Progress in Biophysics & Molecular Biology最新文献

The Extended Evolutionary Synthesis (EES) addresses the issues in evolutionary biology which cannot be explained by neo-Darwinian theory. The EES paradigm recognises teleology and agency in living systems, and identifies that organisms can directly affect their evolutionary trajectory in a goal-directed manner, yet the physiological pathways via which this occurs remain unidentified. Here, I propose a physiological pathway via which organisms can alter their genotype and phenotype by making behavioural decisions with respect their activity levels, partitioning of resources either toward growth, defence against disease, or their behavioural response to stressors. Specifically, I hypothesize that agential, teleological decisions mediated by acetylcholine result in induced nitric oxide (NO) activity, which regulates metabolism, blood flow, and immune response. Nitric oxide, however, is also a key epigenetic molecule, being involved in DNA acetylation, methylation, and de-methylation. Further, NO alters the histone complexes which scaffold nuclear DNA strands, and is thus a good candidate in identifying a system which allows an organisms to make teleological genetic changes. The proposed mechanisms of inheritance of these genetic changes is via the paternal line, whereby epigenetic changes in the somatic Sertoli cells in animals are transcribed by mRNA and included in the germline cells – the male gametes. The microsporangium in plants, and the sporophore cells in fungi, meanwhile, are proposed to form similar systems in response to sensory detection of stressors. Whilst the hypothesis is presented as a simplified model for future testing, it opens new avenues for study in evolutionary biology.

Bone repair is faced with obstacles such as slow repair rates and limited bone regeneration capacity. Delayed healing even nonunion could occur in bone defects, influencing the life quality of patients severely. Photobiomodulation (PBM) utilizes different light sources to derive beneficial therapeutic effects with the advantage of being non-invasive and painless, providing a promising strategy for accelerating bone repair. In this review, we summarize the parameters, mechanisms, and effects of PBM regulating bone repair, and further conclude the current clinical application of PBM devices in bone repair. The wavelength of 635–980 nm, the output power of 40–100 mW, and the energy density of less than 100 J/cm² are the most commonly used parameters. New technologies, including needle systems and biocompatible and implantable optical fibers, offer references to realize an efficient and safe strategy for bone repair. Further research is required to establish the reliability of outcomes from in vivo and in vitro studies and to standardize clinical trial protocols.

The emergence, evolution, and spread of life on Earth have all occurred in the geomagnetic field, and its extensive biological effects on living organisms have been documented. The charged characteristics of metal ions in biological fluids determine that they are affected by electromagnetic field forces, thus affecting life activities. Iron metabolism, as one of the important metal metabolic pathways, keeps iron absorption and excretion in a relatively balanced state, and this process is precisely and completely controlled. It is worth paying attention to how the iron metabolism process of living organisms is changed when exposed to electromagnetic fields. In this paper, the processes of iron absorption, storage and excretion in animals (mammals, fish, arthropods), plants and microorganisms exposed to electromagnetic field were summarized in detail as far as possible, in order to discover the regulation of iron metabolism by electromagnetic field. Studies and data on the effects of electromagnetic field exposure on iron metabolism in organisms show that exposure profiles vary widely across species and cell lines. This process involves a variety of factors, and the complexity of the results is not only related to the magnetic flux density/operating frequency/exposure time and the heterogeneity of the observed object. A systematic review of the biological regulation of iron metabolism by electromagnetic field exposure will not only contributes to a more comprehensive understanding of its biological effects and mechanism, but also is necessary to improve human awareness of the health related risks of electromagnetic field exposure.

The cell is both synchronic and diachronic, based on ontogeny and phylogeny, respectively. As experimental evidence for this holism, absent gravitational force, differentiated lung and bone cells devolve, losing their phenotypes, losing their evolutionary status, reverting to their nonlocal status. Thus, when evolution is seen as serial homeostasis, it is homologous with Quantum Entanglement as the nonlocal means of maintaining homeostatic balance between particles. This monadic perspective on consciousness is one-hundred and eighty degrees out of synch with the conventional way of thinking about consciousness as a diad, or mind and brain. There have been many attempts to explain consciousness, virtually all of them based on the brain as mind. The working hypothesis is that consciousness is a holism constituted by the unicell, the lipid cell membrane forming a barrier between inside and outside of the cell's environment as a topology. Conceptually, both the unicell and ‘two hands clapping’ are holisms, but because the cell is constituted by the ambiguity of negative entropy, and ‘one hand clapping’ requires two hands, they are both pseudo-holisms, constantly striving to be whole again. In the case of the cell, it is incomplete in the sense that there are factors in the ever-changing environment that can homeostatically complete it. That process results in biochemical modification of specific DNA codes in the egg or sperm so that the offspring is able to adapt in subsequent generations epigenetically. The opportunity to trace the evolution of the breath from humans to fish opens up to the further revelation of the interplay between evolution and geological change, tracing it back to invertebrates, sponges, and ultimately to unicellular organisms. And therein is evidence that the Cosmos itself ‘breathes’, providing the ultimate celestial fundament for this trail of holisms.

There is a consensus that we are conscious of something greater than ourselves, as if we are derived from some other primordial set of principles. Classical or Newtonian physics is based on the Laws of Nature. Conversely, in a recent series of articles, it has been hypothesized that the cell was formed from lipid molecules submerged in the primordial ocean that covered the earth 100 million years after it formed. Since lipids are amphiphiles, with both a positively- and negatively-charged pole, the negatively-charged pole is miscible in water. Under the influence of earth's gravity, the lipid molecules stand up perpendicularly to the surface of the water, packing together until the negative charge neutralizes the Van der Waals force for surface tension, causing the lipid molecules to ‘leap’ into the micellar form as a sphere with a semi-permeable membrane. Particles in the water freely enter and exit such spheres based on mass action. Over time such protocells evolved Symbiogenesis, encountering factors that posed existential threats, assimilating them to form physiology to maintain homeostatic control. Importantly, when differentiated lung or bone cells are exposed to zero gravity, they lose their phenotypic identity in their evolved state, which has been interpreted as transiting from local to non-local consciousness.

According to international cancer data, breast cancer (BC) is the leading type of cancer in women. Although significant progress has been made in treating BC, metastasis and drug resistance continue to be the primary causes of mortality for many patients. Reactive oxygen species (ROS) play a dual role in vivo: normal levels can maintain the body's normal physiological function; however, high levels of ROS below the toxicity threshold can lead to mtDNA damage, activation of proto-oncogenes, and inhibition of tumor suppressor genes, which are important causes of BC. Differences in the production and regulation of ROS in different BC subtypes have important implications for the development and treatment of BC. ROS can also serve as an important intracellular signal transduction factor by affecting the antioxidant system, activating MAPK and PI3K/AKT, and other signal pathways to regulate cell cycle and change the relationship between cells and the activity of metalloproteinases, which significantly impacts the metastasis of BC. Hypoxia in the BC microenvironment increases ROS production levels, thereby inducing the expression of hypoxia inducible factor-1α (HIF-1α) and forming “ROS- HIF-1α-ROS” cycle that exacerbates BC development. Many anti-BC therapies generate sufficient toxic ROS to promote cancer cell apoptosis, but because the basal level of ROS in BC cells exceeds that of normal cells, this leads to up-regulation of the antioxidant system, drug efflux, and apoptosis inhibition, rendering BC cells resistant to the drug. ROS crosstalks with tumor vessels and stromal cells in the microenvironment, increasing invasiveness and drug resistance in BC.

Neuroblastoma is a common inflammatory-related cancer during infancy. Standard treatment modalities including surgical interventions, high-dose chemotherapy, radiotherapy, and immunotherapy are not able to increase survival rate and reduce tumor relapse in high-risk patients. Mesenchymal stem cells (MSCs) are known for their tumor-targeting and immunomodulating properties. MSCs could be engineered to express anticancer agents (i.e., growth factors, cytokines, pro-apoptotic agents) or deliver oncolytic viruses in the tumor microenvironment. As many functions of MSCs are mediated through their secretome, researchers have tried to use extracellular vesicles (EVs) from MSCs for targeted therapy of neuroblastoma. Here, we reviewed the studies to figure out whether the use of MSCs could be worthwhile in neuroblastoma therapy or not. Native MSCs have shown a promoting or inhibiting role in cancers including neuroblastoma. Therefore, MSCs are proposed as a vehicle to deliver anticancer agents such as oncolytic viruses to the neuroblastoma tumor microenvironment. Although modified MSCs or their EVs have been shown to suppress the tumorigenesis of neuroblastoma, further pre-clinical and clinical studies are required to come to a conclusion.

The central conclusions of “The Gene: An Appraisal” are that genetic variance does not underpin biological evolution, and, therefore, that genes are not Mendel's units of inheritance. In this response, I will address the criticisms I have received via commentaries on that paper by defending the following statements:

1. Epistasis does not explain the power-law fitness profile of the Long-Term Evolution Experiment (LTEE). The data from the evolution of natural systems displays the power-law form ubiquitously. Epistasis plays no role in evolution.

2. The common characteristics of living things (natural systems) are described by the principle of least action in de Maupertuis's original form, which is synonymous with the 2nd law of thermodynamics and Newton's 2nd law of motion in its complete form, i.e., F = dp/dt. Organisms strive to achieve free energy balance with their environments.

3. Based on an appraisal of the scientific environment between 1880 and 1911, I conclude that Johannsen's genotype conception was perhaps, the only option available to him.

4. The power-law fitness profile of the LTEE falsifies Fisher's Genetical Theory of Natural Selection, Johannsen's genotype conception, and the idea that ‘Darwinian evolution’ is an exception to the generic thermodynamic process of evolution in natural systems.

5. The use of the technique of genome-wide association to identify the causes and the likelihoods of inherited common diseases and behavioural traits is a ‘wild goose chase’ because genes are not the units of inheritance.

Recent papers have emphasized the primary role of cellular information management in biological and evolutionary development. In this framework, intelligent cells collectively measure environmental cues to improve informational validity to support natural cellular engineering as collaborative decision-making and problem-solving in confrontation with environmental stresses. These collective actions are crucially dependent on cell-based memories as acquired patterns of response to environmental stressors. Notably, in a cellular self-referential framework, all biological information is ambiguous. This conditional requirement imposes a previously unexplored derivative. All cellular memories are imperfect. From this atypical background, a novel theory of aging and death is proposed. Since cellular decision-making is memory-dependent and biology is a continuous natural learning system, the accumulation of previously acquired imperfect memories eventually overwhelms the flexibility cells require to react adroitly to contemporaneous stresses to support continued cellular homeorhetic balance. The result is a gradual breakdown of the critical ability to efficiently measure environmental information and effect cell-cell communication. This age-dependent accretion governs senescence, ultimately ending in death as an organism-wide failure of cellular networking. This approach to aging and death is compatible with all prior theories. Each earlier approach illuminates different pertinent cellular signatures of this ongoing, obliged, living process.