Antifouling performance of cross-linked hydrogels: refinement of an attachment model

Poly(ethylene glycol) dimethacrylate (PEGDMA), PEGDMA-co-glycidyl methacrylate (PEGDMA-co-GMA), and PEGDMA-co-hydroxyethyl methacrylate (PEGDMA-co-HEMA) hydrogels were polymerized using ammonium persulfate and ascorbic acid as radical initiators. Surface energies of the hydrogels and a standard, poly(dimethylsiloxane) elastomer (PDMSe), were characterized using captive bubble and sessile drop measurements, respectively (γ = 52 mN/m, γ(0) = 19 mN/m). The chemical composition of the hydrogels was characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. All three hydrogel compositions reduced significantly (p = 0.05) initial attachment of zoospores of the green alga Ulva linza (up to 97%), cells of the diatom Navicula incerta (up to 58%) and the bacterium Cobetia marina (up to 62%), compared to a smooth PDMSe standard. A shear stress (45 Pa), generated in a water channel, eliminated up to 95% of the initially attached cells of Navicula from the smooth hydrogel surfaces relative to smooth PDMSe surfaces. Compared to the PDMSe standard, 79% of the cells of C. marina were removed from all smooth hydrogel compositions when exposed to a 50 Pa wall shear stress. Attachment of spores of the green alga Ulva to microtopographies replicated in PEGDMA-co-HEMA was also evaluated. The Sharklet AF microtopography patterned, PEGDMA-co-HEMA surfaces reduced attachment of spores of Ulva by 97% compared to a smooth PDMSe standard. The attachment densities of spores to engineered microtopographies in PDMSe and PEGDMA-co-HEMA were shown to correlate with a modified attachment model through the inclusion of a surface energy term. Attachment densities of spores of Ulva to engineered topographies replicated in a material other than PDMSe are now correlated with the attachment model (R(2) = 0.80).     

Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo

Lipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called 'guanine nucleotide dissociation inhibitors' (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but remains mechanistically elusive. PDEδ is a putative solubilizing factor for several prenylated Ras-subfamily proteins. Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEδ. The structure explains the nucleotide-independent binding of Rheb to PDEδ and the relaxed specificity of PDEδ. We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. We thus describe a new transport system for farnesylated G proteins involving a GDI-like molecule and an unequivocal GDF. Considering the importance of PDEδ for proper Ras and Rheb signaling, this study is instrumental in developing a new target for anticancer therapy.     

High-value products from transgenic maize

Maize (also known as corn) is a domesticated cereal grain that has been grown as food and animal feed for tens of thousands of years. It is currently the most widely grown crop in the world, and is used not only for food/feed but also to produce ethanol, industrial starches and oils. Maize is now at the beginning of a new agricultural revolution, where the grains are used as factories to synthesize high-value molecules. In this article we look at the diversity of high-value products from maize, recent technological advances in the field and the emerging regulatory framework that governs how transgenic maize plants and their products are grown, used and traded.     

Dopamine D1-histamine H3 receptor heteromers provide a selective link to MAPK signaling in GABAergic neurons of the direct striatal pathway

Previously, using artificial cell systems, we identified receptor heteromers between the dopamine D(1) or D(2) receptors and the histamine H(3) receptor. In addition, we demonstrated two biochemical characteristics of the dopamine D(1) receptor-histamine H(3) receptor heteromer. We have now extended this work to show the dopamine D(1) receptor-histamine H(3) receptor heteromer exists in the brain and serves to provide a novel link between the MAPK pathway and the GABAergic neurons in the direct striatal efferent pathway. Using the biochemical characteristics identified previously, we found that the ability of H(3) receptor activation to stimulate p44 and p42 extracellular signal-regulated MAPK (ERK 1/2) phosphorylation was only observed in striatal slices of mice expressing D(1) receptors but not in D(1) receptor-deficient mice. On the other hand, the ability of both D(1) and H(3) receptor antagonists to block MAPK activation induced by either D(1) or H(3) receptor agonists was also found in striatal slices. Taken together, these data indicate the occurrence of D(1)-H(3) receptor complexes in the striatum and, more importantly, that H(3) receptor agonist-induced ERK 1/2 phosphorylation in striatal slices is mediated by D(1)-H(3) receptor heteromers. Moreover, H(3) receptor-mediated phospho-ERK 1/2 labeling co-distributed with D(1) receptor-containing but not with D(2) receptor-containing striatal neurons. These results indicate that D(1)-H(3) receptor heteromers work as processors integrating dopamine- and histamine-related signals involved in controlling the function of striatal neurons of the direct striatal pathway.     

Macaque long-term nonprogressors resist superinfection with multiple CD8+ T cell escape variants of simian immunodeficiency virus

Human immunodeficiency virus (HIV)-positive individuals can be superinfected with different virus strains. Individuals who control an initial HIV infection are therefore still at risk for subsequent infection with divergent viruses, but the barriers to such superinfection remain unclear. Here we tested long-term nonprogressors' (LTNPs') susceptibility to superinfection using Indian rhesus macaques that express the major histocompatibility complex class I (MHC-I) allele Mamu-B 17, which is associated with control of the pathogenic AIDS virus SIVmac239. The Mamu-B 17-restricted CD8(+) T cell repertoire is focused almost entirely on 5 epitopes. We engineered a series of SIVmac239 variants bearing mutations in 3, 4, or all 5 of these epitopes and used them to serially challenge 2 Mamu-B 17-positive LTNPs. None of the escape variants caused breakthrough replication in LTNPs, although they readily infected Mamu-B 17-negative naive macaques. In vitro competing coculture assays and examination of viral evolution in hosts lacking Mamu-B 17 suggested that the mutant viruses had negligible defects in replicative fitness. Both LTNPs maintained robust immune responses, including simian immunodeficiency virus (SIV)-specific CD8(+) and CD4(+) T cells and neutralizing antibodies. Our results suggest that escape mutations in epitopes bound by "protective" MHC-I molecules may not be sufficient to establish superinfection in LTNPs.     

Evidence for the prevention of enthesitis in HLA‐B27/hβ2m transgenic rats treated with a monoclonal antibody against TNF‐α

Transgenic rats with high expression of HLA‐B27 and human β₂‐microglobulin (B27TR) develop a multisystem inflammatory disease resembling human inflammatory bowel disease (IBD) and spondyloarthropaties (SpA). Tumour necrosis factor α (TNF‐α) has a crucial role in sustaining chronic inflammation in the gut and joints. The aim of this work was to evaluate whether TNF‐α blockade could prevent or reduce the inflammation of peripheral joints in B27TR. A first group of 9‐week‐old B27TR received an anti‐TNF‐α monoclonal antibody (mAb) or an isotypic IgG2a,k up to the age of 18 weeks. An untreated group was monitored up to the age of 18 weeks and then randomly assigned to a 9‐week treatment with anti‐TNF‐α mAb or IgG2a,k. Each rat was monitored for clinical IBD and peripheral joint manifestations. After sacrifice the colon and hind paws were examined for macroscopical and microscopical pathological changes. Early TNF‐α blockade prevented, and late treatment improved IBD signs in B27TR. Erythema, oedema, inflammatory infiltrate close to the tendons and enthesis, proliferating chondrocyte‐like cells, signs of new endochondral bone ossification and bone erosion were observed in peripheral joints of four out of six IgG2a,k‐treated B27TR, both at 18 and 27 weeks. Immunopositivity for phosphorylated Smad1/5/8 indicated that the process of joint remodelling was activated in B27TR. Some entheses showed chondroid nodules. Anti‐TNF‐α treatment reduced inflammation and preserved the enthesis organization in most animals. Occasional and transient erythema and oedema were still present in three of six of the late anti‐TNF‐α‐treated animals. Smad1/5/8 signalling was not inhibited by late anti‐TNF‐α treatment. In B27TR, articular involvement follows IBD onset and develops at entheses. Early TNF‐α blockade prevents the onset of IBD and consequently the development of enthesitis in peripheral joints in the B27TR model of human SpA.     

Qualitative detection of the NSAIDs diclofenac and ibuprofen in the hair of Eurasian otters (Lutra lutra) occupying UK waterways with GC�CMS

The pervasiveness of pharmaceuticals such as nonsteroidal anti-inflammatory drugs (NSAIDs) in the aquatic ecosystem through the discharge of wastewater, and their potential to biomagnify within this ecosystem, is now recognised. Residues of diclofenac and ibuprofen are currently being detected in surface waters and aquatic organisms throughout the UK and Europe. However, the levels of these residues in fish and other aquatic organisms, particularly lower trophic level prey species, have not yet been determined. While exposure to diclofenac is known to adversely affect fish, the degree to which other aquatic organisms are exposed and impacted through continuous ingestion of contaminated prey and interaction with the aquatic habitat remains unknown. The extent and effects of exposure to ibuprofen also remain largely unknown. As an exploratory subset of a broader study to investigate the detectability of diclofenac in alternative biological matrices, we analysed hair samples from Eurasian otters (Lutra lutra, n?=?28) for residues of the two NSAIDs using GC?CMS. The otters were collected from six counties in England as part of an ongoing otter health monitoring project at the Wildlife Veterinary Investigation Centre in Chacewater, UK. Diclofenac was qualitatively detected in five hair wash and 15 extract samples, and ibuprofen was determined to be present in at least two of the hair extract samples. Here, we provide preliminary evidence that otters are exposed to both NSAIDs and argue for further studies to identify residue loads in the otters and their prey to fully assess the pervasiveness of these compounds and potential risks of ongoing exposure to them.     

ELOVL6 genetic variation is related to insulin sensitivity: a new candidate gene in energy metabolism

Background

The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1).

Objective

We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain.

Design

We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants'' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex.

Results

Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA_IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA_IR than those who did not have this allele (P = 0.001).

Conclusions

Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study.