Seasonal and Vertical Distribution, Food Web Dynamics and Contaminant Biomagnification of Cercopagis pengoi in Lake Ontario

During the early growth season of 1999 to 2001, Cercopagis abundance in offshore waters of Lake Ontario remained low (less than 30 individuals/m3). From late July, its abundance increased rapidly until it peaked during August. After first appearing in 1998, maximum offshore abundance in Lake Ontario decreased each year since 1999 (1999:1759/m3; 2000: 679/m3; 2001: 355/m3). Cercopagis appears not to migrate below the thermocline and is restricted to the epilimnion. A comparison of pre- and post-invasion average abundance of Daphnia retrocurva, Bosmina longirostris and Diacyclops thomasi suggests that Cercopagis is having a major effect on zooplankton composition and abundance in Lake Ontario. Abundance of all three species has decreased significantly in the offshore waters since the invasion of Cercopagis. Preliminary results also suggest that insertion of Cercopagis pengoi into the Lake Ontario food web will not elevate levels of hydrophobic organic compounds in salmonids through biomagnification

Esterase mutation is a mechanism of resistance to antimalarial compounds

Pepstatin is a potent peptidyl inhibitor of various malarial aspartic proteases, and also has parasiticidal activity. Activity of pepstatin against cultured Plasmodium falciparum is highly variable depending on the commercial source. Here we identify a minor contaminant (pepstatin butyl ester) as the active anti-parasitic principle. We synthesize a series of derivatives and characterize an analogue (pepstatin hexyl ester) with low nanomolar activity. By selecting resistant parasite mutants, we find that a parasite esterase, PfPARE (P. falciparum Prodrug Activation and Resistance Esterase) is required for activation of esterified pepstatin. Parasites with esterase mutations are resistant to pepstatin esters and to an open source antimalarial compound, MMV011438. Recombinant PfPARE hydrolyses pepstatin esters and de-esterifies MMV011438. We conclude that (1) pepstatin is a potent but poorly bioavailable antimalarial; (2) PfPARE is a functional esterase that is capable of activating prodrugs; (3) Mutations in PfPARE constitute a mechanism of antimalarial resistance

Identification of pathogen genomic variants through an integrated pipeline

Background: Whole-genome sequencing represents a powerful experimental tool for pathogen research. We present methods for the analysis of small eukaryotic genomes, including a streamlined system (called Platypus) for finding single nucleotide and copy number variants as well as recombination events. Results: We have validated our pipeline using four sets of Plasmodium falciparum drug resistant data containing 26 clones from 3D7 and Dd2 background strains, identifying an average of 11 single nucleotide variants per clone. We also identify 8 copy number variants with contributions to resistance, and report for the first time that all analyzed amplification events are in tandem. Conclusions: The Platypus pipeline provides malaria researchers with a powerful tool to analyze short read sequencing data. It provides an accurate way to detect SNVs using known software packages, and a novel methodology for detection of CNVs, though it does not currently support detection of small indels. We have validated that the pipeline detects known SNVs in a variety of samples while filtering out spurious data. We bundle the methods into a freely available package

Valganciclovir for suppression of human herpesvirus-8 replication: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Human herpesvirus-8 (HHV-8) replication is critical in the induction and maintenance of Kaposi sarcoma, primary effusion lymphoma, and some cases of Castleman disease. In vitro and observational studies suggest that ganciclovir inhibits HHV-8 replication, but no randomized clinical trials have been conducted. METHODS: A total of 26 men infected with HHV-8 were randomized to receive 8 weeks of valganciclovir administered orally (900 mg once per day) or 8 weeks of placebo administered orally. After a 2-week washout period, participants in each group received the study drug they had not yet taken (either valganciclovir or placebo), for 8 additional weeks. Oral swab samples were collected daily during the study, and HHV-8 and CMV DNA were quantified by real-time PCR. RESULTS: A total of 16 human immunodeficiency virus (HIV)-positive men and 10 HIV-negative men enrolled in and completed the study. Of the 3,439 swab samples that participants had been expected to provide, 3029 (88%) were available for analysis. HHV-8 was detected on 44% of swabs collected from participants who were receiving placebo, compared with 23% of swabs collected from participants who were receiving valganciclovir (relative risk [RR], 0.54 [95% confidence interval {CI}, 0.33-0.90]; P = .02). Valganciclovir reduced oropharyngeal shedding of cytomegalovirus by 80% (RR, 0.20 [95% CI, 0.08-0.48]; P < .001). Shedding of HHV-8 and shedding of cytomegalovirus were independent. Hematologic, renal, or hepatic toxicities were no more common among participants who received the active drug, compared with those who received placebo, though participants who received valganciclovir reported more days of diarrhea. CONCLUSIONS: Valganciclovir administered orally once per day is well tolerated and significantly reduces the frequency and quantity of HHV-8 replication

Investigating the geometrical preferences of a flexible benzimidazolone-based linker in the synthesis of coordination polymers

A series of new group 2 coordination polymers, MgL ={MgL(H2O)(DMF)0.75}∞, CaL = {CaL(DMF)2}∞, SrL = {SrL(H2O)0.5}∞ and BaL = {BaL(H2O)0.5}∞, were synthesized using a flexible benzimidazolone diacetic acid linker (H2L) in which the two carboxylic acid binding sites are connected to a planar core via {–CH2–} spacers that can freely rotate in solution. In a ‘curiosity-led' diversion from group 2 metals, the first row transition metal salts Mn2+, Cu2+ and Zn2+ were also reacted with L to yield crystals of MnL = {MnL(DMF)(H2O)3.33}∞, Cu3L2 = {Cu3L2(DMF)2(CHO2)2}∞ and ZnL = {ZnL(DMF)}∞. Crystal structures were obtained for all seven materials. All structures form as two-dimensional sheets and contain six-coordinate centres, with the exception of ZnL, which displays tetrahedrally coordinated metal centres, and Cu3L2, which contains square planar coordinated metal centres and Cu paddle-wheels. In each structure, the linker adopts one of two distinct conformations, with the carboxylate groups either cis or trans with respect to the planar core. All materials were also characterized by powder X-ray diffraction and thermogravimetric analysis

Making America A Better Place for All: Sustainable Development Recommendations for the Biden Administration

In 2015, the United Nations Member States, including the United States, unanimously approved 17 Sustainable Development Goals (SDGs) to be achieved by 2030. The SDGs are nonbinding; each nation is to implement them based on its own priorities and circumstances. This Article argues that the SDGs are a critical normative framework the United States should use to improve human quality of life, freedom, and opportunity by integrating economic and social development with environmental protection. It collects the recommendations of 22 experts on steps that the Biden-Harris Administration should take now to advance each of the SDGs. It is part of a book project that will recommend not only federal actions, but also actions by state and local governments, the private sector, and civil society. In the face of multiple challenges and opportunities, this Article is intended to contribute to a robust public discussion about how to accelerate the transition to a sustainable society and make America a better place for all

Making America a Better Place for All: Sustainable Development Recommendations for the Biden Administration

In 2015, the United Nations Member States, including the United States, unanimously approved 17 Sustainable Development Goals (SDGs) to be achieved by 2030. The SDGs are nonbinding; each nation is to implement them based on its own priorities and circumstances. This Article argues that the SDGs are a critical normative framework the United States should use to improve human quality of life, freedom, and opportunity by integrating economic and social development with environmental protection. It collects the recommendations of 22 experts on steps that the Biden-Harris Administration should take now to advance each of the SDGs. It is part of a book project that will recommend not only federal actions, but also actions by state and local governments, the private sector, and civil society. In the face of multiple challenges and opportunities, this Article is intended to contribute to a robust public discussion about how to accelerate the transition to a sustainable society and make America a better place for all

Early human impacts and ecosystem reorganization in southern-central Africa

Modern Homo sapiens engage in substantial ecosystem modification, but it is difficult to detect the origins or early consequences of these behaviors. Archaeological, geochronological, geomorphological, and paleoenvironmental data from northern Malawi document a changing relationship between forager presence, ecosystem organization, and alluvial fan formation in the Late Pleistocene. Dense concentrations of Middle Stone Age artifacts and alluvial fan systems formed after ca. 92 thousand years ago, within a paleoecological context with no analog in the preceding half-million-year record. Archaeological data and principal coordinates analysis indicate that early anthropogenic fire relaxed seasonal constraints on ignitions, influencing vegetation composition and erosion. This operated in tandem with climate-driven changes in precipitation to culminate in an ecological transition to an early, pre-agricultural anthropogenic landscape.info:eu-repo/semantics/publishedVersio