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  Azo synthesis meets molecular iodine catalysis

  Rowshanpour, Rozhin; Dudding, Travis (Royal Society of Chemistry, 2021)

  A metal-free synthetic protocol for azo compound formation by the direct oxidation of hydrazine HN–NH bonds to azo group functionality catalyzed by molecular iodine is disclosed. The strengths of this reactivity include rapid reaction times, low catalyst loadings, use of ambient dioxygen as a stoichiometric oxidant, and ease of experimental set-up and azo product isolation. Mechanistic studies and density functional theory computations offering insight into this reactivity, as well as the events leading to azo group formation are presented. Collectively, this study expands the potential of main-group element iodine as an inexpensive catalyst, while delivering a useful transformation for forming azo compounds.
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  First evidence of the mutations associated with pyrethroid resistance in head lice (Phthiraptera: Pediculidae) from Honduras

  Larkin, Kelsey; Rodriguez, Carol A.; Jamani, Shabana; Fronza, Georgina; Roca‑Acevedo, Gonzalo; Sanchez, Ana; Toloza, Ariel C (BMC, 2020)

  The human head louse, Pediculus humanus capitis, is a cosmopolitan blood-sucking ectoparasite affecting mostly schoolchildren in both developed and developing countries. In Honduras, chemical pediculicides are the first line of treatment, with permethrin as their main active ingredient. Despite the extended use of these products, there is currently no research investigating insecticide resistance in Honduran head lice. In head lice, the most common mechanism is knockdown resistance (kdr), which is the result of two point mutations and the associated amino acid substitutions, T917I and L920F, within the voltage-sensitive sodium channel (VSSC). METHODSGenomic DNA was extracted from 83 head lice collected in the localities of San Buenaventura and La Hicaca, Honduras. Polymerase chain reaction (PCR) was used to amplify a 332-bp fragment of the VSSC gene that contains a site affected by C/T mutation which results in a T917I amino acid substitution on each human head louse genomic DNA fragments. RESULTSThe C/T non-synonymous mutation which results in the T917I kdr amino acid substitution was detected in both head lice populations at frequencies ranging between 0.45-0.5. Globally, the frequency of this substitution was 0.47. Of these, 5 (6.1%) were homozygous susceptible and 78 (93.9%) were heterozygotes. The kdr-resistant homozygote (RR) was not detected in the studied populations. Thus, 93.9% of the head lice collected in Honduras harbored only one T917I allele. Exact test for the Hardy-Weinberg equilibrium for both localities showed that genotype frequencies differed significantly from expectation. In addition, San Buenaventura and La Hicaca populations had an inbreeding coefficient (Fis) < 0, suggesting an excess of heterozygotes. CONCLUSIONSTo our knowledge, this is the first study showing the presence of the C/T mutation responsible of the T917I kdr allele associated with pyrethroid resistance in P. h. capitis from Honduras. The PCR-restriction fragment length polymorphism (RFLP) employed here has demonstrated to be a reliable, economic, and reproducible assay that can be used to accurately genotype individual head lice for the mutation encoding the resistance-conferring T917I amino acid substitution. This highlights the necessity of proactive resistance management programmes designed to detect pyrethroid mutations before they become established within populations of head lice.
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  Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence

  O’Neill, Eric J.; Den Hartogh, Danja J.; Azizi, Karim; Tsiani, Evangeli (MDPI, 2020)

  Cancer is characterized by unrestricted cell proliferation, inhibition of apoptosis, enhanced invasion and migration, and deregulation of signalling cascades. These properties lead to uncontrolled growth, enhanced survival, and the formation of tumours. Carnosol, a naturally occurring phyto-polyphenol (diterpene) found in rosemary, has been studied for its extensive antioxidant, anti-inflammatory, and anticancer effects. In cancer cells, carnosol has been demonstrated to inhibit cell proliferation and survival, reduce migration and invasion, and significantly enhance apoptosis. These anticancer effects of carnosol are mediated by the inhibition of several signalling molecules including extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt, mechanistic target of rapamycin (mTOR) and cyclooxygenase-2 (COX-2). Additionally, carnosol prevents the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promotes apoptosis, as indicated by increased levels of cleaved caspase-3, -8, -9, increased levels of the pro-apoptotic marker Bcl-2-associated X (BAX), and reduced levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl-2). The current review summarizes the existing in vitro and in vivo evidence examining the anticancer effects of carnosol across various tissues.
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  On Whether Task Experience of the Peer Differentially Impacts Feedback Scheduling and Skill Acquisition of a Learner

  Patterson, Jae Todd; Mcrae, Matthew; Hansen, Steve (Frontiers Media, 2019)

  Previous research has shown that peers without task experience provided knowledge of results (KR) as effectively as performers who self-controlled their own KR schedule ( McRae et al., 2015 ). In the present experiment, a group of participants first practiced a motor task while self-controlling their KR during a defined acquisition period. Twenty-four hours after their last retention trial, these participants with motor experience then provided KR to a learner during their skill acquisition. Participants were required to learn a serial-timing task with a goal of 2,500 ms. Participants completed a defined acquisition period and then returned 24 h later for a retention test. In retention, learners who received KR from experienced peers were predicted to outperform learners who received KR from inexperienced peers. The results showed that performers learned the task similarly, independent of the peer’s previous task experience. However, the peer groups differed in their frequency of providing KR to the learner and showed a discrepancy between their self-reported KR provision strategy and when they actually provided KR. The results have theoretical implications for understanding the impact of self-control in motor learning contexts.
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  Electrophysiological correlates of top-down attentional modulation in olfaction

  Singh, Archana K; Touhara, Kazushige; Okamoto, Masako (Nature Research (Part of Springer Nature), 2019)

  The capacity to pay attention is important for the cognitive ability, for example, evaluating an object for its qualities. Attention can selectively prioritize the neural processes that are relevant to a given task. Neuroimaging investigations on human attention are primarily focused on vision to the exclusion of other sensory systems, particularly olfaction. Neural underpinnings of human olfactory attention are still not clearly understood. Here, we combined electroencephalographic measurements of olfactory event related potential with electrical neuroimaging to investigate how the neural responses after inhaling the same odor differ between conditions with varying levels of attention, and, in which brain areas. We examined the neural responses when participants attended to a rose-like odor of phenylethyl alcohol for evaluating its pleasantness versus its passive inhalation. Our results gathered significant evidence for attentional modulation of the olfactory neural response. The most prominent effect was found for the late positive component, P3, of olfactory event related potential within a second from the odor onset. The source reconstruction of this data revealed activations in a distributed network of brain regions predominantly in inferior frontal cortex, insula, and inferior temporal gyrus. These results suggest that the neuronal modulations from attention to olfactory pleasantness may be subserved by this network.
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  Calmodulin-Binding Proteins in Muscle: A Minireview on Nuclear Receptor Interacting Protein, Neurogranin, and Growth-Associated Protein 43

  Moradi, Fereshteh; Copeland, Emily N; Baranowski, Ryan W; Scholey, Aiden E; Stuart, Jeffrey A; Fajardo, Val A (MDPI, 2020)

  Calmodulin (CaM) is an important Ca2+-sensing protein with numerous downstream targets that are either CaM-dependant or CaM-regulated. In muscle, CaM-dependent proteins, which are critical regulators of dynamic Ca2+ handling and contractility, include calcineurin (CaN), CaM-dependant kinase II (CaMKII), ryanodine receptor (RyR), and dihydropyridine receptor (DHPR).CaM-regulated targets include genes associated with oxidative metabolism, muscle plasticity, and repair. Despite its importance in muscle, the regulation of CaM—particularly its availability to bind to and activate downstream targets—is an emerging area of research. In this minireview, we discuss recent studies revealing the importance of small IQ motif proteins that bind to CaM to either facilitate (nuclear receptor interacting protein; NRIP) its activation of downstream targets, or sequester (neurogranin, Ng; and growth-associated protein 43, GAP43) CaM away from their downstream targets. Specifically, we discuss recent studies that have begun uncovering the physiological roles of NRIP, Ng, and GAP43 in skeletal and cardiac muscle, thereby highlighting the importance of endogenously expressed CaM-binding proteins and their regulation of CaM in muscle.
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  High Endemicity of Soil-Transmitted Helminths in a Population Frequently Exposed to Albendazole but No Evidence of Antiparasitic Resistance

  Matamoros, Gabriela; Rueda, Maria Mercedes; Rodriguez, Carol; Gabrie, Jose A; Canales, Maritza; Fontecha, Gustavo; Sanchez, Ana (MDPI, 2019)

  Soil-transmitted helminths (STHs) are gastrointestinal parasites widely distributed in tropical and subtropical areas. Mass drug administration (MDA) of benzimidazoles (BZ) is the most recommended for STH control. These drugs have demonstrated limited efficacy against Trichuris trichiura and the long-term use of single-dose BZ has raised concerns of the possible emergence of genetic resistance. The objective of this investigation was to determine whether genetic mutations associated with BZ resistance were present in STH species circulating in an endemic region of Honduras. Methods: A parasitological survey was performed as part of this study, the Kato–Katz technique was used to determine STH prevalence in children of La Hicaca, Honduras. A subgroup of children received anthelminthic treatment in order to recover adult parasite specimens that were analyzed through molecular biology techniques. Genetic regions containing codons 200, 198, and 167 of the β-tubulin gene of Ascaris lumbricoides and Trichuris trichiura were amplified and sequenced. Results: Stool samples were collected from 106 children. The overall STH prevalence was 75.47%, whereby T. trichiura was the most prevalent helminth (56.6%), followed by A. lumbricoides (17%), and hookworms (1.9%). Eighty-five sequences were generated for adjacent regions to codons 167, 198, and 200 of the β-tubulin gene of T. trichiura and A. lumbricoides specimens. The three codons of interest were found to be monomorphic in all the specimens. Conclusion: Although the inability to find single-nucleotide polymorphisms (SNPs) in the small sample analyzed for the present report does not exclude the possibility of their occurrence, these results suggest that, at present, Honduras’s challenges in STH control may not be related to drug resistance but to environmental conditions and/or host factors permitting reinfections.
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  Metarhizium robertsii ammonium permeases (MepC and Mep2) contribute to rhizoplane colonization and modulates the transfer of insect derived nitrogen to plants

  Moonjely, Soumya; Zhang, Xing; Fang, Weiguo; Bidochka, Michael J (Public Library of Science, 2019)

  The endophytic insect pathogenic fungi (EIPF) Metarhizium promotes plant growth through symbiotic association and the transfer of insect-derived nitrogen. However, little is known about the genes involved in this association and the transfer of nitrogen. In this study, we assessed the involvement of six Metarhizium robertsii genes in endophytic, rhizoplane and rhizospheric colonization with barley roots. Two ammonium permeases (MepC and Mep2) and a urease, were selected since homologous genes in arbuscular mycorrhizal fungi were reported to play a pivotal role in nitrogen mobilization during plant root colonization. Three other genes were selected on the basis on RNA-Seq data that showed high expression levels on bean roots, and these encoded a hydrophobin (Hyd3), a subtilisin-like serine protease (Pr1A) and a hypothetical protein. The root colonization assays revealed that the deletion of urease, hydrophobin, subtilisin-like serine protease and hypothetical protein genes had no impact on endophytic, rhizoplane and rhizospheric colonization at 10 or 20 days. However, the deletion of MepC resulted in significantly increased rhizoplane colonization at 10 days whereas ΔMep2 showed increased rhizoplane colonization at 20 days. In addition, the nitrogen transporter mutants also showed significantly higher 15N incorporation of insect derived nitrogen in barley leaves in the presence of nutrients. Insect pathogenesis assay revealed that disruption of MepC, Mep2, urease did not reduce virulence toward insects. The enhanced rhizoplane colonization of ΔMep2 and ΔMepC and insect derived nitrogen transfer to plant hosts suggests the role of MepC and Mep2 in Metarhizium-plant symbiosis.
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  A Low-Therapeutic Dose of Lithium Inhibits GSK3 and Enhances Myoblast Fusion in C2C12 Cells

  Kurgan, Nigel; Whitley, Kennedy C; Maddalena, Lucas A; Moradi, Fereshteh; Stoikos, Joshua; Hamstra, Sophie I; Rubie, Elizabeth A; Kumar, Megha; Roy, Brian D; Woodgett, James R; et al. (MDPI, 2019)

  Glycogen synthase kinase 3 (GSK3) slows myogenic differentiation and myoblast fusion partly by inhibiting the Wnt/β-catenin signaling pathway. Lithium, a common medication for bipolar disorder, inhibits GSK3 via Mg+ competition and increased Ser21 (GSK3α) or Ser9 (GSK3β) phosphorylation, leading to enhanced myoblast fusion and myogenic differentiation. However, previous studies demonstrating the effect of lithium on GSK3 have used concentrations up to 10 mM, which greatly exceeds concentrations measured in the serum of patients being treated for bipolar disorder (0.5–1.2 mM). Here, we determined whether a low-therapeutic (0.5 mM) dose of lithium could promote myoblast fusion and myogenic differentiation in C2C12 cells. C2C12 myotubes differentiated for three days in media containing 0.5 mM lithium chloride (LiCl) had significantly higher GSK3β (ser9) and GSK3α (ser21) phosphorylation compared with control myotubes differentiated in the same media without LiCl (+2–2.5 fold, p < 0.05), a result associated with an increase in total β-catenin. To further demonstrate that 0.5 mM LiCl inhibited GSK3 activity, we also developed a novel GSK3-specific activity assay. Using this enzyme-linked spectrophotometric assay, we showed that 0.5 mM LiCl-treated myotubes had significantly reduced GSK3 activity (−86%, p < 0.001). Correspondingly, 0.5 mM LiCl treated myotubes had a higher myoblast fusion index compared with control (p < 0.001) and significantly higher levels of markers of myogenesis (myogenin, +3-fold, p < 0.001) and myogenic differentiation (myosin heavy chain, +10-fold, p < 0.001). These results indicate that a low-therapeutic dose of LiCl is sufficient to promote myoblast fusion and myogenic differentiation in muscle cells, which has implications for the treatment of several myopathic conditions
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  Investigating the Muscular and Kinematic Responses to Sudden Wrist Perturbations During a Dynamic Tracking Task

  Forman, Garrick N.; Forman, Davis A.; Avila-Mireles, Edwin J; Zenzeri, Jacopo; Holmes, Michael W R (Nature Research (part of Springer Nature), 2020)

  Sudden disturbances (perturbations) to the hand and wrist are commonplace in daily activities and workplaces when interacting with tools and the environment. It is important to understand how perturbations influence forearm musculature and task performance when identifying injury mechanisms. The purpose of this work was to evaluate changes in forearm muscle activity and co-contraction caused by wrist perturbations during a dynamic wrist tracking task. Surface electromyography was recorded from eight muscles of the upper-limb. Participants performed trials consisting of 17 repetitions of ±40° of wrist flexion/extension using a robotic device. During trials, participants received radial or ulnar perturbations that were delivered during flexion or extension, and with known or unknown timing. Co-contraction ratios for all muscle pairs showed significantly greater extensor activity across all experimental conditions. Of all antagonistic muscle pairs, the flexor carpi radialis (FCR)-extensor carpi radialis (ECR) muscle pair had the greatest change in co-contraction, producing 1602% greater co-contraction during flexion trials than during extensions trials. Expected perturbations produced greater anticipatory (immediately prior to the perturbation) muscle activity than unexpected, resulting in a 30% decrease in wrist displacement. While improving performance, this increase in anticipatory muscle activity may leave muscles susceptible to early-onset fatigue, which could lead to chronic overuse injuries in the workplace.
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  Hyperarousal Is Associated with Socioemotional Processing in Individuals with Insomnia Symptoms and Good Sleepers

  Howlett, Reuben D M; Lustig, Kari A; MacDonald, Kevin J; Cote, Kimberly A (MDPI, 2020)

  Despite complaints of difficulties in waking socioemotional functioning by individuals with insomnia, only a few studies have investigated emotion processing performance in this group. Additionally, the role of sleep in socioemotional processing has not been investigated extensively nor using quantitative measures of sleep. Individuals with insomnia symptoms (n = 14) and healthy good sleepers (n = 15) completed two nights of at-home polysomnography, followed by an afternoon of in-lab performance testing on tasks measuring the processing of emotional facial expressions. The insomnia group self-reported less total sleep time, but no other group differences in sleep or task performance were observed. Greater beta EEG power throughout the night was associated with higher intensity ratings of happy, fearful and sad faces for individuals with insomnia, yet blunted sensitivity and lower accuracy for good sleepers. Thus, the presence of hyperarousal differentially impacted socioemotional processing of faces in individuals with insomnia symptoms and good sleepers.
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  Reasons for Forgiving: Individual Differences and Emotional Outcomes

  Belicki, Kathryn; Decourville, Nancy; Kamble, Shanmukh Vasant; Stewart, Tammy; Rubel, Alicia (SAGE Publications, 2020)

  This research is part of a program to identify common forms of forgiveness and study the outcomes associated with different ways of forgiving. Two samples, one in Canada (N = 274) and one in India (N = 159), completed a third version of the Reasons for Forgiving Questionnaire (R4FQ), several measures of individual differences, as well as measures of affect and mood while imagining their injurer. Nine R4FQ subscales were derived: For the Relationship, To Feel Better, Based on Principle, Because Injurer Reformed, To Demonstrate Moral Superiority, Because Understood Injurer, For God, Because of Social Pressure, and For Pragmatic Reasons. These subscales were differentially related to religiosity, attachment security, trait anger, collectivism, and individualism. Positive emotional outcomes were associated with forgiving for the relationship, based on principle, because injurer reformed, and because understood injurer. In contrast, negative outcomes were associated with forgiving To Demonstrate Moral Superiority, Because of Social Pressure, and For Pragmatic Reasons.
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  Plant microbiome analysis after Metarhizium amendment reveals increases in abundance of plant growth-promoting organisms and maintenance of disease-suppressive soil

  Waller, Alison S.; Behie, Scott W.; Bidochka, Michael J.; Barelli, Larissa (Public Library of Science, 2020-01)

  The microbial community in the plant rhizosphere is vital to plant productivity and disease resistance. Alterations in the composition and diversity of species within this community could be detrimental if microbes suppressing the activity of pathogens are removed. Species of the insect-pathogenic fungus, Metarhizium, commonly employed as biological control agents against crop pests, have recently been identified as plant root colonizers and provide a variety of benefits (e.g. growth promotion, drought resistance, nitrogen acquisition). However, the impact of Metarhizium amendment on the rhizosphere microbiome has yet to be elucidated. Using Illumina sequencing, we examined the community profiles (bacteria and fungi) of common bean (Phaseolus vulgaris) rhizosphere (loose soil and plant root) after amendment with M. robertsii conidia, in the presence and absence of an insect host. Although alpha diversity was not significantly affected overall, there were numerous examples of plant growth-promoting organisms that significantly increased with Metarhizium amendment (Bradyrhizobium, Flavobacterium, Chaetomium, Trichoderma). Specifically, the abundance of Bradyrhizobium, a group of nitrogen-fixing bacteria, was confirmed to be increased using a qPCR assay with genus-specific primers. In addition, the ability of the microbiome to suppress the activity of a known bean root pathogen was assessed. The development of disease symptoms after application with Fusarium solani f. sp. phaseoli was visible in the hypocotyl and upper root of plants grown in sterilized soil but was suppressed during growth in microbiome soil and soil treated with M. robertsii. Successful amendment of agricultural soils with biocontrol agents such as Metarhizium necessitates a comprehensive understanding of the effects on the diversity of the rhizosphere microbiome. Such research is fundamentally important towards sustainable agricultural practices to improve overall plant health and productivity.
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  The colon cancer screening behaviours survey for South Asians: a pilot study of feasibility and psychometric evaluation

  Crawford, Joanne; Morfaw, Frederick; Ahmad, Farah; Thabane, Lehana; Frisina, Angela (Springer Open, 2020)

  The purpose of the study was to pilot test the English and Urdu version of the Colon Cancer Screening Behaviours Survey among South Asians in Canada. The first objective was to evaluate feasibility of administration, data collection using computer assisted personal interviewing software on a tablet, and response burden. The second objective was to examine the prevalence of colorectal cancer screening among South Asians and evaluate the psychometric properties of sub-scales in the survey. Purposive, network and snowball sampling were used to recruit participants for this cross-sectional study. Interviewer-led administration of the Colon Cancer Screening Behaviours Survey was conducted across two cities in Ontario, Canada. Qualitative data analysis assessed feasibility; and sub-scales were evaluated through principal component analysis, item-scale correlations, and construct validity using multiple linear and logistic regression. A total of 328 South Asians participated, 47% Urdu speaking, and 53% English speaking. There was a 23% refusal rate to participate. Feasibility identified: (1) successful recruitment despite reasons for refusal; (2) problematic items and response categories; and (3) computer/tablet limitations. Principal component analysis identified 14 components that explained 68.7% of total variance; 34 items were retained after factor analysis. Internal consistency of 4 scales ranged from 0.79-0.91. There were significant differences in perceived barriers scale scores (- 12.21; 95% CI, - 17.13 to - 7.28; p <  0.0001) between those who participated and those who did not participate in screening. No association was found with years of residence and uptake of screening after adjustment (OR 0.91 (0.46-1.79), p = 0.783). Recruitment and data collection methods are feasible among South Asians if functionality of the tablet selected is improved. The Colon Cancer Screening Behaviours Survey was finalized and retained items in sub-scales demonstrated good psychometric properties to assess behaviours for colon cancer screening among South Asians in Canada. The interviewer-led survey may be used by public health, cancer care or other health practitioners to describe or predict colorectal cancer screening behaviours among South Asians in similar settings or adapted and tested in other contexts.
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  Electrophysiological correlates of the fexible allocation of visual working memory resources

  Salahub, Christine; Lockhart, Holly A; Dube, Blaire; Al-Aidroos, Naseem; Emrich, Stephen (Nature Publishing Group, 2019-12-19)

  Visual working memory is a brief, capacity-limited store of visual information that is involved in a large number of cognitive functions. To guide one’s behavior effectively, one must efficiently allocate these limited memory resources across memory items. Previous research has suggested that items are either stored in memory or completely blocked from memory access. However, recent behavioral work proposes that memory resources can be flexibly split across items based on their level of task importance. Here, we investigated the electrophysiological correlates of flexible resource allocation by manipulating the distribution of resources amongst systematically lateralized memory items. We examined the contralateral delay activity (CDA), a waveform typically associated with the number of items held in memory. Across three experiments, we found that, in addition to memory load, the CDA flexibly tracks memory resource allocation. This allocation occurred as early as attentional selection, as indicated by the N2pc. Additionally, CDA amplitude was better-described when fit with a continuous model predicted by load and resources together than when fit with either alone. Our findings show that electrophysiological markers of attentional selection and memory maintenance not only track memory load, but also the proportion of memory resources those items receive.
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  SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin deficient mice

  Braun, Jessica L.; Hamstra, Sophie I.; Messner, Holt N.; Fajardo, Val A. (The Physiological Society, 2019-08)

  The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is imperative for normal cardiac function regulating both muscle relaxation and contractility. SERCA2a is the predominant isoform in cardiac muscles and is inhibited by phospholamban (PLN). Under conditions of oxidative stress, SERCA2a may also be impaired by tyrosine nitration. Tafazzin (Taz) is a mitochondrial specific transacylase that regulates mature cardiolipin (CL) formation, and its absence leads to mitochondrial dysfunction and excessive production of reactive oxygen/nitrogen species (ROS/RNS). In the present study, we examined SERCA function, SERCA2a tyrosine nitration, and PLN expression/phosphorylation in left ventricles (LV) obtained from young (3-5 months) and old (10-12 months) wild-type (WT) and Taz knockdown (TazKD) male mice. These mice are a mouse model for Barth syndrome, which is characterized by mitochondrial dysfunction, excessive ROS/RNS production, and dilated cardiomyopathy (DCM). Here, we show that maximal SERCA activity was impaired in both young and old TazKD LV, a result that correlated with elevated SERCA2a tyrosine nitration. In addition PLN protein was decreased, and its phosphorylation was increased in TazKD LV compared with control, which suggests that PLN may not contribute to the impairments in SERCA function. These changes in expression and phosphorylation of PLN may be an adaptive response aimed to improve SERCA function in TazKD mice. Nonetheless, we demonstrate for the first time that SERCA function is impaired in LVs obtained from young and old TazKD mice likely due to elevated ROS/RNS production. Future studies should determine whether improving SERCA function can improve cardiac contractility and pathology in TazKD mice
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  Changes to the Human Serum Proteome in Response to High Intensity Interval Exercise: A Sequential Top-Down Proteomic Analysis

  Kurgan, Nigel; Noaman, Nour; Pergande, Melissa R.; Cologna, Stephanie M.; Coorssen, Jens R.; Klentrou, Panagiota (Frontiers, 2019-04-02)

  Exercise has been shown to improve health status and prevent chronic diseases. In contrast, overtraining can lead to maladaptation and detrimental health outcomes. These outcomes appear to be mediated in part by released peptides and, potentially, alterations in protein abundances and their modified forms, termed proteoforms. Proteoform biomarkers that either predict the beneficial effects of exercise or indicate (mal)adaptation are yet to be elucidated. Thus, we assessed the influence of highintensity interval exercise (HIIE) on the human serum proteome to identify novel exerciseregulated proteoforms. To this end, a top-down proteomics approach was used, whereby two-dimensional gel electrophoresis was used to resolve and differentially profile intact proteoforms, followed by protein identification via liquid chromatographytandem mass spectrometry. Blood was collected from six young-adult healthy males, pre-exercise and 5 min and 1 h post-exercise. Exercise consisted of a maximal cycle ergometer test followed by 8 min × 1 min high-intensity intervals at 90% Wmax, with 1 min non-active recovery between intervals. Twenty resolved serum proteoforms changed significantly in abundance at 5 min and/or 1 h post-HIIE, including apolipoproteins, serpins (protease inhibitors), and immune system proteins, known to have broad anti-inflammatory and antioxidant effects, involvement in lipid clearance, and cardio-/neuro-protective effects. This initial screening for potential biomarkers indicates that a top-down analytical proteomic approach may prove useful in further characterizing the response to exercise and in understanding the molecular mechanisms that lead to health benefits, as well as identifying novel biomarkers for exercise (mal)adaptation.
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  Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

  Den Hartogh, Danja J.; Tsiani, Evangelia (MDPI, 2019-03-12)

  Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin
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  Acute exercise and brain BACE1 protein content: a time course study

  Yang, Alex J.; Hayward, Grant C.; MacPherson, Rebecca E. K. (American Physiological Society, 2019-04-08)

  Obesity and insulin resistance are risk factors in the development of neurodegenerative disorders. Previous work suggests that one acute bout of exercise may have beneficial neuro-protective effects in obese mice. The rate limiting enzyme in the production of amyloid-beta peptides, BACE1, was reduced in the prefrontal cortex 2 h post-exercise, however if these effects remain over time is unknown. We aimed to determine how long exercise–induced alterations persist in the prefrontal cortex and hippocampus following a single exercise bout. Male C57BL/6J mice were fed either a low (LFD, 10% kcals from lard) or a high fat diet (HFD, 60% kcals from lard) for 7 weeks. HFD mice then underwent an acute bout of treadmill running (15 m/min, 5% incline, 120 min) followed by 2-, 8-, or 24-h of recovery. The HFD increased body mass (LFD 27.8 1.05 vs. HFD 41.7 0.60 g; P < 0.05) and glucose intolerance (AUC LFD 63.27 4.5 vs. HFD 128.9 4.6; P < 0.05). Prefrontal cortex BACE1 content was reduced 2- and 8-h post-exercise compared to sedentary HFD mice, however BACE1 protein content at 24 h was not different. Hippocampal BACE1 content was reduced 8- and 24-h post-exercise. Compared to the LFD, the HFD had higher prefrontal cortex phosphorylation of p38, JNK, and AMPK, indicative of increased neuronal stress. Post–exercise prefrontal cortex p38 and JNK phosphorylation were no different between the HFD or LFD groups, while ERK phosphorylation was significantly reduced by 24 h. The HFD increased JNK phosphorylation in the hippocampus. These results demonstrate the direct and potent effects of exercise on reducing BACE1 prefrontal cortex and hippocampal content. However the reduction in prefrontal cortex BACE1 content is short lived.
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  Evaluation of neuropathological effects of a high-fat high-sucrose diet in middle-aged male C57BL6/J mice

  Baranowski, Bradley J; Bott, Kirsten N.; MacPherson, Rebecca E. K. (American Physiological Society, 2018-05-15)

  Metabolic dysfunction related to diet-induced obesity has recently been linked to the pathogenesis of sporadic Alzheimer’s disease (AD). However, the underlying mechanisms linking obesity and AD remain unclear. The purpose of this study was to examine early alterations in brain insulin signaling, inflammatory/stress markers, and energetic stress in a model of diet-induced obesity during middle age. Male C57BL/6J mice were randomized to either a control diet (AGE n = 12) or high-fat and sucrose diet (AGE-HFS n = 12) for 13-weeks from 20-weeks of age. Prefrontal cortex and hippocampal samples were collected at 20-weeks of age (BSL n = 11) and at 33-weeks of age (AGE and AGE-HFS). The HFS diet resulted in increased body weight (30%; P = 0.0001), increased %fat mass (28%; P = 0.0001), and decreased %lean mass (33%; P = 0.0001) compared to aged controls. In the prefrontal cortex, AGE-HFS resulted in increased 50 adenosine monophosphate – activated protein kinase (AMPK) phosphorylation (P = 0.045). In the hippocampus, AGEHFS resulted in increased extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation and protein kinase B (Akt) serine473 and glycogen synthase kinase (GSK) phosphorylation (P < 0.05). Results from this study demonstrate that aging combined with a HFS diet results in increased inflammation (pERK and pJNK) and energetic stress (pAMPK) in the hippocampus and prefrontal cortex, respectively. Together these novel results provide important information for future targets in early AD pathogenesis.

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