Redirection of miRNA-Argonaute Complexes to Specific Target Sites by Synthetic Adaptor Molecules.

Dysregulation of miRNAs is connected with a multitude of diseases for which antagomirs and miRNA replacement are discussed as therapeutic options. Here, we suggest an alternative concept based on the redirection of RISCs to non-native target sites. Metabolically stable DNA-LNA mixmers are used to mediate the binding of RISCs to mRNAs without any direct base complementarity to the presented guide RNA strand. Physical redirection of a dye-labeled miRNA model and of specific miRNA-programmed RISC fractions present in HeLa extracts is demonstrated by pull-down experiments with biotinylated capture oligonucleotides.

Quantification of the Central Cardiovascular Network Applying the Normalized Short-time Partial Directed Coherence Approach in Healthy Subjects.

BACKGROUND: The central control of the autonomic nervous system (ANS) and the complex interplay of its components can be described by a functional integrated mode - the central autonomic network (CAN). CAN represents the integrated functioning and interaction between the central nervous system (CNS) and ANS (parasympathetic and sympathetic activity). OBJECTIVE: This study investigates the central cardiovascular network (CCVN) as a part of the CAN, during which heart rate (HR), systolic blood pressure (SYS) and frontal EEG activity in 21 healthy subjects (CON) will be analysed. The objective of this study is to determine how these couplings (central-cardiovascular) are composed by the different regulatory aspects of the CNS-ANS interaction. METHODS: To quantify the short-term instantaneous causal couplings within the CCVN, the normalized short time partial directed coherence (NSTPDC) approach was applied. It is based on an m-dimensional MAR process to determine Granger causality in the frequency domain. RESULTS: We found that CCVN were of bidirectional character, and that the causal influences of central activity towards HR were stronger than those towards systolic blood pressure. This suggests that the central-cardiac closed-loop regulation process in CON focuses mainly on adapting the heart rate via the sinoatrial node rather than focusing on SYS. The CNS-ANS coupling directions with respect to central spectral power bands were characterized as mostly bidirectional, where HR and SYS acted as drivers in nearly every frequency band (unidirectional for α, α1 and α2). CONCLUSION: This study provides a more indepth understanding of the interplay of neuronal and autonomic cardiovascular regulatory processes in healthy subjects, as well as a greater insight into the complex CAN.

Central- and autonomic nervous system coupling in schizophrenia.

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback-feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central-autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age-gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS-ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity.