Biologia futura最新文献

With the development of modern molecular genetics, the original "one gene-one enzyme" hypothesis has been outdated. For protein coding genes, the discovery of alternative splicing and RNA editing provided the biochemical background for the RNA repertoire of a single locus, which also serves as an important pillar for the enormous protein variability of the genomes. Non-protein coding RNA genes were also revealed to produce several RNA species with distinct functions. The loci of microRNAs (miRNAs), encoding for small endogenous regulatory RNAs, were also found to produce a population of small RNAs, rather than a single defined product. This review aims to present the mechanisms contributing to the astonishing variability of miRNAs revealed by the new sequencing technologies. One important source is the careful balance of arm selection, producing sequentially different 5p- or 3p-miRNAs from the same pre-miRNA, thereby broadening the number of regulated target RNAs and the phenotypic response. In addition, the formation of 5', 3' and polymorphic isomiRs, with variable end and internal sequences also leads to a higher number of targeted sequences, and increases the regulatory output. These miRNA maturation processes, together with other known mechanisms such as RNA editing, further increase the potential outcome of this small RNA pathway. By discussing the subtle mechanisms behind the sequence diversity of miRNAs, this review intends to reveal this engaging aspect of the inherited "RNA world", how it contributes to the almost infinite molecular variability among living organisms, and how this variability can be exploited to treat human diseases.

While the existence of post-transcriptional modifications of RNA nucleotides has been known for decades, in most RNA species the exact positions of these modifications and their physiological function have been elusive until recently. Technological advances, such as high-throughput next-generation sequencing (NGS) methods and nanopore-based mapping technologies, have made it possible to map the position of these modifications with single nucleotide accuracy, and genetic screens have uncovered the "writer", "reader" and "eraser" proteins that help to install, interpret and remove such modifications, respectively. These discoveries led to intensive research programmes with the aim of uncovering the roles of these modifications during diverse biological processes. In this review, we assess novel discoveries related to the role of post-transcriptional modifications during animal development, highlighting how these discoveries can affect multiple aspects of development from fertilization to differentiation in many species.

Innovation is a critical component of human society, setting us apart from other animals. We possess a unique capacity to design and produce new things through cultivating a culture that values and encourages innovation. One remarkable instance of innovation in the field of biology and medicine is the mRNA vaccine platform developed by Katalin Karikó and her colleagues. In this article, we delve into the evolution of mRNA-based therapy, beginning with animal models and concluding with the first clinical trials. The history of mRNA research began with the identification of its role in protein synthesis, leading to the development of mRNA vaccine technology. Karikó's pivotal innovation was discovering the need to integrate modified nucleosides into the mRNA, decreasing its recognition by the immune system. Her story offers valuable lessons, including the importance of market demand as a booster effect, the role of emerging technologies, the significance of universities and academic institutions in fostering innovation, the role of perseverance and faith, and the role of chance.

Autophagy is a highly conserved self-degradation process of eukaryotic cells which is required for the effective elimination of damaged and unnecessary cytosolic constituents. Defects in the process can cause the intracellular accumulation of such damages, thereby leading to the senescence and subsequent loss of the affected cell. Defective autophagy hence is implicated in the development of various degenerative processes, including cancer, neurodegenerative diseases, diabetes, tissue atrophy and fibrosis, and immune deficiency, as well as in accelerated aging. The autophagic process is mediated by numerous autophagy-related (ATG) proteins, among which the ATG8/LC3/GABARAP (Microtubule-associated protein 1A/1B-light chain 3/Gammaaminobutyric acid receptor-associated protein) superfamily has a pivotal role in the formation and maturation of autophagosome, a key (macro) autophagic structure (the autophagosome sequesters parts of the cytoplasm which are destined for breakdown). While in the unicellular yeast there is only a single ATG8 protein, metazoan systems usually contain more ATG8 paralogs. ATG8 paralogs generally display tissue-specific expression patterns and their functions are not strictly restricted to autophagy. For example, GABARAP proteins also play a role in intracellular vesicle transport, and, in addition to autophagosome formation, ATG8 also functions in selective autophagy. In this review, we summarize the functional diversity of ATG8/LC3/GABARAP proteins, using tractable genetic models applied in autophagy research.

Managing sustainable marine fisheries is one of the greatest challenges for humanity. The complexity of the issue calls for the development of socio-ecological models and the integration of our knowledge from several disciplines. Here we focus on the ecological aspects of sustainability: how can we increase the catch and, at the same time, possibly decrease negative effects on the marine ecosystem. Coexisting species live in richly interconnected interaction networks. This means that changes in their biomass are caused and may cause various direct and indirect effects on all other coexisting species in the food web. The assessment of maximum sustainable yield values is typically based on single-species analyses, poorly considering this multi-species context. If several fish species are exploited in particular combinations, their effects may not be additive and non-additivity may mean dampening. In these cases, the community response to fishing species A and B together may be smaller than the sum of fishing species A and B separately. We report on some preliminary results on how to develop a network algebra framework for better understanding food web simulation results for pairwise perturbations and their counter-intuitive effects.

The POU domain, class 5, transcription factor 1 (POU5F1), plays a vital role in creating pluripotency and maintaining self-renewal of the spermatogonial stem cells (SSCs). In this experimental research, the gene and protein expression of POU5F1 in two populations of differentiated and undifferentiated spermatogonia were examined, by immunohistochemistry (IMH), immunocytochemistry (ICC) and Fluidigm real-time RT-PCR. Our study was extended with online databases and the creation of PPI networks. The results indicated that the POU5F1 protein was localized in the basal compartment of seminiferous tubules. Under in vitro conditions, isolated SSC colonies were ICC-positive for the POU5F1, but the protein expression level of POU5F1 in the undifferentiated populations was higher than that in differentiated. A significant POU5F1 mRNA expression was seen in passage 4 compared to passage 0 for both populations. POU5F1 has a significantly higher mRNA expression in undifferentiated SSCs than that in differentiated SSCs, also in mESCs than in SSC-like cells. Bioinformatic analysis on POU5F1 shows its impressive connection with other genes involved in spermatogonia differentiation. These results support the advanced investigations of spermatogonia differentiation, both in vitro and in vivo. A better understanding of the POU5F1 gene and its function during differentiation will give the scientific community an open perspective for the development of direct differentiation of SSC to other male germline cells which is very important in infertility treatment.

Understanding why sexual reproduction-which involves syngamy (union of gametes) and meiosis-emerged and how it has subsisted for millions of years remains a fundamental problem in biology. Considered as the essence of sex, meiotic recombination is initiated by a DNA double-strand break (DSB) that forms on one of the pairing homologous chromosomes. This DNA lesion is subsequently repaired by gene conversion, the non-reciprocal transfer of genetic information from the intact homolog. A major issue is which of the pairing homologs undergoes DSB formation. Accumulating evidence shows that chromosomal sites where the pairing homologs locally differ in size, i.e., are heterozygous for an insertion or deletion, often display disparity in gene conversion. Biased conversion tends to duplicate insertions and lose deletions. This suggests that DSB is preferentially formed on the "shorter" homologous region, which thereby acts as the recipient for DNA transfer. Thus, sex primarily functions as a genome (re)loading mechanism. It ensures the restoration of formerly lost DNA sequences (deletions) and allows the efficient copying and, mainly in eukaryotes, subsequent spreading of newly emerged sequences (insertions) arising initially in an individual genome, even if they confer no advantage to the host. In this way, sex simultaneously repairs deletions and increases genetic variability underlying adaptation. The model explains a remarkable increase in DNA content during the evolution of eukaryotic genomes.

In order to solve our ecological crisis, it is crucial to have a fair understanding of its background. In this article I integrate the most important driving forces of human transformation of the biosphere into a general model. First, I show that it is the economic subsystem of society that produces nearly all human transformation of the biosphere. Then I differentiate between direct driving forces, which are the number of people/households, the economic output per capita/per household, the environmental impact of technologies, the structure of the economy and the geographical pattern of the economy; and indirect ones, which are the mind of people, social institutions, biological factors and physical geographical features. The behavior of individuals, groups of people and organizations mediates between indirect and direct driving forces. The model also shows us the basic strategies of environmental sustainability. Cultural changes are needed to attenuate the direct driving forces. In turn, these changes will happen only if those desiring them will have enough power to reshape social institutions and the mind of people.

Membrane theory makes it possible to compute the membrane potential of living cells accurately. The principle is that the plasma membrane is selectively permeable to ions and that its permeability to mobile ions determines the characteristics of the membrane potential. However, an artificial experimental cell system with an impermeable membrane can exhibit a nonzero membrane potential, and its characteristics are consistent with the prediction of the Goldman-Hodgkin-Katz eq., which is a noteworthy concept of membrane theory, despite the membrane's impermeability to mobile ions. We noticed this troublesome facet of the membrane theory. We measured the potentials through permeable and impermeable membranes where we used the broad varieties of membranes. Then we concluded that the membrane potential must be primarily, although not wholly, governed by the ion adsorption-desorption process rather than by the passage of ions across the cell membrane. A theory based on the Association-Induction Hypothesis seems to be a more plausible mechanism for the generation of the membrane potential and to explain this unexpected physiological fact. The Association-Induction Hypothesis states that selective ion permeability of the membrane is not a condition for the generation of the membrane potential in living cells, which contradicts the prediction of the membrane theory. Therefore, the Association-Induction Hypothesis is the actual cause of membrane potential. We continued the theoretical analysis by taking into account the Association-Induction Hypothesis and saw that its universality as a cause of potential generation mechanism. We then concluded that the interfacial charge distribution is one of the fundamental causes of the membrane potential.