Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
Published: February 2012
AI Article Synopsis
Article Abstract
The formation of replication compartments, the subnuclear structures in which the viral DNA genome is replicated, is a hallmark of herpesvirus infections. The localization of proteins and viral DNA within human cytomegalovirus replication compartments is not well characterized. Immunofluorescence analysis demonstrated the accumulation of the viral DNA polymerase subunit UL44 at the periphery of replication compartments and the presence of different populations of UL44 in infected cells. In contrast, the viral single-stranded-DNA binding protein UL57 was distributed throughout replication compartments. Using "click chemistry" to detect 5-ethynyl-2'-deoxyuridine (EdU) incorporation into replicating viral DNA and pulse-chase protocols, we found that viral DNA synthesis occurs at the periphery of replication compartments and that replicated viral DNA subsequently localizes to the interior of replication compartments. The interiors of replication compartments also contain regions in which UL44 and EdU-labeled DNA are absent. The treatment of cells with a viral DNA polymerase inhibitor reversibly caused the dispersal of both UL44 and EdU-labeled viral DNA from replication compartments, indicating that ongoing viral DNA synthesis is necessary to maintain the organization of replication compartments. Our results reveal a previously unappreciated complexity of the organization of human cytomegalovirus replication compartments.
Viroids are single-stranded circular noncoding RNAs that mainly infect crops. Upon infection, nuclear-replicating viroids engage host DNA-dependent RNA polymerase II for RNA-templated transcription, which is facilitated by a host protein TFIIIA-7ZF. The sense-strand and minus-strand RNA intermediates are differentially localised to the nucleolus and nucleoplasm regions, respectively.
The peptidoglycan manifests as a multifaceted component of the bacterial cell wall. Throughout the lifecycle of the bacterium, the peptidoglycan is deconstructed, rebuilt, and remodeled for bacterial cell growth and replication. Degradation products of the peptidoglycan serve as precursors for cell-wall building blocks via recycling processes and as signaling molecules.
PET analysis is conventionally performed as a two-stage process of quantification followed by analysis. We recently introduced SiMBA (Simultaneous Multifactor Bayesian Analysis), a hierarchical model that performs quantification and analysis for all brain regions of all individuals at once, and in so doing improves both the accuracy of parameter estimation as well as inferential efficiency. However until now, SiMBA has only been implemented for the two-tissue compartment model.
Background: Despite established antiviral therapy for herpes simplex (HSV), varicella zoster (VZV) and cytomegalovirus (CMV) encephalitis, outcome remains poor.
Objectives: To assess pharmacokinetic (PK) and -dynamic (PD) data of antiviral drugs in the central nervous system (CNS) to optimize treatment of Herpesviridae encephalitis.
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Background: Finding appropriate model parameters for multi-compartmental neuron models can be challenging. Parameters such as the leak and axial conductance are not always directly derivable from neuron observations but are crucial for replicating desired observations. The objective of this study is to replicate the attenuation behavior of an excitatory postsynaptic potential (EPSP) traveling along a linear chain of compartments on the analog BrainScaleS-2 neuromorphic hardware platform.
