Predicting the success of an invader: Niche shift versus niche conservatism

Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito Aedes albopictus. The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype–environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat‐shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental‐induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of Ae. albopictus in Europe.     

Influence of various soil factors on the effects of ferulic acid on leaf expansion of cucumber seedlings

Summary Cucumber seedlings were grown in a Portsmouth soil-sand system to study how varying soil clay and organic matter content might modify cucumber seedling response to ferulic acid, a reported allelopathic agent. Leaf area expansion of cucumber seedlings, soil respiration, and soil solution concentrations of ferulic acid were monitored. Leaf area, mean absolute rates of leaf expansion, and shoot dry weight of cucumber seedlings were significantly reduced by ferulic acid concentrations ranging from 10 to 70 μg/g dry soil. Ferulic acid was applied every other day, since it rapidly disappeared from soil solution as a result of retention by soil particles, utilization by microbes and/or uptake by roots. The amount of ferulic acid retained (i.e., adsorbed, polymerized,etc.) by soil particles appeared to be secondary to microbial utilization and/or uptake by roots. Varying clay (5.3 to 9.8 g/cup) and organic matter (2.0 to 0.04g/cup) contents of the soil appeared to have little impact on the disappearance of ferulic acid from soil solution under “ideal” growth conditions for cucumber seedlings unless larger amounts of ferulic acid were added to the soil; in this case 200 μg/g. The addition of ferulic acid to the soil materials substantially increased the activity of the soil microbes. This latter conclusion is based on recovery of ferulic acid from soil solution and soil respiration measurements. Paper No. 10347 of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, N C 27695-7601. The use of trade names in this publication does not imply endorsement by the North Carolina Agricultural Research Service of the product named, nor criticism of similar ones not mentioned.     

On the analysis of futile cycles in metabolism

So-called futile cycles in cellular metabolism consist of paired opposing reactions that, if simultaneously operant, act only to degrade free energy of ATP to heat. Previous considerations of the behavior of such substrate cycles have indicated their possible usefulness in regulating flux along metabolic pathways, but such analyses have treated the cycles in isolation, i.e. without taking into account the effects of enzymatic inputs to and outputs from the cycle. We here develop models of three typical substrate cycles that include enzymatic inputs to and outputs from the cycle and allow the enzymes of the cycles per se to be subject to a variety of allosteric modulations. The non-linear equations which describe these models were solved by an iterative procedure for sets of parameter values of metabolic interest. The results, when analyzed using appropriate definitions of regulatory sensitivity and energetic futility, demonstrate that the effects of the enzymes leading into and out of the cycle may cause profound changes in the operation of the substrate cycle and therefore may not be ignored. We find that the structural differences among the three cycles considered here result in corresponding functional differences. Our results suggest that (1) the fructose-6-P/fructose-1,6-di-P cycle acts effectively to gate bidirectional flux, but doesn't appreciably enhance regulation of unidirectional flux, (2) the glucose/glucose-6-P cycle is well suited to perform a homeostatic function and to adjust the set points for these two metabolites, and (3) the cycle at the pyruvate crossroads functions largely as a complex switch box that directs metabolic flow towards gluconeogenesis or glycolysis not only in response to inputs of or requirements for oxaloacetate, pyruvate, and phosphoenolpyruvate, but also in response to the combined action of allosteric modulators on the individual enzymes of this substrate cycle.     

The use of isotope tracers for identifying populations of migratory birds

 To determine whether stable isotopes can be used for identifying the geographic origins of migratory bird populations, we examined the isotopic composition of hydrogen (deuterium, δD), carbon (δ¹³C), and strontium (δ⁸⁷Sr) in tissues of a migratory passerine, the black-throated blue warbler (Dendroica caerulescens), throughout its breeding range in eastern North America. δD and δ¹³C values in feathers, which are grown in the breeding area, varied systematically along a latitudinal gradient, being highest in samples from the southern end of the species’ breeding range in Georgia and lowest in southern Canada. In addition, δD decreased from east to west across the northern part of the breeding range, from New Brunswick to Michigan. δ⁸⁷Sr ratios were highest in the Appalachian Mountains, and decreased towards the west. These patterns are consistent with geographical variation in the isotopic composition of the natural environment, i.e., with that of precipitation, plants, and soils for δD, δ¹³C, and δ⁸⁷Sr, respectively. Preliminary analyses of the δD and δ¹³C composition of feathers collected from warblers in their Caribbean winter grounds indicate that these individuals were mostly from northern breeding populations. Furthermore, variances in isotope ratios in samples from local areas in winter tended to be larger than those in summer, suggesting that individuals from different breeding localities may mix in winter habitats. These isotope markers, therefore, have the potential for locating the breeding origins of migratory species on their winter areas, for quantifying the degree of mixing of breeding populations on migratory and wintering sites, and for documenting other aspects of the population structure migratory animals – information needed for studies of year-round ecology of these species as well as for their conservation. Combining information from several stable isotopes will help to increase the resolution for determining the geographic origins of individuals in such highly vagile populations. Received: 24 April 1995 / Accepted: 2 June 1996     

Molecular mapping of the C locus for presence of pungency in Capsicum.

Pungency owing to the presence of capsaicinoids is a unique character of pepper (Capsicum spp.). Capsaicinoids are produced in the placenta and it has long been known that a single dominant gene, C, is required for pungent genotypes to produce capsaicinoids. We mapped C to pepper chromosome 2 in a cross between a pungent Capsicum frutescens wild accession and a non-pungent Capsicum annuum bell pepper. This position confirmed results from earlier studies. The RFLP marker TG 205 cosegregated with C and two additional RFLP markers were also located within 1 cM. The recessive allele at the C locus is used in breeding programs around the world focused on very diverse germplasm, hence any of these tightly linked markers may be of value as potential sources of useful markers for marker-assisted selection. To demonstrate this point, we developed a PCR-based CAPS (cleaved amplified polymorphic sequence) marker linked to C using the sequence of the Capsicum fibrillin gene located 0.4 cM from C. The use of molecular markers for high-throughput screening for the c allele in pepper breeding programs is discussed.     

Safety and efficacy of the 10-day melarsoprol schedule for the treatment of second stage rhodesiense sleeping sickness

Objective

Assessment of the safety and efficacy of a 10-day melarsoprol schedule in second stage T.b. rhodesiense patients and the effect of suramin-pretreatment on the incidence of encephalopathic syndrome (ES) during melarsoprol therapy.

Design

Sequential conduct of a proof-of-concept trial (n = 60) and a utilization study (n = 78) using historic controls as comparator.

Setting

Two trial centres in the T.b. rhodesiense endemic regions of Tanzania and Uganda. Participants: Consenting patients with confirmed second stage disease and a minimum age of 6 years were eligible for participation. Unconscious and pregnant patients were excluded.

Main Outcome Measures

The primary outcome measures were safety and efficacy at end of treatment. The secondary outcome measure was efficacy during follow-up after 3, 6 and 12 months.

Results

The incidence of ES in the trial population was 11.2% (CI 5–17%) and 13% (CI 9–17%) in the historic data. The respective case fatality rates were 8.4% (CI 3–13.8%) and 9.3% (CI 6–12.6%). All patients discharged alive were free of parasites at end of treatment. Twelve months after discharge, 96% of patients were clinically cured. The mean hospitalization time was reduced from 29 to 13 days (p<0.0001) per patient.

Conclusions

The 10-day melarsoprol schedule does not expose patients to a higher risk of ES or death than does treatment according to national schedules in current use. The efficacy of the 10-day melarsoprol schedule was highly satisfactory. No benefit could be attributed to the suramin pre-treatment.

Trial Registration

Current Controlled Trials ISRCTN40537886     

Formulating a fluorogenic assay to evaluate S-adenosyl-L-methionine analogues as protein methyltransferase cofactors

Protein methyltransferases (PMTs) catalyze arginine and lysine methylation of diverse histone and nonhistone targets. These posttranslational modifications play essential roles in regulating multiple cellular events in an epigenetic manner. In the recent process of defining PMT targets, S-adenosyl-L-methionine (SAM) analogues have emerged as powerful small molecule probes to label and profile PMT targets. To examine efficiently the reactivity of PMTs and their variants on SAM analogues, we transformed a fluorogenic PMT assay into a ready high throughput screening (HTS) format. The reformulated fluorogenic assay is featured by its uncoupled but more robust character with the first step of accumulation of the commonly-shared reaction byproduct S-adenosyl-L-homocysteine (SAH), followed by SAH-hydrolase-mediated fluorogenic quantification. The HTS readiness and robustness of the assay were demonstrated by its excellent Z' values of 0.83-0.95 for the so-far-examined 8 human PMTs with SAM as a cofactor (PRMT1, PRMT3, CARM1, SUV39H2, SET7/9, SET8, G9a and GLP1). The fluorogenic assay was further implemented to screen the PMTs against five SAM analogues (allyl-SAM, propargyl-SAM, (E)-pent-2-en-4-ynyl-SAM (EnYn-SAM), (E)-hex-2-en-5-ynyl-SAM (Hey-SAM) and 4-propargyloxy-but-2-enyl-SAM (Pob-SAM)). Among the examined 8 × 5 pairs of PMTs and SAM analogues, native SUV39H2, G9a and GLP1 showed promiscuous activity on allyl-SAM. In contrast, the bulky SAM analogues, such as EnYn-SAM, Hey-SAM and Pob-SAM, are inert toward the panel of human PMTs. These findings therefore provide the useful structure-activity guidance to further evolve PMTs and SAM analogues for substrate labeling. The current assay format is ready to screen methyltransferase variants on structurally-diverse SAM analogues.     

Copper ions and hydrogen peroxide form hypochlorite from NaCl thereby mimicking myeloperoxidase

Sea urchins have elaborated multiple defenses to assure monospermic fertilization. In this work, we have concentrated on a study of the mechanism(s) by which hydrogen peroxide (H₂O₂) prevents polyspermy in Arbacia punctulata. We found that it is not H₂O₂ but probably hypochlorous acid/hypochlorite (HOCl/OCl^?) derived from H₂O₂ that is toxic to the supernumerary sperm. The spermicidal activity of H₂O₂ is potentiated by at least one order of magnitude by cupric ions (Cu²⁺). This increased toxicity is not due to the formation of hydroxyl radicals (·OH) because ·OH scavengers did not counteract the activity of Cu²⁺. More-over, substitution of Cu²⁺ by ferrous ions (Fe²⁺), which are known to cause formation of ·OH from H₂O₂, had no effect on fertilization even at 10²?10³ times higher concentrations. In contrast, 3-amino-1,2,4-triazole (AT), an HOCl/OCl^? scavenger, totally reversed the toxic effects of Cu²⁺. Furthermore, we found that HOCl/OCl^? is generated in solutions of H₂O₂ and Cu²⁺ in the presence of 0.5 M NaCl and that its accumulation is abolished by AT. Thus it is possible that the antifertility properties of copper are due to its ability to mediate formation of HOCl/OCl^?. HOCl/OCl^? generated by Cu²⁺ from H₂O₂ and Cl^?, a low concentration of exogenously added HOCl/OCl^?, or increased concentrations of H₂O₂ has similar inhibitory effects on the fertilization process in sea urchins. Therefore, we suggest that polyspermy is prevented by the action of a myeloperoxidase that affects the formation of HOCl/OCl^? from the Cl^? present in sea water through reaction with H₂O₂ generated by the newly fertilized egg.     

Robust and efficient walking with spring-like legs

The development of bipedal walking robots is inspired by human walking. A way of implementing walking could be performed by mimicking human leg dynamics. A fundamental model, representing human leg dynamics during walking and running, is the bipedal spring-mass model which is the basis for this paper. The aim of this study is the identification of leg parameters leading to a compromise between robustness and energy efficiency in walking. It is found that, compared to asymmetric walking, symmetric walking with flatter angles of attack reveals such a compromise. With increasing leg stiffness, energy efficiency increases continuously. However, robustness is the maximum at moderate leg stiffness and decreases slightly with increasing stiffness. Hence, an adjustable leg compliance would be preferred, which is adaptable to the environment. If the ground is even, a high leg stiffness leads to energy efficient walking. However, if external perturbations are expected, e.g. when the robot walks on uneven terrain, the leg should be softer and the angle of attack flatter. In the case of underactuated robots with constant physical springs, the leg stiffness should be larger than k = 14 in order to use the most robust gait. Soft legs, however, lack in both robustness and efficiency.     

Loss of TBL1XR1 Disrupts Glucocorticoid Receptor Recruitment to Chromatin and Results in Glucocorticoid Resistance in a B-Lymphoblastic Leukemia Model

Although great advances have been made in the treatment of pediatric acute lymphoblastic leukemia, up to one of five patients will relapse, and their prognosis thereafter is dismal. We have previously identified recurrent deletions in TBL1XR1, which encodes for an F-box like protein responsible for regulating the nuclear hormone repressor complex stability. Here we model TBL1XR1 deletions in B-precursor ALL cell lines and show that TBL1XR1 knockdown results in reduced glucocorticoid receptor recruitment to glucocorticoid responsive genes and ultimately decreased glucocorticoid signaling caused by increased levels of nuclear hormone repressor 1 and HDAC3. Reduction in glucocorticoid signaling in TBL1XR1-depleted lines resulted in resistance to glucocorticoid agonists, but not to other chemotherapeutic agents. Importantly, we show that treatment with the HDAC inhibitor SAHA restores sensitivity to prednisolone in TBL1XR1-depleted cells. Altogether, our data indicate that loss of TBL1XR1 is a novel driver of glucocorticoid resistance in ALL and that epigenetic therapy may have future application in restoring drug sensitivity at relapse.