Synchrotron x-ray measurement and finite element analysis of residual strain in TIG welded aluminium alloy 2024

Residual strains have been measured in a tungsten inert gas (TIG) butt-welded 2024 aluminum alloy plate using synchrotron X-ray diffraction. Novel two-dimensional strain maps spanning the entire plate reveal steep gradients in residual stress and provide detailed validation data for finite element (FE) analysis. Two variants of a FE model have been used to predict the residual strain distributions, incorporating different levels of plate constraint. The model uses decoupled thermal and elastic- plastic mechanical analyses and successfully predicts the longitudinal and transverse residual strain field over the entire weld. For butt weld geometries, the degree of transverse constraint is shown to be a significant boundary condition, compared to simpler bead-on-plate analyses. The importance of transverse residual strains for detailed model validation is highlighted, together with the need for care in selecting the location for line scans. The residual stress is largest in the heat-affected zone (HAZ), being equal to the local postweld yield stress, though the strength increases subsequently by natural aging. In addition, a halving of the diffraction line width has been observed local to the weld, and this correlates with the microstructural changes in the region

Lexico-semantic Impairment in a Case of HSVE to the Left Anterior Temporal Lobe

This study investigates the role of the left anterior temporal lobe (aTL) in semantics. Clinical and neuroscientific investigations propose the aTL bilaterally (BaTL), are implicated in semantics, based on findings that: (1) disruption to BaTL results in a multimodal semantic impairment, observed in semantic dementia (SD) and herpes-simplex-viral-encephalitis (HSVE); (2) impairment can be mimicked by inducing a “virtual lesion” (repetitive-transcranial-magnetic-stimulation) to BaTL in neurologically intact participants; (3) neuroimaging studies identify BaTL activation for semantic tasks (Fig 1, Lambon Ralph et al., 2012, for points 1-3). Anchored in this evidence is the assumption that semantic impairment will result from BaTL damage only. Recently, investigators have suggested a loss of semantic knowledge can result from LaTL damage. Using sensitive tests, this can be observed in chronic stroke (Schwartz et al., 2009) and temporal lobe resection for epilepsy patients (rTLE: Antonucci et al., 2008; Lambon Ralph et al., 2012). Of interest is the striking similarity of rTLE and very early stages of SD (when atrophy is left sided and overlaps with resection) – impairment is mild and the primary symptom is anomia and/or forgetfulness. This builds upon the possibility that a semantic weakness may result from a LaTL lesion. Whilst rTLE studies have provided insight into this notion, one must be cautious – pre-surgical seizures may initiate changes in brain organisation/normal development, and reorganisation of function could occur post-surgery. Chronic stroke studies are problematic since lesions are large and encompass other areas that may contribute to the impairment. Consequently, whether LaTL lesions results in semantic impairment is not entirely understood. The goal of the present case study was to initiate an investigation to determine whether semantic impairment is in fact present following LaTL lesion

Innate Intracellular Antiviral Responses Restrict the Amplification of Defective Virus Genomes of Parainfluenza Virus 5.

During the replication of parainfluenza virus 5 (PIV5), copyback defective virus genomes (DVGs) are erroneously produced and are packaged into "infectious" virus particles. Copyback DVGs are the primary inducers of innate intracellular responses, including the interferon (IFN) response. While DVGs can interfere with the replication of nondefective (ND) virus genomes and activate the IFN-induction cascade before ND PIV5 can block the production of IFN, we demonstrate that the converse is also true, i.e., high levels of ND virus can block the ability of DVGs to activate the IFN-induction cascade. By following the replication and amplification of DVGs in A549 cells that are deficient in a variety of innate intracellular antiviral responses, we show that DVGs induce an uncharacterized IFN-independent innate response(s) that limits their replication. High-throughput sequencing was used to characterize the molecular structure of copyback DVGs. While there appears to be no sequence-specific break or rejoining points for the generation of copyback DVGs, our findings suggest there are region, size, and/or structural preferences selected for during for their amplification.IMPORTANCE Copyback defective virus genomes (DVGs) are powerful inducers of innate immune responses both in vitro and in vivo They impact the outcome of natural infections, may help drive virus-host coevolution, and promote virus persistence. Due to their potent interfering and immunostimulatory properties, DVGs may also be used therapeutically as antivirals and vaccine adjuvants. However, little is known of the host cell restrictions which limit their amplification. We show here that the generation of copyback DVGs readily occurs during parainfluenza virus 5 (PIV5) replication, but that their subsequent amplification is restricted by the induction of innate intracellular responses. Molecular characterization of PIV5 copyback DVGs suggests that while there are no genome sequence-specific breaks or rejoin points for the generation of copyback DVGs, genome region, size, and structural preferences are selected for during their evolution and amplification

Skeletal muscle cells possess a 'memory' of acute early life TNF-α exposure: role of epigenetic adaptation.

Sufficient quantity and quality of skeletal muscle is required to maintain lifespan and healthspan into older age. The concept of skeletal muscle programming/memory has been suggested to contribute to accelerated muscle decline in the elderly in association with early life stress such as fetal malnutrition. Further, muscle cells in vitro appear to remember the in vivo environments from which they are derived (e.g. cancer, obesity, type II diabetes, physical inactivity and nutrient restriction). Tumour-necrosis factor alpha (TNF-α) is a pleiotropic cytokine that is chronically elevated in sarcopenia and cancer cachexia. Higher TNF-α levels are strongly correlated with muscle loss, reduced strength and therefore morbidity and earlier mortality. We have extensively shown that TNF-α impairs regenerative capacity in mouse and human muscle derived stem cells [Meadows et al. (J Cell Physiol 183(3):330-337, 2000); Foulstone et al. (J Cell Physiol 189(2):207-215, 2001); Foulstone et al. (Exp Cell Res 294(1):223-235, 2004); Stewart et al. (J Cell Physiol 198(2):237-247, 2004); Al-Shanti et al. (Growth factors (Chur, Switzerland) 26(2):61-73, 2008); Saini et al. (Growth factors (Chur, Switzerland) 26(5):239-253, 2008); Sharples et al. (J Cell Physiol 225(1):240-250, 2010)]. We have also recently established an epigenetically mediated mechanism (SIRT1-histone deacetylase) regulating survival of myoblasts in the presence of TNF-α [Saini et al. (Exp Physiol 97(3):400-418, 2012)]. We therefore wished to extend this work in relation to muscle memory of catabolic stimuli and the potential underlying epigenetic modulation of muscle loss. To enable this aim; C2C12 myoblasts were cultured in the absence or presence of early TNF-α (early proliferative lifespan) followed by 30 population doublings in the absence of TNF-α, prior to the induction of differentiation in low serum media (LSM) in the absence or presence of late TNF-α (late proliferative lifespan). The cells that received an early plus late lifespan dose of TNF-α exhibited reduced morphological (myotube number) and biochemical (creatine kinase activity) differentiation vs. control cells that underwent the same number of proliferative divisions but only a later life encounter with TNF-α. This suggested that muscle cells had a morphological memory of the acute early lifespan TNF-α encounter. Importantly, methylation of myoD CpG islands were increased in the early TNF-α cells, 30 population doublings later, suggesting that even after an acute encounter with TNF-α, the cells have the capability of retaining elevated methylation for at least 30 cellular divisions. Despite these fascinating findings, there were no further increases in myoD methylation or changes in its gene expression when these cells were exposed to a later TNF-α dose suggesting that this was not directly responsible for the decline in differentiation observed. In conclusion, data suggest that elevated myoD methylation is retained throughout muscle cells proliferative lifespan as result of early life TNF-α treatment and has implications for the epigenetic control of muscle loss

Dynamic variability of the phytoplankton electron requirement for carbon fixation in eastern Australian waters

© 2019 Elsevier B.V. Fast Repetition Rate fluorometry (FRRf) generates high-resolution measures of phytoplankton primary productivity as electron transport rates (ETRs). How ETRs scale to corresponding inorganic carbon (C) uptake rates (the so-called electron requirement for carbon fixation, Φe,C), inherently describes the extent and effectiveness with which absorbed light energy drives C-fixation. However, it remains unclear whether and how Φe,C follows predictable patterns for oceanographic datasets spanning physically dynamic, and complex, environmental gradients. We utilise a unique high-throughput approach, coupling ETRs and 14C-incubations to produce a semi-continuous dataset of Φe,C (n = 80), predominantly from surface waters, along the Australian coast (Brisbane to the Tasman Sea), including the East Australian Current (EAC). Environmental conditions along this transect could be generally grouped into cooler, more nutrient-rich waters dominated by larger size-fractionated Chl-a (>10 μm) versus warmer nutrient-poorer waters dominated by smaller size-fractionated Chl-a (<2 μm). Whilst Φe,C was higher for warmer water samples, environmental conditions alone explained <20% variance of Φe,C, and changes in predominant size-fraction(s) distributions of Chl-a (biomass) failed to explain variance of Φe,C. Instead, normalised Stern-Volmer non-photochemical quenching (NPQNSV = F0′/Fv′) was a better predictor of Φe,C, explaining ~55% of observed variability. NPQNSV is a physiological descriptor that accounts for changes in both long-term driven acclimation in non-radiative decay, and quasi-instantaneous PSII downregulation, and thus may prove a useful predictor of Φe,C across physically-dynamic regimes, provided the slope describing their relationship is predictable. We also consider recent advances in fluorescence-based corrections to evaluate the potential role of baseline fluorescence (Fb) in contributing to overestimation of Φe,C and the correlation between Φe,C and NPQNSV – in doing so, we highlight the need for Fb corrections for future field-based assessments of Φe,C

Divergence of photosynthetic strategies amongst marine diatoms.

Marine phytoplankton, and in particular diatoms, are responsible for almost half of all primary production on Earth. Diatom species thrive from polar to tropical waters and across light environments that are highly complex to relatively benign, and so have evolved highly divergent strategies for regulating light capture and utilization. It is increasingly well established that diatoms have achieved such successful ecosystem dominance by regulating excitation energy available for generating photosynthetic energy via highly flexible light harvesting strategies. However, how different light harvesting strategies and downstream pathways for oxygen production and consumption interact to balance excitation pressure remains unknown. We therefore examined the responses of three diatom taxa adapted to inherently different light climates (estuarine Thalassioisira weissflogii, coastal Thalassiosira pseudonana and oceanic Thalassiosira oceanica) during transient shifts from a moderate to high growth irradiance (85 to 1200 μmol photons m-2 s-1). Transient high light exposure caused T. weissflogii to rapidly downregulate PSII with substantial nonphotochemical quenching, protecting PSII from inactivation or damage, and obviating the need for induction of O2 consuming (light-dependent respiration, LDR) pathways. In contrast, T. oceanica retained high excitation pressure on PSII, but with little change in RCII photochemical turnover, thereby requiring moderate repair activity and greater reliance on LDR. T. pseudonana exhibited an intermediate response compared to the other two diatom species, exhibiting some downregulation and inactivation of PSII, but high repair of PSII and induction of reversible PSII nonphotochemical quenching, with some LDR. Together, these data demonstrate a range of strategies for balancing light harvesting and utilization across diatom species, which reflect their adaptation to sustain photosynthesis under environments with inherently different light regimes

Taxonomic variability in the electron requirement for carbon fixation across marine phytoplankton.

Fast Repetition Rate fluorometry (FRRf) has been increasingly used to measure marine primary productivity by oceanographers to understand how carbon (C) uptake patterns vary over space and time in the global oceans. As FRRf measures electron transport rates through photosystem II (ETRPSII ), a critical, but difficult-to-predict conversion factor termed the "electron requirement for carbon fixation" (Φe,C ) is needed to scale ETRPSII to C-fixation rates. Recent studies have generally focused on understanding environmental regulation of Φe,C , while taxonomic control has been explored by only a handful of laboratory studies encompassing a limited diversity of phytoplankton species. We therefore assessed Φe,C for a wide range of marine phytoplankton (n=17 strains) spanning multiple taxonomic and size-classes. Data mined from previous studies were further considered to determine whether Φe,C variability could be explained by taxonomy versus other phenotypic traits influencing growth and physiological performance (e.g., cell size). We found that Φe,C exhibited considerable variability (~4-10 mol e- · [mol C]-1 ), and was negatively correlated with growth rate (R2 = 0.7, p < 0.01). Diatoms exhibited a lower Φe,C compared to chlorophytes during steady-state, nutrient-replete growth. Inclusion of meta-analysis data did not find significant relationships between Φe,C and class, or growth rate, although confounding factors inherent to methodological inconsistencies between studies likely contributed to this. Knowledge of empirical relationships between Φe,C and growth rate coupled with recent improvements in quantifying phytoplankton growth rates in-situ, facilitate up-scaling of FRRf campaigns to routinely derive Φe,C needed to assess ocean C-cycling

Single molecule protein stabilisation translates to macromolecular mechanics of a protein network

Folded globular proteins are attractive building blocks for biopolymer-based materials, as their mechanically resistant structures carry out diverse biological functionality. While much is now understood about the mechanical response of single folded proteins, a major challenge is to understand and predictably control how single protein mechanics translates to the collective response of a network of connected folded proteins. Here, by utilising the binding of maltose to hydrogels constructed from photo-chemically crosslinked maltose binding protein (MBP), we investigate the effects of protein stabilisation at the molecular level on the macroscopic mechanical and structural properties of a protein-based hydrogel. Rheological measurements show an enhancement in the mechanical strength and energy dissipation of MBP hydrogels in the presence of maltose. Circular dichroism spectroscopy and differential scanning calorimetry measurements show that MBP remains both folded and functional in situ. By coupling these mechanical measurements with mesoscopic structural information obtained by small angle scattering, we propose an occupation model in which higher proportions of stabilised, ligand occupied, protein building blocks translate their increased stability to the macroscopic properties of the hydrogel network. This provides powerful opportunities to exploit environmentally responsive folded protein-based biomaterials for many broad applications