Effects of phosphate-solubilizing bacteria application on soil phosphorus availability in coal mining subsidence area in Shanxi

The effect of phosphate-solubilizing bacteria (PSB) application on phosphorus (P) availability in reclaimed soil in coal mining subsidence region was investigated. Seven treatments were carried out including control, chicken manure (CM), PSB, PSB + tricalcium phosphate (TCP), CM?+?TCP, PSB?+?ground phosphate rock (GPR) and CM?+?GPR. The results showed soil Olsen-P concentration and phosphatase level as well as the yield of pakchoi (Brassica chinensis L.) were significantly higher in PSB application treatments compared to the corresponding CM application treatments. Soil phosphatase, invertase and urease contents were increased most significantly in PSB treatment, 1.18-, 1.31- and 2.32-fold higher than those in the control, respectively. Soil Ca₂-P, Ca₈-P, Fe-P and Al-P concentrations exhibited the greatest increases in PSB?+?TCP treatment, while occluded-P showed minor changes in different treatments. Application of PSB fertilizer reduced the transformation of Olsen-P to Ca₁₀-P, thus increasing P availability in reclaimed soil of coal mining subsidence area.     

1 alpha, 25-Dihydroxyvitamin D3 directly induces fusion of alveolar macrophages by a mechanism involving RNA and protein synthesis, but not DNA synthesis

The results of our present study indicate that 1 alpha, 25-dihydroxyvitamin D3[1 alpha, 25(OH)2D3] directly induces fusion of mouse alveolar macrophages without any participation of T-lymphocytes by a mechanism involving RNA and protein synthesis but not DNA synthesis. We have reported that 1 alpha, 25(OH)2D3 induces fusion of alveolar macrophages by a direct mechanism and by a spleen cell-mediated indirect mechanism [(1983) Proc. Natl. Acad. Sci. USA 80, 5583-5587]. Alveolar macrophages pretreated with or without anti-Thy 1.2 antibody and complement fused similarly when they were incubated with 1 alpha, 25(OH)2D3. The vitamin suppressed DNA synthesis, but it significantly enhanced RNA and protein synthesis. The 1 alpha, 25(OH)2D3-induced fusion was blocked by adding actinomycin D or cycloheximide, but not by hydroxyurea.     

Fish and fisheries in hot water: What is happening and how do we adapt?

Rapid climate changes are currently driving substantial reorganizations of marine ecosystems around the world. A key question is how these changes will alter the provision of ecosystem services from the ocean, particularly from fisheries. To answer this question, we need to understand not only the ecological dynamics of marine systems, but also human adaptation and feedbacks between humans and the rest of the natural world. In this review, we outline what we have learned from research primarily in continental shelf ecosystems and fishing communities of North America. Key findings are that marine animals are highly sensitive to warming and are responding quickly to changes in water temperature, and that such changes are often happening faster than similar processes on land. Changes in species distributions and productivity are having substantial impacts on fisheries, including through changing catch compositions and longer distances traveled for fishing trips. Conflicts over access to fisheries have also emerged as species distributions are no longer aligned with regulations or catch allocations. These changes in the coupled natural-human system have reduced the value of ecosystem services from some fisheries and risk doing so even more in the future. Going forward, substantial opportunities for more effective fisheries management and operations, marine conservation, and marine spatial planning are likely possible through greater consideration of climate information over time-scales from years to decades.     

Scoring functions in protein folding and design

We present an analysis of the assumptions behind some of the most commonly used methods for evaluating the goodness of the fit between a sequence and a structure. Our studies on a lattice model show that methods based on statistical considerations are easy to use and can capture some of the features of protein-like sequences and their corresponding native states, but unfortunately are incapable of recognizing, with certainty, the native-like conformation of a sequence among a set of decoys. Meanwhile, an optimization method, entailing the determination of the parameters of an effective free energy of interaction, is much more reliable in recognizing the native state of a sequence. However, the statistical method is shown to perform quite well in tests of protein design.     

Ultrasound-Targeted Microbubble Destruction (UTMD) for Localized Drug Delivery into Tumor Tissue

Background

Ultrasound-targeted microbubble destruction (UTMD) is a type of ultrasound therapy, in which low frequency moderate power ultrasound is combined with microbubbles to trigger cavitation. Cavitation is the process of oscillation of gas bubbles causing biophysical effects such as pushing and pulling or shock waves that permeabilize biological barriers. In vivo, cavitation results in tissue permeabilization and is used to enable local delivery of nanomedicine. While cavitation can occur in biological liquids when high pressure ultrasound is applied, the use of microbubbles as cavitation nuclei in UTMD largely facilitates the induction of cavitation. UTMD is intensively studied for drug delivery into tumor tissue, but also for the activation of anti-tumor immune responses. The first clinical studies of UTMD-mediated chemotherapy delivery confirmed safety and efficacy of this approach.

MD Simulations and first principles to evaluate the role of binary Fe–V alloys layer on the radiation resistance in the alpha-iron

Radiation damage in reactor materials caused by the collision of the fast neutrons has a great impact on the reliability and safety of nuclear reactors. The element vanadium has attracted interest in many fields due to its advantageous properties in alloys. Thus, molecular dynamics simulation (MD) and first-principles calculation have been executed here to explore the radiation-resistant properties of five materials adding a layer in the bulk (pure iron and four types of Fe–V alloys containing 10%-40% V). The following results were inferred from these simulations. Firstly, the number of Frenkel pairs (FPs) at the stable quenching stage in the bulk decreases when the Fe–V alloy is added as an anti-radiation layer to the bulk. These benefits are evident for the Fe₈₀V₂₀ and alloy layers with more vanadium. The main reason is that the Fe–V binding energy is greater than the Fe-Fe binding energy, which can make the Primary Knock-On atom (PKA) lose more energy at the Fe–V alloy layer. Secondly, the average value of point-defect, cluster and defect clustered fractions in the bulk of Fe–V alloy is smaller than that in the pure iron at the stable quenching stage, especially for the Fe₈₀V₂₀ alloy.     

Multiple Modes of Protein–Protein Interactions Promote RNP Granule Assembly

Eukaryotic cells are known to contain a wide variety of RNA–protein assemblies, collectively referred to as RNP granules. RNP granules form from a combination of RNA–RNA, protein–RNA, and protein–protein interactions. In addition, RNP granules are enriched in proteins with intrinsically disordered regions (IDRs), which are frequently appended to a well-folded domain of the same protein. This structural organization of RNP granule components allows for a diverse set of protein–protein interactions including traditional structured interactions between well-folded domains, interactions of short linear motifs in IDRs with the surface of well-folded domains, interactions of short motifs within IDRs that weakly interact with related motifs, and weak interactions involving at most transient ordering of IDRs and folded domains with other components. In addition, both well-folded domains and IDRs in granule components frequently interact with RNA and thereby can contribute to RNP granule assembly. We discuss the contribution of these interactions to liquid–liquid phase separation and the possible role of phase separation in the assembly of RNP granules. We expect that these principles also apply to other non-membrane bound organelles and large assemblies in the cell.     

Protein translocation through a tunnel induces changes in folding kinetics: a lattice model study

Compaction of a nascent polypeptide chain inside the ribosomal exit tunnel, before it leaves the ribosome, has been proposed to accelerate the folding of newly synthesized proteins following their release from the ribosome. Thus, we used Kinetic Monte Carlo simulations of a minimalist on-lattice model to explore the effect that polypeptide translocation through a variety of channels has on protein folding kinetics. Our results demonstrate that tunnel confinement promotes faster folding of a well-designed protein relative to its folding in free space by displacing the unfolded state towards more compact structures that are closer to the transition state. Since the tunnel only forbids rarely visited, extended configurations, it has little effect on a "poorly designed" protein whose unfolded state is largely composed of low-energy, compact, misfolded configurations. The beneficial effect of the tunnel depends on its width; for example, a too-narrow tunnel enforces unfolded states with limited or no access to the transition state, while a too-wide tunnel has no effect on the unfolded state entropy. We speculate that such effects are likely to play an important role in the folding of some proteins or protein domains in the cellular environment and might dictate whether a protein folds co-translationally or post-translationally.     

Computational, spectroscopic, and resonant mirror biosensor analysis of the interaction of adrenodoxin with native and tryptophan-modified NADPH-adrenodoxin reductase

In steroid hydroxylation system in adrenal cortex mitochondria, NADPH-adrenodoxin reductase (AR) and adrenodoxin (Adx) form a short electron-transport chain that transfers electrons from NADPH to cytochromes P-450 through FAD in AR and [2Fe-2S] cluster in Adx. The formation of [AR/Adx] complex is essential for the electron transfer mechanism in which previous studies suggested that AR tryptophan (Trp) residue(s) might be implicated. In this study, we modified AR Trps by N-bromosuccinimide (NBS) and studied AR binding to Adx by a resonant mirror biosensor. Chemical modification of tryptophans caused inhibition of electron transport. The modified protein (AR*) retained the native secondary structure but showed a lower affinity towards Adx with respect to AR. Activity measurements and fluorescence data indicated that one Trp residue of AR may be involved in the electron transferring activity of the protein. Computational analysis of AR and [AR/Adx] complex structures suggested that Trp193 and Trp420 are the residues with the highest probability to undergo NBS-modification. In particular, the modification of Trp420 hampers the correct reorientation of AR* molecule necessary to form the native [AR/Adx] complex that is catalytically essential for electron transfer from FAD in AR to [2Fe-2S] cluster in Adx. The data support an incorrect assembly of [AR*/Adx] complex as the cause of electron transport inhibition.     

Evaluation of the safety and pharmacokinetics of the multi-targeted receptor tyrosine kinase inhibitor sunitinib during embryo–fetal development in rats and rabbits

BACKGROUND : Angiogenesis plays a key role in embryo–fetal development and, based on nonclinical safety data, the majority of vascular endothelial growth factor (VEGF)-targeted antiangiogenic agents used in cancer therapy are not recommended during pregnancy. We investigated the effects of sunitinib (an oral inhibitor of multiple receptor tyrosine kinases [RTKs] including VEGF-receptors) on embryo–fetal development. METHODS : Presumed-pregnant Sprague-Dawley rats and New Zealand White rabbits received repeated daily oral doses of sunitinib (0–30 mg/kg/day), during the major period of organogenesis. Clinical/physical examinations were performed throughout the gestation phase, and blood samples were collected to determine systemic exposure. Necropsy (including uterine examination) was performed on all animals and fetal morphology was examined. RESULTS : The no-observed-adverse-effect level was 1–5 mg/kg/day for maternal toxicity and 3 mg/kg/day for developmental toxicity in rats; 1 and 0.5 mg/kg/day, respectively, in rabbits. Embryo–fetal toxicity included decreases in the number of live fetuses and increases in the numbers of resorptions and post-implantation/complete litter losses; these were observed at doses of ≥5 mg/kg/day in rats and 5 mg/kg/day in rabbits. Malformations included fetal skeletal malformations (generally thoracic/lumbar vertebral alterations) in rats and cleft lip/palate in rabbits. These developmental effects were observed at ∼5.5- (rats) and ∼0.3-times (rabbits) the human systemic exposure at the approved sunitinib dose (50 mg/day). CONCLUSIONS : Similar effects have been reported with the prototype monoclonal antibody bevacizumab. As is typically observed for potent inhibitors of RTKs involved in angiogenesis, sunitinib was associated with embryo–fetal developmental toxicity in rats and rabbits at clinically relevant dose levels. Birth Defects Res (Part B) 33:204–213, 2009. © 2009 Wiley-Liss, Inc.