Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1).

The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was HPLC fractionated and a cell based assay was used to evaluate the effects of HPLC fractions on parameters of Human Immunodeficiency Virus (HIV-1) infection and cell viability. Candidate HIV-1 inhibitory fractions were then analyzed for the presence of potential HIV-1 inhibitory compounds by mass spectrometry, leading to the identification of three previously characterized compounds, i.e., debromohymenialdisine (DBH), hymenialdisine (HD), and oroidin. Commercially available purified versions of these molecules were re-tested to assess their antiviral potential in greater detail. Specifically, DBH and HD exhibit a 30%-40% inhibition of HIV-1 at 3.1 μM and 13 μM, respectively; however, both exhibited cytotoxicity. Conversely, oroidin displayed a 50% inhibition of viral replication at 50 μM with no associated toxicity. Additional experimentation using a biochemical assay revealed that oroidin inhibited the activity of the HIV-1 Reverse Transcriptase up to 90% at 25 μM. Taken together, the chemical search space was narrowed and previously isolated compounds with an unexplored anti-viral potential were found. Our results support exploration of marine natural products for anti-viral drug discovery

Collective Marketing Arrangements for Geographically Differentiated Agricultural Products: Welfare Impacts and Policy Implications

We examine the incentives of atomistic producers to differentiate and collectively market products. We analyze market and welfare effects of alternative producer organizations, discuss circumstances under which they will evolve, and describe implications for the ongoing debate between the EU and the United States. As fixed costs of development and marketing increase and the anticipated market size falls, it becomes essential to increase the producer organization’s ability to control supply to cover the fixed costs associated with the introduction of differentiated products. Counterintuitively, stronger property right protection for producer organizations may enhance welfare even after a differentiated product has been developed

Identification of a 3-Alkylpyridinium Compound from the Red Sea Sponge Amphimedon chloros with In Vitro Inhibitory Activity against the West Nile Virus NS3 Protease.

Viruses are underrepresented as targets in pharmacological screening efforts, given the difficulties of devising suitable cell-based and biochemical assays. In this study we found that a pre-fractionated organic extract of the Red Sea sponge Amphimedon chloros was able to inhibit the West Nile Virus NS3 protease (WNV NS3). Using liquid chromatography⁻mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy, the identity of the bioactive compound was determined as a 3-alkylpyridinium with m/z = 190.16. Diffusion Ordered Spectroscopy (DOSY) NMR and NMR relaxation rate analysis suggest that the bioactive compound forms oligomers of up to 35 kDa. We observed that at 9.4 μg/mL there was up to 40⁻70% inhibitory activity on WNV NS3 protease in orthogonal biochemical assays for solid phase extracts (SPE) of A. chloros. However, the LC-MS purified fragment was effective at inhibiting the protease up to 95% at an approximate amount of 2 µg/mL with negligible cytotoxicity to HeLa cells based on a High-Content Screening (HCS) cytological profiling strategy. To date, 3-alkylpyridinium type natural products have not been reported to show antiviral activity since the first characterization of halitoxin, or 3-alkylpyridinium, in 1978. This study provides the first account of a 3-alkylpyridinium complex that exhibits a proposed antiviral activity by inhibiting the NS3 protease. We suggest that the here-described compound can be further modified to increase its stability and tested in a cell-based assay to explore its full potential as a potential novel antiviral capable of inhibiting WNV replication

Were Multiple Stressors a \u27Perfect Storm\u27 for Northern Gulf of Mexico Bottlenose Dolphins (Tursiops truncatus) in 2011?

An unusual number of near term and neonatal bottlenose dolphin (Tursiops truncatus) mortalities occurred in the northern Gulf of Mexico (nGOM) in 2011, during the first calving season after two well documented environmental perturbations; sustained cold weather in 2010 and the Deepwater Horizon oil spill (DWHOS). Preceding the stranding event, large volumes of cold freshwater entered the nGOM due to unusually large snowmelt on the adjacent watershed, providing a third potential stressor. We consider the possibility that this extreme cold and freshwater event contributed to the pattern of perinatal dolphin strandings along the nGOM coast. During the 4-month period starting January 2011, 186 bottlenose dolphins, including 46% perinatal calves (nearly double the percentage for the same time period from 2003-2010) washed ashore from Louisiana to western Florida. Comparison of the frequency distribution of strandings to flow rates and water temperature at a monitoring buoy outside Mobile Bay, Alabama (the 4th largest freshwater drainage in the U. S.) and along the nGOM coast showed that dolphin strandings peaked in Julian weeks 5, 8, and 12 (February and March), following water temperature minima by 2-3 weeks. If dolphin condition was already poor due to depleted food resources, bacterial infection, or other factors, it is plausible that the spring freshet contributed to the timing and location of the unique stranding event in early 2011. These data provide strong observational evidence to assess links between the timing of the DWHOS, other local environmental stressors, and mortality of a top local predator. Targeted analyses of tissues from stranded dolphins will be essential to define a cause of death, and our findings highlight the importance of considering environmental data along with biological samples to interpret stranding patterns during and after an unusual mortality event

A Thesis Presented to the President and the Faculty of Marquette University for the Degree of Bachelor of Science in Civil Engineering and Bachelor of Science in Electrical Engineering

In the work covered by this thesis it is desired to examine an undeveloped water power for the purpose of producing electrical energy as a commercial comodity. Experience has taught that it is best to ascertain first where the product will find its market, and to follow up a satisfactory showing at that end by determining the power capacity of the source, the feasibility of harnessing the same, and the cost of accomplishing this. This program would be adopted in any commercial enterprise to insure a reliable conclusion, and will be followed as closely as possible in the work covered by this thesis. Reference was made to the following books; Mead Water Power ; Von Schom Hydro Electric Practice ; Bulletin No. XX of the Wisconsin Geological and Natural Survey, entitled Water Powers of Wisconsin. ; U.S. Weather Reports; Hughes and Saford Hydraulics ; and Gillette\u27s Cost Data

Trial-by-Trial Adjustments of Cognitive Control Following Errors and Response Conflict are Altered in Pediatric Obsessive Compulsive Disorder

Background: Impairments of cognitive control have been theorized to drive the repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from early in the course of illness. However, it remains unclear whether altered trial-by-trial adjustments of cognitive control characterize young patients. To test this hypothesis, we determined whether trial-by-trial adjustments of cognitive control are altered in children with OCD, relative to healthy controls. Methods: Forty-eight patients with pediatric OCD and 48 healthy youth performed the Multi-Source Interference Task. Two types of trial-by-trial adjustments of cognitive control were examined: post-error slowing (i.e., slower responses after errors than after correct trials) and post-conflict adaptation (i.e., faster responses in high-conflict incongruent trials that are preceded by other high-conflict incongruent trials, relative to low-conflict congruent trials). Results: While healthy youth exhibited both post-error slowing and post-conflict adaptation, patients with pediatric OCD failed to exhibit either of these effects. Further analyses revealed that patients with low symptom severity showed a reversal of the post-conflict adaptation effect, whereas patients with high symptom severity did not show any post-conflict adaptation. Conclusion: Two types of trial-by-trial adjustments of cognitive control are altered in pediatric OCD. These abnormalities may serve as early markers of the illness

The Fate of the Merger Remnant in GW170817 and its Imprint on the Jet Structure

The first neutron star binary merger detected in gravitational waves, GW170817 and the subsequent detection of its emission across the electromagnetic spectrum showed that these systems are viable progenitors of short $\gamma$-ray bursts (sGRB). The afterglow signal of GW170817 has been found to be consistent with a structured GRB jet seen off-axis, requiring significant amounts of relativistic material at large angles. This trait can be attributed to the interaction of the relativistic jet with the external wind medium. Here we perform numerical simulations of relativistic jets interacting with realistic wind environments in order to explore how the properties of the wind and central engine affect the structure of successful jets. We find that the angular energy distribution of the jet depends primarily on the ratio between the lifetime of the jet and the time it takes the merger remnant to collapse. We make use of these simulations to constrain the time it took for the merger remnant in GW170817 to collapse into a black hole based on the angular structure of the jet as inferred from afterglow observations. We conclude that the lifetime of the merger remnant in GW170817 was $\approx 1-1.7$s, which, after collapse, triggered the formation of the jet.Comment: 13 figures, 15 pages, accepted in Ap

Perspectives on the Restatement (Fourth) Project

Good morning, everyone, and thank you all for coming. It is great to have this conversation, particularly with so many people who are already helpfully contributing to this project. As Bill said, I just wanted to say a little bit about the treaty prong of the project that was approved for consideration by the ALI a couple of years ago. First of all, I should note we get a lot of questions about whether or not we are addressing executive agreements and congressional executive agreements, in addition to Article II treaties. And the current answer is that we are not. We were originally tasked by the ALI to take up the status of Article II treaties in U.S. domestic law, and that is the current character of the project

Zebrafish Optokinetic Reflex: Minimal Reporting Guidelines and Recommendations

Optokinetic reflex (OKR) assays in zebrafish models are a valuable tool for studying a diverse range of ophthalmological and neurological conditions. Despite its increasing popularity in recent years, there are no clear reporting guidelines for the assay. Following reporting guidelines in research enhances reproducibility, reduces bias, and mitigates underreporting and poor methodologies in published works. To better understand optimal reporting standards for an OKR assay in zebrafish, we performed a systematic literature review exploring the animal, environmental, and technical factors that should be considered. Using search criteria from three online databases, a total of 109 research papers were selected for review. Multiple crucial factors were identified, including larval characteristics, sample size, fixing method, OKR set-up, distance of stimulus, detailed stimulus parameters, eye recording, and eye movement analysis. The outcome of the literature analysis highlighted the insufficient information provided in past research papers and the lack of a systematic way to present the parameters related to each of the experimental factors. To circumvent any future errors and champion robust transparent research, we have created the zebrafish optokinetic (ZOK) reflex minimal reporting guideline