2,667 research outputs found

    Time-lapse 3-D measurements of a glucose biosensor in multicellular spheroids by light sheet fluorescence microscopy in commercial 96-well plates

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    Light sheet fluorescence microscopy has previously been demonstrated on a commercially available inverted fluorescence microscope frame using the method of oblique plane microscopy (OPM). In this paper, OPM is adapted to allow time-lapse 3-D imaging of 3-D biological cultures in commercially available glass-bottomed 96-well plates using a stage-scanning OPM approach (ssOPM). Time-lapse 3-D imaging of multicellular spheroids expressing a glucose Förster resonance energy transfer (FRET) biosensor is demonstrated in 16 fields of view with image acquisition at 10 minute intervals. As a proof-of-principle, the ssOPM system is also used to acquire a dose response curve with the concentration of glucose in the culture medium being varied across 42 wells of a 96-well plate with the whole acquisition taking 9 min. The 3-D image data enable the FRET ratio to be measured as a function of distance from the surface of the spheroid. Overall, the results demonstrate the capability of the OPM system to measure spatio-temporal changes in FRET ratio in 3-D in multicellular spheroids over time in a multi-well plate format

    Effects of Amphetamine on Striatal Dopamine Release, Open-Field Activity, and Play in Fischer 344 and Sprague–Dawley Rats

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    Previous work from our laboratories has shown that juvenile Fischer 344 (F344) rats are less playful than other strains and also appear to be compromised in dopamine (DA) functioning. To determine whether the dysfunctional play in this strain is associated with deficits in the handling and delivery of vesicular DA, the following experiments assessed the extent to which F344 rats are differentially sensitive to the effects of amphetamine. When exposed to amphetamine, striatal slices obtained from F344 rats showed a small increase in unstimulated DA release when compared with slices from Sprague–Dawley rats; they also showed a more rapid high K+-mediated release of DA. These data provide tentative support for the hypothesis that F344 rats have a higher concentration of cytoplasmic DA than Sprague–Dawley rats. When rats were tested for activity in an open field, F344 rats presented a pattern of results that was consistent with either an enhanced response to amphetamine (3 mg/kg) or a more rapid release of DA (10 mg/kg). Although there was some indication that amphetamine had a dose-dependent differential effect on play in the two strains, play in F344 rats was not enhanced to any degree by amphetamine. Although these results are not consistent with our working hypothesis that F344 rats are less playful because of a deficit in vesicular release of DA, they still suggest that this strain may be a useful model for better understanding the role of DA in social behavior during the juvenile period

    Kecerdasan Emosional Dan Psychological Well-being Pada Taruna Semester III Politeknik Ilmu Pelayaran Semarang

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    Psychological well-being adalah kemampuan individu yang ditandai dengan adanya perasaan bahagia, mempunyai kepuasan hidup, dan tidak ada gejala-gejala depresi. Kecerdasan emosional adalah tentang mengelola emosi dan memotivasi diri sehingga subjek dapat menghibur diri, dapat melepaskan kecemasan, kemurungan, ketersinggungan, dapat bangkit kembali dari semua itu, mampu berpikir positif, mampu untuk terus berjuang ketika menghadapi hambatan, tidak putus asa dan kehilangan harapan. Penelitian ini bertujuan untuk mengetahui hubungan antara kecerdasan emosional dengan psychological well-being pada taruna semester III Politeknik Ilmu Pelayaran Semarang. Populasi penelitian adalah 443 taruna dan sampel penelitian berjumlah 210 taruna dengan karakteristik sampel: taruna yang sedang menjalani kehidupan asrama kampus. Sampel ditentukan dengan teknik simple random sampling. Pengumpulan data menggunakan Skala Kecerdasan Emosional (33 aitem, α= 0,923) dan Skala Psychological Well-Being (32 aitem, α= 0,904). Analisis regresi sederhana menunjukkan adanya hubungan positif signifikan antara kecerdasan emosional dengan psychological well-being (rxy = 0,550 dengan p < 0,001) yang berarti bahwa semakin tinggi kecerdasan emosional maka semakin tinggi psychological well-being. Kecerdasan emosional memberikan sumbangan efektif sebesar 30,3% terhadap psychological well-being

    Hierarchical Virtual Screening of Potential New Antibiotics from Polyoxygenated Dibenzofurans against Staphylococcus aureus Strains

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    Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ph16101430/s1, Table S1. Spatial Coordinates of the Pharmacophoric Model.Staphylococcus aureus is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the S. aureus MRSA and VRSA strains. To achieve this goal, tetrahydroxybenzofuran, a promising antibacterial agent according to in vitro tests described in the literature, was adopted as the pivotal molecule and derivative molecules were considered to generate a pharmacophore model, which was used to perform virtual screening on the Pharmit platform. Through this result, twenty-four molecules were selected from the MolPort® database. Using the Tanimoto Index on the BindingDB web server, it was possible to select eighteen molecules with greater structural similarity in relation to commercial antibiotics (methicillin and oxacillin). Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the eighteen most similar molecules, showed that only three exhibited desired properties (LB255, LB320 and LB415). In the molecular docking study, the promising molecules LB255, LB320 and LB415 showed significant values in both molecular targets. LB320 presented better binding affinity to MRSA (−8.18 kcal/mol) and VRSA (−8.01 kcal/mol) targets. Through PASS web server, the three molecules, specially LB320, showed potential for antibacterial activity. Synthetic accessibility (SA) analysis performed on AMBIT and SwissADME web servers showed that LB255 and LB415 can be considered difficult to synthesize and LB320 is considered easy. In conclusion, the results suggest that these ligands, particularly LB320, may bind strongly to the studied targets and may have appropriate ADME/Tox properties in experimental studies

    Potential for a biogenic influence on cloud microphysics over the ocean: a correlation study with satellite-derived data

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    Aerosols have a large potential to influence climate through their effects on the microphysics and optical properties of clouds and, hence, on the Earth's radiation budget. Aerosol–cloud interactions have been intensively studied in polluted air, but the possibility that the marine biosphere plays an important role in regulating cloud brightness in the pristine oceanic atmosphere remains largely unexplored. We used 9 yr of global satellite data and ocean climatologies to derive parameterizations of the temporal variability of (a) production fluxes of sulfur aerosols formed by the oxidation of the biogenic gas dimethylsulfide emitted from the sea surface; (b) production fluxes of secondary organic aerosols from biogenic organic volatiles; (c) emission fluxes of biogenic primary organic aerosols ejected by wind action on sea surface; and (d) emission fluxes of sea salt also lifted by the wind upon bubble bursting. Series of global monthly estimates of these fluxes were correlated to series of potential cloud condensation nuclei (CCN) numbers derived from satellite (MODIS). More detailed comparisons among weekly series of estimated fluxes and satellite-derived cloud droplet effective radius (r[subscript e]) data were conducted at locations spread among polluted and clean regions of the oceanic atmosphere. The outcome of the statistical analysis was that positive correlation to CCN numbers and negative correlation to r[subscript e] were common at mid and high latitude for sulfur and organic secondary aerosols, indicating both might be important in seeding cloud droplet activation. Conversely, primary aerosols (organic and sea salt) showed widespread positive correlations to CCN only at low latitudes. Correlations to r[subscript e] were more variable, non-significant or positive, suggesting that, despite contributing to large shares of the marine aerosol mass, primary aerosols are not widespread major drivers of the variability of cloud microphysics. Validation against ground measurements pointed out that the parameterizations used captured fairly well the variability of aerosol production fluxes in most cases, yet some caution is warranted because there is room for further improvement, particularly for primary organic aerosol. Uncertainties and synergies are discussed, and recommendations of research needs are given
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