Dry sliding wear behaviour of powder metallurgy Al-Mg-Si alloy-MoSi2 composites and the relationship with the microstructure

The effect of the microstructure on the dry sliding wear of six aluminium alloy 6061 matrix composites reinforced with 15vol.% of MoSi2 particles and two monolithic 6061 alloys processed by powder metallurgy with and without ball milling has been studied. Wear testing was undertaken using pin-on-ring configuration against an M2 steel counterface at 0.94m/s and normal load of 42, 91 and 140N. The wear resistance of the aluminium alloys was significantly improved by ball milling and the addition of reinforcing MoSi2 particles due to a more stable and more homogeneous microstructure, which avoids the detachment of the mechanically mixed layer. Wear rate of materials in T6 decreases as solutionized hardness of the materials increases. This behaviour is rationalized by taking into account the precipitation state of the matrix. In addition, wear rate follows a Hall-Petch type relationship, showing that the reduction of matrix grain size plays an important role in the increase in the wear resistance of the composites. The results indicate that the present intermetallic reinforced composites can be considered potential substitutes for ceramic reinforced aluminium alloys in tribological applications. © 2011 Elsevier B.V.Peer Reviewe

The need to account for cell biology in characterizing predatory mixotrophs in aquatic environments

Photosynthesis in eukaryotes first arose through phagocytotic processes wherein an engulfed cyanobacterium was not digested, but instead became a permanent organelle. Other photosynthetic lineages then arose when eukaryotic cells engulfed other already photosynthetic eukaryotic cells. Some of the resulting lineages subsequently lost their ability for phagocytosis, while many others maintained the ability to do both processes. These mixotrophic taxa have more complicated ecological roles, in that they are both primary producers and consumers that can shift more towards producing the organic matter that forms the base of aquatic food chains, or towards respiring and releasing CO2. We still have much to learn about which taxa are predatory mixotrophs as well as about the physiological consequences of this lifestyle, in part, because much of the diversity of unicellular eukaryotes in aquatic ecosystems remains uncultured. Here, we discuss existing methods for studying predatory mixotrophs, their individual biases, and how single-cell approaches can enhance knowledge of these important taxa. The question remains what the gold standard should be for assigning a mixotrophic status to ill-characterized or uncultured taxa—a status that dictates how organisms are incorporated into carbon cycle models and how their ecosystem roles may shift in future lakes and oceans

Antioxidant activity and characterization of whey protein-based beverages: Effect of shelf life and gastrointestinal transit on bioactivity

Whey proteins can exhibit antioxidant activity. The objectives of this study were to formulate model whey based beverages with well-established antioxidants (plant polyphenols, vitamins and astaxanthin) to investigate (1) the antioxidant shelf life over a 24-week period and (2) the antioxidant activity after upper gastrointestinal transit. Pilot scale processing (pasteurization, ultra-high temperature or spray drying) was used to prepare beverages which were representative of current product formats. In vitro gastrointestinal digestion of test samples was performed using the standardised INFOGEST method and antioxidant activity of samples was determined using ABTS, FRAP and ORAC. Results from the antioxidant shelf life study provided evidence that powder products functionality was preserved. Whey beverages (pasteurised or spray dried) increased or maintained antioxidant activity during gastrointestinal transit. Combination of whey with additional antioxidant ingredients increased the bioactivity of formulated products; however, this greater bioactivity was altered after gastrointestinal transit, depending on processing type and antioxidant methodology. Industrial relevance: Whey protein-based antioxidant beverages could benefit the elderly consumer to meet their increased protein requirements and boost their antioxidant status. Consumer's acceptance for whey protein-based beverages often improves with clear formulations. This work generated whey protein-based UHT beverages with greater stability and clarity than pasteurised formulations. A novel combination of plant and marine antioxidants increased antioxidant activity of whey protein-based formulations. Furthermore, to suit export markets this work generated spray dried whey protein formulations that did not alter antioxidant potentialThis work was funded by the Irish Department of Agriculture, Food and the Marine, FIRM 13F354-WheyGSH and 15F604-TOMI). A. R. Corrochano was in receipt of a Teagasc Walsh Fellowship. E. Arranz also received funding from Enterprise Ireland (MF2018-0151) and the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 71365

Approach to the Spanish continental Neogene synthesis and paleoclimatic interpretation

Integrated studies on Neogene geology have been scarce in Spain, but attemps to stratigraphic and sedimentological analysis of continental Tertiary basins have increased considerably lately. The large extent of Neogene basins in Spain, the good quality of the outcrops and the abundance of fossil provide an excellent basis for this kind of studies

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in huntingtin. There are no treatments that are known to slow the neurodegeneration caused by this mutation. Mutant huntingtin causes disease via a toxic gain-of-function mechanism and has the propensity to aggregate and form intraneuronal inclusions. One therapeutic approach for HD is to enhance the degradation of the mutant protein. We have shown that this can be achieved by upregulating autophagy, using the drug rapamycin. In order to find safer ways of inducing autophagy for clinical purposes, we previously screened United States Food and Drug Administration-approved drugs for their autophagy-stimulating potential. This screen suggested that rilmenidine, a well tolerated, safe, centrally acting anti-hypertensive drug, could induce autophagy in cell culture via a pathway that was independent of the mammalian target of rapamycin. Here we have shown that rilmenidine induces autophagy in mice and in primary neuronal culture. Rilmenidine administration attenuated the signs of disease in a HD mouse model and reduced levels of the mutant huntingtin fragment. As rilmenidine has a long safety record and is designed for chronic use, our data suggests that it should be considered for the treatment of HD and related conditions

Characterization of the Temperature-Sensitive Mutations un-7 and png-1 in Neurospora crassa

The model filamentous fungus Neurospora crassa has been studied for over fifty years and many temperature-sensitive mutants have been generated. While most of these have been mapped genetically, many remain anonymous. The mutation in the N. crassa temperature-sensitive lethal mutant un-7 was identified by a complementation based approach as being in the open reading frame designated NCU00651 on linkage group I. Other mutations in this gene have been identified that lead to a temperature-sensitive morphological phenotype called png-1. The mutations underlying un-7 result in a serine to phenylalanine change at position 273 and an isoleucine to valine change at position 390, while the mutation in png-1 was found to result in a serine to leucine change at position 279 although there were other conservative changes in this allele. The overall morphology of the strain carrying the un-7 mutation is compared to strains carrying the png-1 mutation and these mutations are evaluated in the context of other temperature-sensitive mutants in Neurospora

Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations

Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most FUS mutation studies have focused on motor neuron degeneration; little is known about wider systemic or developmental effects. We studied pleiotropic phenotypes in a physiological knock-in mouse model carrying the pathogenic FUSDelta14 mutation in homozygosity. RNA sequencing of multiple organs aimed to identify pathways altered by the mutant protein in the systemic transcriptome, including metabolic tissues, given the link between ALS-frontotemporal dementia and altered metabolism. Few genes were commonly altered across all tissues, and most genes and pathways affected were generally tissue specific. Phenotypic assessment of mice revealed systemic metabolic alterations related to the pathway changes identified. Magnetic resonance imaging brain scans and histological characterisation revealed that homozygous FUSDelta14 brains were smaller than heterozygous and wild-type brains and displayed significant morphological alterations, including a thinner cortex, reduced neuronal number and increased gliosis, which correlated with early cognitive impairment and fatal seizures. These findings show that the disease aetiology of FUS variants can include both neurodevelopmental and systemic alterations

The white collar complex is essential for sexual reproduction but dispensable for conidiation and invasive growth in Fusarium verticillioides

Fvwc1 and Fvwc2, orthologues of the wc-1 and wc-2 genes encoding for proteins of the white collar complex (WCC) in Neurospora crassa were cloned from Fusarium verticillioides and lack-of-function wc mutants were obtained by targeted gene disruption. Photo-conidiation was found to be absent in F. verticillioides, on the contrary, the wild type strain produced less conidia under continuous illumination than in the dark. Inactivation of any of the wc genes led to total female sterility, without affecting male fertility or asexual conidiation. No loss in colonization capability/invasive growth of the wc mutants was observed, when assessed on tomato fruits. Both Fvwc1 and Fvwc2 showed constitutive expression in the wild type cultures incubated in the dark and exposure to light caused only negligible increases in their transcription. Both Fvwc1 and Fvwc2 were down-regulated in a ΔFvmat1-2-1 gene disruption mutant, lacking a functional mating type (mat1-2-1) gene, suggesting that the MAT1-2-1 product has a positive regulatory effect on the white collar genes