Is DNA repair controlled by a biological logic circuit?

The possible utilization of biological logic circuit(s) in the integration and regulation of DNA repair is discussed. The author believes this mode of regulation likely applies to many other areas of cell biology; however, there are currently more experimental data to support its involvement in the control of DNA repair. Sequential logic processes always require a clock to orchestrate the orderly processing of events. In the proposed hypothesis, the pulses in the expression of p53 serve this function. Given the many advantages of logic type control, one would expect that in the course of ~ 3 billion years of evolution, where single cell life forms were likely the only forms of life, a biological logic type control system would have evolved to control at least some biological processes. Several other required components in addition to the ‘clock’ have been identified, such as; a method to temporarily inactivate repair processes when they are not required (e.g. the reversible inactivation of MGMT, a suicide repair protein, by phosphorylation); this prevents complex DNA repair systems with potentially overlapping repair functions from interfering with each other.

Strange Objects

An introductory chapter, intended to set the tone for the entire book. Living things are passing strange. They are bound by all the laws that govern inanimate matter, yet they flaunt capacities that vastly exceed those of rocks, clouds, and water. Their basic building blocks are cells, either one cell or many, each of them an organized and purposeful entity that invariably arises by the reproduction of a previous cell. Life has a long history, nearly as long as that of earth itself, most of it microbial. To understand life one must begin with microorganisms, for the higher organisms that receive most of our attention are all latecomers.

Non-Interventional and High-Precision Temperature Measurement Biochips for Long-Term Monitoring the Temperature Fluctuations of Individual Cells

Monitoring the thermal responses of individual cells to external stimuli is essential for studies of cell metabolism, organelle function, and drug screening. Fluorescent temperature probes are usually employed to measure the temperatures of individual cells; however, they have some unavoidable problems, such as, poor stability caused by their sensitivity to the chemical composition of the solution and the limitation in their measurement time due to the short fluorescence lifetime. Here, we demonstrate a stable, non-interventional, and high-precision temperature-measurement chip that can monitor the temperature fluctuations of individual cells subject to external stimuli and over a normal cell life cycle as long as several days. To improve the temperature resolution, we designed temperature sensors made of Pd–Cr thin-film thermocouples, a freestanding Si3N4 platform, and a dual-temperature control system. Our experimental results confirm the feasibility of using this cellular temperature-measurement chip to detect local temperature fluctuations of individual cells that are 0.3–1.5 K higher than the ambient temperature for HeLa cells in different proliferation cycles. In the future, we plan to integrate this chip with other single-cell technologies and apply it to research related to cellular heat-stress response.

Redox Control of the Dormant Cancer Cell Life Cycle

Following efficient tumor therapy, some cancer cells may survive through a dormancy process, contributing to tumor recurrence and worse outcomes. Dormancy is considered a process where most cancer cells in a tumor cell population are quiescent with no, or only slow, proliferation. Recent advances indicate that redox mechanisms control the dormant cancer cell life cycle, including dormancy entrance, long-term dormancy, and metastatic relapse. This regulatory network is orchestrated mainly through redox modification on key regulators or global change of reactive oxygen species (ROS) levels in dormant cancer cells. Encouragingly, several strategies targeting redox signaling, including sleeping, awaking, or killing dormant cancer cells are currently under early clinical evaluation. However, the molecular mechanisms underlying redox control of the dormant cancer cell cycle are poorly understood and need further exploration. In this review, we discuss the underlying molecular basis of redox signaling in the cell life cycle of dormant cancer and the potential redox-based targeting strategies for eliminating dormant cancer cells.

N6-Methyladenosine and Rheumatoid Arthritis: A Comprehensive Review

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

At the Crossroads: Mechanisms of Apoptosis and Autophagy in Cell Life and Death

Apoptosis and autophagy are conserved processes that regulate cell survival and death under stress conditions. real rolex submariner vs fake Apoptosis aims to remove cells from the body with minimal damage to surrounding tissues. Autophagy promotes removal of damaged organelles, protein aggregates, and cellular pathogens, stimulating cell survival. The signaling pathways involved in the regulation of apoptosis and autophagy largely overlap, leading to both competition and unidirectional interaction, which is of particular interest in investigating them as potential targets for cancer, paul newman rolex replica for saleautoimmune, and neurodegenerative disease therapies. This review analyzes the main pathways of molecular interactions between autophagy and apoptosis, which is necessary for understanding the mechanism maintaining rolex iced out fake the balance between cell death and survival under unfavorable conditions.

An Update on Trichoderma Mitogenomes: Complete De Novo Mitochondrial Genome of the Fungal Biocontrol Agent Trichoderma harzianum (Hypocreales, Sordariomycetes), an Ex-Neotype Strain CBS 226.95, and Tracing the Evolutionary Divergences of Mitogenomes in Trichoderma

Members of the genus Trichoderma (Hypocreales), widely used as biofungicides, biofertilizers, and as model fungi for the industrial production of CAZymes, have actively been studied for the applications of their biological functions. Recently, the study of the nuclear genomes of Trichoderma has expanded in the directions of adaptation and evolution to gain a better understanding of their ecological traits. However, Trichoderma’s mitochondria have received much less attention despite mitochondria being the most necessary element for sustaining cell life. In this study, a mitogenome of the fungus Trichoderma harzianum CBS 226.95 was assembled de novo. A 27,632 bp circular DNA molecule was revealed with specific features, such as the intronless of all core PCGs, one homing endonuclease, and a putative overlapping tRNA, on a closer phylogenetic relationship with T. reesei among hypocrealean fungi. Interestingly, the mitogenome of T. harzianum CBS 226.95 was predicted to have evolved earlier than those of other Trichoderma species and also assumed with a selection pressure in the cox3. Considering the bioavailability, both for the ex-neotype strain of the T. harzianum species complex and the most globally representative commercial fungal biocontrol agent, our results on the T. harzianum CBS 226.95 mitogenome provide crucial information which will be helpful criteria in future studies on Trichoderma.

MK2 degradation as a sensor of signal intensity that controls stress-induced cell fate

Cell survival in response to stress is determined by the coordination of various signaling pathways. The kinase p38α is activated by many stresses, but the intensity and duration of the signal depends on the stimuli. How different p38α-activation dynamics may impact cell life/death decisions is unclear. Here, we show that the p38α-signaling output in response to stress is modulated by the expression levels of the downstream kinase MK2. We demonstrate that p38α forms a complex with MK2 in nonstimulated mammalian cells. Upon pathway activation, p38α phosphorylates MK2, the complex dissociates, and MK2 is degraded. Interestingly, transient p38α activation allows MK2 reexpression, reassembly of the p38α–MK2 complex, and cell survival. In contrast, sustained p38α activation induced by severe stress interferes with p38α–MK2 interaction, resulting in irreversible MK2 loss and cell death. MK2 degradation is mediated by the E3 ubiquitin ligase MDM2, and we identify four lysine residues in MK2 that are directly ubiquitinated by MDM2. Expression of an MK2 mutant that cannot be ubiquitinated by MDM2 enhances the survival of stressed cells. Our results indicate that MK2 reexpression and binding to p38α is critical for cell viability in response to stress and illustrate how particular p38α-activation patterns induced by different signals shape the stress-induced cell fate.