scholarly journals Salicylic Acid Inhibits the Replication of Tomato bushy stunt virus by Directly Targeting a Host Component in the Replication Complex

2015 ◽  
Vol 28 (4) ◽  
pp. 379-386 ◽  
Author(s):  
Miaoying Tian ◽  
Zsuzsanna Sasvari ◽  
Paulina Alatriste Gonzalez ◽  
Giulia Friso ◽  
Elden Rowland ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Rna Virus ◽  
Tomato Bushy Stunt Virus ◽  
Glycolytic Enzyme ◽  
Replication Complex ◽  
Important Host ◽  
Underlying Mechanisms ◽  
Gapdh Protein

Although the plant hormone salicylic acid (SA) plays a central role in signaling resistance to viral infection, the underlying mechanisms are only partially understood. Identification and characterization of SA’s direct targets have been shown to be an effective strategy for dissecting the complex SA-mediated defense signaling network. In search of additional SA targets, we previously developed two sensitive approaches that utilize SA analogs in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology to identify and evaluate candidate SA-binding proteins (SABPs) from Arabidopsis. Using these approaches, we have now identified several members of the Arabidopsis glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein family, including two chloroplast-localized and two cytosolic isoforms, as SABPs. Cytosolic GAPDH is a well-known glycolytic enzyme; it also is an important host factor involved in the replication of Tomato bushy stunt virus (TBSV), a single-stranded RNA virus. Using a yeast cell-free extract, an in vivo yeast replication system, and plant protoplasts, we demonstrate that SA inhibits TBSV replication. SA does so by inhibiting the binding of cytosolic GAPDH to the negative (−)RNA strand of TBSV. Thus, this study reveals a novel molecular mechanism through which SA regulates virus replication.

scholarly journals Selectivity of pyramidal cells and interneurons in the human medial temporal lobe

2011 ◽  
Vol 106 (4) ◽  
pp. 1713-1721 ◽  
Author(s):  
Matias J. Ison ◽  
Florian Mormann ◽  
Moran Cerf ◽  
Christof Koch ◽  
Itzhak Fried ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Visual Information ◽  
Medial Temporal Lobe ◽  
Pyramidal Cells ◽  
Hierarchical Processing ◽  
Plausible Mechanism ◽  
Underlying Mechanisms ◽  
Identification And Characterization

Neurons in the medial temporal lobe (MTL) respond selectively to pictures of specific individuals, objects, and places. However, the underlying mechanisms leading to such degree of stimulus selectivity are largely unknown. A necessary step to move forward in this direction involves the identification and characterization of the different neuron types present in MTL circuitry. We show that putative principal cells recorded in vivo from the human MTL are more selective than putative interneurons. Furthermore, we report that putative hippocampal pyramidal cells exhibit the highest degree of selectivity within the MTL, reflecting the hierarchical processing of visual information. We interpret these differences in selectivity as a plausible mechanism for generating sparse responses.

scholarly journals Cardioprotective Natural Compound Pinocembrin Attenuates Acute Ischemic Myocardial Injury via Enhancing Glycolysis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yanjun Zheng ◽  
Guoqing Wan ◽  
Bo Yang ◽  
Xuefeng Gu ◽  
Jingrong Lin
Keyword(s):  
Contractile Function ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Glycolytic Enzyme ◽  
Isolated Rat Heart ◽  
Cardiac Contractile Function ◽  
Direct Stimulation ◽  
Underlying Mechanisms

Purpose. Emerging evidence has shown that pinocembrin protects the myocardium from ischemic injury in animals. However, it is unknown whether it has cardioprotection when given at the onset of reperfusion. Also, mechanisms mediating the cardioprotective actions of pinocembrin were largely unknown. Thus, this study is aimed at investigating the effects of pinocembrin postconditioning on ischemia-reperfusion (I/R) injury and the underlying mechanisms. Methods. The in vivo mouse model of myocardial I/R injury, ex vivo isolated rat heart with global I/R, and in vitro hypoxia/reoxygenation (H/R) injury model for primary cardiomyocytes were used. Results. We found that pinocembrin postconditioning significantly reduced the infarct size and improved cardiac contractile function after acute myocardial I/R. Mechanically, in primary cardiomyocytes, we found that pinocembrin may confer protection in part via direct stimulation of cardiac glycolysis via promoting the expression of the glycolytic enzyme, PFKFB3. Besides, PFKFB3 inhibition abolished pinocembrin-induced glycolysis and protection in cardiomyocytes. More importantly, PFKFB3 knockdown via cardiotropic adeno-associated virus (AAV) abrogated cardioprotective effects of pinocembrin. Moreover, we demonstrated that HIF1α is a key transcription factor driving pinocembrin-induced PFKFB3 expression in cardiomyocytes. Conclusions. In conclusion, these results established that the acute cardioprotective benefits of pinocembrin are mediated in part via enhancing PFKFB3-mediated glycolysis via HIF1α, which may provide a new therapeutic target to impede the progression of myocardial I/R injury.

scholarly journals Ngoye virus: a novel evolutionary lineage within the genus Flavivirus

2006 ◽  
Vol 87 (11) ◽  
pp. 3273-3277 ◽  
Author(s):  
Gilda Grard ◽  
Jean-Jacques Lemasson ◽  
Massamba Sylla ◽  
Audrey Dubot ◽  
Shelley Cook ◽  
...  
Keyword(s):  
Rna Virus ◽  
Structural Genes ◽  
Degenerate Primers ◽  
Newborn Mice ◽  
Replication Complex ◽  
Viral Particles ◽  
The Family ◽  
Intracerebral Infection ◽  
Distinct Phylogenetic Lineage

By using degenerate primers deduced from conserved patterns in the flavivirus polymerase gene, a novel RNA virus was discovered in Rhipicephalus ticks sampled from members of the family Bovidae in Senegal. It was named Ngoye virus (NGOV) after the location from which it was isolated. Viral particles could be observed by electron microscopy, but isolation in vertebrate or invertebrate cell lines or by intracerebral infection of newborn mice remained unsuccessful. This is atypical of recognized arboviruses. The characterization of 4176 nt of the non-structural genes revealed that NGOV is a novel flavivirus species. It forms a distinct phylogenetic lineage related distantly to previously identified members of the genus Flavivirus. Analysis of genetic data suggested that the processing of the NGOV polyprotein and the organization of its replication complex are similar to those of flaviviruses. Together with other recent data, these findings suggest that a large number of viruses related distantly to ‘classical’ arthropod-borne flaviviruses remain to be discovered.

scholarly journals Runx1 regulates embryonic myeloid fate choice in zebrafish through a negative feedback loop inhibiting Pu.1 expression

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5239-5249 ◽  
Author(s):  
Hao Jin ◽  
Li Li ◽  
Jin Xu ◽  
Fenghua Zhen ◽  
Lu Zhu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Wide Spectrum ◽  
Negative Feedback Loop ◽  
Fate Decision ◽  
Underlying Mechanisms ◽  
Regulatory Loop

Abstract Proper cell fate choice in myelopoiesis is essential for generating correct numbers of distinct myeloid subsets manifesting a wide spectrum of subset-specific activities during development and adulthood. Studies have suggested that myeloid fate choice is primarily regulated by transcription factors; however, new intrinsic regulators and their underlying mechanisms remain to be elucidated. Zebrafish embryonic myelopoiesis gives rise to neutrophils and macrophages and represents a promising system to derive new regulatory mechanisms for myeloid fate decision in vertebrates. Here we present an in vivo study of cell fate specification during zebrafish embryonic myelopoiesis through characterization of the embryos with altered Pu.1, Runx1 activity alone, or their combinations. Genetic analysis shows that low and high Pu.1 activities determine embryonic neutrophilic granulocyte and macrophage fate, respectively. Inactivation and overexpression of Runx1 in zebrafish uncover Runx1 as a key embryonic myeloid fate determinant that favors neutrophil over macrophage fate. Runx1 is induced by high Pu.1 level and in turn transrepresses pu.1 expression, thus constituting a negative feedback loop that fashions a favorable Pu.1 level required for balanced fate commitment to neutrophils versus macrophages. Our findings define a Pu.1-Runx1 regulatory loop that governs the equilibrium between distinct myeloid fates by assuring an appropriate Pu.1 dosage.

scholarly journals Characterization of mosquito-adapted West Nile virus

2008 ◽  
Vol 89 (7) ◽  
pp. 1633-1642 ◽  
Author(s):  
Alexander T. Ciota ◽  
Amy O. Lovelace ◽  
Yongqing Jia ◽  
Lauren J. Davis ◽  
David S. Young ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Nucleotide Substitutions ◽  
West Nile ◽  
Mutant Spectrum ◽  
Underlying Mechanisms ◽  
Virus Adaptation ◽  
Cell Spread

West Nile virus (WNV), a mosquito-borne flavivirus, has significantly expanded its geographical and host range since its 1999 introduction into North America. The underlying mechanisms of evolution of WNV and other arboviruses are still poorly understood. Studies evaluating virus adaptation and fitness in relevant in vivo systems are largely lacking. In order to evaluate the capacity for host-specific adaptation and the genetic correlates of adaptation in vivo, this study measured phenotypic and genotypic changes in WNV resulting from passage in Culex pipiens mosquitoes. An increase in replicative ability of WNV in C. pipiens was attained for the two lineages of WNV tested. This adaptation for replication in mosquitoes did not result in a replicative cost in chickens, but did decrease cell-to-cell spread of virus in vertebrate cell culture. Genetic analyses of one mosquito-adapted lineage revealed a total of nine consensus nucleotide substitutions with no accumulation of a significant mutant spectrum. These results differed significantly from previous in vitro studies. When St Louis encephalitis virus (SLEV), a closely related flavivirus, was passaged in C. pipiens, moderately attenuated growth in C. pipiens was observed for two lineages tested. These results suggest that significant differences in the capacity for mosquito adaptation may exist between WNV and SLEV, and demonstrate that further comparative studies in relevant in vivo systems will help elucidate the still largely unknown mechanisms of arboviral adaptation in ecologically relevant hosts.

scholarly journals A Primary Determinant of Cap-Independent Translation Is Located in the 3′-Proximal Region of the Tomato Bushy Stunt Virus Genome

1999 ◽  
Vol 73 (11) ◽  
pp. 8982-8988 ◽  
Author(s):  
Baodong Wu ◽  
K. Andrew White
Keyword(s):  
Rna Virus ◽  
Present Report ◽  
Tomato Bushy Stunt Virus ◽  
Translational Efficiency ◽  
Genome Replication ◽  
Appreciable Effect ◽  
Positive Strand Rna ◽  
Independent Translation

ABSTRACT Tomato bushy stunt virus (TBSV) is a positive-strand RNA virus and is the prototype member of the genus Tombusvirus. The genomes of members of this genus are not polyadenylated, and prevailing evidence supports the absence of a 5′ cap structure. Previously, a 167-nucleotide-long segment (region 3.5) located near the 3′ terminus of the TBSV genome was implicated as a determinant of translational efficiency (S.K. Oster, B. Wu and K. A. White, J. Virol. 72:5845–5851, 1998). In the present report, we provide evidence that a 3′-proximal segment of the genome, which includes region 3.5, is involved in facilitating cap-independent translation. Our results indicate that (i) a 5′ cap structure can substitute functionally for the absence of region 3.5 in viral and chimeric reporter mRNAs in vivo; (ii) deletion of region 3.5 from viral and chimeric mRNAs has no appreciable effect on message stability; (iii) region 3.5 represents part of a larger 3′ proximal element, designated as the 3′ cap-independent translational enhancer (3′CITE), that is required for proficient cap-independent translation; (iv) the 3′CITE also facilitates cap-dependent translation; (v) none of the major viral proteins are required for 3′CITE activity; and (vi) no significant 3′CITE-dependent stimulation of translation was observed when mRNAs were tested in vitro in wheat germ extract under various assay conditions. This latter property distinguishes the 3′CITE from other characterized plant viral 3′-proximal cap-independent translational enhancers. Additionally, because the 3′CITE overlaps withcis-acting replication signals, it could potentially participate in regulating the initiation of genome replication.

scholarly journals Characterization of immune cell migration using microfabrication

2021 ◽  
Author(s):  
Doriane Vesperini ◽  
Galia Montalvo ◽  
Bin Qu ◽  
Franziska Lautenschläger
Keyword(s):  
Cell Migration ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Advantages And Disadvantages ◽  
Infected Cells ◽  
Immune Cell Migration ◽  
Underlying Mechanisms

AbstractThe immune system provides our defense against pathogens and aberrant cells, including tumorigenic and infected cells. Motility is one of the fundamental characteristics that enable immune cells to find invading pathogens, control tissue damage, and eliminate primary developing tumors, even in the absence of external treatments. These processes are termed “immune surveillance.” Migration disorders of immune cells are related to autoimmune diseases, chronic inflammation, and tumor evasion. It is therefore essential to characterize immune cell motility in different physiologically and pathologically relevant scenarios to understand the regulatory mechanisms of functionality of immune responses. This review is focused on immune cell migration, to define the underlying mechanisms and the corresponding investigative approaches. We highlight the challenges that immune cells encounter in vivo, and the microfabrication methods to mimic particular aspects of their microenvironment. We discuss the advantages and disadvantages of the proposed tools, and provide information on how to access them. Furthermore, we summarize the directional cues that regulate individual immune cell migration, and discuss the behavior of immune cells in a complex environment composed of multiple directional cues.

scholarly journals Roles of MicroRNAs in Osteogenesis or Adipogenesis Differentiation of Bone Marrow Stromal Progenitor Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7210
Author(s):  
Ya-Li Zhang ◽  
Liang Liu ◽  
Yaser Peymanfar ◽  
Paul Anderson ◽  
Cory J. Xian
Keyword(s):  
Bone Marrow ◽  
Bone Growth ◽  
Target Genes ◽  
Microrna Regulation ◽  
Growth Defects ◽  
Multipotent Cells ◽  
Underlying Mechanisms

Bone marrow stromal cells (BMSCs) are multipotent cells which can differentiate into chondrocytes, osteoblasts, and fat cells. Under pathological stress, reduced bone formation in favour of fat formation in the bone marrow has been observed through a switch in the differentiation of BMSCs. The bone/fat switch causes bone growth defects and disordered bone metabolism in bone marrow, for which the mechanisms remain unclear, and treatments are lacking. Studies suggest that small non-coding RNAs (microRNAs) could participate in regulating BMSC differentiation by disrupting the post-transcription of target genes, leading to bone/fat formation changes. This review presents an emerging concept of microRNA regulation in the bone/fat formation switch in bone marrow, the evidence for which is assembled mainly from in vivo and in vitro human or animal models. Characterization of changes to microRNAs reveals novel networks that mediate signalling and factors in regulating bone/fat switch and homeostasis. Recent advances in our understanding of microRNAs in their control in BMSC differentiation have provided valuable insights into underlying mechanisms and may have significant potential in development of new therapeutics.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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