Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Crystallographic structure of the octameric histone core of the nucleosome at a resolution of 3.3 A

The structure of the (H2A-H2B-H3-H4)2 histone octamer has been determined by means of x-ray crystallographic techniques at a resolution of 3.3 angstroms. The octamer is a prolate ellipsoid 110 angstroms long and 65 to 70 angstroms in diameter, and its general shape is that of a rugby ball. The size and shape are radically different from those determined in earlier studies. The most striking feature of the histone octamer is its tripartite organization, that is, a central (H3-H4)2 tetramer flanked by two H2A-H2B dimers. The DNA helix, placed around the octamer in a path suggested by the features on the surface of the protein, appears like a spring holding the H2A-H2B dimers at either end of the (H3-H4)2 tetramer.     

Bacterial rhodopsin: evidence for a new type of phototrophy in the sea

Extremely halophilic archaea contain retinal-binding integral membrane proteins called bacteriorhodopsins that function as light-driven proton pumps. So far, bacteriorhodopsins capable of generating a chemiosmotic membrane potential in response to light have been demonstrated only in halophilic archaea. We describe here a type of rhodopsin derived from bacteria that was discovered through genomic analyses of naturally occuring marine bacterioplankton. The bacterial rhodopsin was encoded in the genome of an uncultivated gamma-proteobacterium and shared highest amino acid sequence similarity with archaeal rhodopsins. The protein was functionally expressed in Escherichia coli and bound retinal to form an active, light-driven proton pump. The new rhodopsin exhibited a photochemical reaction cycle with intermediates and kinetics characteristic of archaeal proton-pumping rhodopsins. Our results demonstrate that archaeal-like rhodopsins are broadly distributed among different taxa, including members of the domain Bacteria. Our data also indicate that a previously unsuspected mode of bacterially mediated light-driven energy generation may commonly occur in oceanic surface waters worldwide.     

Spin-dependent WIMP limits from a bubble chamber

Bubble chambers were the dominant technology used for particle detection in accelerator experiments for several decades, eventually falling into disuse with the advent of other techniques. We report here on a new application for these devices. We operated an ultraclean, room-temperature bubble chamber containing 1.5 kilograms of superheated CF3I, a target maximally sensitive to spin-dependent and -independent weakly interacting massive particle (WIMP) couplings. An extreme intrinsic insensitivity to the backgrounds that commonly limit direct searches for dark matter was measured in this device under operating conditions leading to the detection of low-energy nuclear recoils like those expected from WIMPs. Improved limits on the spin-dependent WIMP-proton scattering cross section were extracted during our experiments, excluding this type of coupling as a possible explanation for a recent claim of particle dark-matter detection.     

How do earthworms influence organic matter quantity and quality in tropical soils?

Earthworms are important regulators of soil structure and soil organic matter (SOM) dynamics; however, quantifying their influence on SOM cycling in tropical ecosystems remains little studied. Simulated rainfall was used to disrupt casts produced by Amynthas khami and their surrounding soil (control) into a range of small sized aggregates (50-250, 250-500, 500-2000 and 2000-5000 μm). To gain insight into how earthworms influence SOM biogeochemical composition in the aggregates, we carried out elemental and stable isotope analysis, and analytical pyrolysis (Py GC/MS). We also characterized their lignin component after oxidation with cupric oxide (CuO).The C content of smaller size fractions (<500 μm) in the control soil was higher than in the larger fractions. Our study therefore suggests that the aggregate hierarchy concept, which is used to understand soil aggregates and SOM dynamics in temperate soils, may not be applicable to the tropical Acrisol studied here. Earthworms modified SOM organization in soil aggregates. Although the isotope analyses were useful for highlighting SOM enrichment in the earthworm casts, aggregate fractions could not be classified according to particle size. Molecular analyses were necessary to indicate that SOM in all size fractions of casts consisted of relatively undecomposed material. Protection of the most labile SOM structures occurred in the smallest aggregate size fraction (50-250 μm). Py GC/MS showed that earthworm casts and control aggregates <2000 μm could be clearly distinguished according to the molecular properties of their SOM. Aggregates larger than 2000 μm, however, were most probably composed of all fractions and were not different. As a consequence, our results indicate that studies to determine the impact of earthworms on SOM turnover in soil are spatially dependant on the scale of observation.     

Implications of global and regional patterns of highly pathogenic avian influenza virus H5N1 clades for risk management

This paper analyses the publicly available data on the distribution and evolution of highly pathogenic avian influenza virus (HPAIV) H5N1 clades, whilst acknowledging the biases resulting from the non-random selection of isolates for gene sequencing. The data indicate molecular heterogeneity in the global distribution of HPAIV H5N1, in particular in different parts of East and Southeast Asia. Analysis of the temporal pattern of haemagglutinin clade data shows a progression from clade 0 (the ‘dominant’ clade between 1996 and 2002) to clade 1 (2003–2005) and then to clade 2.3.4 (2005 onwards). This process continuously produces variants, depending on the frequency of virus multiplication in the host population, which is influenced by geographical variation in poultry density, poultry production systems and also HPAI risk management measures such as vaccination. Increased multilateral collaboration needs to focus on developing enhanced disease surveillance and control targeted at evolutionary ‘hotspots’.     

Effect of drying and rewetting on phosphorus transformations in red brown soils with different soil organic matter content

In this study, the effect of drying and rewetting on native P transformations in two red brown soils with different management history was investigated. Three treatments, T1 (constantly moist), T2 (dried for 4 days and then kept dry), T3 (rewetted after 4 days drying) were used. Drying and rewetting caused a rapid increase in microbial P (Pm) and labile organic P (labile Po) within 1 day and a gradual increase in available inorganic P (Colwell). These increases were only temporarily, as Pm and labile Po decreased with time and were at the same level as in the constantly moist soil by the end of the incubation period of 21 days. The effect of drying and rewetting on P transformations strongly depended on soil organic matter content, being more pronounced in the soil with high organic matter content, compared to the soil with low soil organic matter content.     

Additions of maize root mucilage to soil changed the structure of the bacterial community

The organic compounds released from roots (rhizodeposits) stimulate the growth of the rhizosphere microbial community. They may be responsible for the differences in the structure of the microbial communities commonly observed between the rhizosphere and the bulk soil. Rhizodeposits consists of a broad range of compounds including root mucilage. The aim of this study was to investigate if additions of maize root mucilage, at a rate of 70 μg C g⁻¹ day⁻¹ for 15 days, to an agricultural soil could affect the structure of the bacterial community. Mucilage additions moderately increased microbial C (+23% increase relative to control), which suggests that the turnover rate of microorganisms consuming this substrate was high. Consistent with this, the number of cultivable bacteria was enhanced by +450%. Catabolic (Biolog^® GN2) and 16S-23S intergenic spacer fingerprints exhibited significant differences between control and mucilage treatments. These data indicate that mucilage can affect both the metabolic and genetic structure of the bacterial community as shown by a greater catabolic potential for carbohydrates. We concluded that mucilage is likely to significantly contribute to differences in the structure of the bacterial communities present in the rhizosphere compared to the bulk soil.     

Evaluation of fly ash,apatite and rice straw derived-biochar in varying combinations for in situ remediation of soils contaminated with multiple heavy metals

ABSTRACT

In

-situ sorbent amendment is a relatively low-cost, low-impact approach for remediation of soil contaminated with heavy metals (HMs), and thus is considered a way to be favored in developing countries. In this study, materials of non-hazardous, alkaline agronomic and industrial by-products were used as sorbents to explore their capacity of in situ immobilization of multiple HMs in mining-impacted arable soil. These sorbents included fly ash (FA), biochar (BC) and apatite (AP) and they were implemented with varying ratios of combinations. Results of soil microcosm tests showed that after incubation for 90 days, concentrations of Pb, Zn, and Cd in their exchangeable forms determined by a sequential extraction method significantly decreased in amended soils, as opposed to the unamended control. Of the five sets of amendments, the composite of FA, BC, and AP resulted in the maximum reduction (up to 80%) in the mobility of Pb, Zn, and Cd in soils. The mechanisms underlying the immobilization of HMs in amended soils might involve processes of surface precipitation, ion exchange and complexation, in which the physicochemical properties of sorbent materials played an important role. The immobilization efficacy of sorbent amendments on HMs in soil was further supported by pot experiments in which significant inhibition of HM accumulation in the belowground and aboveground tissues of maize was observed after 50-day cultivation in amended soils as compared with control soil. Together, these results suggest that the application of cost-saving and environmentally friendly materials derived from wastes as sorbents to remediate soils contaminated with multiple HMs is promising for developing countries like Vietnam.