System In Regulation Research Articles

Involvement of noradrenergic system in fear regulation

Involvement of noradrenergic system in fear regulation

Pulsed Electric Fields Alter Expression of NF-κB Promoter-Controlled Gene.

The possibility to artificially adjust and fine-tune gene expression is one of the key milestones in bioengineering, synthetic biology, and advanced medicine. Since the effects of proteins or other transgene products depend on the dosage, controlled gene expression is required for any applications, where even slight fluctuations of the transgene product impact its function or other critical cell parameters. In this context, physical techniques demonstrate optimistic perspectives, and pulsed electric field technology is a potential candidate for a noninvasive, biophysical gene regulator, exploiting an easily adjustable pulse generating device. We exposed mammalian cells, transfected with a NF-κB pathway-controlled transcription system, to a range of microsecond-duration pulsed electric field parameters. To prevent toxicity, we used protocols that would generate relatively mild physical stimulation. The present study, for the first time, proves the principle that microsecond-duration pulsed electric fields can alter single-gene expression in plasmid context in mammalian cells without significant damage to cell integrity or viability. Gene expression might be upregulated or downregulated depending on the cell line and parameters applied. This noninvasive, ligand-, cofactor-, nanoparticle-free approach enables easily controlled direct electrostimulation of the construct carrying the gene of interest; the discovery may contribute towards the path of simplification of the complexity of physical systems in gene regulation and create further synergies between electronics, synthetic biology, and medicine.

Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.

AimSymptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many of these processes are regulated by circadian function, circadian rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence for neurobiological and behavioral mechanisms pertinent to BD.MethodDrawing upon expertise in animal models, biomarkers, physiology, and behavior, CTF analyzed the relevant cross‐disciplinary literature to precisely frame the discussion around circadian rhythm disruption in BD, highlight key findings, and for the first time integrate findings across levels of analysis to develop an internally consistent, coherent theoretical framework.ResultsEvidence from multiple sources implicates the circadian system in mood regulation, with corresponding associations with BD diagnoses and mood‐related traits reported across genetic, cellular, physiological, and behavioral domains. However, circadian disruption does not appear to be specific to BD and is present across a variety of high‐risk, prodromal, and syndromic psychiatric disorders. Substantial variability and ambiguity among the definitions, concepts and assumptions underlying the research have limited replication and the emergence of consensus findings.ConclusionsFuture research in circadian rhythms and its role in BD is warranted. Well‐powered studies that carefully define associations between BD‐related and chronobiologically‐related constructs, and integrate across levels of analysis will be most illuminating.

Optimal configuration of battery energy storage system in primary frequency regulation

This article proposes a novel capacity optimization configuration method of battery energy storage system (BESS) considering the rate characteristics in primary frequency regulation to improve the power system frequency regulation capability and performance. By analyzing the charge or discharge rate characteristics of BESS, combined with the equivalent conversion method of the action time at different rates, the capacity optimization configuration method of BESS for frequency regulation considering the rate characteristic is proposed. Taking typical peak load working condition of a certain power grid as an example, the capacity configuration of three batteries (BESS 1, BESS 2 and BESS 3) considering the rate characteristics under different control methods is compared and analyzed. The results show that rate characteristics take most advantages of the corresponding control method and the high rate battery, and BESS requires a much lower capacity configuration for the same effect in grid frequency regulation. This indicates that the proposed optimal configuration method for BESS considering rate characteristics in frequency regulation can effectively reduce the configuration capacity, and this helps to realize the economic potential of BESS.

The Selective NMDA Receptor GluN2B Subunit Antagonist CP-101,606 with Antidepressant Properties Modulates Cytochrome P450 Expression in the Liver.

Recent research indicates that selective NMDA receptor GluN2B subunit antagonists may become useful for the treatment of major depressive disorders. We aimed to examine in parallel the effect of the selective NMDA receptor GluN2B subunit antagonist CP-101,606 on the pituitary/serum hormone levels and on the regulation of cytochrome P450 in rat liver. CP-101,606 (20 mg/kg ip. for 5 days) decreased the activity of CYP1A, CYP2A, CYP2B, CYP2C11 and CYP3A, but not that of CYP2C6. The alterations in enzymatic activity were accompanied by changes in the CYP protein and mRNA levels. In parallel, a decrease in the pituitary growth hormone-releasing hormone, and in serum growth hormone and corticosterone (but not T3 and T4) concentration was observed. After a 3-week administration period of CP-101,606 less changes were found. A decrease in the CYP3A enzyme activity and protein level was still maintained, though no change in the mRNA level was found. A slight decrease in the serum concentration of corticosterone was also maintained, while GH level returned to the control value. The obtained results imply engagement of the glutamatergic system in the neuroendocrine regulation of cytochrome P450 and potential involvement of drugs acting on NMDA receptors in metabolic drug–drug interactions.

Морфофункциональные показатели подростков, проживающих в городской и сельской местности севера Красноярского края

This paper analyses the morphofunctional parameters of 14–16-year-old adolescents living in urban (Lesosibirsk) and rural (Bor) areas in the north of Krasnoyarsk Krai. Based on the Quetelet index, boys and girls were divided into overweight (3.1 and 5.1 % respectively) and underweight (5.1 and 37.5 % respectively). Thus, the largest proportion of adolescents with a body weight deficit was recorded among boys (37.5 %). Reserve fat below the norm (< 11 %) was identified in 41 % of boy from Lesosibirsk and 80 % of boys from Bor. Moreover, in 9 % of the boys this parameter was critically low (3–4 %), which indicates dystrophy. The somatotype analysis revealed a weak development of the endomorphic component in all the groups under study, with the exception of girls from Lesosibirsk. Especially low values of this indicator were identified among boys from Bor (1.4 ± 0.2 points). All the subjects showed a decrease in respiratory parameters, namely, vital capacity was lower than the norm (р < 0.05) in girls by 0.9–1.1 litres and in boys by 0.5–0.7 litres. In general, vital capacity and peak expiratory flow were lower in adolescents from urban areas than in those from rural areas. The share of adolescents with an increased heart rate (> 90 beats/min) was largest among girls from Lesosibirsk (38 %); this group also had the biggest share of subjects with high Baevsky Stress Index (45 %). The share of subjects with high Baevsky Stress Index among boys varied in the range of 23.5–26.6 % and in girls, of 38.9–45.0 %. On the whole, the analysis of variational pulsometry parameters demonstrated a balance of the autonomic nervous system in heart regulation in 47.1–73.3 % of the subjects.

Impacts of wind farms with multi-terminal HVDC system in frequency regulation using quasi-opposition pathfinder algorithm

Impacts of wind farms with multi-terminal HVDC system in frequency regulation using quasi-opposition pathfinder algorithm

Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions.

Increasing evidence indicates that the melanocortin system is not only a central player in energy homeostasis, food intake and glucose level regulation, but also in the modulation of cardiovascular functions, such as blood pressure and heart rate. The melanocortins, and in particular α- and γ-MSH, have been shown to exert their cardiovascular activity both at the central nervous system level and in the periphery (e.g., in the adrenal gland), binding their receptors MC3R and MC4R and influencing the activity of the sympathetic nervous system. In addition, some studies have shown that the activation of MC3R and MC4R by their endogenous ligands is able to improve the outcome of cardiovascular diseases, such as myocardial and cerebral ischemia. In this brief review, we will discuss the current knowledge of how the melanocortin system influences essential cardiovascular functions, such as blood pressure and heart rate, and its protective role in ischemic events, with a particular focus on the central regulation of such mechanisms.

Pupil dilation predicts individual self-regulation success across domains

Multiple theories have proposed that increasing central arousal through the brain’s locus coeruleus—norepinephrine system may facilitate cognitive control and memory. However, the role of the arousal system in emotion regulation is less well understood. Pupil diameter is a proxy to infer upon the central arousal state. We employed an emotion regulation paradigm with a combination of design features that allowed us to dissociate regulation from emotional arousal in the pupil diameter time course of 34 healthy adults. Pupil diameter increase during regulation predicted individual differences in emotion regulation success beyond task difficulty. Moreover, the extent of this individual regulatory arousal boost predicted performance in another self-control task, dietary health challenges. Participants who harnessed more regulation-associated arousal during emotion regulation were also more successful in choosing healthier foods. These results suggest that a common arousal-based facilitation mechanism may support an individual’s self-control across domains.

Interconnection between Adrenergic and Dopaminergic Systems in Feeding Behavior in Neonatal Chicks.

Central dopaminergic (DAergic) and adrenergic systems have a prominent role in appetite regulation; however, their interaction(s) have not been studied in neonatal layer chickens.Therefore, the current study aimed to determine the interaction of central DAergic and noradrenergic systems in food intake regulation in neonatal layer chickens. In the first experiment, chickens received the intracerebroventricular (ICV) injection of a control solution, prazosin (i.e., α1 adrenergic receptor antagonist; 10 nmol), dopamine (DA; 40 nmol), and prazosin plus DA. The second to fifth experiments were similar to the first experiment except that the birds were injected with yohimbine (i.e., α2 receptor antagonist; 13 nmol), metoprolol (i.e., β1 adrenergic receptor antagonist; 24 nmol), ICI 118,551 (i.e., β2 adrenergic receptor antagonist; 5 nmol), and SR59230R (i.e., β3 adrenergic receptor antagonist; 20 nmol) instead of prazosin. In the sixth experiment, the chickens received ICV injection with the control solution and noradrenaline (NA; 75, 150, and 300 nmol). In the seventh experiment, the birds were injected with the control solution, SCH23390 (i.e., D1 DAergic receptor antagonist; 5 nmol), NA (300 nmol), and SCH23390 plus NA In the eighth experiment, the control solution, AMI-193 (i.e., D2 DAergic receptor antagonist; 5 nmol), NA (300 nmol), and AMI-193 plus NA were injected. Then, cumulative food intake was recorded at 30, 60, and 120 min after the injection. According to the obtained results, the ICV injection of DA (40 nmol) significantly decreased food intake in comparison to that reported for the control group (p <0.05). The co-injection of yohimbine plus DA significantly amplified DA-induced hypophagia in the neonatal chickens (p <0.05). In addition, the co-administration of ICI 118,551 plus DA significantly inhibited the hypophagic effect of DA in the neonatal chickens (p <0.05). Furthermore, NA (75, 150, and 300 nmol) significantly reduced food intake in a dose-dependent manner (p <0.05). The co-injection of SCH23390 plus NA decreased the hypophagic effect of NA in the neonatal chickens, compared to that reported for the control group (p <0.05). The co-injection of AMI-193 plus NA diminished NA-induced hypophagia, compared to that reported for the control group (p <0.05). The aforementioned results suggested that there is an interconnection between central DAergic and noradrenergic systems through α2/β2 adrenergic and D1/D2 DAergic receptors in food intake regulation in neonatal chicks.

Structural basis of Staphylococcus aureus Cas9 inhibition by AcrIIA14.

Bacteriophages have evolved a range of anti-CRISPR proteins (Acrs) to escape the adaptive immune system of prokaryotes, therefore Acrs can be used as switches to regulate gene editing. Herein, we report the crystal structure of a quaternary complex of AcrIIA14 bound SauCas9–sgRNA–dsDNA at 2.22 Å resolution, revealing the molecular basis for AcrIIA14 recognition and inhibition. Our structural and biochemical data analysis suggest that AcrIIA14 binds to a non-conserved region of SauCas9 HNH domain that is distinctly different from AcrIIC1 and AcrIIC3, with no significant effect on sgRNA or dsDNA binding. Further, our structural data shows that the allostery of the HNH domain close to the substrate DNA is sterically prevented by AcrIIA14 binding. In addition, the binding of AcrIIA14 triggers the conformational allostery of the HNH domain and the L1 linker within the SauCas9, driving them to make new interactions with the target-guide heteroduplex, enhancing the inhibitory ability of AcrIIA14. Our research both expands the current understanding of anti-CRISPRs and provides additional culues for the rational use of the CRISPR-Cas system in genome editing and gene regulation.

Insulin-Like Peptide Receptor-Mediated Signaling Pathways Orchestrate Regulation of Growth in the Pacific Oyster (Crassostrea gigas), as Revealed by Gene Expression Profiles.

The involvement of insulin/insulin-like growth factor signaling (IIS) pathways in the growth regulation of marine invertebrates remains largely unexplored. In this study, we used a fast-growing Pacific oyster (Crassostrea gigas) variety “Haida No.1” as the material with which to unravel the role of IIS systems in growth regulation in oysters. Systematic bioinformatics analyses allowed us to identify major components of the IIS signaling pathway and insulin-like peptide receptor (ILPR)-mediated signaling pathways, including PI3K-AKT, RAS-MAPK, and TOR, in C. gigas. The expression levels of the major genes in IIS and its downstream signaling pathways were significantly higher in “Haida No.1” than in wild oysters, suggesting their involvement in the growth regulation of C. gigas. The expression profiles of IIS and its downstream signaling pathway genes were significantly altered by nutrient abundance and culture temperature. These results suggest that the IIS signaling pathway coupled with the ILPR-mediated signaling pathways orchestrate the regulation of energy metabolism to control growth in Pacific oysters.

A regulatory variant of tryptophan hydroxylase gene modulates transcription activity and biases growth rate in the Pacific oyster, Crassostrea gigas

Growth is an important trait with significant impact on economic value of cultured organisms. Identification of critical genes and nucleotide variations associated with growth is an important step toward molecular breeding of growth-related traits. In this study, we showed that tryptophan hydroxylase (TPH), the rate-limiting enzyme of serotonin (5-HT) biosynthesis, played an indispensable role in growth regulation in the Pacific oyster, Crassostrea gigas. We identified the C. gigas TPH (CgTPH) and performed comparative analyses of its expression and nucleotide variations between selectively bred fast-growing Pacific oysters (“Haida No. 1”) and wild oysters. Expression profiling and RNA localization showed that CgTPH was specifically expressed in the nerve-rich tissues. Notably, expression level of CgTPH was significantly higher in fast-growing “Haida No.1” than wild oysters. Association and haplotype analysis of single nucleotide polymorphisms (SNPs) in upstream regulatory region of CgTPH revealed four SNPs (located at −904, −522, −272, −262 bp) and two haplotypes (CCCC and TCTC) that were significantly associated with growth rate of C. gigas. Luciferase reporter assay identified the core transcription regulatory element located at −403 ~ −179 bp, in which the SNP -272C/T was critical for transcription activity of CgTPH. Further analysis revealed that the different transcription activity was due to the distinct binding efficiency with two transcription factors, FoxO and CUX. Together, we showed that a critical SNP in the regulatory region of CgTPH leading to differential transcription regulation by FoxO and CUX, which would affect 5-HT synthesis and growth in C. gigas. This work is of great significance for elucidating the role of 5-HT system in regulation of growth in mollusks and provides a marker for molecular breeding of growth with other production and performance traits in C. gigas.

Optimal Strategy for Participation of Commercial HVAC Systems in Frequency Regulation

In this article, an optimal strategy is proposed for heating, ventilation, and air conditioning (HVAC) systems in commercial buildings to fairly ensure the occupants’ comfort, while participating in frequency regulation. With the nonlinear relationship between temperature setpoint and the fan power, the differences between indoor temperatures and temperature setpoints are considered as the objective to fairly ensure the occupants’ comfort. By the proposed strategy, the task for frequency regulation is optimally distributed according to the capacity of HVAC systems in a load aggregator. Therefore, performing frequency regulation and fairly ensuring occupants’ comfort are achieved simultaneously. Simulations on a two-area interconnected power system show that the proposed optimal strategy can improve the quality of frequency, reduce traditional generator regulation, and ensure the occupants’ comfort fairly.

State coordinated voltage control in an active distribution network with on-load tap changers and photovoltaic systems

Decreasing costs and favorable policies have resulted in increased penetration of solar photovoltaic (PV) power generation in distribution networks. As the PV systems penetration is likely to increase in the future, utilizing the reactive power capability of PV inverters to mitigate voltage deviations is being promoted. In recent years, droop control of inverter- based distributed energy resources has emerged as an essential tool for use in this study. The participation of PV systems in voltage regulation and its coordination with existing controllers, such as on-load tap changers, is paramount for controlling the voltage within specified limits. In this work, control strategies are presented that can be coordinated with the existing controls in a distributed manner. The effectiveness of the proposed method was demonstrated through simulation results on a distribution system.

Detection of Pathogens and Regulation of Immunity by the Caenorhabditis elegans Nervous System.

Although Caenorhabditis elegans has been used as a model host for studying host-pathogen interactions for more than 20 years, the mechanisms by which it identifies pathogens are not well understood. This is largely due to its lack of most known pattern recognition receptors (PRRs) that recognize pathogen-derived molecules. Recent behavioral research in C. elegans indicates that its nervous system plays a major role in microbe sensing. With the increasing integration of neurobiology in immunological research, future studies may find that neuronal detection of pathogens is an integral part of C. elegans-pathogen interactions. Similar to that of mammals, the C. elegans nervous system regulates its immune system to maintain immunological homeostasis. Studies in the nematode have revealed unprecedented details regarding the molecules, cells, and signaling pathways involved in neural regulation of immunity. Notably, some of the studies indicate that some neuroimmune regulatory circuits need not be "activated" by pathogen infection because they are tonically active and that there could be a predetermined set point for internal immunity, around which the nervous system adjusts immune responses to internal or external environmental changes. Here, we review recent progress on the roles of the C. elegans nervous system in pathogen detection and immune regulation. Because of its advantageous characteristics, we expect that the C. elegans model will be critical for deciphering complex neuroimmune signaling mechanisms that integrate and process multiple sensory cues.

The effective graph reveals redundancy, canalization, and control pathways in biochemical regulation and signaling

The ability to map causal interactions underlying genetic control and cellular signaling has led to increasingly accurate models of the complex biochemical networks that regulate cellular function. These network models provide deep insights into the organization, dynamics, and function of biochemical systems: for example, by revealing genetic control pathways involved in disease. However, the traditional representation of biochemical networks as binary interaction graphs fails to accurately represent an important dynamical feature of these multivariate systems: some pathways propagate control signals much more effectively than do others. Such heterogeneity of interactions reflects canalization-the system is robust to dynamical interventions in redundant pathways but responsive to interventions in effective pathways. Here, we introduce the effective graph, a weighted graph that captures the nonlinear logical redundancy present in biochemical network regulation, signaling, and control. Using 78 experimentally validated models derived from systems biology, we demonstrate that 1) redundant pathways are prevalent in biological models of biochemical regulation, 2) the effective graph provides a probabilistic but precise characterization of multivariate dynamics in a causal graph form, and 3) the effective graph provides an accurate explanation of how dynamical perturbation and control signals, such as those induced by cancer drug therapies, propagate in biochemical pathways. Overall, our results indicate that the effective graph provides an enriched description of the structure and dynamics of networked multivariate causal interactions. We demonstrate that it improves explainability, prediction, and control of complex dynamical systems in general and biochemical regulation in particular.

A Novel Intrusion Mitigation Unit for Interconnected Power Systems in Frequency Regulation to Enhance Cybersecurity

Cyberattacks (CAs) on modern interconnected power systems are currently a primary concern. The development of information and communication technology (ICT) has increased the possibility of unauthorized access to power system networks for data manipulation. Unauthorized data manipulation may lead to the partial or complete shutdown of a power network. In this paper, we propose a novel security unit that mitigates intrusion for an interconnected power system and compensates for data manipulation to augment cybersecurity. The studied two-area interconnected power system is first stabilized to alleviate frequency deviation and tie-line power between the areas by designing a fractional-order proportional integral derivative (FPID) controller. Since the parameters of the FPID controller can also be influenced by a CA, the proposed security unit, named the automatic intrusion mitigation unit (AIMU), guarantees control over such changes. The effectiveness of the AIMU is inspected against a CA, load variations, and unknown noises, and the results show that the proposed unit guarantees reliable performance in all circumstances.

The Rcs System in Enterobacteriaceae: Envelope Stress Responses and Virulence Regulation.

The bacterial cell envelope is a protective barrier at the frontline of bacterial interaction with the environment, and its integrity is regulated by various stress response systems. The Rcs (regulator of capsule synthesis) system, a non-orthodox two-component regulatory system (TCS) found in many members of the Enterobacteriaceae family, is one of the envelope stress response pathways. The Rcs system can sense envelope damage or defects and regulate the transcriptome to counteract stress, which is particularly important for the survival and virulence of pathogenic bacteria. In this review, we summarize the roles of the Rcs system in envelope stress responses (ESRs) and virulence regulation. We discuss the environmental and intrinsic sources of envelope stress that cause activation of the Rcs system with an emphasis on the role of RcsF in detection of envelope stress and signal transduction. Finally, the different regulation mechanisms governing the Rcs system’s control of virulence in several common pathogens are introduced. This review highlights the important role of the Rcs system in the environmental adaptation of bacteria and provides a theoretical basis for the development of new strategies for control, prevention, and treatment of bacterial infections.

Therapeutic Role of Marijuana in Migraine

Marijuana has been known for a long time to have a variety of therapeutic implications in pain management. The role of the cannabinoid system in regulation of migraine headaches highlights the potential of marijuana as a treatment option. Marijuana has the ability to modulate the migraine associated pain pathway via the cannabinoid receptors. Endocannabinoid deficiency has been theorized to contribute to the pathophysiology of migraine. People who have used marijuana for their migraine headaches have reported a decrease in the frequency of their headaches, especially the population who failed to show response with the conventional treatment options. Also, marijuana has a more tolerable side effect profile and administering this along with conventional treatment options can help reduce their dosages and side effects. Large scale clinical trials are needed to further find out about the different strains, formulations, prefer- red delivery method and doses of marijuana required for effective treatment.