White matter microstructure in athletes with a history of concussion: Comparing diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI)

Sport concussion is associated with disturbances in brain function in the absence of gross anatomical lesions, and may have long-term health consequences. Diffusion-weighted magnetic resonance imaging (MRI) methods provide a powerful tool for investigating alterations in white matter microstructure reflecting the long-term effects of concussion. In a previous study, diffusion tensor imaging (DTI) showed that athletes with a history of concussion had elevated fractional anisotropy (FA) and reduced mean diffusivity (MD) parameters. To better understand these effects, this study compared DTI results to neurite orientation dispersion and density imaging (NODDI), which was used to estimate the intracellular volume fraction (VIC ) and orientation dispersion index (ODI). Sixty-eight (68) varsity athletes were recruited, including 37 without a history of concussion and 31 with concussion >6 months prior to imaging. Univariate analyses showed elevated FA and decreased MD for concussed athletes, along with increased VIC and reduced ODI, indicating greater neurite density and coherence of neurite orientation within white matter. Multivariate analyses also showed that for athletes with a history of concussion, white matter regions with increased FA had increased VIC and decreased ODI, with greater effects among athletes who were imaged a longer time since their last concussion. These findings enhance our understanding of the relationship between the biophysics of water diffusion and concussion neurobiology for young, healthy adults. Hum Brain Mapp 38:4201-4211, 2017. © 2017 Wiley Periodicals, Inc

Bond between microwave cured repair and concrete substrate

The bond strength between a concrete substrate and repair patch is critical to its durability. This paper investigates the effect of microwave curing the freshly applied repair, for 45 min at 132 Watts, on the 28 day bond strength between substrate concrete and different commercial repair materials. The repairs were applied at different ambient temperatures of 20, 10, 2 and −5 °C. Tensile split tests on repaired cube specimens were performed to determine the interfacial bond strength. The ability of microwave curing to prevent the detrimental effects of freezing at early age on the bond and compressive strength of repair patches is investigated. Experimental results show that microwave curing prevents loss of long term (28 day) repair/substrate bond strength of repair materials applied at freezing temperatures (−5 °C), relative to the repairs applied at higher temperatures (2–20 °C), except one lightweight repair formulation. In comparison, the control samples (non-microwave cured) of repairs applied at −5 °C suffered severe loss of bond strength and compressive strength due to early age freezing. In addition, no adverse effects on the bond strength and a small reduction of 6.75% in the 28 day compressive strength are observed in the early age microwave cured repairs applied at ambient temperatures of 2–20 °C. The repair/substrate bond strength is independent of the compressive strength of the repair material at all temperatures of repair application. Microwave curing can accelerate the concrete repair process and facilitate construction activity in cold weather

Cognitive performance in healthy older adults relates to spontaneous switching between states of functional connectivity during rest

Growing evidence has shown that brain activity at rest slowly wanders through a repertoire of different states, where whole-brain functional connectivity (FC) temporarily settles into distinct FC patterns. Nevertheless, the functional role of resting-state activity remains unclear. Here, we investigate how the switching behavior of resting-state FC relates with cognitive performance in healthy older adults. We analyse resting-state fMRI data from 98 healthy adults previously categorized as being among the best or among the worst performers in a cohort study of >1000 subjects aged 50+ who underwent neuropsychological assessment. We use a novel approach focusing on the dominant FC pattern captured by the leading eigenvector of dynamic FC matrices. Recurrent FC patterns - or states - are detected and characterized in terms of lifetime, probability of occurrence and switching profiles. We find that poorer cognitive performance is associated with weaker FC temporal similarity together with altered switching between FC states. These results provide new evidence linking the switching dynamics of FC during rest with cognitive performance in later life, reinforcing the functional role of resting-state activity for effective cognitive processing.This project was financed by the Fundação Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project “Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)”), co-financed by Portuguese North Regional Operational Program (ON.2) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298) and under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement through the European Regional Development Fundinfo:eu-repo/semantics/publishedVersio

Total synthesis of Escherichia coli with a recoded genome

Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon—out of up to 6 synonyms—to encode each amino acid. Synonymous codon choice has diverse and important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms. We create a variant of Escherichia coli with a four-megabase synthetic genome through a high-fidelity convergent total synthesis. Our synthetic genome implements a defined recoding and refactoring scheme—with simple corrections at just seven positions—to replace every known occurrence of two sense codons and a stop codon in the genome. Thus, we recode 18,214 codons to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids, and enables the deletion of a previously essential transfer RNA

Dual Infection and Superinfection Inhibition of Epithelial Skin Cells by Two Alphaherpesviruses Co-Occur in the Natural Host

Hosts can be infected with multiple herpesviruses, known as superinfection; however, superinfection of cells is rare due to the phenomenon known as superinfection inhibition. It is believed that dual infection of cells occurs in nature, based on studies examining genetic exchange between homologous alphaherpesviruses in the host, but to date, this has not been directly shown in a natural model. In this report, gallid herpesvirus 2 (GaHV-2), better known as Marek’s disease virus (MDV), was used in its natural host, the chicken, to determine whether two homologous alphaherpesviruses can infect the same cells in vivo. MDV shares close similarities with the human alphaherpesvirus, varicella zoster virus (VZV), with respect to replication in the skin and exit from the host. Recombinant MDVs were generated that express either the enhanced GFP (eGFP) or monomeric RFP (mRFP) fused to the UL47 (VP13/14) herpesvirus tegument protein. These viruses exhibited no alteration in pathogenic potential and expressed abundant UL47-eGFP or -mRFP in feather follicle epithelial cells in vivo. Using laser scanning confocal microscopy, it was evident that these two similar, but distinguishable, viruses were able to replicate within the same cells of their natural host. Evidence of superinfection inhibition was also observed. These results have important implications for two reasons. First, these results show that during natural infection, both dual infection of cells and superinfection inhibition can co-occur at the cellular level. Secondly, vaccination against MDV with homologous alphaherpesvirus like attenuated GaHV-2, or non-oncogenic GaHV-3 or meleagrid herpesvirus (MeHV-1) has driven the virus to greater virulence and these results implicate the potential for genetic exchange between homologous avian alphaherpesviruses that could drive increased virulence. Because the live attenuated varicella vaccine is currently being administered to children, who in turn could be superinfected by wild-type VZV, this could potentiate recombination events of VZV as well

Serial femtosecond crystallography reveals that photoactivation in a fluorescent protein proceeds via the hula twist mechanism

Chromophore cis/trans photoisomerization is a fundamental process in chemistry and in the activation of many photosensitive proteins. A major task is understanding the effect of the protein environment on the efficiency and direction of this reaction compared to what is observed in the gas and solution phases. In this study, we set out to visualize the hula twist (HT) mechanism in a fluorescent protein, which is hypothesized to be the preferred mechanism in a spatially constrained binding pocket. We use a chlorine substituent to break the twofold symmetry of the embedded phenolic group of the chromophore and unambiguously identify the HT primary photoproduct. Through serial femtosecond crystallography, we then track the photoreaction from femtoseconds to the microsecond regime. We observe signals for the photoisomerization of the chromophore as early as 300 fs, obtaining the first experimental structural evidence of the HT mechanism in a protein on its femtosecond-to-picosecond timescale. We are then able to follow how chromophore isomerization and twisting lead to secondary structure rearrangements of the protein β-barrel across the time window of our measurements

Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity

Recent studies have revealed an important role for hormones in plant immunity. We are now beginning to understand the contribution of crosstalk among different hormone signaling networks to the outcome of plant–pathogen interactions. Cytokinins are plant hormones that regulate development and responses to the environment. Cytokinin signaling involves a phosphorelay circuitry similar to two-component systems used by bacteria and fungi to perceive and react to various environmental stimuli. In this study, we asked whether cytokinin and components of cytokinin signaling contribute to plant immunity. We demonstrate that cytokinin levels in Arabidopsis are important in determining the amplitude of immune responses, ultimately influencing the outcome of plant–pathogen interactions. We show that high concentrations of cytokinin lead to increased defense responses to a virulent oomycete pathogen, through a process that is dependent on salicylic acid (SA) accumulation and activation of defense gene expression. Surprisingly, treatment with lower concentrations of cytokinin results in increased susceptibility. These functions for cytokinin in plant immunity require a host phosphorelay system and are mediated in part by type-A response regulators, which act as negative regulators of basal and pathogen-induced SA–dependent gene expression. Our results support a model in which cytokinin up-regulates plant immunity via an elevation of SA–dependent defense responses and in which SA in turn feedback-inhibits cytokinin signaling. The crosstalk between cytokinin and SA signaling networks may help plants fine-tune defense responses against pathogens

Multifractal and entropy analysis of resting-state electroencephalography reveals spatial organization in local dynamic functional connectivity

Functional connectivity of the brain fluctuates even in resting-state condition. It has been reported recently that fluctuations of global functional network topology and those of individual connections between brain regions expressed multifractal scaling. To expand on these findings, in this study we investigated if multifractality was indeed an inherent property of dynamic functional connectivity (DFC) on the regional level as well. Furthermore, we explored if local DFC showed region-specific differences in its multifractal and entropy-related features. DFC analyses were performed on 62-channel, resting-state electroencephalography recordings of twelve young, healthy subjects. Surrogate data testing verified the true multifractal nature of regional DFC that could be attributed to the presumed nonlinear nature of the underlying processes. Moreover, we found a characteristic spatial distribution of local connectivity dynamics, in that frontal and occipital regions showed stronger long-range correlation and higher degree of multifractality, whereas the highest values of entropy were found over the central and temporal regions. The revealed topology reflected well the underlying resting-state network organization of the brain. The presented results and the proposed analysis framework could improve our understanding on how resting-state brain activity is spatio-temporally organized and may provide potential biomarkers for future clinical research