Supplementary data for the article: Selaković, Z.; Soloveva, V.; Gharaibeh, D. N.; Wells, J.; Šegan, S.; Panchal, R. G.; Šolaja, B. A. Anti-Ebola Activity of Diazachrysene Small Molecules. ACS Infectious Diseases 2016, 1 (6), 264–271. https://doi.org/10.1021/acsinfecdis.5b00028

Supporting information for: [https://doi.org/10.1021/acsinfecdis.5b00028]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2035

Supplementary data for the article: Selaković, Z.; Soloveva, V.; Gharaibeh, D. N.; Wells, J.; Šegan, S.; Panchal, R. G.; Šolaja, B. A. Anti-Ebola Activity of Diazachrysene Small Molecules. ACS Infectious Diseases 2016, 1 (6), 264–271. https://doi.org/10.1021/acsinfecdis.5b00028

Supporting information for: [https://doi.org/10.1021/acsinfecdis.5b00028]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2035

Long-term trends in human body size track regional variation in subsistence transitions and growth acceleration linked to dairying

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis.

Excess Post-Exercise Oxygen Consumption (Epoc) Following Multiple Effort Sprint and Moderate Aerobic Exercise

The purpose of this study was to investigate the effects of 30-second all-out sprint interval exercise (SIE) vs. moderate aerobic exercise (MA) on excess post-exercise oxygen consumption (EPOC). Six recreationally-trained males (age=23.3 +/- 1.4 yrs, weight=81.8 +/- 9.9 kg, height=180.8 +/- 6.3 cm) completed a sprint interval exercise session consisting of three repeated 30-second Wingate cycling tests separated by four minutes (duration similar to 11minutes) as well as a moderate aerobic exercise session consisting of 30-minute cycling at 60% heart rate reserve (HRR) in a random counterbalanced design. Baseline oxygen consumption (VO2) was determined by an average VO2 from the final five minutes of a 30-minute supine rest period prior to each trial. Following each protocol, VO2 was measured for 30 minutes or until baseline measures were reached. EPOC was determined by subtracting baseline VO2 from post-exercise VO2 measurements. Energy expenditure (kJ) was determined by multiplying kJ per liter of oxygen by the average VO2 during recovery. EPOC values were significantly higher in SIE (7.5 +/- 1.3 L) than MA (1.8 +/- 0.7 L). SIE produced a higher recovery caloric expenditure (156.9 kJ) compared to MA (41.0 kJ) and remained significantly elevated (p=.024) over resting levels during the entire recovery period (30 minutes) compared to MA (6 minutes, p=.003). The energy required to recover from three repeated maximal effort 30-second Wingate cycling tests was greater than 30 minutes of moderate aerobic exercise. Future studies should examine the chronic effects of maximal effort sprint training protocol on cardiovascular fitness and body composition

AVI-7288 for Marburg Virus in Nonhuman Primates and Humans

BACKGROUND: AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its safety in humans is undetermined. METHODS: We assessed the efficacy of AVI-7288 in a series of studies involving a lethal challenge with MARV in nonhuman primates. The safety of AVI-7288 was evaluated in a randomized, multiple-ascending-dose study in which 40 healthy humans (8 humans per dose group) received 14 once-daily infusions of AVI-7288 (1 mg, 4 mg, 8 mg, 12 mg, or 16 mg per kilogram of body weight) or placebo, in a 3: 1 ratio. We estimated the protective dose in humans by comparing pharmacokinetic variables in infected nonhuman primates, uninfected nonhuman primates, and uninfected humans. RESULTS: Survival in infected nonhuman primates was dose-dependent, with survival rates of 0%, 30%, 59%, 87%, 100%, and 100% among monkeys treated with 0 mg, 3.75 mg, 7.5 mg, 15 mg, 20 mg, and 30 mg of AVI-7288 per kilogram, respectively (P < 0.001 with the use of the log-rank test for the comparison of survival across groups). No safety concern was identified at doses up to 16 mg per kilogram per day in humans. No serious adverse events were reported. Drug exposure (the area under the curve) was dose-dependent in both nonhuman primates and humans; drug clearance was independent of dose but was higher in nonhuman primates than in humans. The protective dose in humans was initially estimated, on the basis of exposure, to be 9.6 mg per kilogram per day (95% confidence interval, 6.6 to 12.5) for 14 days. Monte Carlo simulations supported a dose of 11 mg per kilogram per day to match the geometric mean protective exposure in nonhuman primates. CONCLUSIONS: This study shows that, on the basis of efficacy in nonhuman primates and pharmacokinetic data in humans, AVI-7288 has potential as postexposure prophylaxis for MARV infection in humans

Influence of Gender and Muscle Architecture Asymmetry on Jump and Sprint Performance

Muscle architecture is a determinant for sprinting speed and jumping power, which may be related to anaerobic sports performance. In the present investigation, the relationships between peak (PVJP) and mean (MVJP) vertical jump power, 30m maximal sprinting speed (30M), and muscle architecture were examined in 28 college-aged, recreationally-active men (n = 14; 24.3 +/- 2.2y; 89.1 +/- 9.3kg; 1.80 +/- 0.07 m) and women (n = 14; 21.5 +/- 1.7y; 65.2 +/- 12.4kg; 1.63 +/- 0.08 m). Ultrasound measures of muscle thickness (MT), pennation angle (PNG), cross-sectional area (CSA), and echo intensity (ECHO) were collected from the rectus femoris (RF) and vastus lateralis (VL) of both legs; fascicle length (FL) was estimated from MT and PNG. Men possessed lower ECHO, greater muscle size (MT & CSA), were faster, and were more powerful (PVJP & MVJP) than women. Stepwise regression indicated that muscle size and quality influenced speed and power in men. In women, vastus lateralis asymmetry negatively affected PVJP (MT: r = -0.73; FL: r = -0.60) and MVJP (MT: r = -0.76; FL: r = -0.64), while asymmetrical ECHO (VL) and FL (RF) positively influenced MVJP (r = 0.55) and 30M (r = 0.57), respectively. Thigh muscle architecture appears to influence jumping power and sprinting speed, though the effect may vary by gender in recreationally-active adults. Appropriate assessment of these ultrasound variables in men and women prior to training may provide a more specific exercise prescription

The Changing Face of Winter: Lessons and Questions From the Laurentian Great Lakes

Among its many impacts, climate warming is leading to increasing winter air temperatures, decreasing ice cover extent, and changing winter precipitation patterns over the Laurentian Great Lakes and their watershed. Understanding and predicting the consequences of these changes is impeded by a shortage of winter-period studies on most aspects of Great Lake limnology. In this review, we summarize what is known about the Great Lakes during their 3–6 months of winter and identify key open questions about the physics, chemistry, and biology of the Laurentian Great Lakes and other large, seasonally frozen lakes. Existing studies show that winter conditions have important effects on physical, biogeochemical, and biological processes, not only during winter but in subsequent seasons as well. Ice cover, the extent of which fluctuates dramatically among years and the five lakes, emerges as a key variable that controls many aspects of the functioning of the Great Lakes ecosystem. Studies on the properties and formation of Great Lakes ice, its effect on vertical and horizontal mixing, light conditions, and biota, along with winter measurements of fundamental state and rate parameters in the lakes and their watersheds are needed to close the winter knowledge gap. Overcoming the formidable logistical challenges of winter research on these large and dynamic ecosystems may require investment in new, specialized research infrastructure. Perhaps more importantly, it will demand broader recognition of the value of such work and collaboration between physicists, geochemists, and biologists working on the world\u27s seasonally freezing lakes and seas

Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial

Aims: Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction. Methods and results: We studied the effects of danicamtiv on LV and LA function in non‐clinical studies (ex vivo : skinned muscle fibres and myofibrils; in vivo : dogs with heart failure) and in a randomized, double‐blind, single‐ and multiple‐dose phase 2a trial in patients with stable HFrEF (placebo, n = 10; danicamtiv, n = 30; 50–100 mg twice daily for 7 days). Danicamtiv increased ATPase activity and calcium sensitivity in LV and LA myofibrils/muscle fibres. In dogs with heart failure, danicamtiv improved LV stroke volume (+10.6 mL, P &lt; 0.05) and LA emptying fraction (+10.7%, P &lt; 0.05). In patients with HFrEF (mean age 60 years, 25% women, ischaemic heart disease 48%, mean LV ejection fraction 32%), treatment‐emergent adverse events, mostly mild, were reported in 17 patients (57%) receiving danicamtiv and 4 patients (40%) receiving placebo. Danicamtiv (at plasma concentrations ≥2000 ng/mL) increased stroke volume (up to +7.8 mL, P &lt; 0.01), improved global longitudinal (up to −1.0%, P &lt; 0.05) and circumferential strain (up to −3.3%, P &lt; 0.01), decreased LA minimal volume index (up to −2.4 mL/m2, P &lt; 0.01) and increased LA function index (up to 6.1, P &lt; 0.01), when compared with placebo. Conclusions: Danicamtiv was well tolerated and improved LV systolic function in patients with HFrEF. A marked improvement in LA volume and function was also observed in patients with HFrEF, consistent with pre‐clinical findings of direct activation of LA contractility