Feedback and feedforward widely exist in life system, both of them are the basic processes of control system. While the concept of feedback has been widely used in life science, feedforward regulation was systematically studied in neurophysiology, awaiting further evidence and mechanism in molecular biology and cell biology. The authors put forward a hypothesis about the feedforward regulation of membrane bound macrophage colony stimulation factor (mM-CSF) on the basis of their previous work. This hypothesis might provide a new direction for the study on the biological effects of mM-CSF on leukemia and solid tumors, and contribute to the study on other membrane bound cytokines.
Feedback, Physiological ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Leukemia ; Systems Biology

The physiological feedback regulation mechanism of the heart rate variation due to the blood pressure variation is studied. The continuous closed-loop mathematical model of the heart rate feedback regulation system is constructed. Numerical simulation is completed based on the above model. The simulation results demonstrate that the regulation system has the ability to constrain the fluctuation of the blood pressure to certain extent. The results are helpful for the pathological studies of some hypertensive diseases.
Blood Pressure ; physiology ; Computer Simulation ; Feedback, Physiological ; Heart Rate ; physiology ; Humans ; Mathematics ; Models, Cardiovascular

OBJECTIVETo explore the core mechanism of cell cycle compensation using a mathematical model.

METHODSA set of ordinary differential equations were used to describe the interactions between the core cell cycle molecules. Continuous and cyclic changes of the concentrations of these molecules were computed to capture the discrete events of molecular interactions.

RESULTSThe calculated molecule concentrations and captured signaling events agreed with the experimental results.

CONCLUSIONE2F transcription factor 1 is the pivotal element linking the positive and negative feedbacks and regulating G1/S and G2/M phase compensation.

Animals ; Cell Cycle ; Drosophila ; cytology ; E2F1 Transcription Factor ; Feedback, Physiological ; Models, Theoretical

Because of the concern about escape of antibiotic- or herbicide-resistant transgenes from transgenic crops, selectable marker genes from plant origin would be an alternative choice for plant transformation. In this study, a feedback-insensitive anthranilate synthase gene ( ASA2 ) cloned from a tobacco cell line was tested for Agrobacterium-mediated transformation of axis tissue of soybean mature embryo, with a tryptophan analogue 5-methyltryptophan (5-MT) as the selective agent. Southern blot analysis of the To transgenic lines confirmed the integration of the ASA2 gene into the soybean genome. Northern blot analysis showed the ASA2 gene was also expressed in the leave tissue, and the free tryptophan content in the leaf tissue of transgenic soybean was about 59% to 123% more than that in the wild type. PCR analysis of the T1 progeny showed that the transgene was inherited in a Mendelian fashion. All these results indicate that this feedback-insensitive ASA2 gene can be used as a selectable marker gene for plant transformation. This work also demonstrated that the ASA2 gene coding for the a-subunits from one plant (tobacco) can interact with the n-subunits of a heterologous plant (soybean) to form an active anthranilate synthase enzyme. The use of this feedback-insensitive gene as a novel selectable marker for plant transformation is also discussed.
Anthranilate Synthase ; genetics ; Feedback, Physiological ; Plants, Genetically Modified ; genetics ; Soybeans ; genetics ; Transformation, Genetic ; Tryptophan ; analogs & derivatives ; metabolism

p53 is an important target for studying vascular aging. However, as people gradually learned more about the miR-34s and the relationship between miR-34s and p53, new research idea emerged. This paper tries to elaborate the feature of p53, microRNA and miR-34s in-depth, analyze the regulatory action of miR-34s on p53, and offer some new prevention and treatment prospects about vascular aging in Chinese medicine.
Blood Vessels ; pathology ; Cellular Senescence ; Feedback, Physiological ; Humans ; Medicine, Chinese Traditional ; MicroRNAs ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Thyroglobulin is the most important and abundant protein in thyroid follicles and has been widely studied as a tumor marker of thyroid cancer recurrence and persistence. Tg is considered the material basis of thyroid hormone synthesis and does not participate in the regulation of thyroid hormone synthesis and secretion. This review summarizes the recent progress in the research of thyroid hormone synthesis and secretion regulation via a negative feedback regulation mechanism by the thyroid-hypothalamus-pituitary axis. Thyroglobulin can negatively regulate the synthesis of thyroid hormone by thyroid follicular cells and antagonize the positive regulation of thyrotropin TSH. The function of thyroid follicular cells is presumably a result of Tg and TSH interaction, and a follicular cycle model is proposed to explain the causes of follicular heterogeneity in glands. We also discuss the prospects and clinical significance of studies into the negative feedback regulation mechanism of the thyroid-hypothalamus-pituitary axis and compare two theories for this mechanism.
Feedback, Physiological ; Humans ; Hypothalamo-Hypophyseal System ; physiology ; Neoplasm Recurrence, Local ; Thyroglobulin ; metabolism ; Thyroid Gland ; physiology ; Thyroid Hormones ; metabolism ; Thyrotropin ; metabolism

To have a thorough understanding of the CPR quality based on patients' various physiological states, the doctors must do something to simulate the chest compression physiological feedback parameters (CCPFP). The CCPFP simulation plays an important role in raising efficiency of CPR training and improving chest compression quality. In this study, the CCPFP, including cardiac output (CO), coronary perfusion pressure (CPP), partial pressure of End-tidal CO2 (PETCO2) and mean arterial relaxation pressure (MARP), was simulated using Charles F. Babbs' Model. Simulation results showed that the effect of compression depth upon CCPFP was important in the range of 2-6 cm, whereas compression rate had little effect on the CCPFP higher than 100/min; the thoracic factor is inversely proportional to the CCPFP with fixed compression depth and compression rate. The CCPFP simulation can be implemented at the various physiological statuses, and verified well with the animal experimental results and the clinical results.
Blood Pressure ; physiology ; Carbon Dioxide ; blood ; Cardiac Output ; physiology ; Chest Wall Oscillation ; Computer Simulation ; Feedback, Physiological ; physiology ; Humans ; Models, Biological ; Partial Pressure

OBJECTIVEIn Corynebacterium crenatum, the adjacent D311 and D312 of N-acetyl-L-glutamate kinase (NAGK), as a key rate-limiting enzyme of L-arginine biosynthesis under substrate regulatory control by arginine, were initially replaced with two arginine residues to investigate the L-arginine feedback inhibition for NAGK.

METHODSNAGK enzyme expression was evaluated using a plasmid-based method. Homologous recombination was employed to eliminate the proB.

RESULTSThe IC50 and enzyme activity of NAGK M4, in which the D311R and D312R amino acid substitutions were combined with the previously reported E19R and H26E substitutions, were 3.7-fold and 14.6% higher, respectively, than those of the wild-type NAGK. NAGK M4 was successfully introduced into the C. crenatum MT genome without any genetic markers; the L-arginine yield of C. crenatum MT-M4 was 26.2% higher than that of C. crenatum MT. To further improve upon the L-arginine yield, we constructed the mutant C. crenatum MT-M4 proB. The optimum concentration of L-proline was also investigated in order to determine its contribution to L-arginine yield. After L-proline was added to the medium at 10 mmol/L, the L-arginine yield reached 16.5 g/L after 108 h of shake-flask fermentation, approximately 70.1% higher than the yield attained using C. crenatum MT.

CONCLUSIONFeedback inhibition of L-arginine on NAGK in C. crenatum is clearly alleviated by the M4 mutation of NAGK, and deletion of the proB in C. crenatum from MT to M4 results in a significant increase in arginine production.

Animals ; Arginine ; biosynthesis ; Corynebacterium ; genetics ; metabolism ; Escherichia coli ; Feedback, Physiological ; Gene Deletion ; Mutagenesis, Site-Directed ; Phosphotransferases (Carboxyl Group Acceptor) ; genetics ; Proline ; metabolism

Siva-1, as a p53-inducible gene, has been shown to induce extensive apoptosis in a number of different cell lines. Recent evidence suggests that Siva-1 functions as a part of the auto-regulatory feedback loop that restrains p53 through facilitating Mdm2-mediated p53 degradation. Also, Siva-1 plays an important role in suppressing tumor metastasis. Here we review the current understanding of Siva-1-mediated apoptotic signaling pathway. We also add comments on the p53-Siva-1 feedback loop, the novel function of Siva-1 in suppressing tumor metastasis, and their potential implications.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Feedback, Physiological ; Humans ; Models, Biological ; Neoplasm Metastasis ; Neoplasms ; pathology ; Proto-Oncogene Proteins c-mdm2 ; metabolism ; Signal Transduction ; Tumor Suppressor Protein p53 ; metabolism

Kisspeptins are a group of peptide fragments encoded by the KISS1 gene in humans. They bind to kisspeptin receptors with equal efficacy. Kisspeptins and their receptors are expressed by neurons in the arcuate and anteroventral periventricular nuclei of the hypothalamus. Oestrogen mediates negative feedback of gonadotrophin-releasing hormone secretion via the arcuate nucleus. Conversely, it exerts positive feedback via the anteroventral periventricular nucleus. The sexual dimorphism of these nuclei accounts for the differential behaviour of the hypothalamic-pituitary-gonadal axis between genders. Kisspeptins are essential for reproductive function. Puberty is regulated by the maturation of kisspeptin neurons and by interactions between kisspeptins and leptin. Hence, kisspeptins have potential diagnostic and therapeutic applications. Kisspeptin agonists may be used to localise lesions in cases of hypothalamic-pituitary-gonadal axis dysfunction and evaluate the gonadotrophic potential of subfertile individuals. Kisspeptin antagonists may be useful as contraceptives in women, through the prevention of premature luteinisation during in vitro fertilisation, and in the treatment of sex steroid-dependent diseases and metastatic cancers.
Animals ; Arcuate Nucleus of Hypothalamus ; metabolism ; Estrogens ; metabolism ; Feedback, Physiological ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; metabolism ; Homeostasis ; Humans ; Kisspeptins ; physiology ; Male ; Mice ; Neoplasms ; metabolism ; Neurons ; metabolism ; Protein Binding ; Rats ; Reproduction ; Sex Factors ; Signal Transduction