Contact-dependent inhibition of growth in Escherichia coli

Bacteria have developed mechanisms to communicate and compete with each other for limited environmental resources. We found that certain Escherichia coli, including uropathogenic strains, contained a bacterial growth-inhibition system that uses direct cell-to-cell contact. Inhibition was conditional, dependent upon the growth state of the inhibitory cell and the pili expression state of the target cell. Both a large cell-surface protein designated Contact-dependent inhibitor A (CdiA) and two-partner secretion family member CdiB were required for growth inhibition. The CdiAB system may function to regulate the growth of specific cells within a differentiated bacterial population.     

Rationing health care: the choice before us

Rapid technological advances and upward pressure on wages of hospital personnel are leading to a steady increase in health care spending that is absorbing an ever-larger fraction of gross national product. Eliminating inefficiencies in the system can provide brief fiscal relief, but rationing of beneficial services, even to the well-insured, offers the only prospect for sustained reduction in the growth of health care spending. The United States, which has negligible direct experience with rationing, can learn about choices it will face from the experience of Great Britain where health care has been rationed explicitly for many years.     

Asymmetric electrophilic fluorination using an anionic chiral phase-transfer catalyst

The discovery of distinct modes of asymmetric catalysis has the potential to rapidly advance chemists' ability to build enantioenriched molecules. As an example, the use of chiral cation salts as phase-transfer catalysts for anionic reagents has enabled a vast set of enantioselective transformations. Here, we present evidence that a largely overlooked analogous mechanism wherein a chiral anionic catalyst brings a cationic species into solution is itself a powerful method. The concept is applied to the enantioselective fluorocyclization of olefins with a cationic fluorinating agent and a chiral phosphate catalyst. The reactions proceed in high yield and stereoselectivity, especially considering the scarcity of alternative approaches. This technology can in principle be applied to the large portion of reaction space that uses positively charged reagents and reaction intermediates.     

The mutational landscape of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.     

Observation of transient structural-transformation dynamics in a Cu2S nanorod

The study of first-order structural transformations has been of great interest to scientists in many disciplines. Expectations from phase-transition theory are that the system fluctuates between two equilibrium structures near the transition point and that the region of transition broadens in small crystals. We report the direct observation of structural fluctuations within a single nanocrystal using transmission electron microscopy. We observed trajectories of structural transformations in individual nanocrystals with atomic resolution, which reveal details of the fluctuation dynamics, including nucleation, phase propagation, and pinning of structural domains by defects. Such observations provide crucial insight for the understanding of microscopic pathways of phase transitions.     

ImmuneDEX: a strategy for the genetic improvement of immune competence in Australian Angus cattle

In animal breeding and genetics, the ability to cope with disease, here defined as immune competence (IC), with minimal detriment to growth and fertility is a desired objective which addresses both animal production and welfare considerations. However, defining and objectively measuring IC phenotypes using testing methods which are practical to apply on-farm has been challenging. Based on previously described protocols, we measured both cell-mediated immune response (Cell-IR) and antibody-mediated immune response (Ab-IR) and combined these measures to determine an animal’s IC. Using a population of 2,853 Australian Angus steers and heifers, we compared 2 alternative methods to combine both metrics into a single phenotype to be used as a tool for the genetic improvement of IC. The first method, named Z_MEAN, is obtained by taking the average of the individual metrics after subjecting each to a Z-score standardization. The second, ImmuneDEX (IDEX), is a weighted average that considers the correlation between Cell-IR and Ab-IR, as well as the difference in ranking of individuals by each metric, and uses these as weights in the averaging. Both simulation and real data were used to understand the behavior of Z_MEAN and IDEX. To further ascertain the relationship between IDEX and other traits of economic importance, we evaluated a range of traits related to growth, feedlot performance, and carcass characteristics. We report estimates of heritability of 0.31 ± 0.06 for Cell-IR, 0.42 ± 0.06 for Ab-IR, 0.42 ± 0.06 for Z_MEAN and 0.370 ± 0.06 for IDEX, as well as a unity genetic correlation (r_g) between Z_MEAN and IDEX. While a moderately positive r_g was estimated between Cell-IR and Ab-IR (r_g = 0.33 ± 0.12), strongly positive estimates were obtained between IDEX and Cell-IR (r_g = 0.80 ± 0.05) and between IDEX and Ab-IR (r_g = 0.85 ± 0.04). We obtained a moderately negative r_g between IC traits and growth including an r_g = −0.38 ± 0.14 between IDEX and weaning weight, and negligible with carcass fat measurements, including an r_g = −0.03 ± 0.12 between IDEX and marbling. Given that breeding with a sole focus on production might inadvertently increase susceptibility to disease and associated antibiotic use, our analyses suggest that ImmuneDEX will provide a basis to breed animals that are both highly productive and with an enhanced ability to resist disease.     

Modeling fate and transport of sulfate and alkalinity in an acidified lake

Acid mine drainage from Contrary Creek flows into an entire arm of Lake Anna. Much of the acid inflow is neutralized by bacterial sulfate reduction in the lake sediments. We developed a simple model to track the seasonal fate and mass transport of sulfate and alkalinity along the acidified arm. The loss of sulfate from the water column was characterized by a first-order decay reaction. A gain in alkalinity due to sulfate removal was also incorporated in the model. In addition, CO₂ acidity and pH in the water column were calculated. The model was calibrated with data collected in 1983 and 1984. Model sensitivity runs were conducted to demonstrate the importance of sulfate reduction in the system.     

The effect of nitrate and organic matter upon mobility of selenium in groundwater and in a water treatment process

Kesterson Reservoir in Merced County, California was formerly used as a storage and evaporation facility for Se-contaminated agricultural drain water. Very little Se entered the shallow aquifer below the ponds with percolating pond water. With few localized exceptions, most of the Se was removed from the water and retained in the first decimeter of soil, which was rich in decaying organic matter. Where it was present in groundwater, Se was nearly always associated with nitrate. Nitrate induces mildly oxidizing conditions (Eh ≈ 350 mV) and inhibits microbial fixation of Se. In the absence of nitrate, relatively reducing conditions prevail in the groundwater (Eh ≈ -50 mV), and Se is quickly removed. Selenate follows oxygen and nitrate in the order that soil microbes utilize electron acceptors. The process of Se removal from water by soil was reproduced in the laboratory, and the effect of nitrate was confirmed. This natural process might be applied to water treatment for Se removal. The deep water ecosystem at Kesterson Reservoir was highly productive. Vegetation growing in water treatment ponds should supply enough organic matter to maintain anaerobic conditions in the sediment. This process, including algae culture, was operated in an outdoor 79 cm column for 100 days. At percolation rates of 15 and 30 m yr^?1 Se removal averaged 94%, with an additional 2% converted to volatile compounds.     

Five native tree species and manioc under slash-and-mulch agroforestry in the eastern Amazon of Brazil: plant growth and soil responses

Throughout the Amazon of Brazil, manioc (Manihot esculenta) is a staple crop produced through slash-and-burn agriculture. Nutrient losses during slash-and-burn can be large and nutrient demand by food crops so great that fields are often abandoned after two years. In recent decades, farmers have reduced the fallow phase from 20 to ~5 years, limiting plant nutrient accumulation to sustain crop yields. Improved fallows through simultaneous planting of trees with food crops may accelerate nutrient re-accumulation. In addition, slash-and-mulch technology may prevent loss of nutrients due to burning and mulch decomposition may serve as a slow-release source of nutrients. This study in Pará, Brazil, in a 7-year-old secondary forest following slashing and mulching of the vegetation, involved two main plot treatments (with and without P and K fertilizers) and two sub-plot treatments (with or without a N₂-fixer Inga edulis). A mixed-culture of trees and manioc was planted in all plots. P and K fertilizer increased tree mortality due to weed competition but growth of surviving trees in four of the five tree species tested also increased as did biomass production of manioc. In the N₂-fixer treatment trends of greater growth and survival of four of five tree species and manioc biomass were also observed. Fertilization increased the biomass of competing vegetation, but there was a fertilizer by N₂-fixer interaction as I. edulis caused a reduction in competing biomass in the fertilized treatment. After one year, fertilization increased decomposition of the mulch such that Ca, Mg, and N contents within the mulch all decreased. In contrast, P and K contents of mulch increased in all treatments. No influence of the N₂-fixer on 0–10 cm soil N contents was observed. Two years after establishment, this agroforestry system succeeded in growing a manioc crop and leaving a well-maintained tree fallow after the crop harvest.