184 research outputs found

    Efficacy of atovaquone combined with clindamycin against murine infection with a cystogenic (Me49) strain of Toxoplasma gondii

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    The efficacy of atovaquone (ATO) combined with clindamycin (CLI) against Toxoplasma gondii was examined in murine models of infection with a mouse-non-virulent (Me49) strain. Swiss-Webster mice inoculated by mouth with 10 or 20 cysts were treated with ATO and CLI alone or combined at dosages of ATO 5-100 and CLI 25-400 mg/kg/day for 2-4 weeks. Drug treatment was initiated (i) day 4 post-infection (acute infection), (ii) 3 months post-infection (chronic infection) and (iii) following a 2-3 week course of treatment with dexamethasone (DXM) alone or combined with cortisone-acetate (CA) introduced 3 months post-infection (reactivated toxoplasmosis). In acute infection, whereas treatment with any drug or drug combination significantly enhanced survival and reduced the brain cyst burden, in mice treated with ATO alone or combined with CLI, the cyst counts were significantly lower than in mice treated with CLI alone. In chronic infection, the decrease in the cyst burden observed 2 weeks after treatment with either drug alone was significant only in mice treated with the combined drugs. Most importantly, in reactivated toxoplasmosis, whereas an effect for the combined drugs was shown in mice suppressed with both DXM alone and combined with CA, in mice pre-treated with DXM a 3 week course of ATO greater than or equal to25 and CLI 50 mg/kg/day significantly increased survival and markedly decreased the cyst burden. The latter effect was long-term, since the cyst burdens in treated mice continued to decrease up to 3 months later, whereas they increased in the untreated mice. The results warrant clinical evaluation of the combination of ATO and CLI in the treatment of toxoplasmosis in both immunocompetent and, more importantly, immunosuppressed patients

    ELECTRONS OR PROTONS: WHAT IS THE CAUSE OF FOREST FIRES IN WESTERN EUROPE ON JUNE 18, 2017?

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    Forest fires in Portugal (June 17–24, 2017) destroyed 64 lives and caused considerable material damage. The coronal hole CH807 and the energy region S5710 were in the geoeffective position on the Sun immediately before the outbreak of fires. In the period that preceded it, as well as at the time of the fires, increased values of the solar wind (SW) parameters (temperature, speed and density of particles) were recorded. In addition, a geomagnetic disorder was recorded. The shape and size of the burning areas, as well as the low air pressure over Portugal indicate the possibility of the effect of positively charged particles that came from the area south, i.e. southwest of Portugal. Nevertheless, it is a specific case that would have to be investigated in more detail

    Positive effects of naringenin on near-surface membrane fluidity in human erythrocytes

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    Purpose: Deformability/rheologic behavior of erythrocytes are related to near-surface membrane fluidity. Specific agents can increase erythrocyte membrane fluidity in order to adjust hemodynamics in cardiovascular diseases. Grapefruit flavanone naringenin has been proposed for potential use in an alternative therapy of cardiovascular conditions. In respect to this, we assessed here effects of two nutritionally relevant concentrations of naringenin (0.1 and 1 μg/ml) on near-surface membrane fluidity in human erythrocytes. Methods: We used electron paramagnetic resonance spectroscopy and fatty acid spin probes (5-DS and 7-DS), the spectra of which are dependent on membrane fluidity. Results: The results showed a significant (p = 0.029) increase of membrane fluidity near the hydrophilic surface in erythrocytes treated with higher concentration of naringenin. In the deeper layer, just below the erythrocyte membrane phospholipid heads, both lower and higher concentration of naringenin significantly increased membrane fluidity (p = 0.036 and p = 0.028, respectively). Conclusions: These data document the positive and dose dependent effect of naringenin on near-surface membrane fluidity in human erythrocytes, recommending its use in the cardiovascular conditions characterized by disturbed hemodynamics

    Topological network alignment uncovers biological function and phylogeny

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    Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology, and disease. Comparison and alignment of biological networks will likely have a similar impact. Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. In this paper, we present a novel algorithm based solely on network topology, that can be used to align any two networks. We apply it to biological networks to produce by far the most complete topological alignments of biological networks to date. We demonstrate that both species phylogeny and detailed biological function of individual proteins can be extracted from our alignments. Topology-based alignments have the potential to provide a completely new, independent source of phylogenetic information. Our alignment of the protein-protein interaction networks of two very different species--yeast and human--indicate that even distant species share a surprising amount of network topology with each other, suggesting broad similarities in internal cellular wiring across all life on Earth.Comment: Algorithm explained in more details. Additional analysis adde

    An Introductory Guide to Aligning Networks Using SANA, the Simulated Annealing Network Aligner.

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    Sequence alignment has had an enormous impact on our understanding of biology, evolution, and disease. The alignment of biological networks holds similar promise. Biological networks generally model interactions between biomolecules such as proteins, genes, metabolites, or mRNAs. There is strong evidence that the network topology-the "structure" of the network-is correlated with the functions performed, so that network topology can be used to help predict or understand function. However, unlike sequence comparison and alignment-which is an essentially solved problem-network comparison and alignment is an NP-complete problem for which heuristic algorithms must be used.Here we introduce SANA, the Simulated Annealing Network Aligner. SANA is one of many algorithms proposed for the arena of biological network alignment. In the context of global network alignment, SANA stands out for its speed, memory efficiency, ease-of-use, and flexibility in the arena of producing alignments between two or more networks. SANA produces better alignments in minutes on a laptop than most other algorithms can produce in hours or days of CPU time on large server-class machines. We walk the user through how to use SANA for several types of biomolecular networks

    Connection of Solar Activities and Forest Fires in 2018: Events in the USA (California), Portugal and Greece

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    The impact of solar activity on environmental processes is difficult to understand and complex for empirical modeling. This study aimed to establish forecast models of the meteorological conditions in the forest fire areas based on the solar activity parameters applying the neural networks approach. During July and August 2018, severe forest fires simultaneously occurred in the State of California (USA), Portugal, and Greece. Air temperature and humidity data together with solar parameters (integral flux of solar protons, differential electron flux and proton flux, solar wind plasma parameters, and solar radio flux at 10.7 cm data) were used in long short-term memory (LSTM) recurrent neural network ensembles. It is found that solar activity mostly affects the humidity for two stations in California and Portugal (an increase in the integral flux of solar protons of > 30 MeV by 10% increases the humidity by 3.25%, 1.65%, and 1.57%, respectively). Furthermore, an increase in air temperature of 10% increases the humidity by 2.55%, 2.01%, and 0.26%, respectively. It is shown that temperature is less sensitive to changes in solar parameters but depends on previous conditions (previous increase of 10% increases the current temperature by 0.75%, 0.34%, and 0.33%, respectively). Humidity in Greece is mostly impacted by solar flux F10.7 cm and previous values of humidity. An increase in these factors by 10% will lead to a decrease in the humidity of 3.89% or an increase of 1.31%, while air temperature mostly depends on ion temperature. If this factor increases by 10%, it will lead to air temperature rising by 0.42%
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