Σάββατο, 24 Φεβρουαρίου 2018

New Mutations of Penicillin-Binding Proteins in Streptococcus agalactiae Isolates from Cattle with Decreased Susceptibility to Penicillin

Microbial Drug Resistance , Vol. 0, No. 0.


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First Report of an ST410 OXA-181 and CTX-M-15 Coproducing Escherichia coli Clone in Italy: A Whole-Genome Sequence Characterization

Microbial Drug Resistance , Vol. 0, No. 0.


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Comparison of Clinical Isolates of Aeromonas from Singapore and Malaysia with Regard to Molecular Identification, Virulence, and Antimicrobial Profiles

Microbial Drug Resistance , Vol. 0, No. 0.


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Antibacterial Properties of Four Novel Hit Compounds from a Methicillin-Resistant Staphylococcus aureus–Caenorhabditis elegans High-Throughput Screen

Microbial Drug Resistance , Vol. 0, No. 0.


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Distribution of gonadotropin-inhibitory hormone (GnIH) in male Luchuan piglets

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Publication date: Available online 24 February 2018
Source:Gene Expression Patterns
Author(s): Xiaoye Wang, Xun Li, Chuanhuo Hu
Gonadotropin inhibitory hormone (GnIH) has emerged as a novel hypothalamic neuropeptide that actively inhibits gonadotropin release in birds and mammals. Recent evidence indicates that GnIH not only acts as a key neurohormone that controls vertebrate reproduction but is also involved in stress response, food intake, and aggressive and sexual behaviors, suggesting a broad physiological role for this neuropeptide. To elucidate its multiple sites of action and potential functions, studying the detailed distribution of GnIH in different organs, except for the hypothalamus-pituitary-ovary/testis axis, is necessary. Therefore, in the present study, in different central nervous system (CNS) and peripheral organs of male Luchuan piglets, the distribution of GnIH was systemically determined using immunohistochemistry, and the expression of GnIH mRNA was investigated using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Our results demonstrate that GnIH immune reactive (GnIH-ir) neurons were widely distributed in the pig CNS, but the number and size of the GnIH-ir neurons varied and exhibited morphological diversity. In the peripheral organs, GnIH immunoreactive cells were observed in the respiratory tract, alimentary tract, endocrine organs, genitourinary tract and lymphatic organs. GnIH mRNA was highly expressed in the CNS, with the highest expression in the hypothalamus. In the peripheral organs, high GnIH mRNA levels were detected in the testis, while no GnIH expression was observed in the liver, lungs and heart et al. These results demonstrated that GnIH might play an important role in modulating a variety of physiological functions and provided the morphological data for further study of GnIH in pigs.



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Purinergic signalling and TRPV1 receptors is associated with the carotid body plasticity induced by an apnea-like stimulus

Abstract

Aerobic organisms rely on oxygen (O2) as the final acceptor of the electrons from oxidative metabolism which is essential to keep electron flow through the respiratory chain, adenosine triphosphate (ATP) synthesis, and therefore cell function.

This article is protected by copyright. All rights reserved



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A tRNA's fate is decided at its 3′ end: Collaborative actions of CCA-adding enzyme and RNases involved in tRNA processing and degradation

Publication date: Available online 31 January 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Karolin Wellner, Heike Betat, Mario Mörl
tRNAs are key players in translation and are additionally involved in a wide range of distinct cellular processes. The vital importance of tRNAs becomes evident in numerous diseases that are linked to defective tRNA molecules. It is therefore not surprising that the structural intactness of tRNAs is continuously scrutinized and defective tRNAs are eliminated. In this process, erroneous tRNAs are tagged with single-stranded RNA sequences that are recognized by degrading exonucleases. Recent discoveries have revealed that the CCA-adding enzyme – actually responsible for the de novo synthesis of the 3′-CCA end – plays an indispensable role in tRNA quality control by incorporating a second CCA triplet that is recognized as a degradation tag. In this review, we give an update on the latest findings regarding tRNA quality control that turns out to represent an interplay of the CCA-adding enzyme and RNases involved in tRNA degradation and maturation. In particular, the RNase-induced turnover of the CCA end is now recognized as a trigger for the CCA-adding enzyme to repeatedly scrutinize the structural intactness of a tRNA. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



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HMGB1-mediated DNA bending: Distinct roles in increasing p53 binding to DNA and the transactivation of p53-responsive gene promoters

Publication date: March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 3
Author(s): Michal Štros, Martin Kučírek, Soodabeh Abbasi Sani, Eva Polanská
HMGB1 is a chromatin-associated protein that has been implicated in many important biological processes such as transcription, recombination, DNA repair, and genome stability. These functions include the enhancement of binding of a number of transcription factors, including the tumor suppressor protein p53, to their specific DNA-binding sites. HMGB1 is composed of two highly conserved HMG boxes, linked to an intrinsically disordered acidic C-terminal tail. Previous reports have suggested that the ability of HMGB1 to bend DNA may explain the in vitro HMGB1-mediated increase in sequence-specific DNA binding by p53. The aim of this study was to reinvestigate the importance of HMGB1-induced DNA bending in relationship to the ability of the protein to promote the specific binding of p53 to short DNA duplexes in vitro, and to transactivate two major p53-regulated human genes: Mdm2 and p21/WAF1. Using a number of HMGB1 mutants, we report that the HMGB1-mediated increase in sequence-specific p53 binding to DNA duplexes in vitro depends very little on HMGB1-mediated DNA bending. The presence of the acidic C-terminal tail of HMGB1 and/or the oxidation of the protein can reduce the HMGB1-mediated p53 binding. Interestingly, the induction of transactivation of p53-responsive gene promoters by HMGB1 requires both the ability of the protein to bend DNA and the acidic C-terminal tail, and is promoter-specific. We propose that the efficient transactivation of p53-responsive gene promoters by HMGB1 depends on complex events, rather than solely on the promotion of p53 binding to its DNA cognate sites.



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Suppression of gluconeogenic gene transcription by SIK1-induced ubiquitination and degradation of CRTC1

Publication date: March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 3
Author(s): Wei-Wei Gao, Hei-Man Vincent Tang, Yun Cheng, Ching-Ping Chan, Chi-Ping Chan, Dong-Yan Jin
CRTCs are a group of three transcriptional coactivators required for CREB-dependent transcription. CREB and CRTCs are critically involved in the regulation of various biological processes such as cell proliferation, metabolism, learning and memory. However, whether CRTC1 efficiently induces gluconeogenic gene expression and how CRTC1 is regulated by upstream kinase SIK1 remain to be understood. In this work, we demonstrated SIK1-induced phosphorylation, ubiquitination and degradation of CRTC1 in the context of the regulation of gluconeogenesis. CRTC1 protein was destabilized by SIK1 but not SIK2 or SIK3. This effect was likely mediated by phosphorylation at S155, S167, S188 and S346 residues of CRTC1 followed by K48-linked polyubiquitination and proteasomal degradation. Expression of gluconeogenic genes such as that coding for phosphoenolpyruvate carboxykinase was stimulated by CRTC1, but suppressed by SIK1. Depletion of CRTC1 protein also blocked forskolin-induced gluconeogenic gene expression, knockdown or pharmaceutical inhibition of SIK1 had the opposite effect. Finally, SIK1-induced ubiquitination of CRTC1 was mediated by RFWD2 ubiquitin ligase at a site not equivalent to K628 in CRTC2. Taken together, our work reveals a regulatory circuit in which SIK1 suppresses gluconeogenic gene transcription by inducing ubiquitination and degradation of CRTC1. Our findings have implications in the development of new antihyperglycemic agents.



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Bistability and phase variation in Salmonella enterica

Publication date: Available online 31 January 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Lucía García-Pastor, Elena Puerta-Fernández, Josep Casadesús
Cell-to-cell differences in bacterial gene expression can merely reflect the occurrence of noise. In certain cases, however, heterogeneous gene expression is a programmed event that results in bistable expression. If bistability is heritable, bacterial lineages are formed. When programmed bistability is reversible, the phenomenon is known as phase variation. In certain cases, bistability is controlled by genetic mechanisms (e. g., DNA rearrangement). In other cases, bistability has epigenetic origin. A robust epigenetic mechanism for the formation of bacterial lineages is the formation of heritable DNA methylation patterns. However, bistability can also arise upon propagation of gene expression patterns by feedback loops that are stable upon cell division. This review describes examples of bistability and phase variation in Salmonella enterica and discusses their adaptive value, sometimes in a speculative manner.



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Long noncoding RNA complementarity and target transcripts abundance

Publication date: March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 3
Author(s): Richard W. Zealy, Mikhail Fomin, Sylvia Davila, Daniel Makowsky, Haley Thigpen, Catherine H. McDowell, James C. Cummings, Edward S. Lee, Sang-Ho Kwon, Kyung-Won Min, Je-Hyun Yoon
Eukaryotic mRNA metabolism regulates its stability, localization, and translation using complementarity with counter-part RNAs. To modulate their stability, small and long noncoding RNAs can establish complementarity with their target mRNAs. Although complementarity of small interfering RNAs and microRNAs with target mRNAs has been studied thoroughly, partial complementarity of long noncoding RNAs (lncRNAs) with their target mRNAs has not been investigated clearly. To address that research gap, our lab investigated whether the sequence complementarity of two lncRNAs, lincRNA-p21 and OIP5-AS1, influenced the quantity of target RNA expression. We predicted a positive correlation between lncRNA complementarity and target mRNA quantity. We confirmed this prediction using RNA affinity pull down, microarray, and RNA-sequencing analysis. In addition, we utilized the information from this analysis to compare the quantity of target mRNAs when two lncRNAs, lincRNA-p21 and OIP5-AS1, are depleted by siRNAs. We observed that human and mouse lincRNA-p21 regulated target mRNA abundance in complementarity-dependent and independent manners. In contrast, affinity pull down of OIP5-AS1 revealed that changes in OIP5-AS1 expression influenced the amount of some OIP5-AS1 target mRNAs and miRNAs, as we predicted from our sequence complementarity assay. Altogether, the current study demonstrates that partial complementarity of lncRNAs and mRNAs (even miRNAs) assist in determining target RNA expression and quantity.



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MAX to MYCN intracellular ratio drives the aggressive phenotype and clinical outcome of high risk neuroblastoma

Publication date: March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 3
Author(s): Francesca Ferrucci, Roberto Ciaccio, Sara Monticelli, Paolo Pigini, Simone di Giacomo, Stefania Purgato, Daniela Erriquez, Roberto Bernardoni, Murray Norris, Michelle Haber, Giorgio Milazzo, Giovanni Perini
Childhood neuroblastoma, a disease of the sympathetic nervous system, is the most common solid tumour of infancy, remarkably refractory to therapeutic treatments. One of the most powerful independent prognostic indicators for this disease is the amplification of the MYCN oncogene, which occurs at high levels in approximately 25% of neuroblastomas. Interestingly, amplification and not just expression of MYCN has a strong prognostic value, although this fact appears quite surprising as MYCN is a transcription factor that requires dimerising with its partner MAX, to exert its function. This observation greatly suggests that the role of MYCN in neuroblastoma should be examined in the context of MAX expression.In this report, we show that, in contrast to what is found in normal cells, MAX expression is significantly different among primary NBs, and that its level appears to correlate with the clinical outcome of the disease. Importantly, controlled modulation of MAX expression in neuroblastoma cells with different extents of MYCN amplification, demonstrates that MAX can instruct gene transcription programs that either reinforce or weaken the oncogenic process enacted by MYCN.In general, our work illustrates that it is the MAX to MYCN ratio that can account for tumour progression and clinical outcome in neuroblastoma and proposes that such a ratio should be considered as an important criterion to the design and development of anti-MYCN therapies.



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miR-1275 controls granulosa cell apoptosis and estradiol synthesis by impairing LRH-1/CYP19A1 axis

Publication date: March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 3
Author(s): Jiying Liu, Xinyu Li, Yong Yao, Qiqi Li, Zenxiang Pan, Qifa Li
miR-1275 is one of the microRNAs (miRNAs) that are differentially expressed during follicular atresia in pig ovaries, as identified by a miRNA microarray assay in our previous study [1]. However, its functions in follicular atresia remain unknown. In this study, we showed that miR-1275 promotes early apoptosis of porcine granulosa cells (pGCs) and the initiation of follicular atresia, and inhibits E2 release and expression of CYP19A1, the key gene in E2 production. Bioinformatics and luciferase reporter assays revealed that liver receptor homolog (LRH)-1, not CYP19A1, is a direct functional target of miR-1275. In vitro overexpression and knockdown experiments showed that LRH-1 significantly repressed apoptosis and induced E2 secretion and CYP19A1 expression in pGCs. LRH-1, whose expression was regulated by miR-1275, prevented apoptosis in pGCs. Furthermore, luciferase and chromatin immunoprecipitation assays demonstrated that LRH-1 protein bound to the CYP19A1 promoter and increased its activity. Our findings suggest that miR-1275 attenuates LRH-1 expression by directly binding to its 3'UTR. This prevents the interaction of LRH-1 protein with the CYP19A1 promoter, represses E2 synthesis, promotes pGC apoptosis, and initiates follicular atresia in porcine ovaries.



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Epigenetic regulation by CpG methylation splits strong from retarded IFNγ-induced IL-18BP in epithelial versus monocytic cells

Publication date: March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 3
Author(s): Malte Bachmann, Josef Pfeilschifter, Heiko Mühl
Interferon (IFN)-γ-inducing interleukin (IL)-18 is a crucial inflammatory cytokine systemically provided by monocytes. It is counteracted by IL-18 binding protein (IL-18BP), a decoy receptor that displays IFNγ-inducibility thus curbing inflammation by negative feedback. Since IL18BP inducibility is pronounced in human epithelial cells but diminished in monocytes, differential IL18BP regulation was investigated herein in both types of cells. Interestingly, DNA-demethylating 5-aza-2′-deoxycytidine enhanced IFNγ-induced IL-18BP only in monocytic but not in epithelial cells. Subsequent promoter analysis brought into focus a specific CpG (coined CpG2) neighboring a γ-activated site responsible for IL18BP induction. CpG2 was consistently methylated in monocytic but unmethylated in epithelial cells. Notably, demethylation by 5-aza-2′-deoxycytidine treatment of monocytic cells impeded methyl-CpG-binding protein-2 (MeCP2) interaction with CpG2, increased adjacent histone H3K9-acetylation, and enhanced RNA-polymerase-II recruitment to the nearby IL18BP transcriptional start. Both latter observations are indicative of a gene locus displaying augmented transcriptional activity. Data suggest that epigenetic silencing by single CpG methylation determines differential IL18BP inducibility in monocytic versus epithelial cells. This regulatory principle should serve and control pivotal IL-18-related cell type-specific (patho)-physiological functions. Whereas epithelial IL-18BP evidently counteracts pathological inflammation at biological barriers, retarded IL18BP inducibility in monocytes may be key to combat blood-borne infections in IL-18-dependent manner.



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A large transcribed enhancer region regulates C. elegans bed-3 and the development of egg laying muscles

Publication date: Available online 24 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Kah Yee Goh, Takao Inoue
Gene expression is regulated by the interaction of the RNA polymerase with various transcription factors at promoter and enhancer elements. Transcriptome analyses found that many non-protein-coding regions are transcribed to produce long non-coding RNAs and enhancer-associated RNAs. Production of these transcripts is associated with activation of nearby protein-coding genes, and at least in some cases, the transcripts themselves mediate this activation. Non-coding transcripts are also reported from large enhancers or clusters of enhancers. However, not much is known about the function of large transcribed enhancer regions during organismal development. Here we investigated a transcribed 10.6 kb intergenic region located upstream of the C. elegans bed-3 gene. We found that parts of this region exhibit tissue-specific promoter and enhancer activities. Deletion of the region disrupts egg laying, a phenotype also observed in bed-3 mutants, but with the severity correlating with the size of the deletion. This phenotype is not caused by overall reduction in bed-3 expression. Rather, deletions reduce bed-3 expression specifically in the mesoderm lineage. We found that bed-3 has a previously unknown function in the generation of sex myoblast (SM) cells from the M lineage, and deletions cause loss of SM cells leading to loss of vulval muscles required for egg laying. Furthermore, injection of dsRNA targeting non-coding transcripts from this region disrupted egg laying in the wild type but not in RNAi-defective mutants. Therefore, the region upstream of bed-3 is required for robust expression of bed-3 in a specific tissue, and non-coding transcripts may mediate this interaction.



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Transfer RNA modification and infection – Implications for pathogenicity and host responses

Publication date: Available online 31 January 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Cha San Koh, L. Peter Sarin
Transfer RNA (tRNA) molecules are sumptuously decorated with evolutionary conserved post-transcriptional nucleoside modifications that are essential for structural stability and ensure efficient protein translation. The tRNA modification levels change significantly in response to physiological stresses, altering translation in a number of ways. For instance, tRNA hypomodification leads to translational slowdown, disrupting protein homeostasis and reducing cellular fitness. This highlights the importance of proper tRNA modification as a determinant for maintaining cellular function and viability during stress. Furthermore, the expression of several microbial virulence factors is induced by changes in environmental conditions; a process where tRNA 2-thiolation is unequivocal for pathogenicity. In this review, we discuss the multifaceted implications of tRNA modification for infection by examining the roles of nucleoside modification in tRNA biology. Future development of novel methods and combinatory utilization of existing technologies will bring tRNA modification-mediated regulation of cellular immunity and pathogenicity to the limelight.



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PRDM14, a putative histone methyl-transferase, interacts with and decreases the stability and activity of the HOXA1 transcription factor

Publication date: Available online 20 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Amandine Draime, Laure Bridoux, Magali Belpaire, Tamara Pringels, Janne Tys, René Rezsohazy
Understanding how the activity of transcription factors like HOX proteins is regulated remains a widely open question. In a recent screen for proteins interacting with HOXA1, we identified a PRDM protein family member, PRDM14, which is known to be transiently co-expressed with HOXA1 in epiblast cells before their specification towards somatic versus germ cell fate. Here, we confirm PRDM14 is an interactor of HOXA1 and we identify the homeodomain of HOXA1 as well as the PR domain and Zinc fingers of PRDM14 to be required for the interaction. An 11-His repeat of HOXA1 previously highlighted to contribute to HOXA1-mediated protein-protein interactions is also involved. At a functional level, we provide evidence that HOXA1 displays an unexpectedly long half-life and demonstrate that PRDM14 can reduce the stability and affect the transcriptional activity of HOXA1.



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Regulation of the replication initiator DnaA in Caulobacter crescentus

Publication date: Available online 31 January 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Michele Felletti, Deike J. Omnus, Kristina Jonas
The decision to initiate DNA replication is a critical step in the cell cycle of all organisms. In nearly all bacteria, replication initiation requires the activity of the conserved replication initiation protein DnaA. Due to its central role in cell cycle progression, DnaA activity must be precisely regulated. This review summarizes the current state of DnaA regulation in the asymmetrically dividing α-proteobacterium Caulobacter crescentus, an important model for bacterial cell cycle studies. Mechanisms will be discussed that regulate DnaA activity and abundance under optimal conditions and in coordination with the asymmetric Caulobacter cell cycle. Furthermore, we highlight recent findings of how regulated DnaA synthesis and degradation collaborate to adjust DnaA abundance under stress conditions. The mechanisms described provide important examples of how DNA replication is regulated in an α-proteobacterium and thus represent an important starting point for the study of DNA replication in many other bacteria. This article is part of a Special Issue entitled: Dynamic gene expression, edited by Prof. Patrick Viollier.



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UHRF1 regulates CDH1 via promoter associated non-coding RNAs in prostate cancer cells

Publication date: Available online 18 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Elena Magnani, Filippo Macchi, Monica Mancini, Vanessa Lomazzi, Sara Cogliati, Christian Pistore, Martina Mandruzzato, Anne-Catherine Dock-Bregeon, Ian Marc Bonapace
Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region can affect the expression of the corresponding coding genes. It has been shown that sense-directed ncRNAs arising from the promoter region of the E-cadherin gene (CDH1) mediate its repression. Here, we show that an antisense-directed ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression. The binding of epigenetic regulators to paCRDH1-AS, indeed, prevents their localization to the chromatin on CDH1 promoter. Moreover, paRCDH1-AS silencing induces CDH1 repression and a switch of the epigenetic profile on the promoter towards a more closed chromatin. Using bioinformatic and experimental approaches we defined that the promoter of the paRCDH1-AS is shared with the E-cadherin gene, showing a bidirectional promoter activity. We found that UHRF1 controls both CDH1 and paRCDH1-AS by directly binding this bidirectional promoter region. Our study provides evidences, for the first time, that UHRF1 recruitment can be affected by promoter-associated non-coding RNAs, opening new perspective regarding the role of UHRF1 in these complex regulatory networks.



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Cdk-related kinase 9 regulates RNA polymerase II mediated transcription in Toxoplasma gondii

Publication date: Available online 18 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Abhijit S. Deshmukh, Pallabi Mitra, Ashok Kolagani, Rajkumar Gurupwar
Cyclin-dependent kinases are an essential part of eukaryotic transcriptional machinery. In Apicomplexan parasites, the role and relevance of the kinases in the multistep process of transcription seeks more attention given the absence of full repertoire of canonical Cdks and cognate cyclin partners. In this study, we functionally characterize T. gondii Cdk-related kinase 9 (TgCrk9) showing maximal homology to eukaryotic Cdk9. An uncanonical cyclin, TgCyclin L, colocalizes with TgCrk9 in the parasite nucleus and co-immunoprecipitate, could activate the kinase in-vitro. We identify two threonines in conserved T-loop domain of TgCrk9 that are important for its activity. The activated TgCrk9 phosphorylates C-terminal domain (CTD) of TgRpb1, the largest subunit of RNA polymerase II highlighting its role in transcription. Selective chemical inhibition of TgCrk9 affected serine 2 phosphorylation in the heptapeptide repeats of TgRpb1-CTD towards 3′ end of genes consistent with a role in transcription elongation. Interestingly, TgCrk9 kinase activity is regulated by the upstream TgCrk7 based CAK complex. TgCrk9 was found to functionally complement the role of its yeast counterpart Bur1 establishing its role as an important transcriptional kinase. In this study, we provide robust evidence that TgCrk9 is an important part of transcription machinery regulating gene expression in T. gondii.



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Interactions between RNAP III transcription machinery and tRNA processing factors

Publication date: Available online 9 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): G. Aneeshkumar Arimbasseri
Eukaryotes have at least three nuclear RNA polymerases to carry out transcription. While RNA polymerases I and II are responsible for ribosomal RNA transcription and messenger RNA transcription, respectively, RNA Polymerase III transcribes approximately up to 300 nt long noncoding RNAs, including tRNA. For all three RNAPs, the nascent transcripts generated undergo extensive post-transcriptional processing. Transcription of mRNAs by RNAP II and their processing are coupled with the aid of the C-terminal domain of the RNAP II. RNAP I transcription and the processing of its transcripts are co-localized to the nucleolus and to some extent, rRNA processing occurs co-transcriptionally. Here, I review the current evidence for the interaction between tRNA processing factors and RNA polymerase III. These interactions include the moonlighting functions of tRNA processing factors in RNAP III transcription and the indirect effect of tRNA transcription levels on tRNA modification machinery.



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Regulation of tRNA synthesis by the general transcription factors of RNA polymerase III - TFIIIB and TFIIIC, and by the MAF1 protein

Publication date: Available online 6 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Damian Graczyk, Małgorzata Cieśla, Magdalena Boguta
The synthesis of transfer RNA (tRNA) is directed by RNA polymerase III (Pol III) specialized in high-level transcription of short DNA templates. Pol III recruitment to tRNA genes is controlled by two general initiation factors, TFIIIB and TFIIIC. They are multi-protein complexes regulated at the level of expression of individual subunits, as well as through phosphorylation and interaction with partner proteins. Here, we describe particular aspects of TFIIIB and TFIIIC control in yeast and human cells. Under stress conditions, tRNA synthesis is negatively regulated by the MAF1 protein, which interacts directly with Pol III. Sequence and function of MAF1 are conserved among eukaryotic organisms from yeast to humans. MAF1 is a phosphoprotein which mediates diverse regulatory signals to Pol III. Interestingly, there is a subset of housekeeping tRNA genes, both in the yeast and human genome, which are less sensitive to MAF1-dependent repression. The possible mechanisms responsible for this differential regulation of tRNA synthesis by MAF1 are discussed.



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Pseudomonas aeruginosa zinc homeostasis: Key issues for an opportunistic pathogen

Publication date: Available online 2 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Manuel R. Gonzalez, Verena Ducret, Sara Leoni, Karl Perron
Zinc is an essential trace element for almost all living organisms. In the opportunistic bacterial pathogen Pseudomonas aeruginosa, zinc has been shown to play an important role in virulence, in colonization of the host organism and has also been shown to be involved in antibiotic resistance. P. aeruginosa possesses numerous systems enabling it to thrive in zinc-depleted conditions as well as high-zinc situations, two environments that are encountered during human infection. These capabilities account for its pathogenic strength. The main aim of this review is to focus on zinc homeostasis in P. aeruginosa and the genetic regulation of the systems involved. The interconnection with virulence, as well as the mechanism of co-regulation between metal and antibiotic resistance, are of prime interest for understanding the molecular mechanisms allowing P. aeruginosa to switch from its existence as a common environmental bacterium to a severe opportunistic pathogen. This article is part of a Special Issue entitled: Dynamic gene expression, edited by Prof. Patrick Viollier.



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One signal stimulates different transcriptional activation mechanisms

Publication date: February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 2
Author(s): Marina Yu. Mazina, Elena V. Kovalenko, Polina K. Derevyanko, Julia V. Nikolenko, Aleksey N. Krasnov, Nadezhda E. Vorobyeva
Transcriptional activation is often represented as a "one-step process" that involves the simultaneous recruitment of co-activator proteins, leading to a change in gene status. Using Drosophila developmental ecdysone-dependent genes as a model, we demonstrated that activation of transcription is instead a continuous process that consists of a number of steps at which different phases of transcription (initiation or elongation) are stimulated. Thorough evaluation of the behaviour of multiple transcriptional complexes during the early activation process has shown that the pathways by which activation proceeds for different genes may vary considerably, even in response to the same induction signal. RNA polymerase II recruitment is an important step that is involved in one of the pathways. RNA polymerase II recruitment is accompanied by the recruitment of a significant number of transcriptional coactivators as well as slight changes in the chromatin structure. The second pathway involves the stimulation of transcriptional elongation as its key step. The level of coactivator binding to the promoter shows almost no increase, whereas chromatin modification levels change significantly.

Graphical abstract

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Editorial Board

Publication date: February 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 2





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La involvement in tRNA and other RNA processing events including differences among yeast and other eukaryotes

Publication date: Available online 31 January 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Nathan H. Blewett, Richard J. Maraia
The conserved nuclear RNA-binding factor known as La protein arose in an ancient eukaryote, phylogenetically associated with another eukaryotic hallmark, synthesis of tRNA by RNA polymerase III (RNAP III). Because 3′-oligo(U) is the sequence-specific signal for transcription termination by RNAP III as well as the high affinity binding site for La, the latter is linked to the intranuclear posttranscriptional processing of eukaryotic precursor-tRNAs. The pre-tRNA processing pathway must accommodate a variety of substrates that are destined for both common steps as well as tRNA-specific events. The order of intranuclear pre-tRNA processing steps is mediated in part by three activities derived from interaction with La protein: 3′-end protection from untimely decay by 3′ exonucleases, nuclear retention and chaperone activity that helps prevent pre-tRNA misfolding and mischanneling into offline pathways. A focus of this perspective will be on differences between yeast and mammals in the subcellular partitioning of pre-tRNA intermediates and differential interactions with La. We review how this is most relevant to pre-tRNA splicing which occurs in the cytoplasm of yeasts but in nuclei of higher eukaryotes. Also divergent is La architecture, comprised of three RNA-binding domains in organisms in all examined branches of the eukaryal tree except yeast, which have lost the C-terminal RNA recognition motif-2α (RRM2α) domain. We also review emerging data that suggest mammalian La interacts with nuclear pre-tRNA splicing intermediates and may impact this branch of the tRNA maturation pathway. Finally, because La is involved in intranuclear tRNA biogenesis we review relevant aspects of tRNA-associated neurodegenerative diseases. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



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Compliance of Adolescent Girls to Repeated Deployments of Wrist-worn Accelerometers

AbstractPurposeTo determine the cross-sectional and cumulative compliance of adolescent girls to accelerometer wear at three deployment points and to identify variables associated with compliance.MethodsGirls from 20 secondary schools were recruited: 10 schools were participating in the 'Girls Active' intervention and 10 were control schools. Physical activity was measured using the GENEActiv accelerometer worn on the non-dominant wrist 24 hours/day for up to 7-days at baseline, 7-months and 14-months. Demographic and anthropometric characteristics were recorded.ResultsSeven valid days (≥16 hours) of accelerometer wear were obtained from 83%, 77% and 68% of girls at baseline (n = 1734), 7-months (n = 1381) and 14-months (n = 1326), respectively. 68% provided 7-valid days for both baseline and 7-months, 59% for baseline and 14-months and 52% for all three deployment points. Estimates of physical activity level from 3-days of measurement could be considered equivalent to a 7-day measure (i.e. they fell within a ±5% equivalence zone). Cross-sectionally, 3-valid days were obtained from at least 91% of girls; cumulatively, this was obtained from ≥88% of girls across any two deployment points and 84% of girls across all three deployment points. When controlling for clustering at school level and other potential predictors, physical activity level, being South Asian, being in the intervention group and prior compliance were positively associated with monitor wear.ConclusionCompliance reduced across deployment points, with the reduction increasing as the deployment points got further apart. High prior compliance and high physical activity level were associated with the most additional wear-time. Purpose To determine the cross-sectional and cumulative compliance of adolescent girls to accelerometer wear at three deployment points and to identify variables associated with compliance. Methods Girls from 20 secondary schools were recruited: 10 schools were participating in the 'Girls Active' intervention and 10 were control schools. Physical activity was measured using the GENEActiv accelerometer worn on the non-dominant wrist 24 hours/day for up to 7-days at baseline, 7-months and 14-months. Demographic and anthropometric characteristics were recorded. Results Seven valid days (≥16 hours) of accelerometer wear were obtained from 83%, 77% and 68% of girls at baseline (n = 1734), 7-months (n = 1381) and 14-months (n = 1326), respectively. 68% provided 7-valid days for both baseline and 7-months, 59% for baseline and 14-months and 52% for all three deployment points. Estimates of physical activity level from 3-days of measurement could be considered equivalent to a 7-day measure (i.e. they fell within a ±5% equivalence zone). Cross-sectionally, 3-valid days were obtained from at least 91% of girls; cumulatively, this was obtained from ≥88% of girls across any two deployment points and 84% of girls across all three deployment points. When controlling for clustering at school level and other potential predictors, physical activity level, being South Asian, being in the intervention group and prior compliance were positively associated with monitor wear. Conclusion Compliance reduced across deployment points, with the reduction increasing as the deployment points got further apart. High prior compliance and high physical activity level were associated with the most additional wear-time. Corresponding author: Alex Rowlands, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK. alex.rowlands@le.ac.uk. Tel: +44 116 258 8595 The Girls Active evaluation was funded by the NIHR Public Health Research Programme (13/90/30). Professors Davies and Khunti are NIHR Senior Investigators. University of Leicester authors are supported by the NIHR Leicester-Loughborough Biomedical Research Unit 92012-2017), the NIHR Leicester Biomedical Research Centre (2017-2022) and the Collaboration for leadership in Applied Health Research and Care (CLAHRC) East Midlands. The Girls Active evaluation was undertaken in collaboration with the Leicester Clinical Trials Unit, a UKCRC-registered clinical trials unit in receipt of NIHR CTU support funding. The Youth Sport trust or the aforementioned funders had no involvement in the data analysis, data interpretation, data collection, or writing of this manuscript. There are no other conflicts of interest. The results of the present study do not constitute endorsement by the ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. © 2018 American College of Sports Medicine

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Health-related Fitness in Preschool Children with and without Motor Delays

AbstractPurposeSchool-age children with Developmental Coordination Disorder (DCD) have poor health-related fitness (HRF), but little is known about when these deficits emerge. The purpose of this study was to determine if 4- and 5-year old children who meet the criteria for DCD exhibit poorer HRF than typically developing (TD) children, and if this relationship is mediated by vigorous physical activity (VPA) engagement.MethodsFive-hundred and ninety-two children participated (age 5.0±0.6 years) from the Coordination and Activity Tracking in CHildren (CATCH) study. Motor skills were assessed using the Movement Assessment Battery for Children-2 (MABC-2), with groups defined as having DCD (≤5th %ile), at risk for DCD (rDCD; 6th-16th%ile), and typically developing (TD; >16th percentile). Measures of body composition included body mass index, waist circumference, and body fat percentage. Musculoskeletal fitness assessments included standing long jump distance, as well as peak and mean power assessed using a 30s Wingate protocol on a pediatric cycle ergometer. Time to exhaustion on a progressive, treadmill test was used to determine aerobic fitness. Flexibility and VPA were assessed using a sit-and-reach test and 7-day accelerometry, respectively.ResultsChildren in the DCD group had the poorest musculoskeletal and aerobic fitness, whereas TD children had the highest. No differences in body composition among groups were found. Daily vigorous physical activity was similar among groups and did not explain HRF differences.ConclusionsPreschool children with DCD have decreased anaerobic and aerobic fitness compared to TD children; however, VPA and body composition appear to be less affected by DCD in the early years. Early motor interventions may be able to improve fitness and reduce the risk of hypoactivity and obesity as children with DCD get older. Purpose School-age children with Developmental Coordination Disorder (DCD) have poor health-related fitness (HRF), but little is known about when these deficits emerge. The purpose of this study was to determine if 4- and 5-year old children who meet the criteria for DCD exhibit poorer HRF than typically developing (TD) children, and if this relationship is mediated by vigorous physical activity (VPA) engagement. Methods Five-hundred and ninety-two children participated (age 5.0±0.6 years) from the Coordination and Activity Tracking in CHildren (CATCH) study. Motor skills were assessed using the Movement Assessment Battery for Children-2 (MABC-2), with groups defined as having DCD (≤5th %ile), at risk for DCD (rDCD; 6th-16th%ile), and typically developing (TD; >16th percentile). Measures of body composition included body mass index, waist circumference, and body fat percentage. Musculoskeletal fitness assessments included standing long jump distance, as well as peak and mean power assessed using a 30s Wingate protocol on a pediatric cycle ergometer. Time to exhaustion on a progressive, treadmill test was used to determine aerobic fitness. Flexibility and VPA were assessed using a sit-and-reach test and 7-day accelerometry, respectively. Results Children in the DCD group had the poorest musculoskeletal and aerobic fitness, whereas TD children had the highest. No differences in body composition among groups were found. Daily vigorous physical activity was similar among groups and did not explain HRF differences. Conclusions Preschool children with DCD have decreased anaerobic and aerobic fitness compared to TD children; however, VPA and body composition appear to be less affected by DCD in the early years. Early motor interventions may be able to improve fitness and reduce the risk of hypoactivity and obesity as children with DCD get older. Corresponding author: John Cairney, Faculty of Kinesiology and Physical Education, University of Toronto, 55 Harbord Street, WSB Rm 2044, Toronto ON, Canada M5S 2W6. 416-978-6563. john.cairney@utoronto.ca The CATCH study is funded by the Canadian Institutes of Health Research (MOP 126015). SKD is funded by an Ontario Women's Heath Scholars Award. BWT is supported by a Canada Research Chair in Child Health & Exercise Medicine. CM is supported by the Lillie Chair in Childhood Disability Research. The authors have no conflicts of interest to declare. The results of the present study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation and do not constitute endorsement by ACSM. © 2018 American College of Sports Medicine

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Acute Serum Cartilage Biomarker Response following Walking and Drop-Landing

ABSTRACTIntroductionAn in depth understanding of the healthy cartilage response to activities of daily living is needed to better understand the complex relationship between cartilage health and loading. The purpose was to assess the role of loading on the acute serum cartilage oligomeric matrix protein (COMP) response in recreationally active individuals.Methods40 individuals without previous lower extremity injury participated in this repeated measures study in which each participant completed all conditions during independent data collection sessions separated by at least one week. An antecubital blood draw was performed before and after walking, drop-landing, and control (i.e., sitting) conditions. Commercially available enzyme-linked immunosorbent assays measured COMP concentration. The acute COMP response was quantified as the percent change of COMP concentration from before to after each condition. A one-way, repeated measures ANOVA compared the acute COMP response between conditions. Post hoc Pearson product moment correlation and chi square analysis determined the relationship between the walking and drop-landing acute COMP response within individuals.ResultsAcute COMP response was greater following walking (+4.2, p=0.008) and drop-landing (+4.6%, p=0.002) compared to control (−2.3%), but did not differ between the walking and drop-landing conditions (p=0.596). The magnitudes of the acute COMP response during walking and drop-landing were correlated (r=0.56, p

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Blood Pressure Response during Cardiopulmonary Exercise Testing in Heart Failure

AbstractIntroductionThe prognostic value of peak VO2 and VE/VCO2 slope measured during cardiopulmonary exercise (CPX) testing has been well established in patients with advanced heart failure, but blood pressure response to exercise is less well characterized.MethodsWe retrospectively studied 151 outpatients who underwent CPX testing as part of an advanced heart failure (HF) evaluation. The outcome of interest was failure of medical management, defined by death, cardiac transplantation, or left ventricular assist device placement. Patients were stratified into tertiles by change in systolic blood pressure (SBP) ( 20 mmHg were associated with an increased hazard (HR 1.046, 95% CI 1.018, 1.075).ConclusionIn conclusion, changes in SBP during CPX testing provide additional prognostic information above standard clinical variables. The peculiar increase in risk noted in those with a rise in SBP > 20 mmHg is less clear and needs to be investigated further. Introduction The prognostic value of peak VO2 and VE/VCO2 slope measured during cardiopulmonary exercise (CPX) testing has been well established in patients with advanced heart failure, but blood pressure response to exercise is less well characterized. Methods We retrospectively studied 151 outpatients who underwent CPX testing as part of an advanced heart failure (HF) evaluation. The outcome of interest was failure of medical management, defined by death, cardiac transplantation, or left ventricular assist device placement. Patients were stratified into tertiles by change in systolic blood pressure (SBP) ( 20 mmHg were associated with an increased hazard (HR 1.046, 95% CI 1.018, 1.075). Conclusion In conclusion, changes in SBP during CPX testing provide additional prognostic information above standard clinical variables. The peculiar increase in risk noted in those with a rise in SBP > 20 mmHg is less clear and needs to be investigated further. Accepted for Publication: 14 February 2018 Corresponding Author: Zachary J. Il'Giovine, MD, Duke University Medical Center, 2301 Erwin Road Durham, NC 27710, USA, Email: zachary.il.giovine@dm.duke.edu The authors attest that the results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and statement that results of the present study do not constitute endorsement by ACSM. This manuscript was funded internally by the Duke Clinical Research Institute, Durham, NC. © 2018 American College of Sports Medicine

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Vascular Nitric Oxide–Superoxide Balance and Thrombus Formation after Acute Exercise

AbstractIntroductionAn acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity.MethodsAt different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (•O2-) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α.ResultsAn acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of •O2- in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations.ConclusionAn acute bout of strenuous exercise in mice reduced NO and in parallel increased •O2- production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased •O2- production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice. Introduction An acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity. Methods At different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (•O2-) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α. Results An acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of •O2- in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations. Conclusion An acute bout of strenuous exercise in mice reduced NO and in parallel increased •O2- production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased •O2- production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice. Accepted for Publication: 17 February 2018 Correspondence: Stefan Chlopicki, Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348 Krakow, Poland, e-mail: stefan.chlopicki@jcet.eu This work was supported by the National Science Centre, Poland, grant Preludium No. 2017/25/N/NZ4/02073. The authors declare no conflicts of interest. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification or inappropriate data manipulation. © 2018 American College of Sports Medicine

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Physical Activity and Bone Accretion: Isotemporal Modeling and Genetic Interactions

AbstractPurposeTo determine if replacing time spent in high and low impact physical activity (PA) predicts changes in pediatric bone mineral density (BMD) and content (BMC).MethodsWe analyzed data from the longitudinal Bone Mineral Density in Childhood Study (N=2,337 with up to 7 visits). The participants were aged 5-19 years at baseline, 51.2% were female and 80.6% were non-Black. Spine, total hip, and femoral neck areal BMD (aBMD) and total body less head (TBLH) BMC Z-scores were calculated. Hours per day (h/d) spent in high and low impact PA were self-reported. Standard covariate adjusted (partition model) and time allocation sensitive isotemporal substitution modeling frameworks were applied to linear mixed models. Statistical interactions with sex, self-reported ancestry, age and bone fragility genetic scores (percentage of aBMD lowering alleles carried) were tested.ResultsIn standard models, high impact PA was positively associated with bone Z-score at all four skeletal sites (e.g., TBLH-BMC Z-score: beta=0.05, P=2.0x10-22), whereas low impact PA was not associated with any of the bone Z-scores. In isotemporal substitution models, replacing 1 h/d of low-for-high impact PA was associated with higher bone Z-scores (e.g., TBLH-BMC Z-score: beta=0.06, P=2.9x10-15). Conversely, replacing 1 h/d of high-for-low impact PA was associated with lower bone Z-scores (e.g., TBLH-BMC Z-score: beta=-0.06, P=2.9x10-15). The substitution associations were similar for each sex and ancestry group, and for those with higher and lower genetic scores for bone fragility (P-interactions >0.05), but increased in strength among the older adolescents (P-age interactions 0.05), but increased in strength among the older adolescents (P-age interactions

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Exercise Training in “at Risk” Black and White Women: A Comparative Cohort Analyses

ABSTRACTPurposeFew data are available regarding the impact of exercise interventions in black women at risk for cardiovascular disease (CVD).MethodsWomen ≥18 years without known CVD with ≥1 coronary risk factor were enrolled in a community-based exercise program ≥3 days per/week for ≥30 min/session for 6 months. Exercise training intensity ~50[FIGURE DASH]80% of functional capacity, using heart rate (HR) and/or rating of perceived exertion (RPE) as the primary intensity modulators. Pre-versus post conditioning quality of life (QOL) assessments (depression and level of daytime sleepiness), dietary fat intake, Duke Activity Status Index (DASI score), changes in cardiovascular efficiency (systolic/diastolic blood pressure [SBP/DBP], HR, RPE during a standardized submaximal workload), and anthropometric measures, including body weight, body mass index (BMI), and waist circumference, were evaluated.ResultsOf 556 volunteers, 143 were excluded, leaving 413 women (222 white, 191 black; mean ± SD age = 61 ± 9) who met compliance criteria. Both groups demonstrated significant (P

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Predicting Diaphyseal Cortical Bone Status Using Measures of Muscle Force Capacity

AbstractPurposeMuscle cross sectional area (MCSA) is often used as a surrogate for the forces applied to bones during physical activity. Though MCSA is a strong predictor of cortical bone status, its use makes assumptions about the relationship between muscle size and force that are inaccurate. Furthermore, to measure MCSA and other muscle force surrogates typically requires expensive and/or radiative laboratory equipment. Thus, this study aimed to determine whether clinical lab- and field-based methodologies for measuring muscular force capacity accounted for similar variance in diaphyseal cortical bone status as a commonly used muscular force surrogate; MCSA, at the mid-tibia in young men and women.MethodsHealthy young adults (n = 142, 19.7 ± 0.7 yo, 52.8% female) were assessed via peripheral quantitative computed tomography at the mid-tibia for cortical bone status and MCSA. Muscle force capacity was measured via Biodex dynamometer, Nottingham leg extensor power rig, and Vertec vertical jump. Regression analysis compared the independent variance predicted by each muscle force measure to that of MCSA, accounting for relevant confounders.ResultsMCSA, knee extension peak torque, and peak anaerobic power from vertical jump were independent predictors of select cortical structural outcomes (cortical thickness and area, periosteal and endosteal circumference, and estimated strength) accounting for up to 78.4% of the variance explained (all p<.05 however cortical volumetric bone mineral density was unrelated to any measure or surrogate of muscle force capacity.conclusionsmcsa is a strong independent predictor structure both lab- and field-based measures peak torque anaerobic power are promising alternatives explaining similar sometimes greater variance than mcsa. purpose cross sectional area often used as for the forces applied bones during physical activity. though mcsa status its use makes assumptions about relationship between size that inaccurate. furthermore other surrogates typically requires expensive radiative laboratory equipment. thus this study aimed determine whether clinical methodologies measuring muscular capacity accounted in diaphyseal commonly at mid-tibia young men women. methods healthy adults yo female were assessed via peripheral quantitative computed tomography measured biodex dynamometer nottingham leg extensor rig vertec vertical jump. regression analysis compared predicted by each accounting relevant confounders. results knee extension from jump predictors select structural outcomes thickness periosteal endosteal circumference estimated strength up explained p capacity. conclusions accepted publication: february corresponding author: simon higgins department exercise science koury center elon university campus box nc telephone: e-mail: shiggins8 no sources funding preparation manuscript. presented clearly honestly without fabrication falsification inappropriate data manipulation. authors declare conflict interest. present do not constitute endorsement american college sports medicine. medicine>

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Physical Activity Alters Inflammation in Older Adults by Different Intensity Levels

AbstractPurposeTo examine the influence of reallocating time spent at different objectively measured physical activity (PA) behaviours on markers of systemic inflammation in older women with different levels of metabolic risk.MethodsAccelerometer-based monitoring of PA was conducted in a population of community-dwelling older women (n = 111; age = 65-70 yr) for determination of daily sedentary time, time in light (LPA) and moderate-to-vigorous physical activity (MVPA). Blood samples were collected for the assessment of the systemic inflammatory markers CRP, fibrinogen and adiponectin. Metabolic risk was assessed by standardized procedures based on definitions for the metabolic syndrome. Data were analysed by linear regression models based on isotemporal substitution analysis.ResultsReallocating 30 minutes of sedentary time with either time in LPA (β = -0.47; p

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Evaluating personality as a moderator of the association between life events stress and cardiovascular reactivity to acute stress

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Publication date: Available online 24 February 2018
Source:International Journal of Psychophysiology
Author(s): Stephen Gallagher, Adam O'Riordan, Grace McMahon, Ann-Marie Creaven
The present study investigated the possible interaction between life events stress and personality in predicting cardiovascular stress responses. Participants (N = 184) completed psychometric measures of life event stress and personality styles and had cardiovascular responses monitored during a standardised stress testing protocol. In adjusted models, the observed blunted association between life event stress and SBP and DBP was moderated by openness; this was more evident at −1SD below the mean openness value. Further, the association between life event stress and TPR vascular resistance was found to be moderated by conscientiousness. In particular, we found conscientiousness at both the mean and 1SD above the mean buffered against the negative impact of life stress on TPR reactivity. The findings are discussed in relation to theory and future directions.



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Dissociating absolute and relative reward- and punishment-related electrocortical processing: An event-related potential study

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Publication date: Available online 24 February 2018
Source:International Journal of Psychophysiology
Author(s): Miles Wischnewski, Dennis J.L.G. Schutter
The meaning of reward and punishment signals depends on context. Receiving a small reward where a larger reward could have been obtained can be considered a punishment, while a small loss in the context of avoiding a larger loss can be experienced as a reward. The aim of this study was to investigate the electrophysiological processes associated with absolute and relative reward and punishment signals. Twenty healthy right-handed volunteers performed a decision-making task and were instructed to judge which of two neutral objects was the most expensive. The received outcome was presented together with the non-received outcome for the alternative choice. The feedback-related potentials P200, FRN and P300 were recorded in response to absolute (i.e., received) outcome and relative (i.e., received in the context of the alternative) outcome. Absolute rewards yielded higher P200 amplitudes as compared to relative rewards, while the P200 amplitude was largest for relative as compared to absolute punishments. The P300 amplitude showed a main effect of valence with larger amplitudes for more positive relative and absolute outcomes. No effect of absolute or relative outcome was observed for the feedback-related negativity (FRN). Our findings suggest distinct processes associated with context-dependent and context-independent processing during feedback processing.



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Correction to: The Effect of a Change Agent on Use of Evidence-Based Mental Health Practices

Abstract

The original version of this article unfortunately contained a mistake.



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Pain-motor Integration and Chronic Pain: One Step Ahead

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Publication date: Available online 24 February 2018
Source:Clinical Neurophysiology
Author(s): A. Di Santo, F. Asci, A. Suppa




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Laser evoked potential amplitude and laser-pain rating reduction during high-frequency non-noxious somatosensory stimulation

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Publication date: Available online 24 February 2018
Source:Clinical Neurophysiology
Author(s): Massimiliano Valeriani, Costanza Pazzaglia, Vincenzo Rizzo, Angelo Quartarone, Catello Vollono
ObjectiveTo investigate the mechanism subtending the analgesic effect of high frequency non-painful somatosensory stimulation.MethodsLaser evoked potentials (LEPs) and laser-pain rating were obtained from healthy subjects to stimulation of different parts of the body. LEPs were recorded at baseline and during non-painful electrical stimulation of the superficial branch of the right radial nerve (RRES).ResultsRRES reduced N2/P2 LEP amplitude to right radial (F(8,10)=82.4, p<0.001), left radial (F(8,10)=22.2, p<0.001), and right ulnar (F(8,10)=7.2, p=0.008) stimulation, while the N2/P2 amplitude to left ulnar territory stimulation remained unchanged (F(8,10)=3.6, p=0.07). The laser-pain rating was reduced by RRES to bilateral radial territory stimulation (p<0.05). In a control experiment, laser-pain rating and LEPs to left foot stimulation were not modified by RRES (p>0.05).ConclusionsOur study confirms that the non-nociceptive afferents dampen the nociceptive input. The spatial pattern of this interaction suggests that, when conditioning higher frequency non-painful stimulation is used, the inhibition takes place at the spinal cord.SignificanceOur experimental design reproduces what happens when non-painful somatosensory stimuli are used to reduce pain, such as rubbing a wound or during transcutaneous electrical nerve stimulation. Therefore, in these situations the analgesia is likely to occur at the spinal cord level.



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