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.     

A perovskite oxide optimized for oxygen evolution catalysis from molecular orbital principles

The efficiency of many energy storage technologies, such as rechargeable metal-air batteries and hydrogen production from water splitting, is limited by the slow kinetics of the oxygen evolution reaction (OER). We found that Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-δ) (BSCF) catalyzes the OER with intrinsic activity that is at least an order of magnitude higher than that of the state-of-the-art iridium oxide catalyst in alkaline media. The high activity of BSCF was predicted from a design principle established by systematic examination of more than 10 transition metal oxides, which showed that the intrinsic OER activity exhibits a volcano-shaped dependence on the occupancy of the 3d electron with an e(g) symmetry of surface transition metal cations in an oxide. The peak OER activity was predicted to be at an e(g) occupancy close to unity, with high covalency of transition metal-oxygen bonds.     

Asynchronous bends in Pacific seamount trails: a case for extensional volcanism?

The Gilbert Ridge and Tokelau Seamounts are the only seamount trails in the Pacific Ocean with a sharp 60 degrees bend, similar to the Hawaii-Emperor bend (HEB). These two bends should be coeval with the 47-million-year-old HEB if they were formed by stationary hot spots, and assuming Pacific plate motion only. New 40Ar/39Ar ages indicate that the bends in the Gilbert Ridge and Tokelau seamount trail were formed much earlier than the HEB at 67 and 57 million years ago, respectively. Such asynchronous bends cannot be reconciled with the stationary hot spot paradigm, possibly suggesting hot spot motion or magmatism caused by short-term local lithospheric extension.     

Comparative genomics of trypanosomatid parasitic protozoa

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.     

Outlier identification of soil phosphorus and its implication for spatial structure modeling

Outliers are classified as global outliers and spatial outliers. Up to now, there is little information about the outliers especially the spatial outliers and their influence on the spatial structure modeling of soil properties. A total of 537 soil samples were collected based on a 30 × 30 m grid in a permanent dairy farm in southeast Ireland. Graphic methods of histogram and box plot combined with Moran’s I were applied to detect the outliers of soil phosphorus (P). Sixteen outliers (5 global outliers and 11 spatial outliers) of soil P were found in the study area. Compared to the raw data, the data with global outliers excluded always had the larger global Moran’s I value indicating a stronger spatial autocorrelation. Clear spatial clusters (High–High and Low–Low clusters) were observed based on local Moran’s I. The High–High spatial clusters were located around the main farm yard and near the traffic route due to more intensive management by farmers. The Low–Low spatial clusters were mainly close to the river. For these areas, P fertilizer or slurry should be applied for healthy grass growth. The dataset with outliers excluded had a reliable semi-variogram model with a low nugget/sill ratio (32.4 %), which was closed to its corresponding transformed data (30.5 %). The cross-validation results revealed that the dataset without outliers had the strongest linear regression model (r = 0.768), indicating that the outliers played an important role in the spatial structure modeling.     

The toxicity of selected acaricides against five stored product mites under laboratory assay

In laboratory tests, the toxicity of acaricides targeted against house dust mites was tested on five species of stored product mites (Acarus siro, Aleuroglyphus ovatus, Carpoglyphus lactis, Lepidoglyphus destructor, and Tyroborus lini). The formulations of benzyl-benzoate, benzyl-benzoate/permethrin/pyriproxyfen, and neem were diluted in water and applied to filter paper in an unventilated chamber. The mortality of mites was observed after 24 h of exposure to acaricide-impregnated filter paper. All of the tested acaricides were toxic to all of the mite species. There were significant differences in mortality among the species and the acaricides. Benzyl-benzoate/permethrin/pyriproxyfen was the most effective, followed by benzyl-benzoate and neem. L. destructor (LD₅₀ 0.01–0.11 μg) was the most sensitive mite species, followed by A. siro (LD₅₀ 0.04–0.12 μg), T. lini (LD₅₀ 2–21 μg), A. ovatus (LD₅₀ 3–18 μg), and C. lactis (LD₅₀ 4–64 μg). Based on the highly toxic effects of the tested acaricides against the stored product mites, the acaricides should be considered as a potential tool in the control of stored product mites, although next screening is necessary.     

Texas entry-year agriculture teachers' perceptions, practices, and preparation regarding safety and health in agricultural education

The purpose of this study was to gather benchmark data for the assessment of the knowledge, attitudes, and perceptions regarding agricultural safety issues and curricula held by Texas agricultural teachers with less than two full years of teaching experience (entry-year teachers). Seventy-four of 118 well-distributed teachers responded to this survey. Researchers concluded that more females were entering a traditionally male-dominated field. Overall, teachers addressed safety within units of instruction rather than as separate units. The most useful forms of new teaching resources that this group of teachers would like to see produced were safety videos and study guides, and class demonstration/simulation activities. There was a significant difference in rankings between teachers less than 26 years old and teachers more than 26 years old regarding the usefulness of transparencies as a new teaching resource (F = 5.00, p = 0.0268). Few teachers were currently CPR and first aid certified, even though most had received training and completed a general safety and/or health related course while in college. Teachers generally agreed philosophically with most practices and exhibited personal beliefs consistent with proper safety preparedness and practice in agricultural settings. However, many of these teachers failed to practice what was expected of safe tractor operators, such as wearing safety belts and allowing younger drivers to operate the equipment.     

An animal model for interface tissue formation in cemented hip replacements

OBJECTIVE: To create a model in sheep for investigation of early changes related to the formation of an interface membrane in hip prosthesis. STUDY DESIGN: Experimental study. ANIMALS: Twenty-four female adult Swiss Alpine sheep. METHODS: Sheep were divided into 2 groups of 12 for unilateral cemented total hip arthroplasty. In Group I, the prosthesis was fixed with retrograde cement gun injection to achieve a complete cement mantle, whereas in Group II a primary cement mantle defect was produced. Groups I and II were further divided into 2 sub-groups with study end points of 2 and 8.5 months after surgery. Radiographs were evaluated postoperatively and at euthanasia for migration of the femoral component and bone resorption. Histologic sections were evaluated semiquantitatively for changes in cell types and numbers, and bone reactions; and quantitatively for size of interface membrane and new bone formation. RESULTS: Radiographically, there tended to be an increase in bone resorption and periosteal bone formation throughout the femoral shaft in Group II compared with Group I, but this was only statistically significant at the region of the femoral neck (R5) at both time periods (P<.05). Semiquantitative histologic evaluation revealed significant increases (P<.05) in cellularity, numbers of fibroblasts, giant cells, macrophages, and mononuclear cells, in Group II primarily at 2 months after surgery. This was also true for interface membrane formation and bone remodeling. Quantitative data showed an increased in the size of the interface membrane and area of bone formation at 8.5 months in Group II. CONCLUSIONS: The cement defect model offered controlled and repeatable production of an interface membrane. The results suggest that a primary cement mantle defect could be a possible trigger for implant instability, eliciting a cascade of biomechanical and molecular events in bone tissue leading to aseptic loosening. CLINICAL RELEVANCE: The results show the effect of defects in the cement mantle in promoting interface membrane formation. Long-term and biochemical studies are required to evaluate the relevance of this interface membrane formation.