Vectorial transport of toxins from the dinoflagellate Gymnodinium breve through copepods to fish

Toxins from the dinoflagellate Gymnodinium breve were tracedthrough experimental food chains from dinoflagellates, throughcopepod grazers, to juvenile fish. The generality of this foodweb transfer was demonstrated using three different combinationsof copepods and juvenile fish during different seasons. Fishwere not exposed directly to the toxic dinoflagellates but werefed toxin-laden copepods in order to examine sublethal vectorialintoxication. Toxins were shown to move from fish viscera tomuscle tissue within periods of 2–6 h to 25 h. A new toxindetection method was used in this first stepwise demonstrationof multi-trophic-level intoxication of a planktonic food chainby G.breve. Micellar electrokinetic capillary electrophoresiswith laser-induced fluorescence allowed measurements of toxinsat trace levels and nanoliter-sized volumes critical for planktonicfood web transfer studies.     

Hydrogen sulphide demand of long-lived vestimentiferan tube worm aggregations modifies the chemical environment at deep-sea hydrocarbon seeps

Abstract Lamellibrachia luymesi is a long‐lived vestimentiferan polychaete that produces biogenic habitat at hydrocarbon seeps on the upper Louisiana slope of the Gulf of Mexico. Lamellibrachia luymesi relies on endosymbiotic, chemoautotrophic bacteria for nutrition which are supplied with hydrogen sulphide acquired from seep sediments by the tube worms. In this study, an individual‐based model is developed for L. luymesi aggregations. The results show that aggregations can persist for centuries because of extremely low mortality rates. Recruitment patterns reflect intraspecific competition for settlement space, with the recruitment period estimated between 11 and 68 years. Substantial hydrogen sulphide requirements are estimated for large aggregations of L. luymesi, exceeding 30 mmol h^?1. In addition to modifying habitat through physical structure, L. luymesi may be considered to be an ecosystem engineer because of its profound effect on the chemical environment at hydrocarbon seep sites.     

Synergistic interventions to control COVID-19: Mass testing and isolation mitigates reliance on distancing

Stay-at-home orders and shutdowns of non-essential businesses are powerful, but socially costly, tools to control the pandemic spread of SARS-CoV-2. Mass testing strategies, which rely on widely administered frequent and rapid diagnostics to identify and isolate infected individuals, could be a potentially less disruptive management strategy, particularly where vaccine access is limited. In this paper, we assess the extent to which mass testing and isolation strategies can reduce reliance on socially costly non-pharmaceutical interventions, such as distancing and shutdowns. We develop a multi-compartmental model of SARS-CoV-2 transmission incorporating both preventative non-pharmaceutical interventions (NPIs) and testing and isolation to evaluate their combined effect on public health outcomes. Our model is designed to be a policy-guiding tool that captures important realities of the testing system, including constraints on test administration and non-random testing allocation. We show how strategic changes in the characteristics of the testing system, including test administration, test delays, and test sensitivity, can reduce reliance on preventative NPIs without compromising public health outcomes in the future. The lowest NPI levels are possible only when many tests are administered and test delays are short, given limited immunity in the population. Reducing reliance on NPIs is highly dependent on the ability of a testing program to identify and isolate unreported, asymptomatic infections. Changes in NPIs, including the intensity of lockdowns and stay at home orders, should be coordinated with increases in testing to ensure epidemic control; otherwise small additional lifting of these NPIs can lead to dramatic increases in infections, hospitalizations and deaths. Importantly, our results can be used to guide ramp-up of testing capacity in outbreak settings, allow for the flexible design of combined interventions based on social context, and inform future cost-benefit analyses to identify efficient pandemic management strategies.     

Ontogeny of body size variation in African apes

Size variation in African apes (Gorilla gorilla [gorilla], Pan paniscus [pygmy chimpanzee], and Pan troglodytes [“common” chimpanzee]) is substantial, both within and between species. We investigate the possible evolutionary significance of this variation through an analysis of the ontogeny of size variation in this group. In addition, we highlight possible areas of future endocrinological research, and evaluate recently proposed alternative models that attempt to account for ontogenetic variation in apes. The present study shows that intergeneric variation in size is largely a consequence of differences among species in the rate of body weight growth. Interspecific size variation in Pan is a product of both rate and duration differences in growth. The ontogenetic bases of sexual dimorphism vary in this group. Dimorphism is largely a result of sex differences in the duration of body weight growth in gorillas and pygmy chimpanzees, but results from differences in the rate of growth in common chimpanzees. Ontogenetic analyses largely confirm earlier interpretations, but with better data and methods. The great degree of ontogenetic variation within and among these species, especially in the timing and magnitude of “pubertal” growth spurts, implies that studies of endocrine growth control in African apes could be a productive line of future research. We also suggest that ontogenetic variation can be understood with respect to ecological risks. Growth rates seem to be negatively correlated with ecological risk in African apes, suggesting links between ontogenetic patterns and social and ecological variables. High growth rates in gorillas compared to Pan are most consistent with this model. Variation between chimpanzees and pygmy chimpanzees (especially females) also seem to fit predictions of this model. © 1996 Wiley-Liss, Inc.     

Dissection of 6.5 dpc mouse embryos

Analysis of gene expression patterns during early stages of mammalian embryonic development can provide important clues about gene function, cell-cell interaction and signaling mechanisms that guide embryonic patterning. However, dissection of the mouse embryo from the decidua shortly after implantation can be a challenging procedure, and detailed step-by-step documentation of this process is lacking. Here we demonstrate how post-implantation (6.5 dpc) embryos are isolated by first dissecting the uterus of a pregnant mouse (detection of the vaginal plug was designated day 0.5 poist coitum) and subsequently dissecting the embryo from maternal decidua. The dissection of Reichert's membrane is described as well as the removal of the ectoplacental cone.     

Allosteric effects of the antipsychotic drug trifluoperazine on the energetics of calcium binding by calmodulin

Trifluoperazine (TFP; Stelazine?) is an antagonist of calmodulin (CaM), an essential regulator of calcium‐dependent signal transduction. Reports differ regarding whether, or where, TFP binds to apo CaM. Three crystallographic structures (1CTR, 1A29, and 1LIN) show TFP bound to (Ca²⁺)₄‐CaM in ratios of 1, 2, or 4 TFP per CaM. In all of these, CaM domains adopt the “open” conformation seen in CaM‐kinase complexes having increased calcium affinity. Most reports suggest TFP also increases calcium affinity of CaM. To compare TFP binding to apo CaM and (Ca²⁺)₄‐CaM and explore differential effects on the N‐ and C‐domains of CaM, stoichiometric TFP titrations of CaM were monitored by ¹⁵N‐HSQC NMR. Two TFP bound to apo CaM, whereas four bound to (Ca²⁺)₄‐CaM. In both cases, the preferred site was in the C‐domain. During the titrations, biphasic responses for some resonances suggested intersite interactions. TFP‐binding sites in apo CaM appeared distinct from those in (Ca²⁺)₄‐CaM. In equilibrium calcium titrations at defined ratios of TFP:CaM, TFP reduced calcium affinity at most levels tested; this is similar to the effect of many IQ‐motifs on CaM. However, at the highest level tested, TFP raised the calcium affinity of the N‐domain of CaM. A model of conformational switching is proposed to explain how TFP can exert opposing allosteric effects on calcium affinity by binding to different sites in the “closed,” “semi‐open,” and “open” domains of CaM. In physiological processes, apo CaM, as well as (Ca²⁺)₄‐CaM, needs to be considered a potential target of drug action. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

Aerobic TNT Reduction via 2-Hydroxylamino-4,6-Dinitrotoluene by Pseudomonas aeruginosa Strain MX Isolated from Munitions-Contaminated Soil

Bioremediation of munitions-contaminated soil requires effective transformation and detoxification of high concentrations of 2,4,6-trinitrotoluene (TNT). Pseudomonas aeruginosa strain MX, isolated from munitions-contaminated soil, aerobically transformed TNT (100 mg/L) in culture medium within 15 h, causing transient accumulation of hydroxylaminodinitrotoluenes (HADNTs). The predominance of 2-hydroxylamino-4,6-dinitrotoluene (2HADNT), as well as 2-amino-4,6-dinitrotoluene (2ADNT) and 4,4' ,6,6' -tetranitro-2,2' -azoxytoluene (2,2'AZT), indicated preferential reduction of the TNT ortho nitro group. While only 12% of the TNT was transformed to 2ADNT, up to 65% was transformed to tetranitroazoxytoluenes (AZTs), which accumulated as a precipitate. The precipitate was formed by microscopic particles adhering to bacterial cells, which subsequently formed clusters containing lysed cells. Toxicity toward bacteria was primarily attributed to 2ADNT, because pure AZTs preincubated with sterile medium had little effect on the strain. While the culture medium containing TNT exhibited toxicity toward corn (Zea mays L.) and witchgrass (Panicum capillare L.), little phytotoxicity was observed after incubating with P. aeruginosa strain MX for 4 d. Strong binding of HADNTs to soil and low AZT bioavailability may further promote the detoxification of TNT in soil.     

TNT Biotransformation and Detoxification by a Pseudomonas Aeruginosa Strain

Successful microbial-mediated remediation requires transformationpathways that maximize metabolism and minimize the accumulation of toxic products. Pseudomonas aeruginosa strain MX, isolated from munitions-contaminated soil, degraded 100 mg TNT L^-1 in culture medium within 10 h under aerobic conditions. The major TNT products were 2-amino-4,6-dinitrotoluene (2ADNT, primarily in the supernatant) and 2,2'-azoxytoluene (2,2'AZT, primarily in the cell fraction), which accumulated as major products via the intermediate2-hydroxylamino-4,6-dinitrotoluene (2HADNT). The 2HADNT and2,2'AZT were relatively less toxic to the strain than TNT and 2ADNT. Aminodinitrotoluene (ADNT) production increased when yeast extract was added to the medium. While TNT transformation rate was not affected by pH, more HADNTs accumulated at pH 5.0 than at pH 8.0 and AZTs did not accumulate at the lower pH. The appearance of 2,6-diamino-4-nitrotoluene (2,6DANT) and 2,4-diamino-6-nitrotoluene (2,4DANT); dinitrotoluene (DNT) and nitrotoluene (NT); and 3,5-dinitroaniline (3,5DNA) indicated various routes of TNT metabolism and detoxification by P. aeruginosa strain MX.     

The value of decreasing the duration of the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R₀) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R₀ 2.0). With R₀ 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R₀ 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration.