Additional file 1:Figure S1. of Life-history traits of Drosophila melanogaster populations exhibiting early and late eclosion chronotypes

Schematic of eclosion profile of D. melanogaster under laboratory LD12:12 (12 h of light and dark each) cycles at 25 °C. The shaded area represents night and the unshaded area represents day. Zeitgeber Time (ZT) depicts the time of day with ZT00 indicating lights-ON and ZT12 representing lights-OFF. Figure S2: Schematic of laboratory selection protocol employed for the early and the late populations. Zeitgeber Time (ZT) 21-00 represents the early window during which flies for the early populations are collected and ZT09-13 represents the late window during which flies for the late populations are collected. Figure S3: Proportion of individuals pupariated as a function of time from egg collection for the early (panel 1), the early-control (panel 2), the control (panel 3), the late-control (panel 4) and the late (panel 5) populations in (a) LD12:12 and (b) DD. R1-R4 represents the four replicates of the respective populations used for the study. The black and white horizontal bars at the bottom represent night and day respectively. Figure S4: Proportion of individuals eclosed as a function of time from egg collection for the early (panel 1), the early-control (panel 2), the control (panel 3), the late-control (panel 4) and the late (panel 5) populations in (a) LD12:12 and (b) DD. R1-R4 represents the four replicates of the respective populations used for the study. The black and white horizontal bars at the bottom represent night and day respectively. Table S1. Median egg-to-puparium and egg-to-adult duration presented as mean (± SD) in hours for all populations in LD12:12 and DD light regimes. Table S2: Percentage egg-to-puparium survivorship and egg-to-adult survivorship presented as mean (± SD) for all populations in LD12:12 and DD light regimes. Table S3: Average dry-weight at pupariation and at eclosion presented as mean (± SD) in μg for all populations in LD12:12 and DD light regimes. Table S4: Average eggs laid/female on day 11 post-eclosion, dry-weight in μg at pre- and post-fecundity assay stages, and median longevity of all populations in LD12:12. All values are presented as mean (± SD). (PDF 14678 kb

A New Nucleoside Analogue with Potent Activity against Mutant sr39 Herpes Simplex Virus-1 (HSV-1) Thymidine Kinase (TK)

Nucleoside analogues, such as penciclovir, ganciclovir, acyclovir, and their fluoro-substituted derivatives, have wide utility as antivirals. Among these analogues, FHBG (¹⁸F-Fluorohydroxybutylguanine) is a well-validated PET (positron emission tomography) probe for monitoring reporter gene expression. To evaluate whether or not imposing rigidity into the flexible side chain of FHBG 4 could also impact its interaction, with amino acid residues within the binding site of HSV1-TK (Herpes Simplex Virus-1 Thymidine Kinase), thus influencing its cytotoxic activity. Herein, the synthesis of a new fluorinated nucleoside analogue <b>6</b> (conceived via ligand-docking studies) is reported. Agent <b>6</b> demonstrates selective activity against HeLa cells stably transfected with mutant HSV1-sr39TK and is also 47-fold more potent than FHBG

Pharmacokinetic data of 5a in WT and <i>mdr1a/1b^(−/−)</i> mice (n = 3).

<p>In WT mice, <b>5a</b> clears from the liver and does not penetrate significantly into the brain, but shows high and stable retention in heart tissue (a Pgp negative organ) in both WT and <i>mdr1a/1b^(−/−)</i> mice. Values represent the mean of 3 determinations; bar denotes ±SEM.</p

Additional file 1: Table S1 of The Montreal cognitive assessment is superior to national institute of neurological disease and stroke-Canadian stroke network 5-minute protocol in predicting vascular cognitive impairment at 1Â year

Cognitive domains and individual tests on the formal neuropsychological battery. (DOCX 16 kb

Representative MicroPET/CT Images.

<p>Sprague-Dawley rats (n = 3) were injected intravenously with HPLC-purified ⁶⁸Ga-labeled <b>5b</b> (600 µCi) and images were acquired 60 min post injection. <b>Top Panel</b>, microPET images co-registered with CT; <b>Lower Panel</b>, microPET images alone. Note retention of <b>5b</b> in the heart (white arrow) and rapid clearance of the tracer from the liver (white arrow head) into the intestines, properties ideal for a myocardial perfusion imaging agent.</p

Heart to Tissue Ratio of ⁶⁷Ga-Complex <b>5a</b> in WT mice (n = 3).

<p>Heart to Tissue Ratio of ⁶⁷Ga-Complex <b>5a</b> in WT mice (n = 3).</p

Characterization of ⁶⁷Ga-labeled 5a <i>in cellulo</i>.

<p><b>A.</b> Cellular accumulation of <b>5a</b> in human MCF-7 cells (Pgp-) and stably transfected MCF-7/<i>MDR1</i> (Pgp+) cells. <i>Inset</i>: Immunodetectable levels of Pgp in plasma membrane preparations using mAb C219; MCF-7 cells (lane 1) and MCF-7/<i>MDR1</i> cells (lane 2). Arrows demarcate Pgp (170 kDa) and γ-tubulin (γ-t) loading control. <b>B.</b> Cellular accumulation of <b>5a</b> in KB-3–1 cells (Pgp-) and KB-8–5 (Pgp+). Shown are net uptakes at 90 min (fmol (mg protein)⁻¹ (nM₀)⁻¹) using control buffer in the absence (open column) or presence (solid column) of the MDR modulator LY335979 (1 µM). Each column represents the mean of 4 determinations; bar denotes ±SEM.</p

Biodistribution Data (%ID/g) for ⁶⁷Ga-Complex <b>5a</b> in <i>mdr1a/1b</i>^(−/−) mice (n = 3).

<p>Biodistribution Data (%ID/g) for ⁶⁷Ga-Complex <b>5a</b> in <i>mdr1a/1b</i>^(−/−) mice (n = 3).</p

Representative metabolite analysis of ⁶⁷Ga-labeled 5a at 60 min post injection into a Sprague-Dawley rat (a time point compatible with ⁶⁸Ga imaging).

<p>Peaks are offset for clarity. Note the presence of a parental compound in all tissues.</p

Projection view of the cationic gallium(III) complex Ga-[3-isopropoxy-ENBDMPI]⁺ (4), with the iodide (I⁻) counteranion, showing the crystallographic numbering scheme.

<p>Projection view of the cationic gallium(III) complex Ga-[3-isopropoxy-ENBDMPI]⁺ (4), with the iodide (I⁻) counteranion, showing the crystallographic numbering scheme.</p