Progress in Biophysics & Molecular Biology最新文献

The paper presents a review of mechanistic modelling studies of DNA damage and DNA repair, and consequences to follow in mammalian cell nucleus. We hypothesize DNA deletions are consequences of repair of double strand breaks leading to the modifications of genome that play crucial role in long term development of genetic inheritance and diseases. The aim of the paper is to review formation mechanisms underlying naturally occurring DNA deletions in the human genome and their potential relevance for bridging the gap between induced DNA double strand breaks and deletions in damaged human genome from endogenous and exogenous events. The model of the cell nucleus presented enables simulation of DNA damage at molecular level identifying the spectrum of damage induced in all chromosomal territories and loops. Our mechanistic modelling of DNA repair for double stand breaks (DSB), single strand breaks (SSB) and base damage (BD), shows the complexity of DNA damage is responsible for the longer repair times and the reason for the biphasic feature of mammalian cells repair curves. In the absence of experimentally determined data, the mechanistic model of repair predicts the in vivo rate constants for the proteins involved in the repair of DSB, SSB, and of BD.

Natural selection has a formal definition as the natural process that results in the survival and reproductive success of individuals or groups best adjusted to their environment, leading to the perpetuation of those genetic qualities best suited to that organism's environmental niche. Within conventional Neo-Darwinism, the largest source of those variations that can be selected is presumed to be secondary to random genetic mutations. As these arise, natural selection sustains adaptive traits in the context of a 'struggle for existence'. Consequently, in the 20th century, natural selection was generally portrayed as the primary evolutionary driver. The 21st century offers a comprehensive alternative to Neo-Darwinian dogma within Cognition-Based Evolution. The substantial differences between these respective evolutionary frameworks have been most recently articulated in a revision of Crick's Central Dogma, a former centerpiece of Neo-Darwinism. The argument is now advanced that the concept of natural selection should also be comprehensively reappraised. Cognitive selection is presented as a more precise term better suited to 21st century biology. Since cognition began with life's origin, natural selection represents cognitive selection.

Gene regulatory network (GRN) comprises complicated yet intertwined gene-regulator relationships. Understanding the GRN dynamics will unravel the complexity behind the observed gene expressions. Insect gene regulation is often complicated due to their complex life cycles and diverse ecological adaptations. The main interest of this review is to have an update on the current mathematical modelling methods of GRNs to explain insect science. Several popular GRN architecture models are discussed, together with examples of applications in insect science. In the last part of this review, each model is compared from different aspects, including network scalability, computation complexity, robustness to noise and biological relevancy.

For more than half a century, biologist Julian Huxley's term, the “Modern Synthesis”, has been used as a label for a model of biological evolution where genetic influences are viewed as a principal source of creativity and change. Over the years, as evidence has accumulated that there are many other, far more important factors at work in evolution, theoretical “compromises,” such as the so-called “Extended Synthesis”, have been proposed. This is no longer tenable. It is time to abandon the Modern Synthesis, and its doppelganger “The Selfish Gene”. Here is the case for a new, multi-faceted, open-ended, “inclusive” evolutionary synthesis, where living systems themselves are recognized as purposeful (teleonomic) “agents” and cooperative effects (synergies) of various kinds are seen as all-important influences.

Dysregulation of long non-coding RNA (lncRNA) HOXA-AS3 has been shown to contribute to the development of multiple cancer types. Several studies have presented the tumour-modulatory role or prognostic significance of this lncRNA in various kinds of cancer. Overall, HOXA-AS3 can act as a competing endogenous RNA (ceRNA) that inhibits the activity of seven microRNAs (miRNAs), including miR-29a-3p, miR-29 b-3p, miR-29c, miR-218–5p, miR-455–5p, miR-1286, and miR-4319. This relieves the downstream messenger RNA (mRNA) targets of these miRNAs from miRNA-mediated translational repression, allowing them to exert their effect in regulating cellular activities. Examples of the pathways regulated by lncRNA HOXA-AS3 and its associated downstream targets include the WNT/β-catenin and epithelial-to-mesenchymal transition (EMT) activities. Besides, HOXA-AS3 can interact with other cellular proteins like homeobox HOXA3 and HOXA6, influencing the oncogenic signaling pathways associated with these proteins. Generally, HOXA-AS3 is overexpressed in most of the discussed human cancers, making this lncRNA a potential candidate to diagnose cancer or predict the clinical outcomes of cancer patients. Hence, targeting HOXA-AS3 could be a new therapeutic approach to slowing cancer progression or as a potential biomarker and therapeutic target. A drawback of using lncRNA HOXA-AS3 as a biomarker or therapeutic target is that most of the studies that have reported the tumour-regulatory roles of lncRNA HOXA-AS3 are single observational, in vitro, or in vivo studies. More in-depth mechanistic and large-scale clinical trials must be conducted to confirm the tumour-modulatory roles of lncRNA HOXA-AS3 further. Besides, no lncRNA HOXA-AS3 inhibitor has been tested preclinically and clinically, and designing such an inhibitor is crucial as it may potentially slow cancer progression.

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.