Contrasting impacts of a native and an invasive exotic shrub on flood‐plain succession

Abstract. Question: How do Coriaria arborea, an N‐fixing native shrub, and Buddleja davidii, a non‐N‐fixing exotic shrub, affect N:P stoichiometry in plants and soils during early stages of primary succession on a flood‐plain? Location: Kowhai River Valley, northeast South Island, New Zealand. Methods: We measured soil and foliar nutrient concentrations, light levels, plant community composition and the above‐ground biomass of Coriaria and Buddleja in four successional stages: open, young, vigorous and mature. Results: Coriaria occurred at low density but dominated above‐ground biomass by the vigorous stage. Buddleja occurred at 5.3 ± 1.0 stems/m² in the young stage and reached a maximum biomass of 520–535 g.m^‐2 during the young and vigorous stages. Mineral soil N increased with above‐ground Coriaria biomass (r²= 0.45), but did not vary with Buddleja biomass. In contrast, soil P increased with Buddleja biomass (r²= 0.35), but not with Coriaria biomass. In early successional stages, 70–80% of the species present were exotic, but this declined to about 15% by the mature stage. Exotic plant species richness declined with increasing Coriaria biomass, but no other measures of diversity varied with either Coriaria or Buddleja biomass. Conclusion: These results demonstrate that Buddleja dominates early succession and accumulates P whereas Coriaria dominates later succession and accumulates N. A key ecosystem effect of the invasive exotic Buddleja is alteration of soil N:P stoichiometry.     

The controlled display of biomolecules on nanoparticles: a challenge suited to bioorthogonal chemistry

Interest in developing diverse nanoparticle (NP)-biological composite materials continues to grow almost unabated. This is motivated primarily by the desire to simultaneously exploit the properties of both NP and biological components in new hybrid devices or materials that can be applied in areas ranging from energy harvesting and nanoscale electronics to biomedical diagnostics. The utility and effectiveness of these composites will be predicated on the ability to assemble these structures with control over NP/biomolecule ratio, biomolecular orientation, biomolecular activity, and the separation distance within the NP-bioconjugate architecture. This degree of control will be especially critical in creating theranostic NP-bioconjugates that, as a single vector, are capable of multiple functions in vivo, including targeting, image contrast, biosensing, and drug delivery. In this review, a perspective is given on current and developing chemistries that can provide improved control in the preparation of NP-bioconjugates. The nanoscale properties intrinsic to several prominent NP materials are briefly described to highlight the motivation behind their use. NP materials of interest include quantum dots, carbon nanotubes, viral capsids, liposomes, and NPs composed of gold, lanthanides, silica, polymers, or magnetic materials. This review includes a critical discussion on the design considerations for NP-bioconjugates and the unique challenges associated with chemistry at the biological-nanoscale interface-the liabilities of traditional bioconjugation chemistries being particularly prominent therein. Select bioorthogonal chemistries that can address these challenges are reviewed in detail, and include chemoselective ligations (e.g., hydrazone and Staudinger ligation), cycloaddition reactions in click chemistry (e.g., azide-alkyne cyclyoaddition, tetrazine ligation), metal-affinity coordination (e.g., polyhistidine), enzyme driven modifications (e.g., HaloTag, biotin ligase), and other site-specific chemistries. The benefits and liabilities of particular chemistries are discussed by highlighting relevant NP-bioconjugation examples from the literature. Potential chemistries that have not yet been applied to NPs are also discussed, and an outlook on future developments in this field is given.     

A mechanistic model for the organization of microtubule asters by motor and non-motor proteins in a mammalian mitotic extract

We used computer simulation to understand the functional relationships between motor (dynein, HSET, and Eg5) and non-motor (NuMA) proteins involved in microtubule aster organization. The simulation accurately predicted microtubule organization under all combinations of motor and non-motor proteins, provided that microtubule cross-links at minus-ends were dynamic, and dynein and HSET were restricted to cross-linking microtubules in parallel orientation only. A mechanistic model was derived from these data in which a combination of two aggregate properties, Net Minus-end-directed Force and microtubule Cross-linking Orientation Bias, determine microtubule organization. This model uses motor and non-motor proteins, accounts for motor antagonism, and predicts that alterations in microtubule Cross-linking Orientation Bias should compensate for imbalances in motor force during microtubule aster formation. We tested this prediction in the mammalian mitotic extract and, consistent with the model, found that increasing the contribution of microtubule cross-linking by NuMA compensated for the loss of Eg5 motor activity. Thus, this model proposes a precise mechanism of action of each noncentrosomal protein during microtubule aster organization and suggests that microtubule organization in spindles involves both motile forces from motors and static forces from non-motor cross-linking proteins.     

Rhesus monkey (Macaca mulatta) complex learning skills reassessed

Results from three experiments on basic learning and transfer in rhesus monkeys (Macaca mulatta) are reported in which fully automated testing paradigms, afforded by the Language Research Center's Computerized Test System (LRC-CTS), were employed. Performance levels for discrimination learning set, transfer index, and mediational-learning testing were uniformly higher than was predicted from the literature, in contrast to previous reports of compromised learning under similar conditions (automated apparatus, planimetric stimuli, spatial discontiguity between stimuli and response loci). Analyses reveal relatively advanced learning set performance, transfer-index ratios, and positive transfer of learning even at stringent criterion levels. Moreover, the data suggest that rhesus monkeys tested in these experiments exhibit mediational instead of associative learning strategies, as do great apes and in contrast to previous reports of rhesus learning. We argue that the LRC-CTS enhances learning by nonhuman primate subjects, obviating those factors, reported in the literature from experiments in which manual or other automated systems were employed, that compromise learning.     

Job Preferences of Nurses and Midwives for Taking Up a Rural Job in Peru: A Discrete Choice Experiment

Background

Robust evidence on interventions to improve the shortage of health workers in rural areas is needed. We assessed stated factors that would attract short-term contract nurses and midwives to work in a rural area of Peru.

Methods and Findings

A discrete choice experiment (DCE) was conducted to evaluate the job preferences of nurses and midwives currently working on a short-term contract in the public sector in Ayacucho, Peru. Job attributes, and their levels, were based on literature review, qualitative interviews and focus groups of local health personnel and policy makers. A labelled design with two choices, rural community or Ayacucho city, was used. Job attributes were tailored to these settings. Multiple conditional logistic regressions were used to assess the determinants of job preferences. Then we used the best-fitting estimated model to predict the impact of potential policy incentives on the probability of choosing a rural job or a job in Ayacucho city. We studied 205 nurses and midwives. The odds of choosing an urban post was 14.74 times than that of choosing a rural one. Salary increase, health center-type of facility and scholarship for specialization were preferred attributes for choosing a rural job. Increased number of years before securing a permanent contract acted as a disincentive for both rural and urban jobs. Policy simulations showed that the most effective attraction package to uptake a rural job included a 75% increase in salary plus scholarship for a specialization, which would increase the proportion of health workers taking a rural job from 36.4% up to 60%.

Conclusions

Urban jobs were more strongly preferred than rural ones. However, combined financial and non-financial incentives could almost double rural job uptake by nurses and midwifes. These packages may provide meaningful attraction strategies to rural areas and should be considered by policy makers for implementation.     

Taurocholate is more potent than cholate in suppression of bile salt synthesis in the rat

Synthesis of bile salts is regulated through negative feedback inhibition by bile salts returning to the liver. Individual bile salts have not been distinguished with regard to inhibitory potential. We assessed inhibition of bile salt synthesis by either cholate or its taurine conjugate in bile fistula rats. After allowing synthesis to maximize, baseline synthesis was determined by measuring bile salt output in four consecutive 6-hr periods. Next, sodium cholate (+[(14)C]cholate) or taurocholate (+[(14)C]taurocholate) was infused into the jugular vein for 36 hr and bile was collected in 6-hr aliquots. Hepatic flux of exogenous bile salt was determined by measuring output of radioactivity in bile divided by specific activity of the infusate. Synthesis was determined during the last four 6-hr periods of infusion by subtracting exogenous bile salt secretion from the total bile salt output. Thirteen studies using cholate and 13 using taurocholate were performed. Hepatic flux of infused bile salt varied from 1 to 12 micro mol/100 g per rat per hr. Percent suppression of synthesis varied directly with hepatic flux of exogenous bile salt for both cholate and taurocholate in a linear fashion (r = 0.66, P < 0.01 and r = 0.87, P < 0.0005, respectively). Slope of the taurocholate line was 7.82 (% suppression/ micro mol per 100 g per hr), while slope of the cholate line was 3.66 (P < 0.05), indicating that taurocholate was approximately twice as potent as cholate in suppression of synthesis. At fluxes of 10-12 micro mol/100 g per hr, taurocholate suppressed synthesis 84 +/- 8 (SEM) % while cholate suppressed synthesis only 42 +/- 12% (P < 0.02). The x-intercept of the taurocholate line was 0.65 ( micro mol/100 g per hr), while that of the cholate line was -1.01 (NS) suggesting that the threshold for initial suppression of synthesis did not differ for these two bile salts. We conclude that taurocholate is a more effective inhibitor of hepatic bile salt synthesis than cholate, and that intestinal deconjugation of bile salts may play a role in the regulation of synthesis.-Pries, J. M., A. Gustafson, D. Wiegand, and W. C. Duane. Taurocholate is more potent than cholate in suppression of bile salt synthesis in the rat.     

Synthesis,in vitro structure–activity relationship,and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents

A series of (2RS,4R)-2-arylthiazolidine-4-carboxylic acid amide (ATCAA) was synthesized. Antiproliferative activity against melanoma and prostate cancer cells compared with control cells (fibroblast and RH7777, respectively) was evaluated. Compound 3id showed the best selectivity and growth-inhibition activity against three melanoma cell lines (B16-F1, A375, and WM-164). Compounds 15b and 3ac had good selectivity and potency against four prostate cancer cell lines (DU 145, PC-3, LNCaP, and PPC-1). The structure–activity relationship (SAR) of the side chain, the thiazolidine ring, and phenyl substituents is discussed. Cell cycle analysis showed that the percentage of cancer cells undergoing apoptosis (sub-G1 phase) increased after treatment with 1b and 3ad, which also strongly inhibited melanoma colony formation. In vivo studies on nude mice bearing A375 melanoma tumors showed that compound 1b inhibited tumor growth in a dose-dependent manner. At a dose of 10 mg/kg, 1b significantly inhibited melanoma tumor growth and showed higher efficacy than did dacarbazine at 60 mg/kg.     

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2’-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used.     

Lack of effect of experimental ascorbic acid deficiency on bile acid metabolism, sterol balance, and biliary lipid composition in man

Extensive studies in animal models indicate that subclinical ascorbic acid deficiency impairs the conversion of cholesterol to bile acid, elevates plasma cholesterol levels, and predisposes to development of cholesterol cholelithiasis. The present study was designed to see if this is also true in man. Five normal volunteers were hospitalized in a metabolic ward and placed on a controlled diet containing 3-4 mg of ascorbic acid each day. Ascorbic acid supplementation was given as follows: control period I (days 1-33), 75 mg/day; deficient period (days 34-96), 0 mg/day; and repletion period (days 97-101), 1000 mg/day. In addition, three of the subjects were studied during a second control period (days 102-139) during which they were given 75 mg/day of ascorbic acid. Ascorbate levels at the end of both control periods were 0.87-1.34 mg/dl in plasma and 19.4-29.5 micrograms/10(8) cells in leukocytes. At the end of the deficient period these levels were 0.09-0.15 mg/dl in plasma and 6.2-10.0 micrograms/10(8) cells in leukocytes, levels approaching those seen in scurvy. There was no effect of ascorbic acid deficiency on plasma cholesterol and triglycerides; plasma cholesterol in high, very low, and low density lipoprotein fractions; biliary lipid composition and saturation index of gallbladder bile; synthesis, fractional turnover, or pool size of either cholic or chenodeoxycholic acids; output of fecal acid or neutral sterols; and fecal sterol balance. Total bile acid pool size calculated by the one-sample technique was reduced 11% in the deficient period compared to control period I (P less than 0.005), and increased to 98.7% of the baseline levels in control period II. However, total bile acid pool calculated by the Lindstedt method did not change during deficiency. These data demonstrate that short-term subclinical ascorbic acid deficiency near the scorbutic range has no significant effect on bile acid and cholesterol metabolism in man.     

Bayesian analysis of wildlife age-at-harvest data

SUMMARY: State and federal natural resource management agencies often collect age-structured harvest data. These data represent finite realizations of stochastic demographic and sampling processes and have long been used by biologists to infer population trends. However, different sources of data have been combined in ad hoc ways and these methods usually failed to incorporate sampling error. In this article, we propose a "hidden process" (or state-space) model for estimating abundance, survival, recovery rate, and recruitment from age-at-harvest data that incorporate both demographic and sampling stochasticity. To this end, a likelihood for age-at-harvest data is developed by embedding a population dynamics model within a model for the sampling process. Under this framework, the identification of abundance parameters can be achieved by conducting a joint analysis with an auxiliary data set. We illustrate this approach by conducting a Bayesian analysis of age-at-harvest and mark-recovery data from black bears (Ursus americanus) in Pennsylvania. Using a set of reasonable prior distributions, we demonstrate a substantial increase in precision when posterior summaries of abundance are compared to a bias-corrected Lincoln-Petersen estimator. Because demographic processes link consecutive abundance estimates, we also obtain a more realistic biological picture of annual changes in abundance. Because age-at-harvest data are often readily obtained, we argue that this type of analysis provides a valuable strategy for wildlife population monitoring.