neighboring microbes using a type VI secretion system (T6SS) to deliver toxins that target different essential cellular features. Despite the conserved nature of these targets, T6SS potency can vary across recipient species. To understand the functional basis of intrinsic T6SS susceptibility, we screened for essential Escherichia coli (Eco) genes that affect its survival when antagonized by a cell wall-degrading T6SS toxin from Pseudomonas aeruginosa, Tae1. We revealed genes associated with both the cell wall and a separate layer of the cell envelope, lipopolysaccharide, that modulate Tae1 toxicity in vivo. Disruption of genes in early lipopolysaccharide biosynthesis provided Eco with novel resistance to Tae1, despite significant cell wall degradation. These data suggest that Tae1 toxicity is determined not only by direct substrate damage, but also by indirect cell envelope homeostasis activities. We also found that Tae1-resistant Eco exhibited reduced cell wall synthesis and overall slowed growth, suggesting that reactive cell envelope maintenance pathways could promote, not prevent, self-lysis. Together, our study reveals the complex functional underpinnings of susceptibility to Tae1 and T6SS which regulate the impact of toxin-substrate interactions in vivo.


Assuntos
Lipopolissacarídeos , Sistemas de Secreção Tipo VI , Lipopolissacarídeos/metabolismo , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Tipo VI/metabolismo , Escherichia coli/metabolismo , Parede Celular/metabolismo , Pseudomonas aeruginosa/metabolismo
3.
Chemistry ; 30(30): e202400403, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38527230

RESUMO

An intramolecular electrochemical dehydration reaction of dicarboxylic acids to their cyclic anhydrides is presented. This electrolysis allows dicarboxylic acids as naturally abundant, inexpensive, safe, and readily available starting materials to be transformed into carboxylic anhydrides under mild reaction conditions. No conventional dehydration reagent is required. The obtained cyclic anhydrides are highly valuable reagents in organic synthesis, and in this report, we use them in-situ for acylation reactions of amines to synthesize amides. This work is part of the recent progress in electrochemical dehydration, which - in contrast to electrochemical dehydrogenative reactions for example - is an underexplored field of research. The reaction mechanism was investigated by 18O isotope labeling, revealing the formation of sulfate by electrochemical oxidation and hydrolysis of the thiocyanate-supporting electrolyte. This transformation is not a classical Kolbe electrolysis, because it is non-decarboxylative, and all carbon atoms of the carboxylic acid starting material are contained in the carboxylic anhydride. In total, 20 examples are shown with NMR yields up to 71 %.

4.
Infection ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700656

RESUMO

PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).

5.
Phys Chem Chem Phys ; 26(9): 7363-7370, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38375909

RESUMO

Substituting CC with the isoelectronic BN units is a promising approach to modify the optoelectronic properties of polycyclic aromatic hydrocarbons. While computational studies have already addressed trends in the electronic structure of the various isosteres, experimental data are still scarce. Here, the excited state spectroscopy and dynamics of 4a,8a-azaboranaphthalene were studied by picosecond time-resolved photoionization in a supersonic jet and analyzed with the aid of XMS-CASPT2 and time-dependent DFT calculations. A resonance-enhanced multiphoton ionization spectrum (REMPI) reveals the S1 origin at  = 33 830 ± 12 cm-1. Several vibrational bands were resolved and assigned by comparison with the computations. A [1+1] photoelectron spectrum via the S1 origin yielded an adiabatic ionization energy of 8.27 eV. Selected vibrational bands were subsequently investigated by pump-probe photoionization. While the origin as well as several low-lying vibronic states exhibit lifetimes in the ns-range, a monoexponential decay is observed at higher excitation energies, ranging from 400 ps at +1710 cm-1 to 13 ps at +3360 cm-1. The deactivation is attributed to an internal conversion of the optically excited S1 state via a barrier that gives access to a conical intersection (CI) to the S0 state. The doping significantly changes the energetic ordering of CIs and lowers the corresponding energy barrier for the associated deactivation pathway, as revealed by nudged elastic band (NEB) calculations.

6.
EMBO J ; 38(18): e100825, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31403721

RESUMO

Protein translocation by the bacterial type VI secretion system (T6SS) is driven by a rapid contraction of a sheath assembled around a tube with associated effectors. Here, we show that TssA-like or TagA-like proteins with a conserved N-terminal domain and varying C-terminal domains can be grouped into at least three distinct classes based on their role in sheath assembly. The proteins of the first class increase speed and frequency of sheath assembly and form a stable dodecamer at the distal end of a polymerizing sheath. The proteins of the second class localize to the cell membrane and block sheath polymerization upon extension across the cell. This prevents excessive sheath polymerization and bending, which may result in sheath destabilization and detachment from its membrane anchor and thus result in failed secretion. The third class of these proteins localizes to the baseplate and is required for initiation of sheath assembly. Our work shows that while various proteins share a conserved N-terminal domain, their roles in T6SS biogenesis are fundamentally different.


Assuntos
Proteínas de Bactérias/metabolismo , Bactérias Gram-Negativas/metabolismo , Lipoproteínas/metabolismo , Sistemas de Secreção Tipo VI/metabolismo , Proteínas de Bactérias/química , Membrana Celular/metabolismo , Lipoproteínas/química , Modelos Moleculares , Conformação Proteica , Domínios Proteicos
7.
EMBO J ; 37(4)2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29255010

RESUMO

The bacterial Type VI secretion system (T6SS) assembles from three major parts: a membrane complex that spans inner and outer membranes, a baseplate, and a sheath-tube polymer. The baseplate assembles around a tip complex with associated effectors and connects to the membrane complex by TssK. The baseplate assembly initiates sheath-tube polymerization, which in some organisms requires TssA. Here, we analyzed both ends of isolated non-contractile Vibrio cholerae sheaths by cryo-electron microscopy. Our analysis suggests that the baseplate, solved to an average 8.0 Å resolution, is composed of six subunits of TssE/F2/G and the baseplate periphery is decorated by six TssK trimers. The VgrG/PAAR tip complex in the center of the baseplate is surrounded by a cavity, which may accommodate up to ~450 kDa of effector proteins. The distal end of the sheath, resolved to an average 7.5 Å resolution, shows sixfold symmetry; however, its protein composition is unclear. Our structures provide an important step toward an atomic model of the complete T6SS assembly.


Assuntos
Proteínas de Bactérias/química , Microscopia Crioeletrônica/métodos , Proteínas de Membrana/química , Sistemas de Secreção Tipo VI/ultraestrutura , Vibrio cholerae/ultraestrutura , Vibrio cholerae/citologia , Vibrio cholerae/metabolismo
8.
J Sleep Res ; 28(2): e12694, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29722079

RESUMO

As the prevalence of sleep disorders is increasing, new methods for ambulatory sleep measurement are required. This paper presents electrodermal activity in different sleep stages and a sleep detection algorithm based on electrodermal activity. We analysed electrodermal activity and polysomnographic data of 43 healthy subjects and 48 patients with sleep disorders. Electrodermal activity was measured using an ambulatory device worn at the wrist. Two parameters to describe electrodermal activity were defined based on previous literature: EDASEF (electrodermal activity-smoothed feature) as parameter for skin conductance level; and EDAcounts (number of electrodermal activity-peaks) as skin conductance responses. Analysis of variance indicated significant EDASEF differences between the sleep stages wake versus N1, wake versus N2, wake versus slow-wave sleep, and wake versus rapid eye movement. The analysis of EDAcounts also showed significant differences, especially in the stages slow-wave sleep versus rapid eye movement. Between healthy subjects and patients, a significant disparity of EDAcounts was revealed in stage N1. Furthermore, the variances of EDASEF and EDAcounts in N1, N2 slow-wave sleep and rapid eye movement were higher in the patient group (p [F test] < .05). Next, an electrodermal activity-based sleep/wake discriminating algorithm was constructed. The optimized algorithm achieved an average sensitivity and specificity for sleep detection of 97% and 75%. The epoch agreement rate (average accuracy) was 86%. These outcomes are comparative to sleep detection algorithms based on actigraphy or heart rate variability. The results of this study indicate that electrodermal activity is not only a robust parameter for describing sleep, but also a potential suitable method for ambulatory sleep monitoring.


Assuntos
Resposta Galvânica da Pele/fisiologia , Polissonografia/métodos , Fases do Sono/fisiologia , Transtornos do Sono-Vigília/classificação , Adulto , Algoritmos , Feminino , Humanos , Masculino
9.
Chemphyschem ; 19(17): 2272-2280, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29790269

RESUMO

We investigated the adsorption of different free-base carboxyl-functionalized porphyrins, 5,10,15,20-tetrakis(4-carboxyphenyl)-21,23H-porphyrin (2H-TCPP) and 5(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin (2H-MCTPP), on MgO nanocubes combining IR, UV/Vis and photoluminescence emission spectroscopy. The thermal behavior of the films was monitored in-situ during annealing. Both porphyrins bind to the nanocubes via one and two acid groups respectively, yielding monolayer films consisting of tilted molecules. For 2H-TCPP, two acid groups remain free and give rise to a characteristic IR band. Self-assembly in a tilted adsorbate layer suppresses metalation at room temperature, in contrast to non-functionalized 2H-TPP, which adsorbs flat-lying. Upon heating, 2H-MCTPP undergoes full metalation at temperatures below 280 °C, whereas 2H-TCPP does not metalate at all. The hindered metalation reaction is attributed to the rigidity of the adsorbate film preventing complexation. Our results show that the properties of porphyrin films on oxides can be tuned in a wide range via the position and arrangement of carboxyl anchoring groups.

10.
Phys Chem Chem Phys ; 20(38): 24858-24868, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30230482

RESUMO

Hybrid materials consisting of functional organic molecules on metal oxide nanomaterials are key components in emerging technologies, for example in energy conversion and molecular electronics. In this work, we present the results of a comparative study of carboxyl-functionalized porphyrins on different oxide nanomaterials. Specifically, we investigated the interaction of 5(3-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin (2H-3-MCTPP) and 5(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin (2H-4-MCTPP), on MgO, TiO2, and Co3O4 nanoparticles (NPs) using isothermal and temperature-programmed diffuse reflection infrared Fourier transform spectroscopy (DRIFTS). We show that both porphyrins bind to the NPs, yielding stable monolayer films consisting of tilted surface carboxylates. In all cases, anchoring through the carboxylic acid group suppresses self-metalation of the porphyrin unit. Upon annealing, all anchored porphyrin films undergo metalation. The position of the acid group has no major influence on the reactivity. The same is true for the nature of the metal oxide, suggesting that the observed behaviour is general for most anchored porphyrin films on oxide nanomaterials.

11.
PLoS Genet ; 11(4): e1005140, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25909364

RESUMO

Lipid rafts are membrane microdomains specialized in the regulation of numerous cellular processes related to membrane organization, as diverse as signal transduction, protein sorting, membrane trafficking or pathogen invasion. It has been proposed that this functional diversity would require a heterogeneous population of raft domains with varying compositions. However, a mechanism for such diversification is not known. We recently discovered that bacterial membranes organize their signal transduction pathways in functional membrane microdomains (FMMs) that are structurally and functionally similar to the eukaryotic lipid rafts. In this report, we took advantage of the tractability of the prokaryotic model Bacillus subtilis to provide evidence for the coexistence of two distinct families of FMMs in bacterial membranes, displaying a distinctive distribution of proteins specialized in different biological processes. One family of microdomains harbors the scaffolding flotillin protein FloA that selectively tethers proteins specialized in regulating cell envelope turnover and primary metabolism. A second population of microdomains containing the two scaffolding flotillins, FloA and FloT, arises exclusively at later stages of cell growth and specializes in adaptation of cells to stationary phase. Importantly, the diversification of membrane microdomains does not occur arbitrarily. We discovered that bacterial cells control the spatio-temporal remodeling of microdomains by restricting the activation of FloT expression to stationary phase. This regulation ensures a sequential assembly of functionally specialized membrane microdomains to strategically organize signaling networks at the right time during the lifespan of a bacterium.


Assuntos
Bacillus subtilis/genética , Microdomínios da Membrana/genética , Proteínas de Membrana/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/biossíntese , Transporte Proteico/genética , Transdução de Sinais/genética
12.
Chemistry ; 22(5): 1744-9, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26682774

RESUMO

We show that both single-crystalline and nanostructured MgO surfaces convert free-base tetraphenyl porphyrin (2HTPP) into magnesium tetraphenyl porphyrin (MgTPP) at room temperature. The reaction can be viewed as an ion exchange between the two aminic protons of the 2HTPP molecule with a Mg(2+) ion from the surface. The driving force for the reaction is the strong stability of the formed hydroxyl groups along the steps and at defects on the MgO surface. We have used an integrated characterization approach that includes UV/Vis diffuse reflectance measurements on nanostructured powders, X-ray photoelectron spectroscopic investigation of atomically clean MgO(100) single-crystalline thin films, and density functional theory (DFT) calculations on model systems. The DFT calculations demonstrate that MgTPP formation is strongly exothermic at the corners, edges and steps, but slightly endothermic on terrace sites. This agrees well with the UV/Vis diffuse reflectance, which upon adsorption of 2HTPP shows a decrease in the absorption band associated with corner and edge sites on MgO nanocube powders.

13.
Environ Sci Technol ; 50(20): 10814-10822, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27709900

RESUMO

Atmospheric oxidation of volatile organic compounds (VOCs) yields a large number of different organic molecules which comprise a wide range of volatility. Depending on their volatility, they can be involved in new particle formation and particle growth, thus affecting the number concentration of cloud condensation nuclei in the atmosphere. Here, we identified oxidation products of VOCs in the particle phase during a field study at a rural mountaintop station in central Germany. We used atmospheric pressure chemical ionization mass spectrometry ((-)APCI-MS) and aerosol mass spectrometry for time-resolved measurements of organic species and of the total organic aerosol (OA) mass in the size range of 0.02-2.5 and 0.05-0.6 µm, respectively. The elemental composition of organic molecules was determined by offline analysis of colocated PM 2.5 filter samples using liquid chromatography coupled to electrospray ionization ultrahigh-resolution mass spectrometry. We found extremely low volatile organic compounds, likely from sesquiterpene oxidation, being the predominant signals in the (-)APCI-MS mass spectrum during new particle formation. Low volatile organic compounds started to dominate the spectrum when the newly formed particles were growing to larger diameters. Furthermore, the APCI-MS mass spectra pattern indicated that the average molecular weight of the OA fraction ranged between 270 and 340 amu, being inversely related to OA mass. Our observations can help further the understanding of which biogenic precursors and which chemical processes drive particle growth after atmospheric new-particle formation.

14.
Environ Sci Technol ; 50(20): 10823-10832, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27709898

RESUMO

Aerosol hygroscopic properties were linked to its chemical composition by using complementary online mass spectrometric techniques in a comprehensive chemical characterization study at a rural mountaintop station in central Germany in August 2012. In particular, atmospheric pressure chemical ionization mass spectrometry ((-)APCI-MS) provided measurements of organic acids, organosulfates, and nitrooxy-organosulfates in the particle phase at 1 min time resolution. Offline analysis of filter samples enabled us to determine the molecular composition of signals appearing in the online (-)APCI-MS spectra. Aerosol mass spectrometry (AMS) provided quantitative measurements of total submicrometer organics, nitrate, sulfate, and ammonium. Inorganic sulfate measurements were achieved by semionline ion chromatography and were compared to the AMS total sulfate mass. We found that up to 40% of the total sulfate mass fraction can be covalently bonded to organic molecules. This finding is supported by both on- and offline soft ionization techniques, which confirmed the presence of several organosulfates and nitrooxy-organosulfates in the particle phase. The chemical composition analysis was compared to hygroscopicity measurements derived from a cloud condensation nuclei counter. We observed that the hygroscopicity parameter (κ) that is derived from organic mass fractions determined by AMS measurements may overestimate the observed κ up to 0.2 if a high fraction of sulfate is bonded to organic molecules and little photochemical aging is exhibited.

15.
Microbiology (Reading) ; 161(9): 1871-1887, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26297017

RESUMO

Scaffold proteins are ubiquitous chaperones that bind to proteins and facilitate the physical interaction of the components of signal transduction pathways or multi-enzymic complexes. In this study, we used a biochemical approach to dissect the molecular mechanism of a membrane-associated scaffold protein, FloT, a flotillin-homologue protein that is localized in functional membrane microdomains of the bacterium Bacillus subtilis. This study provides unambiguous evidence that FloT physically binds to and interacts with the membrane-bound sensor kinase KinC. This sensor kinase activates biofilm formation in B. subtilis in response to the presence of the self-produced signal surfactin. Furthermore, we have characterized the mechanism by which the interaction of FloT with KinC benefits the activity of KinC. Two separate and synergistic effects constitute this mechanism: first, the scaffold activity of FloT promotes more efficient self-interaction of KinC and facilitates dimerization into its active form. Second, the selective binding of FloT to KinC prevents the occurrence of unspecific aggregation between KinC and other proteins that may generate dead-end intermediates that could titrate the activity of KinC. Flotillin proteins appear to play an important role in prokaryotes in promoting effective binding of signalling proteins with their correct protein partners.


Assuntos
Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Membrana/metabolismo , Bacillus subtilis/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Membrana Celular/metabolismo , Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/química , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Agregados Proteicos , Ligação Proteica , Multimerização Proteica
16.
Langmuir ; 31(9): 2770-6, 2015 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-25668706

RESUMO

Stability parameters and dissolution behavior of engineered nanomaterials in aqueous systems are critical to assess their functionality and fate under environmental conditions. Using scanning electron microscopy, transmission electron microscopy, and X-ray diffraction, we investigated the stability of cubic MgO particles in water. MgO dissolution proceeding via water dissociation at the oxide surface, disintegration of Mg(2+)-O(2-) surface elements, and their subsequent solvation ultimately leads to precipitation of Mg(OH)2 nanosheets. At a pH ≥ 10, MgO nanocubes with a size distribution below 10 nm quantitatively dissolve within few minutes and convert into Mg(OH)2 nanosheets. This effect is different from MgO cubes originating from magnesium combustion in air. With a size distribution in the range 10 nm ≤ d ≤ 1000 nm they dissolve with a significantly smaller dissolution rate in water. On these particles water induced etching generates (110) faces which, above a certain face area, dissolve at a rate equal to that of (100) planes.1 The delayed solubility of microcrystalline MgO is attributed to surface hydroxide induced self-inhibition effects occurring at the (100) and (110) microplanes. The present work underlines the importance of morphology evolution and surface faceting of engineered nanomaterials particles during their dissolution.

17.
Proc Natl Acad Sci U S A ; 108(19): 7674-8, 2011 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-21521789

RESUMO

For an intriguing variety of switching processes in nature, the underlying complex system abruptly changes from one state to another in a highly discontinuous fashion. Financial market fluctuations are characterized by many abrupt switchings creating upward trends and downward trends, on time scales ranging from macroscopic trends persisting for hundreds of days to microscopic trends persisting for a few minutes. The question arises whether these ubiquitous switching processes have quantifiable features independent of the time horizon studied. We find striking scale-free behavior of the transaction volume after each switching. Our findings can be interpreted as being consistent with time-dependent collective behavior of financial market participants. We test the possible universality of our result by performing a parallel analysis of fluctuations in time intervals between transactions. We suggest that the well known catastrophic bubbles that occur on large time scales--such as the most recent financial crisis--may not be outliers but single dramatic representatives caused by the formation of increasing and decreasing trends on time scales varying over nine orders of magnitude from very large down to very small.

18.
Vet Anaesth Analg ; 41(3): 297-304, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24576316

RESUMO

OBJECTIVE: To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs. STUDY DESIGN: Prospective part-randomized pre-clinical research trial. ANIMALS: Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12-15 months. METHODS: On different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1). RESULTS: Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on µ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states.


Assuntos
Doenças do Cão/tratamento farmacológico , Morfina/uso terapêutico , Medição da Dor/veterinária , Dor/tratamento farmacológico , Fenóis/uso terapêutico , Tramadol/uso terapêutico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Animais , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Masculino , Morfina/administração & dosagem , Fenóis/administração & dosagem , Receptores Opioides mu/agonistas , Tapentadol , Tramadol/administração & dosagem
19.
Materials (Basel) ; 17(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38998285

RESUMO

Despite extensive sorting, packaging waste often contains a mixture of different materials that make high-quality recycling difficult, especially in the case of flexible packaging. This is partly due to the widespread use of multi-layer laminates and packaging consisting of different inseparably combined materials. To improve the post-consumer recyclate quality and develop optimised recycling processes, it is important to generate a comprehensive understanding of the composition of the sorted packaging waste streams. Therefore, in this study, polyolefin sorting fractions for flexible packaging waste from three European countries are analysed in detail. By selective extraction of the different plastics, their mass fractions in the waste streams are determined. This shows that the PE-rich sorting fractions for flexible packaging are made up of 85-90% of PE, but also contain a certain proportion of foreign materials. A detailed analysis of the layer structures of various types of packaging also provides information on the prevalence of multi-layer packaging and the polymer and non-polymer materials used therein. This shows that particularly in food packaging, with 63-84% of multi-layer and 50-70% of multi-material packaging, a high proportion of foreign materials is used and introduced into the sorting fractions. These insights provide a valuable contribution to the development of recyclable packaging, potential sorting streams and recycling processes, especially with regard to the challenges of the closed-loop recycling of food packaging.

20.
Commun Chem ; 7(1): 120, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824266

RESUMO

Droplet Interface Bilayers (DIBs) constitute a commonly used model of artificial membranes for synthetic biology research applications. However, their practical use is often limited by their requirement to be surrounded by oil. Here we demonstrate in-situ bilayer manipulation of submillimeter, hydrogel-encapsulated droplet interface bilayers (eDIBs). Monolithic, Cyclic Olefin Copolymer/Nylon 3D-printed microfluidic devices facilitated the eDIB formation through high-order emulsification. By exposing the eDIB capsules to varying lysophosphatidylcholine (LPC) concentrations, we investigated the interaction of lysolipids with three-dimensional DIB networks. Micellar LPC concentrations triggered the bursting of encapsulated droplet networks, while at lower concentrations the droplet network endured structural changes, precisely affecting the membrane dimensions. This chemically-mediated manipulation of enclosed, 3D-orchestrated membrane mimics, facilitates the exploration of readily accessible compartmentalized artificial cellular machinery. Collectively, the droplet-based construct can pose as a chemically responsive soft material for studying membrane mechanics, and drug delivery, by controlling the cargo release from artificial cell chassis.

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