Investigation of the role of hydrophilic chain length in amphiphilic perfluoropolyether/poly(ethylene glycol) networks: towards high-performance antifouling coatings

The facile preparation of amphiphilic network coatings having a hydrophobic dimethacryloxy-functionalized perfluoropolyether (PFPE-DMA; M(w) = 1500 g mol(-1)) crosslinked with hydrophilic monomethacryloxy functionalized poly(ethylene glycol) macromonomers (PEG-MA; M(w) = 300, 475, 1100 g mol(-1)), intended as non-toxic high-performance marine coatings exhibiting antifouling characteristics is demonstrated. The PFPE-DMA was found to be miscible with the PEG-MA. Photo-cured blends of these materials containing 10 wt% of PEG-MA oligomers did not swell significantly in water. PFPE-DMA crosslinked with the highest molecular weight PEG oligomer (ie PEG1100) deterred settlement (attachment) of algal cells and cypris larvae of barnacles compared to a PFPE control coating. Dynamic mechanical analysis of these networks revealed a flexible material. Preferential segregation of the PEG segments at the polymer/air interface resulted in enhanced antifouling performance. The cured amphiphilic PFPE/PEG films showed decreased advancing and receding contact angles with increasing PEG chain length. In particular, the PFPE/PEG1100 network had a much lower advancing contact angle than static contact angle, suggesting that the PEG1100 segments diffuse to the polymer/water interface quickly. The preferential interfacial aggregation of the larger PEG segments enables the coating surface to have a substantially enhanced resistance to settlement of spores of the green seaweed Ulva, cells of the diatom Navicula and cypris larvae of the barnacle Balanus amphitrite as well as low adhesion of sporelings (young plants) of Ulva, adhesion being lower than to a polydimethyl elastomer, Silastic T2.     

Design and synthesis of piperazine-indole p38α MAP kinase inhibitors with improved pharmacokinetic profiles

Derivatives of the 4-fluorobenzyl dimethylpiperazine-indole class of p38α MAP kinase inhibitors are described. Biological evaluation of these compounds focused on maintaining activity while improving pharmacokinetic (PK) properties. Improved properties were observed for structures bearing substitutions on the benzylic methylene.     

Complex determinants in human immunodeficiency virus type 1 envelope gp120 mediate CXCR4-dependent infection of macrophages

Host cell range, or tropism, combined with coreceptor usage defines viral phenotypes as macrophage tropic using CCR5 (M-R5), T-cell-line tropic using CXCR4 (T-X4), or dually lymphocyte and macrophage tropic using CXCR4 alone or in combination with CCR5 (D-X4 or D-R5X4). Although envelope gp120 V3 is necessary and sufficient for M-R5 and T-X4 phenotypes, the clarity of V3 as a dominant phenotypic determinant diminishes in the case of dualtropic viruses. We evaluated D-X4 phenotype, pathogenesis, and emergence of D-X4 viruses in vivo and mapped genetic determinants in gp120 that mediate use of CXCR4 on macrophages ex vivo. Viral quasispecies with D-X4 phenotypes were associated significantly with advanced CD4+-T-cell attrition and commingled with M-R5 or T-X4 viruses in postmortem thymic tissue and peripheral blood. A D-X4 phenotype required complex discontinuous genetic determinants in gp120, including charged and uncharged amino acids in V3, the V5 hypervariable domain, and novel V1/V2 regions distinct from prototypic M-R5 or T-X4 viruses. The D-X4 phenotype was associated with efficient use of CXCR4 and CD4 for fusion and entry but unrelated to levels of virion-associated gp120, indicating that gp120 conformation contributes to cell-specific tropism. The D-X4 phenotype describes a complex and heterogeneous class of envelopes that accumulate multiple amino acid changes along an evolutionary continuum. Unique gp120 determinants required for the use of CXCR4 on macrophages, in contrast to cells of lymphocytic lineage, can provide targets for development of novel strategies to block emergence of X4 quasispecies of human immunodeficiency virus type 1.     

Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling

Conformational sampling of pre- and post-therapy subtype B HIV-1 protease sequences derived from a pediatric subject infected via maternal transmission with HIV-1 were characterized by double electron–electron resonance spectroscopy. The conformational ensemble of the PRE construct resembles native-like inhibitor bound states. In contrast, the POST construct, which contains accumulated drug-pressure selected mutations, has a predominantly semi-open conformational ensemble, with increased populations of open-like states. The single point mutant L63P, which is contained in PRE and POST, has decreased dynamics, particularly in the flap region, and also displays a closed-like conformation of inhibitor-bound states. These findings support our hypothesis that secondary mutations accumulate in HIV-1 protease to shift conformational sampling to stabilize open-like conformations, while maintaining the predominant semi-open conformation for activity.     

Life-cycle assessment and techno-economic analysis of biochar produced from forest residues using portable systems

The International Journal of Life Cycle Assessment - Producing biochar from forest residues can help resolve environmental issues by reducing forest fires and mitigating climate change. However,...     

Effects of climate change on the delivery of soil‐mediated ecosystem services within the primary sector in temperate ecosystems: a review and New Zealand case study

Future human well‐being under climate change depends on the ongoing delivery of food, fibre and wood from the land‐based primary sector. The ability to deliver these provisioning services depends on soil‐based ecosystem services (e.g. carbon, nutrient and water cycling and storage), yet we lack an in‐depth understanding of the likely response of soil‐based ecosystem services to climate change. We review the current knowledge on this topic for temperate ecosystems, focusing on mechanisms that are likely to underpin differences in climate change responses between four primary sector systems: cropping, intensive grazing, extensive grazing and plantation forestry. We then illustrate how our findings can be applied to assess service delivery under climate change in a specific region, using New Zealand as an example system. Differences in the climate change responses of carbon and nutrient‐related services between systems will largely be driven by whether they are reliant on externally added or internally cycled nutrients, the extent to which plant communities could influence responses, and variation in vulnerability to erosion. The ability of soils to regulate water under climate change will mostly be driven by changes in rainfall, but can be influenced by different primary sector systems' vulnerability to soil water repellency and differences in evapotranspiration rates. These changes in regulating services resulted in different potentials for increased biomass production across systems, with intensively managed systems being the most likely to benefit from climate change. Quantitative prediction of net effects of climate change on soil ecosystem services remains a challenge, in part due to knowledge gaps, but also due to the complex interactions between different aspects of climate change. Despite this challenge, it is critical to gain the information required to make such predictions as robust as possible given the fundamental role of soils in supporting human well‐being.     

Multicopper oxidase-3 is a laccase associated with the peritrophic matrix of Anopheles gambiae

The multicopper oxidase (MCO) family of enzymes includes laccases, which oxidize a broad range of substrates including polyphenols and phenylendiamines; ferroxidases, which oxidize ferrous iron; and several other oxidases with specific substrates such as ascorbate, bilirubin or copper. The genome of Anopheles gambiae, a species of mosquito, encodes five putative multicopper oxidases. Of these five, only AgMCO2 has known enzymatic and physiological functions: it is a highly conserved laccase that functions in cuticle pigmentation and tanning by oxidizing dopamine and dopamine derivatives. AgMCO3 is a mosquito-specific gene that is expressed predominantly in adult midguts and Malpighian tubules. To determine its enzymatic function, we purified recombinant AgMCO3 and analyzed its activity. AgMCO3 oxidized hydroquinone (a p-diphenol), the five o-diphenols tested, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), and p-phenylenediamine, but not ferrous iron. The catalytic efficiencies of AgMCO3 were similar to those of cuticular laccases (MCO2 orthologs), except that AgMCO3 oxidized all of the phenolic substrates with similar efficiencies whereas the MCO2 isoforms were less efficient at oxidizing catechol or dopa. These results demonstrate that AgMCO3 can be classified as a laccase and suggest that AgMCO3 has a somewhat broader substrate specificity than MCO2 orthologs. In addition, we observed AgMCO3 immunoreactivity in the peritrophic matrix, which functions as a selective barrier between the blood meal and midgut epithelial cells, protecting the midgut from mechanical damage, pathogens, and toxic molecules. We propose that AgMCO3 may oxidize toxic molecules in the blood meal leading to detoxification or to cross-linking of the molecules to the peritrophic matrix, thus targeting them for excretion.     

The RAVE complex is essential for stable assembly of the yeast V-ATPase

Vacuolar proton-translocating ATPases are composed of a peripheral complex, V(1), attached to an integral membrane complex, V(o). Association of the two complexes is essential for ATP-driven proton transport and is regulated post-translationally in response to glucose concentration. A new complex, RAVE, was recently isolated and implicated in glucose-dependent reassembly of V-ATPase complexes that had disassembled in response to glucose deprivation (Seol, J. H., Shevchenko, A., and Deshaies, R. J. (2001) Nat. Cell Biol. 3, 384-391). Here, we provide evidence supporting a role for RAVE in reassembly of the V-ATPase but also demonstrate an essential role in V-ATPase assembly under other conditions. The RAVE complex associates reversibly with V(1) complexes released from the membrane by glucose deprivation but binds constitutively to cytosolic V(1) sectors in a mutant lacking V(o) sectors. V-ATPase complexes from cells lacking RAVE subunits show serious structural and functional defects even in glucose-grown cells or in combination with a mutation that blocks disassembly of the V-ATPase. RAVE small middle dotV(1) interactions are specifically disrupted in cells lacking V(1) subunits E or G, suggesting a direct involvement for these subunits in interaction of the two complexes. Skp1p, a RAVE subunit involved in many different signal transduction pathways, binds stably to other RAVE subunits under conditions that alter RAVE small middle dotV(1) binding; thus, Skp1p recruitment to the RAVE complex does not appear to provide a signal for V-ATPase assembly.     

The influence of surface wettability on the adhesion strength of settled spores of the green alga enteromorpha and the diatom amphora

In this paper we report on the effect of surface wettabilityon surface selection and adhesion properties of settled (adhered)spores of the biofouling marine alga Enteromorpha and cellsof the diatom Amphora, through the use of patterned self-assembledmonolayers (SAMs). The SAMs were formed from alkanethiols terminatedwith methyl (CH₃) or hydroxyl (OH) groups, or mixtures of thetwo, creating a discontinuous gradient of wettability as measuredby advancing water contact angle. In the case of Enteromorpha,primary adhesion, as measured by the transition from a motilespore to a settled, sessile organism, is strongly promoted bythe hydrophobic surfaces. On the other hand, adhesion strengthof the settled spores, as measured by resistance to detachmentin a turbulent flow cell, is greatest on a hydrophilic surface.In the case of Amphora, there is little influence of surfacewettability on the primary adhesion of this organism, but motilityis inhibited at contact angles