Evolving Trend of Drug Delivery System in Uveitis

<p>Evolving Trend of Drug Delivery System in Uveitis; Pranita Sahay MBBS, Devesh Kumawat MBBS, Koushik Tripathy MD, DNB, Vijay Kumar Sharma MS<br>DOS Times - Vol. 20, No. 3 September, 2014</p> <p> </p

Sleep in males during social interaction.

<p>(a) Sleep profiles of males across 4 days of social interaction. (b) Sleep profiles of females across 4 days of social interaction. (c) Change in sleep bars (mean ± SEM) for males (<i>n</i> = 16 and 24, for socialized and control groups respectively) and females (<i>n</i> = 14 and 22, for socialized and control groups respectively), where white and dark bars represent sleep during day as well as nighttime. Sleep of socially interacting males is not significantly different (<i>p</i> = 0.99 for daytime and <i>p</i> = 0.50 for nighttime, Student’s <i>t</i>-test) from that of solitary controls. Sleep of socially interacting females is also not significantly different (<i>p</i> = 0.98 for daytime and <i>p</i> = 0.76 for nighttime, Student’s <i>t</i>-test) from that of solitary controls. (d, e) Sleep latency of socially interacting (d) males and (e) females is comparable (<i>p ></i> 0.05, Student’s <i>t</i>-test) to that of solitary controls. Other details are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0150596#pone.0150596.g001" target="_blank">Fig 1</a>.</p

Social Experience Is Sufficient to Modulate Sleep Need of <i>Drosophila</i> without Increasing Wakefulness

<div><p>Organisms quickly learn about their surroundings and display synaptic plasticity which is thought to be critical for their survival. For example, fruit flies <i>Drosophila melanogaster</i> exposed to highly enriched social environment are found to show increased synaptic connections and a corresponding increase in sleep. Here we asked if social environment comprising a pair of same-sex individuals could enhance sleep in the participating individuals. To study this, we maintained individuals of <i>D</i>. <i>melanogaster</i> in same-sex pairs for a period of 1 to 4 days, and after separation, monitored sleep of the previously socialized and solitary individuals under similar conditions. Males maintained in pairs for 3 or more days were found to sleep significantly more during daytime and showed a tendency to fall asleep sooner as compared to solitary controls (both measures together are henceforth referred to as “sleep-enhancement”). This sleep phenotype is not strain-specific as it is observed in males from three different “wild type” strains of <i>D</i>. <i>melanogaster</i>. Previous studies on social interaction mediated sleep-enhancement presumed ‘waking experience’ during the interaction to be the primary underlying cause; however, we found sleep-enhancement to occur without any significant increase in wakefulness. Furthermore, while sleep-enhancement due to group-wise social interaction requires Pigment Dispersing Factor (PDF) positive neurons; PDF positive and CRYPTOCHROME (CRY) positive circadian clock neurons and the core circadian clock genes are not required for sleep-enhancement to occur when males interact in pairs. Pair-wise social interaction mediated sleep-enhancement requires dopamine and olfactory signaling, while visual and gustatory signaling systems seem to be dispensable. These results suggest that socialization alone (without any change in wakefulness) is sufficient to cause sleep-enhancement in fruit fly <i>D</i>. <i>melanogaster</i> males, and that its neuronal control is context-specific.</p></div

Enhanced stability in adult emergence of selected population persists under semi-natural (SN) condition.

<p>(A) Waveform of adult emergence (left panel) in selected (<i>PP</i>) and control (<i>CP</i>) populations averaged across five consecutive cycles under laboratory (LAB). Percentage of flies emerged in 2 h bins are plotted along <i>y</i>-axis and External Time in h along <i>x</i>-axis. The square wave line above the Figure represents 12∶12 h light/dark (LD) cycles under laboratory condition. Peak of emergence in <i>PP</i> and <i>CP</i> populations under LAB (right panel). (B) Waveform of emergence (left panel) of <i>PP</i> and <i>CP</i> populations averaged across five consecutive cycles under SN. Peak of emergence in <i>PP</i> and <i>CP</i> populations under SN (right panel). Upper panels of 2B show average profiles of light (lux), temperature (°C) and humidity (%RH) for the entire duration of the experiment. A greater percentage of <i>PP</i> flies emerge during the selection window compared to <i>CP</i>. Concurrent to the increase in percentage emergence during the selection window there is a decrease in percentage emergence prior-to the selection window, with reduced anticipation to lights-on. Shaded box on the <i>x</i>-axis represents the selection window. Under SN, <i>PP</i> flies sustain robust waveform of emergence with more prominent peak and narrower gate-width. Error bars represent 95% comparison intervals (95%CI) around the mean for visual hypothesis testing. For this assay, ten vials for each of the four replicate populations were used under each environmental condition. The mean values of four replicates and variance in terms of 95% comparison interval (95%CI) were used to draw emergence profiles and error bars.</p

Sleep-enhancement in two other strains of <i>D</i>. <i>melanogaster</i>.

<p>(a, left) Sleep profiles of <i>Oregon R</i> (<i>OR</i>) males following 4 days of pair-wise social interaction. (a, right) Daytime and nighttime sleep latency is significantly lower (<i>p <</i> 0.05, Student’s <i>t</i>-test) as compared to that of solitary controls. (b, left) Sleep profiles of <i>Iso31</i> males following 4 days of pair-wise social interaction. (b, right) Although sleep latency of socialized males is also decreased, it did not reach statistically significant levels (<i>p ></i> 0.05, Student’s <i>t</i>-test). (c) Daytime sleep of socialized <i>OR</i> males (<i>p <</i> 0.0001, Student’s <i>t</i>-test; <i>n</i> = 16 for each group) and <i>Iso31</i> males (<i>p <</i> 0.0005, Student’s <i>t</i>-test; <i>n</i> = 15 for each group) is significantly greater as compared to that of solitary controls. Other details are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0150596#pone.0150596.g001" target="_blank">Fig 1</a>.</p

Sleep-enhancement in males due to pair-wise social interaction.

<p>(a, left) Sleep profiles of <i>Canton S</i> (<i>CS</i>) males following pair-wise social interaction with other males for (1D) 1 day, (2D) 2 days, (3D) 3 days or (4D) 4 days. In the sleep profiles, black circles and dark broken lines represent sleep of flies subjected to pair-wise social interaction, whereas grey circles and grey solid lines represent sleep of solitary controls. (a, right) Bar graphs show change in sleep of socialized males as compared to solitary controls and there is an increase in daytime sleep (white bars) in socialized males as compared to solitary controls (<i>p</i> = 0.09 for 1D, <i>p</i> = 0.06 for 2D, <i>p <</i> 0.0005 for 3D and 4D, ANOVA followed by post hoc multiple comparison by Tukey’s test). Nighttime sleep (dark bars) of socialized males does not differ from that of solitary controls. (b) Sleep profiles of <i>CS</i> females following pair-wise social interaction with other females for (1D) 1 day, (2D) 2 days, (3D) 3 days or (4D) 4 days. Both daytime and nighttime sleep does not differ between socialized and solitary control females (<i>p</i> > 0.05, ANOVA followed by post hoc by Tukey’s test). (c) Following 4 days of social interaction, daytime sleep latency of males is significantly reduced (<i>p <</i> 0.01, Student’s <i>t</i>-test) as compared to solitary controls. Although nighttime sleep latency also shows a similar decrease, it did not reach statistically significant levels (<i>p</i> > 0.05, Student’s <i>t</i>-test). In case of females, both daytime and nighttime sleep latency does not differ between socialized and solitary individuals. (d) While there is a statistically significant increase in sleep bout length during nighttime (<i>p</i> < 0.05, Student’s <i>t</i>-test) in socialized males as compared to solitary controls, bout number does not different significantly among socialized and solitary control males. Data is presented as mean ± SEM (standard error of means) and <i>n</i> = 16 for each group of males and females. Asterisks over each bar indicate statistically significant difference between socialized and solitary control flies unless mentioned otherwise, where <i>p <</i> 0.05 is represented by single asterisk, <i>p <</i> 0.005 by two asterisks and <i>p <</i> 0.0005 by three asterisks. Other details about the bar graphs are same as in 1a.</p

Flies from selected populations exhibit enhanced activity during the morning peak.

<p>(A) Activity profiles of flies from selected (<i>PP</i>) and control (<i>CP</i>) populations under laboratory (LAB) and semi-natural (SN) conditions. The percentage of activity averaged over 8–10 successive cycles is plotted along <i>y</i>-axis and time of the day in h along the <i>x</i>-axis. Flies from selected populations showed increased activity during the morning peak under LAB as well as in SN. The day-to-day variations in light, temperature and humidity are plotted as error bars (SEM) on their daily profiles. Other details are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050379#pone-0050379-g002" target="_blank">Figure 2a</a>. (B) Percentage activity during the morning peak, daytime, nighttime in flies from selected and control populations. Flies from <i>PP</i> were more active during the selection window under LAB and SN. (C, D) Synchrony and accuracy under LAB and SN. Enhanced synchrony and accuracy in the phase of morning activity peak in <i>PP</i> flies persisted under SN. About 32 flies were used for each of the four replicate populations under each environmental regime. The mean values of four replicates and variance in terms of 95% comparison interval (95%CI) were used to draw emergence profiles and error bars. All other details are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050379#pone-0050379-g002" target="_blank">Figure 2</a>.</p

Exciton Dynamics in Colloidal Quantum-Dot LEDs under Active Device Operations

Colloidal quantum-dot light-emitting diodes (QLEDs) are lucrative options for color-pure lighting sources. To achieve high-performance QLEDs, besides developing high-efficiency quantum dots (QDs), it is essential to understand their device physics. However, little understanding of the QD emission behavior in active QLEDs is one of the main factors hindering the improvement of device efficiency. In this work, we systematically studied the exciton dynamics of gradient composition CdSe@ZnS QDs during electroluminescence in a working QLED. With time-resolved photoluminescence analyses using fluorescence lifetime imaging microscopy we analyzed a large population of QDs spatially spreading over an extended area inside and outside the device. This allows us to reveal the statistically significant changes in the behavior of QD emission in the device at different levels of applied voltages and injection currents. We find that the QD emission efficiency first drops in device fabrication with Al electrode deposition and that the QD exciton lifetime is then statistically reduced further under the QLED’s working conditions. This implies the nonradiative Auger recombination process is active in charged QDs as a result of imbalanced charge injection in a working QLED. Our results help to understand the exciton behavior during the operation of a QLED and demonstrate a new approach to explore the exciton dynamics statistically with a large QD population

Enhanced robustness in adult emergence of selected population persists under semi-natural (SN).

<p>(A) Circadian waveform of emergence of selected (<i>PP</i>) and control (<i>CP</i>) flies under laboratory (LAB). Percentage of flies that emerged in 2 h bins over five successive cycles is plotted along <i>y</i>-axis and External Time (in h) along <i>x</i>-axis. The square wave indicated above the figure represents 12∶12 h light/dark (LD) cycles. (B) Circadian waveform of emergence under SN. Percentage of flies that emerged in 2 h bins over five successive cycles are plotted along <i>y</i>-axis and External Time in h along <i>x</i>-axis. Upper panels of 1B show daily profiles of light (lux), temperature (^°C) and humidity (%RH) for the entire duration of the experiment. Under LAB, greater percentage of <i>PP</i> flies emerged during the peak which persisted under SN. For this assay, ten vials for each of the four replicate populations were used under each environmental condition. The mean values of four replicates and variance in terms of 95% comparison interval (95%CI) were used to draw emergence profiles and error bars.</p

Olfactory cues mediate sleep-enhancement.

<p>(a) Sleep profiles of <i>norpA</i> males following 4 days of pair-wise social interaction in 12:12 h light/dark cycles (LD12:12). (b) Sleep profiles of <i>CS</i> and <i>Iso31</i> males following pair-wise social interaction for 4 days in constant darkness (DD). (c) Sleep analysis revealed that daytime sleep is significantly increased in socialized <i>norpA</i> males as compared to solitary controls (<i>p <</i> 0.0005 for daytime and <i>p <</i> 0.02 for nighttime, Student’s <i>t</i>-test; <i>n</i> = 21 and 24 for socialized and control groups respectively). Daytime sleep of socialized <i>CS</i> (<i>p <</i> 0.02, Student’s <i>t</i>-test; <i>n</i> = 14 and 16 for socialized and control groups respectively) and <i>Iso31</i> (<i>p <</i> 0.01, Student’s <i>t</i>-test; <i>n</i> = 29 and 18 for socialized and control groups respectively) males is also significantly increased as compared to that of solitary controls. (d, left) Sleep profiles and (d, right) change in sleep of <i>Gr66aGAL4>UAShid</i> and <i>Gr33aGAL4>UASdti</i> males following 4 days of pair-wise social interaction. Daytime sleep of socialized <i>Gr66aGAL4>UAShid</i> males (<i>p <</i> 0.0001, Student’s <i>t</i>-test; <i>n</i> = 16 and 14 for socialized and control groups respectively) and socialized <i>Gr33aGAL4>UASdti</i> males (<i>p <</i> 0.0001, Student’s <i>t</i>-test; <i>n</i> = 32 and 19 for socialized and control groups respectively) is significantly increased in comparison to that of solitary controls. Nighttime sleep of <i>Gr33aGAL4>UASdti</i> males is also significantly increased (<i>p <</i> 0.0005, Student’s <i>t</i>-test) in comparison to that of that of solitary controls. (e, left) Sleep profiles and (e, right) change in sleep of <i>Orco</i> males following 4 days of pair-wise social interaction. Sleep analysis revealed that day as well as nighttime sleep of socialized <i>Orco</i> males is comparable (<i>p ></i> 0.05; <i>n</i> = 27 and 20 for socialized and control groups respectively) to solitary controls, whereas daytime sleep of socialized <i>Iso31</i> males is significantly greater as compared to that of solitary controls (<i>p <</i> 0.05; <i>n</i> = 13 and 10 for socialized and control groups respectively), daytime sleep-enhancement in <i>Iso31</i> flies is significantly greater (<i>p <</i> 0.05) than that of <i>Orco</i> flies. (f, left) Sleep profiles and (f, right) change in sleep of <i>Or83bGAL4>UASKir2</i>.<i>1</i> males following 4 days of pair-wise social interaction. (f, right) Day as well as nighttime sleep of socialized <i>Or83bGAL4>UASKir2</i>.<i>1</i> males is comparable (<i>p ></i> 0.05) to that of solitary controls (e, right), whereas socialized parental (<i>Or83bGAL4/+</i>, <i>p <</i> 0.05 and <i>UASKir2</i>.<i>1/+</i>, <i>p <</i> 0.005; <i>n</i> = 13–16 per group per genotype) males show a statistically significant increase in sleep as compared to solitary controls. Daytime sleep-enhancement in parental control flies is significantly greater (<i>p <</i> 0.0001 for both) than that in silenced flies. Horizontal lines with asterisks above a pair of bars indicate statistically significant difference in sleep-enhanced in the experimental versus control genotypes. Other details are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0150596#pone.0150596.g001" target="_blank">Fig 1</a>.</p