ARTICLE | doi:10.20944/preprints201904.0251.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: biology education; sustaiable development goals; new biology; biology science
Online: 23 April 2019 (10:59:39 CEST)
Today in times of increasing inequality, climate change, and major social challenges, education is the best way to equip citizens, scholars and leaders to implement meaningful change and prevent future crises. Biologi education and science will solve these problems to supporting sustainable development goals especially in soil remediation, clean water, education quality and clean and affordable energy. This paper will describe how biological education could solve these problems. New biology can solve the problem about hunger use biotech, use synthetic biological material to find new advance material. New biology could driving intersectorial, interdisciplinary and international connectivity, and the leveraging of existing investments in synthetic biology, materials science, allied science and technology areas, are the major challenges in delivering the Materials from Biology vision.
ARTICLE | doi:10.20944/preprints202104.0058.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: evolutionary biology; astrobiology; philosophy of biology; epistemology
Online: 2 April 2021 (11:42:18 CEST)
The details of abiogenesis to date remain a matter of debate and constitute a key mystery in science and philosophy. The prevailing scientific hypothesis implies an evolutionary process of increasing complexity on earth starting from (self-) replicating polymers. Defining the cut-off point where life begins is another moot point beyond the scope of this article. We will instead walk through the known evolutionary steps that lead from these first exceptional polymers to the vast network of living biomatter that spans our world today, focusing in particular on perception, from simple biological feedback mechanisms to the complexity that allows for abstract thought. We then will project from the well-known to the unknown to gain a glimpse on what the universe aims to accomplish with living matter, just to find that if the universe had ever planned to be comprehended, evolution still has a long way to go.
ARTICLE | doi:10.20944/preprints202002.0195.v1
Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: biology; mathematics; computational biology; linear algebra; abstract algebra
Online: 14 February 2020 (10:54:57 CET)
This dissertation is a rigorous study of ecology and macrocellular biology as a subfield of abstract algebra. We begin with the creation of an axiomatic paradigm, then move onto constructing a universal genetic code of biology. We use this to define increasingly complex algebraic structures (ecosystem, evolving populations, etc.). We prove a variety of theorems regarding to the members of the previous mathematical constructs, notably the following three: 1. There is one unique phenotypic representation of each organism. For example, if you subdivide any piece of genetic code into its phenotypic components, then two identical organisms have identical decomposed DNA 2. There are a finite number of indivisible phenotypic traits. 3. The three sophioid-definitions are equivalent: (a) dynamical evolutionary enlargement of the medial temporal lobe and frontal lobe, (b) reliance upon intelligence, (c) the existence of an intellectually- or socially-hierarchical society. Much has yet to be done on this work, but as a first draft, it stands as a jumping point for future exploits; I am working on an entirely revised second draft.
REVIEW | doi:10.20944/preprints202111.0203.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: flower development; epigenetics; RNA biology; Genomics; single cell biology
Online: 10 November 2021 (11:00:03 CET)
The rise of data science in biology stimulates interdisciplinary collaborations to address fundamental questions. Here, we report the outcome of the first SINFONIA symposium focused on revealing the mechanisms governing plant reproductive development across biological scales. The intricate and dynamic target networks of known regulators of flower development remain poorly understood. To analyze development from the genome to the final floral organ morphology, high-resolution data that capture spatiotemporal regulatory activities are necessary and require advanced computational methods for analysis and modeling. Moreover, frameworks to share data, practices and approaches that facilitate the combination of varied expertise to advance the field are called for. Training young researchers in interdisciplinary approaches and science communication offers the opportunity to establish a collaborative mindset to shape future research.
ARTICLE | doi:10.20944/preprints201909.0219.v2
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: Systems Biology; Horticulture; Computational Biology; Complex System; Fertilization; System Modeling
Online: 9 June 2020 (04:04:16 CEST)
Differential equation models to understand interaction between plant and nutrient solution are presented. The root cells selectively emit H+ ions with active transport consuming ATPs to establish electrical gradient along the cell membrane. It establishes electrical field with Nernst potential to make positively charged ions outside the cell membrane flow into the root cell. Anion influx is also modulated by H+ ion concentration because plant root cell absorbs negatively charged particles with symport. If an anion collides with H+ cell to make net charge as neutral, at symport channel, it can flow through. In this paper, mathematical models for cation and anion absorption are introduced. Cation absorption model was induced from Ohm's law combined with Goldman's equation. Anion absorption model is similar to chemical reaction rate model. Both models have physiological terms influenced by gene expression pattern, species or phenotypes. Cation model also includes terms for ion's kinetic and electrical properties, growth of plant and interaction between the root and the surroundings. Simulation for 20 different sets of coefficients showed that the physiology-related coefficient has important role on nutrition absorption tendencies of plants.
ARTICLE | doi:10.20944/preprints201608.0108.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: developmental biology; computational biology; lineage trees; embryogenesis; biological complexity
Online: 10 August 2016 (11:36:39 CEST)
Embryonic development proceeds through a series of differentiation events. The mosaic version of this process (binary cell divisions) can be analyzed by comparing early development of Ciona intestinalis and Caenorhabditis elegans. To do this, we reorganize lineage trees into differentiation trees using the graph theory ordering of relative cell volume. Lineage and differentiation trees provide us with means to classify each cell using binary codes. Extracting data characterizing lineage tree position, cell volume, and nucleus position for each cell during early embryogenesis, we conduct several statistical analyses, both within and between taxa. We compare both cell volume distributions and cell volume across developmental time within and between single species and assess differences between lineage tree and differentiation tree orderings. This enhances our understanding of the differentiation events in a model of pure mosaic embryogenesis and its relationship to evolutionary conservation. We also contribute several new techniques for assessing both differences between lineage trees and differentiation trees, and differences between differentiation trees of different species. The results suggest that at the level of differentiation trees, there are broad similarities between distantly related mosaic embryos that might be essential to understanding evolutionary change and phylogeny reconstruction. Differentiation trees may therefore provide a basis for an Evo-Devo Postmodern Synthesis.
REVIEW | doi:10.20944/preprints202212.0209.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Systems Biology; Systems Medicine; Disease Mechanisms; Disease Maps; Network Biology
Online: 13 December 2022 (01:06:32 CET)
As a conceptual model of disease mechanisms, a disease map integrates available knowledge and is applied for data interpretation, predictions and hypothesis generation. It is possible to model disease mechanisms on different levels of granularity and adjust the approach to the goals of a particular project. This rich environment together with requirements for high-quality network reconstruction makes it challenging for new curators and groups to be quickly introduced to the development methods. In this review, we offer a step-by-step guide for developing a disease map within its mainstream pipeline that involves using the CellDesigner tool for creating and editing diagrams and the MINERVA Platform for online visualisation and exploration. We also describe how the Neo4j graph database environment can be used for managing and querying efficiently such a resource. For assessing the interoperability and reproducibility we apply FAIR principles.
REVIEW | doi:10.20944/preprints202110.0185.v1
Subject: Computer Science And Mathematics, Mathematical And Computational Biology Keywords: systems biology; integrative bioinformatics; interactomics; eukaryotes; non-models; network biology
Online: 12 October 2021 (14:24:56 CEST)
Interactome analyses have traditionally been applied to yeast, human and other model organisms due to the availability of protein-protein interactions data for these species. Recently these techniques have been applied to more diverse species using computational interaction prediction from genome sequence and other data types. This review describes the various types of computational interactome networks that can be created and how they have been used in diverse eukaryotic species, highlighting some of the key interactome studies in non-model organisms.
REVIEW | doi:10.20944/preprints202007.0751.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: tunable; genetic part; control; adaptation; cybergenetics; synthetic biology; systems biology
Online: 6 October 2020 (13:32:00 CEST)
Biological systems often need to operate in complex environments where conditions can rapidly change. This is possible due to their inherent ability to sense changes and adapt their behavior in response. Here, we detail recent advances in the creation of synthetic genetic parts and circuits whose behaviors can be dynamically tuned through a variety of intra- and extra-cellular signals. We show how this capability lays the foundation for implementing control engineering schemes in living cells and allows for the creation of biological systems that are able to self-adapt, ensuring their functionality is maintained in the face of varying environmental and physiological conditions. We end by discussing some of the broader implications of this technology for the safe deployment of synthetic biology.
REVIEW | doi:10.20944/preprints202007.0022.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: Multiscale modelling; cell-based modelling; computational biology; multicellular systems biology
Online: 3 July 2020 (08:43:36 CEST)
The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviours, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regeneration is to understand how relationships between scales produce emergent tissue-scale behaviours. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionised our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modelling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics and signalling. Yet such models remain technically challenging: modelling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarise recent progress in multiscale modelling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation and validation of such models.
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: sequencing; omics; synthetic biology; systems biology; machine learning; biological design
Online: 23 April 2020 (03:47:02 CEST)
The ability to read and quantify nucleic acids such as DNA and RNA using sequencing technologies has revolutionized our understanding of life. With the emergence of synthetic biology, these tools are now being put to work in new ways - enabling de novo biological design. Here, we show how sequencing is supporting the creation of a new wave of biological parts and systems, as well as providing the vast data sets needed for the machine learning of design rules for predictive bioengineering. However, we believe this is only the tip of the iceberg and end by providing an outlook on recent advances that will likely broaden the role of sequencing in synthetic biology and its deployment in real-world environments.
CONCEPT PAPER | doi:10.20944/preprints201810.0277.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antibody; network; sequence; structure; clonality; B cell; systems biology; quantitative biology
Online: 12 October 2018 (17:01:13 CEST)
Based on the key molecule of humoral adaptive immunity, the antibody, evolution of the system comprises molecular genetic, cell biologic and immunologic mechanisms, and as a network the system is likely governed and can be characterized by physical rules as well. While deep sequencing can provide vast amounts of data related primarily to clonal relationships, functional interpretation of such data is hampered by the inherent limitations of converting sequence to structure to function. In this paper a novel model of structural interaction space, termed radial adjustment of system resolution, or RADARS, is proposed. The model is based on the radial growth of resolution of structural recognition, corresponding to increasing affinity of immune reactivity, and the virtual infinity of directions of growth, corresponding to the ability to respond to almost any molecular structure. Levels of interaction strength appear as shells of the sphere representing the system. B-cell development and immune responses can be readily interpreted in the model and quantitative properties of the antibody network can be inferred from the physical properties of a quasi-spherical system growing multi-radially. The system is described by double-Pareto distribution, sampling the lognormally distributed equilibrium constants at a rate of phi square. Finally, general strategies for merging antibody sequence space into structural space are outlined.
REVIEW | doi:10.20944/preprints202107.0307.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Retinogenesis; Quantiative Biology; Imaging
Online: 13 July 2021 (12:18:20 CEST)
The study of the development of the vertebrate retina can be addressed from several perspectives: from purely qualitative to a more quantitative approach that takes into account its spatiotemporal features, its three dimensional structure and also the regulation and properties at the systems level. Here we review the ongoing transition towards a full four-dimensional characterization of the developing vertebrate retina, focusing on the challenges at the experimental, image acquisition, image processing and quantification. Using the developing zebrafish retina, we illustrate how quantitative data extracted from these type of highly dense three-dimensional tissues depends strongly on the image quality, image processing and algorithms used to segment and quantify. Therefore, we propose that the scientific community that focuses on developmental systems could strongly benefit from a more detailed disclosure of the tools and pipelines used to process and analyze images from biological samples.
REVIEW | doi:10.20944/preprints201801.0267.v1
Subject: Biology And Life Sciences, Virology Keywords: Adenovirus; biology; immunocompetent; immunocompromised
Online: 29 January 2018 (05:13:08 CET)
Adenovirus is a family of double stranded DNA viruses that are a significant cause of upper respiratory tract infections in children and adults. Less commonly, the adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Most adenovirus infections are self-limited in the immunocompetent host and are treated with supportive measures. Fatal infections can occur in immunocompromised patients and less frequently in the healthy. Adenoviral vectors are being studied for novel biomedical applications including gene therapy and immunization. In this review we will focus on the spectrum of adenoviral infections in humans.
REVIEW | doi:10.20944/preprints202209.0095.v2
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: endothelium; vascular biology; lipid; angiogenesis
Online: 28 November 2022 (02:22:27 CET)
The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune response under normal physiological conditions, and their dysfunction is closely associated with pathologies such as cardiovascular diseases. Abnormal EC metabolism, especially fatty acid (FA) dysfunctional metabolism, contributes to the development of many diseases including pulmonary hypertension (PH). In this review, we focus on discussing the latest advances in FA metabolism in ECs under normal and pathological conditions with an emphasis on PH. We also highlight areas of research that warrant further investigation.
REVIEW | doi:10.20944/preprints202201.0196.v1
Subject: Social Sciences, Education Keywords: education; online; chemical biology; interdisciplinary
Online: 13 January 2022 (18:27:07 CET)
The Covid‐19 pandemic, evolving needs of students & mentors, and the drive for global educational equality are collectively shifting how courses are packaged/distributed, ushering a more holistic approach and blending of fields. We recently created interdisciplinary courses in chemical biology aimed at massive open online and small private levels. These courses cover biology, chemistry, & physics, and concepts underlying modern chemical‐biology tools. We discuss what we learned while creating/overseeing these courses: content optimization and maintaining material freshness while fostering a stimulating learning environment. We outline mechanisms that help sustain student attention throughout rapidly‐moving courses, how to integrate adaptability to students’ needs in the short & long term, and speculate how we could have improved. We believe this will be an important guide for anyone wanting to develop online learning formats ideal for nurturing interdisciplinary scientists of tomorrow.
ARTICLE | doi:10.20944/preprints201901.0022.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Synthetic biology; Sustainable Development Goals
Online: 3 January 2019 (13:14:42 CET)
Advances in genetic engineering have placed synthetic biology at a prime position to develop new products, materials, and services that could contribute to the 2030 UN Sustainable Development goals. These include novel materials for water purification, new bio-based products to replace toxic industrial chemicals, and engineered organisms for bioremediation. Supporting the development of synthetic biology initiatives in developing countries is needed to ensure these benefits are open to all.
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: artificial intelligence; bioinformatics; computational biology; data mining & machine learning; evolutionary studies; mathematical biology; animal behavior
Online: 6 November 2019 (05:07:24 CET)
Industrial pig farming is associated with negative technological pressure on the bodies of pigs. Leg weakness and lameness are the sources of significant economic loss in raising pigs. Therefore, it is important to identify predictors of limb condition. This work presents assessments of the state of limbs using indicators of growth and meat characteristics of pigs based on machine learning algorithms. We have evaluated and compared the accuracy of prediction for several ML classification algorithms (Random Forest, K-Nearest Neighbors, Artificial Neural Networks, C50Tree, Support Vector Machines, Naive Bayes, Generalized Linear Models, Boost, and Linear Discriminant Analysis) and have identified the Random Forest and K-Nearest Neighbors as the best performing algorithms for predicting pig leg weakness using a small set of simple measurements that can be taken at an early stage of animal development. Muscle Thickness, Back Fat amount, and Average Daily Gain serve as significant predictors of conformation of pig limbs. Our work demonstrates the utility and relative ease of using machine learning algorithms to assess the state of limbs in pigs based on growth rate and meat characteristics.
REVIEW | doi:10.20944/preprints202311.0143.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: Plants; Molecular Biology; Genomic; Transcriptomic; Epigenetic
Online: 2 November 2023 (10:11:14 CET)
The methods used to introduce CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas-mediated genome editing into fruit species, as well as the impacts of the application of this technology to activate and knock out of target genes in different fruit trees species including tree development, yield, fruit quality, and tolerance to biotic and abiotic stresses have been firstly described in this review. The application of this gene editing technology could allow the development of new generations of fruit crops with improved traits by targeting different genetic segments or even could facilitate the introduction of traits in elite cultivars without changing other traits. However, at this moment, the scarcity of efficient regeneration and transformation protocols in some species, the fact that many of those procedures are the genotype-dependent or the convenience of segregating the transgenic parts of the CRISPR system represent the main handicaps limiting the potential of genetic editing techniques for fruit trees. Finally, latest news on the legislation and regulations about the use of plants modified through CRISPR/Cas systems has been also discussed.
ARTICLE | doi:10.20944/preprints202310.1073.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Genetics and Genomics; Evolutionary Biology; Zoology
Online: 17 October 2023 (10:34:30 CEST)
Brown-Spotted Pit viper (Protobothrops mucrosquamatus), also known as the Chinese habu, is a widespread and highly venomous snake distributed from from northeastern India to eastern China. Genomics research can help provide much insight in understanding venom components and natural selection in vipers. Here, we collected, sequenced and assembled the genome of a male P. mucrosquamatus individual from China, producing a highly continuous reference genome, with the length of 1.53 Gb and 41.18% repeat element content. From this 24,799 genes were identified, and 97.97% genes could be annotated. Nuclear genome single-copy genes phylogenetic tree including 6 species verified the validity of our genome assembly and annotation process. This research will contribute to further study on Protobothrops biology and the genetic basis of the snake venom.
ARTICLE | doi:10.20944/preprints202309.1225.v1
Subject: Physical Sciences, Biophysics Keywords: genetics; molecular biology; biophysics; quantum mechanics
Online: 19 September 2023 (05:18:03 CEST)
This study investigates the impact of temperature-induced quantum proton tunneling probability on DNA amplification during polymerase chain reactions (PCR). Using a simulation model based on a Gaussian wavefunction and finite-difference time-domain method, quantum tunneling of protons across square potential barriers is examined. The results unveil consistent probability distributions for quantum tunneling across various PCR temperatures, with distinct oscillation patterns emerging post-barrier crossing. Acknowledging limitations in initial conditions due to temperature-dependent proton energy, the study highlights the need for refined models and experimental validation. These findings accentuate the potential interplay between quantum mechanics and biological systems, prompting further research to understand quantum tunnelling’s comprehensive effect on genetic variations and molecular processes.
ARTICLE | doi:10.20944/preprints202308.1451.v1
Subject: Biology And Life Sciences, Other Keywords: Genetics and Genomics; Evolutionary Biology; Zoology
Online: 22 August 2023 (03:43:10 CEST)
The Oriental ratsnake Ptyas mucosa is a common non-venomous snake of the colubrid family, with a wide geographic range spanning much of South and Southeast Asia. P. mucosa is widely cultivated dut to it used in traditional medicine, scientific research, and handicrafts. Therefore, genome resources could play an important role in the efficacy of traditional medicine and the analysis of the living environment of the species. We collected a snake sample in Hezhou, Guangxi, China, which was identified as P. mucosa by morphological identification. Here we present a highly continuous P. mucosa genome with a genome size of 1.74Gb. The scaffold N50 length is 9.57Mb and the maximal length of scaffold is 78.3Mb, the P. mucosa genome has a CG content of 37.9% and the integrity of the gene reached 86.6%.Assembled using long-reads, the total length of the repeat sequence in the genome reached 735 Mb, and its repeat content was as high as 42.19%. A total of 24,869 functional genes were annotated. This study will assist in the understanding of the P. mucosa, and also provide a basis for medicinal research.
DATA DESCRIPTOR | doi:10.20944/preprints202306.0658.v1
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Genetics and Genomics; Evolutionary Biology; Zoology
Online: 9 June 2023 (03:30:56 CEST)
Snakes are a vital component of wildlife resources and are widely distributed across the globe. Bungarus multicinctus, a highly venomous snake, is found in central and southern China. B. multicinctus is a highly venomous snake and is distributed in central and southern China. Snakes are an ancient group of reptiles, and their genome resources can provide important clues for understanding the evolutionary history of reptiles. Meanwhile, genomic resources play a crucial role in comprehending the evolution of species. So far, the genomic resources of snakes are a rarity. In 2021, a snake sample was collected from Beiliu Longgukeng, Guangxi, which was identified as B. multicinctus through morphological identification. In this study, we present a highly contiguous genome of B. multicinctus with a size of 1.51 Gb. The genome contains a repeat content of 40.15%, with a total length exceeding 620 Mb. Additionally, we annotated a total of 24,869 functional genes. This research is of great significance for comprehending the evolution of B. multicinctus and provides a genomic basis for the genes involved in venom gland function.
ARTICLE | doi:10.20944/preprints202305.1482.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: genetic manipulation; pleiotropic effects; systems biology
Online: 22 May 2023 (09:03:52 CEST)
In T. gondii, as well as in other model organisms, gene knock-out using CRISPR-Cas9 is a suitable tool to identify the role of specific genes. The general consensus implies that only the gene of interest is affected by the knock-out. Is this really the case? In a previous study, we have generated knock-out (KO) clones of TgRH88_077450 (SRS29B; SAG1) which differed in the numbers of integrated dihydrofolate-reductase-thymidylate-synthase (MDHFR-TS) drug-selectable marker. Clones 18 and 33 had a single insertion of MDHFR-TS within SRS29B. Clone 6 was disrupted by the insertion of a short unrelated DNA-sequence, but the marker was integrated elsewhere. In clone 30, the marker was inserted into SRS29B and several other MDHFR-TS copies were found in the genome. KO and wild-type (WT) tachyzoites had similar shape, dimensions and vitality. This prompted us to investigate the impact of the genetic engineering as such on the overall proteome patterns of the four clones as compared to the respective WT. Comparative shotgun proteomics of the five strains was performed. Overall, 3236 proteins were identified. Principal component analysis of the proteomes revealed five distinct clusters corresponding to the five strains by both iTop3 and iLFQ algorithms. Detailed analysis of the differentially expressed proteins revealed that the target of the KO, srs29B, was lacking in all KO clones. Besides this protein, twenty other proteins were differentially expressed between KO clones and WT or between different KO clones. The protein exhibiting the highest variation between the five strains was srs36D encoded by TgRH_016110. The deregulated expression of SRS36D was further validated by quantitative PCR. Moreover, the transcript levels of three other selected SRS genes, namely SRS36B, SRS46, and SRS57 exhibited significant differences between individual strains. These results indicate that knocking out a given gene may affect the expression of other genes. Therefore, care must be taken when specific phenotypes are regarded as a direct consequence of the KO of a given gene.
Subject: Biology And Life Sciences, Biophysics Keywords: biology; thermodynamics; biothermodynamics; entropy; Gibbs energy
Online: 21 October 2022 (09:58:33 CEST)
During the last 50 years, an interdisciplinary approach in research in various scientific fields has become widely spread. This process significantly deepens and widens our scientific knowledge, but on the other hand makes more difficult choosing a discipline to be used by students and young researchers. The dynamic development of science makes this choice even harder. There is a widely spread opinion that thermodynamics uses a rigorous mathematical apparatus. This paper describes that knowledge of the fundamental principles of thermodynamics is required for deep understanding of crucial biological processes. Thus the effort put into learning classical and nonequilibrium thermodynamics does not make harder, but easier gaining a better knowledge of biological processes. This essay is an attempt to convey personal experience in using thermodynamics to describe biological systems and processes they perform.
REVIEW | doi:10.20944/preprints202209.0455.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: systems biology; machine learning; surrogate model
Online: 29 September 2022 (07:17:28 CEST)
Mechanistic models have been used for centuries to describe complex interconnected processes, including biological ones. As the scope of these models has widened, so have their computational demands. This complexity can limit their suitability when running many simulations or when real-time results are required. Surrogate machine learning models can be used to approximate the behaviour of complex mechanistic models, and once built, their computational demands are several orders of magnitude lower. This paper provides an overview of the relevant literature, both from an applicability and a theoretical perspective. For the latter, the paper focuses on the design and training of the underlying machine learning models. Application-wise, we show how machine learning surrogates have been used to approximate different mechanistic models. We present a perspective on how these approaches can be applied to models representing biological processes with potential industrial applications (e.g., metabolism and whole-cell modelling) and show why surrogate machine learning models may hold the key to making the simulation of complex biological models possible using a typical desktop computer.
REVIEW | doi:10.20944/preprints202112.0416.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: macrophage, bistability, metabolism, systems biology, miRNA
Online: 25 December 2021 (00:02:25 CET)
Macrophages are essential innate immune cells characterized by a high diversity and plasticity. In vitro, their full dynamic range of activation profiles include the classical pro-inflammatory (M1) and the alternative anti-inflammatory (M2) program. Bistability usually arises in biological systems that contain a positive-feedback loop or a mutually inhibitory, double-negative-feedback loop, which are common regulatory motifs reported for macrophage transitions from one activation state to the other one. This switch-like behavior of macrophage is observed at four different levels. First, a decision-making module in signal transduction includes mutual inhibitory interactions between M1 (STAT1 and NF-KB/p50-p65) and M2 (STAT3 and NF-KB/p50-p50) signaling pathways. Second, a switch-like behavior at the gene expression level includes complex network motifs of transcription factors and miRNAs. Third, those changes impact metabolic gene expression leading to several switches in energy production, NADPH and ROS production, TCA cycle functionality, biosynthesis and nitrogen metabolism. Fourth, metabolic changes are monitored by specialized metabolic sensors coupled to AMPK and mTOR activity to provide stability by maintaining the signals to promote either M1 or M2 activation. The targeting of robust molecular switches has the potential to treat a broad range of widespread diseases such as sepsis, cancer or chronic inflammatory diseases.
ARTICLE | doi:10.20944/preprints202106.0639.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Microscopy; Bacterial cell biology; Nanofabrication; Microfluidics
Online: 28 June 2021 (10:38:11 CEST)
Light microscopy is indispensable for analysis of bacterial spatial organization. However, imaging in bacteria is difficult due to their small sizes and the fact that most species are non-spherical, meaning they typically lie horizontally on a microscope coverslip. This is especially problematic when considering that many essential bacterial processes—such as cell division—occur along the short axes of these cells, and so are viewed side-on by standard microscopy. We recently developed a pair of methods to overcome this problem by forcing cells to stand vertically during imaging, named VerCINI (Vertical Cell Imaging by Nanostructured Immobilisation) and µVerCINI (Microfluidic VerCINI). The concept behind both methods is that cells are imaged while confined vertically inside cell traps made from a nanofabricated mould. By doing so, the short axes of the cells are rotated parallel to the microscope imaging plane and are imaged with high resolution. μVerCINI combines the vertical cell confinement with microfluidics so that vertical imaging can be done during fluid exchange, such as during antibiotic perturbations. Here, we provide a practical guide to implementing both VerCINI and µVerCINI, with detailed protocols and experience-based tips so that interested researchers can easily use one or both imaging methods to complement their current approaches.
HYPOTHESIS | doi:10.20944/preprints202006.0168.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: pattern formation; morphogenesis; systems biology; embryology
Online: 14 June 2020 (12:29:45 CEST)
Development encompasses processes that occur at multiple length-scales, includ- ing gene regulatory interactions, cell movements and reorganisation, cell signalling and growth. It is essential that the timing of events in all of these different processes are coordinated to generate well patterned tissues and organs. However, how the timing of intrinsic cell state changes is coordinated with events at the multi-tissue and whole organism level is unknown. Here, we argue that an important mechanism which accounts for integration of timing across levels of organisation is provided by tissue tectonics: i.e. how morphogenetic events driving tissue shape change result in the relative displacement of signalling and responding tissues and coordinate devel- opmental timing across scales. In doing so, tissue tectonics provides a mechanism by which the cell specification events intrinsic to cells can be modulated by the temporal exposure to extracellular signals. This exposure is in turn regulated by higher-order properties of the embryo such as their physical properties, rates of growth and the combination of dynamic cell behaviours impacting tissue morphogenesis. Tissue tec- tonics creates a downward flow of information from higher to lower levels of biological organisation, providing an instance of downward causation in development.
BRIEF REPORT | doi:10.20944/preprints202001.0280.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atherosclerosis; vascular biology; calcification; genetics; 9p21
Online: 24 January 2020 (11:17:21 CET)
Background: Genome-wide association studies have identified the chromosome 9p21 locus as one of the most important genetic risk factors for cardiovascular disease. However, the mechanism by which this locus promotes disease remains unclear due to difficulty identifying the causal genes and lack of a suitable animal model. Methods and Results: A total of 180 coronary artery autopsy specimens were analyzed histopathologically. The genotype of 9p21 (rs1333049) was not associated with any coronary risk factors nor the vulnerable plaque phenotype, but carriers of 9p21 risk allele did demonstrate more lesional calcification. To extend these studies into an animal model, mice with a targeted deletion of the orthologous 70-kb non-coding interval on chromosome 4 (chr4D70kb/D70kb) were bred onto ApoE-/- and fed with high fat diet. Targeted deletion of the 9p21 risk interval increased susceptibility to atherosclerotic plaque progression, but did not affect plaque rupture in the tandem stenosis model. Coronary risk factors such as body weight, blood pressure, lipid, and glucose levels did not differ between genotypes. Von Kossa staining revealed that chr4D70kb/D70kb, ApoE-/- developed more calcification in the plaque compared with chr4+/+, ApoE-/- mice, and that this this change was accompanied by increased aortic mRNA expression of Runx2, a key osteogenic transcription factor. Primarily cultured smooth muscle cells from chr4D70kb/D70kb were hyperproliferative, and showed a calcification-prone phenotype after exposure to high-phosphate medium. Treatment with Palbociclib, a selective inhibitor of cyclin-dependent kinase 4/6, reduced mRNA expression of osteogenic genes in smooth muscle cells. Conclusion: Results from human and mouse studies indicate that the 9p21 non coding risk interval is associated with larger atherosclerotic plaque burden, but not with plaque rupture. 9p21 may promote lesion expansion by inducing the proliferation of de-differentiated and osteogenic smooth muscle cells.
REVIEW | doi:10.20944/preprints201902.0030.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: biomarkers; miRNAs; heart failure; system biology
Online: 4 February 2019 (11:44:17 CET)
Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI predict molecular insights of this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicts 13 miRNAs and 3 of these miRNAs were validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicts 24 miRNAs among 1310 molecules and 6 of these miRNAs were selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.
ARTICLE | doi:10.20944/preprints202306.1875.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Enzyme kinetics; Hydrogen peroxide; Isothermal titration calorimetry; Oligomerisation; Parameter estimation; Peroxiredoxin; Quantitative redox biology; Systems biology
Online: 27 June 2023 (09:46:07 CEST)
Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 93.0 µM-4·s-1 and 102 s-1, respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.
CONCEPT PAPER | doi:10.20944/preprints202108.0416.v1
Subject: Physical Sciences, Fluids And Plasmas Physics Keywords: Natural selection; individuality; levels of selection; evolutionary biology; physics; philosophy of biology; exobiology; origins of life
Online: 20 August 2021 (13:42:15 CEST)
Natural selection is commonly seen not just as an explanation for adaptive evolution, but as the inevitable consequence of “heritable variation in fitness among individuals”. Although it remains embedded in biological concepts, such a formalisation makes it tempting to explore whether this precondition may be met not only in life as we know it, but also in other physical systems. This would imply that these systems are subject to natural selection and may perhaps be investigated in a biological framework, where properties are typically examined in light of their putative functions. Here we relate the major questions that were debated during a three-day workshop devoted to discussing whether natural selection may take place in non-living physical systems. We start this report with a brief overview of research fields dealing with “life-like” or “proto-biotic” systems, where mimicking evolution by natural selection in test tubes stands as a major objective. We contend the challenge may be as much conceptual as technical. Taking the problem from a physical angle, we then discuss the framework of dissipative structures. Although life is viewed in this context as a particular case within a larger ensemble of physical phenomena, this approach does not provide general principles from which natural selection could be derived. Turning back to evolutionary biology, we ask to what extent the most general formulations of the necessary conditions or signatures of natural selection may be applicable beyond biology. In our view, such a cross-disciplinary jump is in large part impeded by reliance on individuality as a central yet implicit and loosely defined concept. Overall, these discussions thus lead us to conjecture that understanding, in physico-chemical terms, how individuality emerges and how it can be recognised, will be essential in the search for instances of evolution by natural selection outside of living systems.  Natural Selection Beyond Life? Observing the physico-chemical world through Darwinian glasses; 12-15 November 2019 - Institut d'Etudes Scientifiques, Cargèse, France
ARTICLE | doi:10.20944/preprints201811.0233.v1
Subject: Physical Sciences, Condensed Matter Physics Keywords: entropy generation; entropy acceleration; glucose catabolism; irreversible reactions; heat transfer; matter transfer; cancer biology; stem cell biology
Online: 9 November 2018 (03:49:41 CET)
The heat and matter transfer during glucose catabolism in living systems and their relation with entropy production are a challenging subject of the classical thermodynamics applied to biology. In this respect, an analogy between mechanics and thermodynamics has been performed via the definition of the entropy density acceleration expressed by the time derivative of the rate of entropy density and related to heat and matter transfer in minimum living systems. Cells are regarded as open thermodynamic systems that exchange heat and matter resulting from irreversible processes with the intercellular environment. Prigogine’s minimum energy dissipation principle is reformulated using the notion of entropy density acceleration applied to glucose catabolism. It is shown that, for out-of-equilibrium states, the calculated entropy density acceleration is finite and negative and approaches as a function of time a zero value at global thermodynamic equilibrium for heat and matter transfer independently of the cell type and the metabolic pathway. These results could be important for a deeper understanding of entropy generation and its correlation with heat transfer in cell biology with special regard to glucose catabolism representing the prototype of irreversible reactions and a crucial metabolic pathway in stem cells and cancer stem cells.
ARTICLE | doi:10.20944/preprints202305.1717.v2
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Ecological networks; bioengineering; synthetic biology; invasion dynamics
Online: 24 October 2023 (16:46:07 CEST)
The possibility of abrupt transitions threatens to poise ecosystems into irreversibly degraded states. Recently, it has been proposed the use of engineered microbiomes in endangered ecosystems to prevent them to cross tipping points and avoid collapse. Potential targets for such interventions include some of the most prominent life-support systems in the biosphere: drylands and coral reefs. Since engineering can require the introduction of microorganisms not present in resident communities, how can we weight the potential outcomes? One way is to use general models of species interactions where the "synthetic" strain is incorporated into a standard multispecies model. Here we follow this approach by modelling a resource-consumer community where one of the species is a modified one that acts by preserving some key resource. We show how the indirect effect of damping the decay of shared resources results in biodiversity increase, and last but not less, the successful incorporation of the synthetic within the ecological network. Further extensions and implications for future restoration and terraformation strategies are discussed.
ARTICLE | doi:10.20944/preprints202308.1126.v1
Subject: Physical Sciences, Quantum Science And Technology Keywords: Complexity theory, Emergence, Biology, Technology, Agency, Symmetries
Online: 16 August 2023 (11:46:46 CEST)
This paper discusses complexity theory, that is, the many theories that have been proposed for emergence of complexity from the underlying physics. Our aim is to identify which aspects have turned out to be the more fundamental ones as regards the emergence of biology, engineering, and digital computing, as opposed to those that are in fact more peripheral in these contexts. In the cases we consider, complexity arises via adaptive modular hierarchical structures that are open systems involving broken symmetries. Each emergent level is causally effective because of the meshing together of upwards and downwards causation that takes place consistently with the underlying physics. Various physical constraints limit the outcomes that can be achieved. The underlying issue concerns the origin of consciousness and agency given the basis of life in physics, which is structured starting from symmetries and variational principles with no trace of agency. A possible solution is to admit that consciousness is an irreducible emergent property of matter.
ARTICLE | doi:10.20944/preprints202308.0775.v1
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Genetics and Genomics; Animal Genetics; Evolutionary Biology
Online: 9 August 2023 (10:51:51 CEST)
The study of the currently known >3,000 species of snakes can provide valuable insights into the evolution of their genomes. Deinagkistrodon acutus, also known as Sharp-nosed Pit Viper, one hundred-pacer viper or five-pacer viper, is a venomous snake with significant economic, medicinal and scientific importance. Widely distributed in southeastern China and South-East Asia, D. acutus has been primarily studied for its venom. Here, we employed next-generation sequencing to assemble and annotate a highly continuous genome of D. acutus. The genome size is 1.46 Gb; its scaffold N50 length is 6.21 Mb, the repeat content is 42.81%, and 24,402 functional genes were annotated. This study helps to further understand and utilize D. acutus and its venom at the genetic level.
REVIEW | doi:10.20944/preprints202307.1278.v1
Subject: Biology And Life Sciences, Aging Keywords: evolution, evolvability, biology, gerontology, lifespan, senescence, genetics
Online: 19 July 2023 (04:18:37 CEST)
As recently as 2002 programmed aging in mammals was widely thought to be theoretically impossible based on generally accepted concepts regarding the evolution process. However, as described in this article, genetics discoveries, results of selective breeding, and other direct evidence strongly support the idea that aging creates an evolutionary advantage and that therefore complex biological mechanisms evolved that control mammal aging. Like similar life-cycle programs that control reproduction, growth, and menopause the aging program can adjust the aging trait during an individual’s life to compensate for temporary or local changes in external conditions that alter the optimum lifespan for a particular species population. In addition, genetics discoveries strongly support the evolvability concept to the effect that sexually reproducing species can evolve design features that increase their ability to evolve, and that aging is one such feature.
REVIEW | doi:10.20944/preprints202105.0036.v2
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: Electrophile; Drug Design; Covalent Drug; Chemical Biology
Online: 19 October 2021 (10:28:15 CEST)
Of the manifold concepts in drug discovery and design, covalent drugs have re-emerged as one of the most promising over the past 20-or so years. All such drugs harness the ability of a covalent bond to drive an interaction between a target biomolecule, typically a protein, and a small molecule. Formation of a covalent bond necessarily prolongs target engagement, opening avenues to targeting shallower binding sites, protein complexes, and other difficult to drug manifolds, amongst other virtues. This opinion piece discusses frameworks around which to develop covalent drugs. Our argument, based on results from our research program on natural electrophile signaling, is that targeting specific residues innately involved in native signaling programs are ideally poised to be targeted by covalent drugs. We outline ways to identify electrophile-sensing residues, and discuss how studying ramifications of innate signaling by endogenous molecules can provide a means to predict drug mechanism and function and assess on- versus off-target behaviors.
REVIEW | doi:10.20944/preprints202102.0351.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: telomeres; shelterins; telomere biology diseases; cancer; dyskeratosis
Online: 17 February 2021 (09:34:55 CET)
Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. In a classic view, telomere biology impinges on intracellular signaling pathways regulating DNA damage repair and cell cycle arrest, but new roles of telomeric proteins and transcripts emerge from recent literature. Telomere biology diseases are human disorders associated to telomere attrition. This review wants to overview the recent findings in the field of telomere’s metabolism and to deepen molecular mechanisms of inherited and acquired telomeropathies, explaining new critical connections between telomeric factors and disease pathogenesis
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: mechanistic; hypothesis; physiology; biology; pharmaceutical; biomedicine; preclinical
Online: 20 September 2020 (15:01:28 CEST)
This two-part series describes how to test hypotheses on molecular mechanisms that underlie biological phenomena, using preclinical drug testing as a simplified example. While pursuing drug testing in preclinical research, it is important for students to understand the limitations of descriptive as well as mechanistic studies. The former does not identify any causal links between two or more variables; it identifies the presence or absence of correlations. The latter has caveats presented in Parts I and II of this series. Part II also describes how to test for a causal link between drug-induced activation of biological targets and therapeutic outcomes. Here, the mechanism of action of the drug is identified with pharmacological or genetic approaches that modify the expression/activity of the drug targets. Without interference with the proposed mechanism of action, a causal link between activation (or inhibition) of the target P and the therapeutic outcomes of drug D cannot be established. Using pharmacological agonists and antagonists, gene knockout and overexpression, or protein knockdown tools, designing a full-factorial three-way ANOVA forces the investigator to include the appropriate control groups, mitigating the risk of false positive or false negative conclusions. Upon completion of this series, the educator and student will have some of the tools in hand to design mechanistic studies and interpret various experimental outcomes, with knowledge of strengths and limitations of preclinical research.
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: mechanistic; hypothesis; physiology; biology; pharmaceutical; biomedicine; preclinical
Online: 20 September 2020 (15:00:30 CEST)
Many discoveries in the biological sciences have emerged from observational studies, but student researchers also need to learn how to design experiments that distinguish correlation from causation. For example, identifying the physiological mechanism of action of drugs with therapeutic potential requires the establishment of causal links. Only by specifically interfering with the purported mechanisms of action of a drug can the researcher determine how the drug “causes” its physiological effects. Typically, pharmacological or genetic approaches are employed to modify the expression and/or activity of the biological drug target or downstream pathways, to test if the salutary properties of the drug are thereby abolished. However, experimental techniques have caveats that tend to be underappreciated, particularly for the newer methods. In this two-part series, the caveats and strengths of mechanistic preclinical research are described, using the intuitive example of pharmaceutical drug testing in experimental models of human diseases. This series is not intended to tackle the perpetual clash between the frequentist approach to statistics and other schools of thought. Rather, Part I focuses on technical practicalities and common pitfalls of cellular and animal models designed for drug testing, and Part II describes in simple terms how to leverage a full-factorial three-way ANOVA, to test for causality in the link between drug-induced activation (or inhibition) of a biological target and therapeutic outcomes. Upon completion of this series, the student is expected to appreciate the strengths as well as limitations of mechanistic research and to avoid some of its pitfalls.
REVIEW | doi:10.20944/preprints202002.0239.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: interpretable machine learning; deep learning; predictive biology
Online: 17 February 2020 (04:12:20 CET)
Machine learning (ML) has emerged as a critical tool for making sense of the growing amount of genetic and genomic data available because of its ability to find complex patterns in high dimensional and heterogeneous data. While the complexity of ML models is what makes them powerful, it also makes them difficult to interpret. Fortunately, recent efforts to develop approaches that make the inner workings of ML models understandable to humans have improved our ability to make novel biological insights using ML. Here we discuss the importance of interpretable ML, different strategies for interpreting ML models, and examples of how these strategies have been applied. Finally, we identify challenges and promising future directions for interpretable ML in genetics and genomics.
REVIEW | doi:10.20944/preprints202002.0017.v1
Subject: Social Sciences, Safety Research Keywords: synthetic biology; food security; biosafety; regulation; GMO
Online: 3 February 2020 (05:37:23 CET)
Synthetic biology (SynBio) is an interdisciplinary field that has developed rapidly in the last two decades. It involves the design and construction of new biological systems and processes from standardized biological components, networks and synthetic pathways. The goal of Synbio is to create logical forms of cellular control. Biological systems and their parts can be re-designed to carry out completely new functions. SynBio is poised to greatly impact human health, environment, biofuels and chemical production with huge economic benefits. SynBio presents opportunities for the highly agro-based African economies to overcome setbacks that threaten food security: The setbacks are brought about by climate change, land degradation, over-reliance on food imports, global competition, and water and energy security issues among others. With appropriate regulatory frameworks and systems in place, the benefits of harnessing SynBio to boost development in African economies by far potentially outweigh the risks. Countries that are already using GMOs such as South Africa and Kenya should find the application of SynBio seamless, as it would be a matter of expanding the already existing regulations and policies for GMO use.
ARTICLE | doi:10.20944/preprints202303.0446.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Control coefficients; Metabolic Control Analysis; Systems Biology; Genomics; Pharmacokinetic principles; systems biology and PBPK; time-dependent control analysis
Online: 27 March 2023 (05:04:24 CEST)
Dynamic variables in the non-equilibrium systems of life are determined by catalytic activities. These relate to the expression of the genome. The extent to which such a variable depends on the catalytic activity defined by a gene has become more and more important in view of the possibilities to modulate gene expression or intervene with enzyme function through the use of medicinal drugs. With all the complexity of cellular systems biology, there are still some very simple principles that guide the control of variables such as fluxes, concentrations, and half-times. Using time-unit invariance we here derive a multitude of laws governing the sums of the control coefficients that quantify the control of multiple variables by all the catalytic activities. We show that the sum of the control coefficients of any dynamic variable over all catalytic activities is determined by the control of the same property by time. When the variable is at a maximum, minimum or steady, this limits the sums to simple integers like 0, -1, 1, and -2, depending on the variable under consideration. Some of the implications for biological control are discussed as is the dependence of these results on the precise definition of control.
ARTICLE | doi:10.20944/preprints202107.0420.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: CURE; undergraduate research; natural selection; experimental evolution; molecular biology; genetics; structure- 46 function relationships; introductory biology; laboratory exercise
Online: 19 July 2021 (15:47:18 CEST)
Course-based Undergraduate Research Experiences (CUREs) in high-enrollment, introductory classes are a 37 potentially transformative approach to retaining more students in STEM majors. We developed and piloted a CURE 38 in the introductory biology courses at the University of Washington. This CURE focuses on analyzing experimental 39 evolution of antibiotic resistance in Escherichia coli and generates data on two topics relevant to clinical practice: 40 compensatory mutations and cross-drug effects. By studying mutations in central cellular machinery that confer drug 41 resistance, students not only gain insight into fundamental cellular phenomena, but also recognize the molecular 42 basis of a medically important form of evolutionary change, connecting genetics, microbiology, and evolution.
REVIEW | doi:10.20944/preprints202005.0058.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: synthetic biology; multi-agent modelling; individual-based modelling; agent-based modelling; systems biology; emergence; multi-scale; bioengineering; consortia; collectives
Online: 5 May 2020 (03:45:16 CEST)
Many complex behaviours in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans multiple length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modelling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modelling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviours offers a means to take synthetic biology beyond single molecules or cells and towards the creation of systems with functions that can only emerge from collectives at multiple scales.
ARTICLE | doi:10.20944/preprints202310.1146.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: bioinformatics; structural biology; CagY protein; T4SS; deep learning
Online: 18 October 2023 (09:56:34 CEST)
CagY is the largest and most complex protein from Helicobacter pylori's type IV secretion system (T4SS) and may participate in the modulation of gastric tissue inflammation. A three-dimensional structure has been reported for only two segments of the protein. To build a more complete model, particularly the region that spans between the outer membrane (OM) and the inner membrane (IM), we employed different approaches, including homology modeling, ab initio, and deep learning techniques. For the long-middle repeat region (MRR), modeling was performed using deep learning techniques and Molecular Dynamics. The modeled segments were assembled into a chain of 1595 aa, and a 14-chain CagY multimer structure was composed by structural alignment. The final multimer structure correlated with previously published struc-tures and allows to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric epithelial cells. The model further confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain probably functions as a contractile region that may play an essential role in the modulatory activity of CagY on tissue inflammation.
ARTICLE | doi:10.20944/preprints202310.0840.v1
Subject: Biology And Life Sciences, Biophysics Keywords: membrane pump theory; membrane potential; mathematics; Biophysics; Biology
Online: 13 October 2023 (16:43:12 CEST)
The generation and maintenance of membrane potential is considered a fundamental element of the cellular machinery. They are based on elements of physics and chemistry. Mathematics is used to validate the equations and evaluate the results. However, this computation process can lead to a misunderstanding of the phenomena involved or to the masking of crucial events. It is even possible that the calculation no longer corresponds to the hypothesis considered. Membrane theory is no exception to these trivial considerations, which are essential for normal theory validation.
REVIEW | doi:10.20944/preprints202309.0897.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; SARS-CoV-2; Coronavirus; Biology; Genetics
Online: 14 September 2023 (03:41:29 CEST)
Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019 and has since spread worldwide, is the latest human pandemic, and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented.
COMMUNICATION | doi:10.20944/preprints202309.0079.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: computational biology; genomics; sequencing; data literacy; bioinformatics; education
Online: 4 September 2023 (04:32:42 CEST)
With an ever increasing amount of research data available, it becomes constantly more important to possess data literacy skills to benefit from this valuable resource. An integrative course was developed to teach students the fundamentals of data literacy through an engaging genome sequencing project. Each cohort of students performed planning of the experiment, DNA extraction, nanopore sequencing, genome sequence assembly, prediction of genes in the assembled sequence, and assignment of functional annotation terms to predicted genes. Students learned how to communicate science through writing a protocol in the form of a scientific paper, providing comments during a peer-review process, and presenting their findings as part of an international symposium. Many students enjoyed the opportunity to own a project and to work towards a meaningful objective.
REVIEW | doi:10.20944/preprints202308.1454.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: ChatGPT; GPT-4; Artificial intelligence; Biology; Medicine; Dentistry
Online: 22 August 2023 (02:56:53 CEST)
Chat generative pre-trained transformer (ChatGPT) is a developed language model and a subgroup of artificial intelligence (AI) which has demonstrated noticeable innovation in interactions between computer models and human studies. The release of ChatGPT in November 2022 attracted over 100 million users in a short time. It has unlimited applications in different fields of studies such as technology and science. ChatGPT utilizes deep learning and internet text to produce responses that resemble human language, although their accuracy is not always guaranteed. ChatGPT and GPT-4 can make a huge revolution in biology, medical, dental research, and health care. However, it's important to acknowledge the limitations of ChatGPT such as limitation in accessing the latest data. ChatGPT has generated both excitement and concern regarding its potential misuse. Its utilization in scientific publications has sparked debates and prompted the development of policies to govern the use of it. Although ChatGPT has certain limitations, it could impact on many different fields of study. There are challenges associated with using ChatGPT in the field of laboratory medicine and biology, particularly in the interpretation of test results. In this article, we review some of the applications of ChatGPT and GPT-4 in biology, dental and medical studies, and concerns about ChatGPT. Despite ChatGPT's conversational abilities are impressive, there are important considerations regarding its use in different fields of research and academic public.
HYPOTHESIS | doi:10.20944/preprints202308.1004.v1
Subject: Medicine And Pharmacology, Reproductive Medicine Keywords: reproductive biology; ovarian function; PRP; extracellular matrix; entropy
Online: 14 August 2023 (10:31:12 CEST)
Diminished ovarian reserve can be regarded as a sentinel indicator to foreshadow severe follicular loss and, ultimately, systemic aging. The negative slope of human ovulatory fidelity begins with a robust follicular endowment which gradually declines over time. In contrast, the youthful ovarian phenotype requires the coordinated work of endothelial, granulosa, immune, perivascular, stromal and possibly germline stem cells. Such a diverse tissue matrix can, in general, be influenced by platelet (PLT)-derived factors but this has not yet been specifically confirmed in the ovary after platelet-rich plasma (PRP). How could a comparable response be validated? Here a prospective, experimental study is proposed whereby eligible patients already undergoing scheduled laparoscopy provide ovarian tissue via biopsy submitted for co-culture with autologous Ca+2 activated PRP. Recognizing the interlocking, central roles of nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α), incubated samples would be assessed for these in vitro before vs. after PRP exposure, in addition to stereomicroscopy. A mathematical model is available to track NF-κB oscillations and estimate gene expression, cell development, growth, apoptosis, and key immune and inflammatory actions. Since NF-κB and TNF-α are discharged in activated PLT releasate (or react to its cargo proteins) this audit permits extraction of response markers observed post-stimulus, thus linking discrete signals to transcriptional output, cellular fitness, and ovarian cytoarchitecture. From this, a hypothesis could emerge where intraovarian PRP is found to make no direct impact on follicles, although modified ovarian field function and curtailed local entropy incidentally favor optimized oocyte competence as a secondary effect.
ARTICLE | doi:10.20944/preprints202307.2065.v1
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Daisyworld; homeostasis; Earth Systems Science; synthetic biology; terraformation
Online: 31 July 2023 (09:50:42 CEST)
The idea that the Earth system self-regulates in a habitable state was proposed in the 1970s by James Lovelock, who conjectured that life plays a self-regulatory role on a planetary-level scale. A formal approach to such hypothesis was presented afterwards under a toy model known as the Daisyworld. The model showed how such life-geosphere homeostasis was an emergent property of the system, where two species with different properties adjusted their populations to the changing external environment. So far, this ideal world exists only as a mathematical or computational construct, but it would be desirable to have a real, biological implementation of Lovelock's picture beyond our one Biosphere. Inspired in the exploration of synthetic ecosystems using genetic engineering and recent cell factory designs, here we propose such a living, microbial Daisyworld. This is based on a synthetic microbial ecosystem using pH as the external, abiotic control parameter. Several case studies are considering, including two, three and multiple species assemblies. Despite that oscillatory dynamics and chaos emerge in the latter case, it is shown that global regulation is also achieved in most cases as species diversity increases. The alternative implementations and their implications of this model in other synthetic biology scenarios, including ecosystem engineering, are outlined.
REVIEW | doi:10.20944/preprints202302.0337.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Pulmonary vasculature; BMP signaling; angiogenesis; vascular biology; lung
Online: 20 February 2023 (09:39:09 CET)
Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.
REVIEW | doi:10.20944/preprints202301.0315.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: mammary biology; mammogenesis; lactation; lactogenesis; quantitative trait loci
Online: 18 January 2023 (02:49:09 CET)
Milk is a complex liquid, and the concentrations of many of its components are under genetic control. Many genes and pathways are known to regulate milk compositon, and the purpose of this review is to highlight how the discoveries of quantitative trait loci (QTL) for milk phenotypes can elucidate these pathways. The main body of this review focusses primarily on QTL discovered in cattle (Bos taurus) as a model species for lactation biology, with occasional references to other ruminant species, and some comparisons with human milk composition are also presented. The following section describes a range of techniques that can be used to help identify the causative genes underlying QTL when the underlying mechanism involves the regulation of gene expression. As genotype and phenotype data bases continue to grow and diversify, new QTL will continue to be discovered, and, although proving the causality of underlying genes and variants remains difficult, these new data sets will further enhance our understanding of lactation biology.
ARTICLE | doi:10.20944/preprints202210.0470.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: metastasis; cancer evolution; bioinformatics; cancer biology; cancer genomics
Online: 31 October 2022 (07:06:45 CET)
: Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasize, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8,332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8,332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.
ARTICLE | doi:10.20944/preprints202208.0385.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Developmental Field; Gompertz Equation; Information Theory; Developmental Biology
Online: 22 August 2022 (15:42:19 CEST)
A model for cell proliferation in developmental fields is derived from information theory using a few biological postulates. The model provides an explanation for the success of the Gompertz equation in describing the growth of embryonic, neoplastic, and regenerative systems. Although this equation has been applied to many growth phenomena, its use has been entirely empirical. A theoretical justification for the use of the Gompertz equation in characterizing developmental processes is presented. The model also accounts for a reported relationship among the parameters of the Gompertz equation. A method for quantification and comparison of the determination of developmental fields at different levels of organization is suggested.
ARTICLE | doi:10.20944/preprints202208.0381.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Endophitic Fungi; Phylopgeny; Biodiversity; Molecular Biology; Growth experiments
Online: 22 August 2022 (11:00:55 CEST)
Antarctica is one of the most inhospitable continents on the planet, with lichens and mosses being the most common terrestrial organisms in ice-free areas. Antarctica is represented by only two species of Angiosperms, Deschampsia antarctica Desv. (Poaceae) and Colobanthus quitensis (Kunth) Bartl. (Caryophyllaceae). In this study, we characterized fungi isolated from the leaves of this grass species. The fungi were isolated from 4 individual plants from Half Moon Island (246 leave fragments investigated), and 7 from King George Island - Keller Peninsula (with 111 leave fragments investigated) Antarctica. Neoascochyta paspali, Phaeosphaeria elongata, Pyrenophora cf. chaetomioides and Alternaria sp. were associated with the plant and identified through analysis of the sequences of the internal transcribed spacer region (ITS) of the rDNA and nuclear ribosomal large subunit rRNA gene (LSU) as well as macro and micro-morphological characteristics. The isolates showed a better growth rate ranging from 10–20°C. An interesting result was that the fungi are already recognize as both plant pathogens and endophytic fungi. The results demonstrate that D. antarctica is an interesting fungal source. Those species might provide important information about the relationship on the endemic Antarctic biota.
ARTICLE | doi:10.20944/preprints202207.0376.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: information theory; embryogenesis; regeneration; cell biology; morphogenesis; calcium
Online: 25 July 2022 (12:35:28 CEST)
There is a growing appreciation in the fields of Cell and Developmental Biology that cells collectively process information in time and space. While many powerful molecular tools exist to observe biophysical dynamics biologists must find ways to quantitatively understand these phenomena at the systems level. Here, we present a guide for application of well-established information theory metrics to biological datasets and explain these metrics using examples from cell, developmental and regenerative biology. We introduce a novel computational tool (CAIM) for simple, rigorous application of these metrics to timeseries datasets. Finally, we use CAIM to study calcium and cytoskeletal Actin information flow patterns between Xenopus laevis embryonic animal cap stem cells. The tools that we present here will enable biologists to apply information theory to develop systems level understanding of a diverse array of experimental systems.
REVIEW | doi:10.20944/preprints202203.0170.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cancer; DNA informational entropy; cell compartmentation; evolutionary Biology; lactate dehydrogenase (LDH); lactic acid; metabolism; thermodynamic entropy; Warburg effect
Online: 17 March 2022 (03:37:53 CET)
Attempts to find and quantify the supposed low entropy of organisms and its preservation are revised. Absolute entropy of the mixed components of non-living biomass (around -1.6 x 103 J K-1 L-1) is the reference to which other entropy decreases would be ascribed to life. Compartmentation of metabolites and departure from the equilibrium of metabolic reactions account for 1 and 40-50 J K-1 L-1, respectively, decreases of entropy and, though small, are distinctive features of living tissues. DNA and proteins do not supply significant decreases of thermodynamic entropy, but their low informational entropy is relevant for life and its evolution. No other living feature contributes significantly to the low entropy associated to life. The photosynthetic conversion of radiant energy to biomass energy accounts for the most of entropy (2.8 x 105 J K-1 carbon kg-1) produced by living beings. The comparative very low entropy produced in other processes (around 4.8 x102 J K-1 L-1 day-1 in human body) must be rapidly exported outside as heat to preserve the low entropy decreases due to compartmentation and non-equilibrium metabolism. Enzymes and genes are described whose control minimize the rate of production of entropy and could explain selective pressures in biological evolution and the rapid proliferation of cancer cells.
REVIEW | doi:10.20944/preprints202202.0303.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: 3D bioprinting; 3D printing; bioink; cancer; cell biology
Online: 24 February 2022 (08:08:44 CET)
Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models, and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.
ARTICLE | doi:10.20944/preprints202202.0160.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: membrane pump theory; membrane potential; diffusion; Biophysics; Biology
Online: 11 February 2022 (10:27:36 CET)
The generation and maintenance of membrane potential is a fundamental part of Membrane Pump Theory. One of the key points of this hypothesis is based on a natural or facilitated molecular diffusion through several types of ion channels and pumps like the Na/K ATPase. Chemistry, physics and especially electrochemistry, however, bring strong contradictions to this theoretical assumption. By respecting the principles of chemistry and electrostatics, it becomes obvious that this theoretical hypothesis cannot work. The ionic diffusion that would be at the origin of this potential cannot take place. Indeed, the topology and the forces involved definitively exclude the current model, which must absolutely be revised according to the current state of our knowledge and allow an advance in the understanding of the phenomena and open new research perspectives.
SHORT NOTE | doi:10.20944/preprints202201.0166.v1
Subject: Physical Sciences, Applied Physics Keywords: Theoretical Biophysics; Mathematical Biophysics; Theoretical Biology; Molecular Biophysics
Online: 12 January 2022 (13:38:59 CET)
ATP Synthase is an essential molecule in cell and molecular biology. It is responsible for the production of ATP during cellular respiration, a molecule that provides the energy required to drive a number of cellular processes. In this paper, I explore the rotational physics of ATP Synthase’s rotor, a part of the protein that spins during the production of ATP. Firstly, I discuss some elementary rotational kinematics of the rotor. I then derive two alternate formulations for the total linear acceleration of the rotor. Finally, I derive formulas for the moment of inertia, angular momentum, net torque, and kinetic energy of the rotor. Through this, I hope to provide a theoretical and mathematical insight into the mechanics of ATP Synthase during the production of ATP.
ARTICLE | doi:10.20944/preprints202011.0311.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: autism genetics; family microarrays; pathway enrichment; network biology
Online: 10 November 2020 (12:33:35 CET)
The genetic heterogeneity of autism has stymied the search for causes and cures. Whole-genomic studies on large numbers of families have helped identify combinations of inherited and de novo signal. In the present work, we re-analyze DNA microarrays using a novel strategy that takes prior knowledge of genetic relationships into account and that was designed to boost signal important to our understanding of the molecular basis of autism. Our strategy was designed to identify significant genomic variation within a priori defined biological concepts and improves signal detection while lessening the severity of multiple test correction seen in standard analysis of genome-wide association data. Upon application of our approach using 3,244 biological concepts, we detected genomic variation in 68 biological concepts with significant association to autism in comparison to family-based controls. These concepts clustered naturally into a total of 19 classes, principally including cell adhesion, cancer, and immune response. The top-ranking concepts contained high percentages of genes already suspected to play roles in autism or in a related neurological disorder. In addition, many of the sets associated with autism at the DNA level also proved to be predictive of changes in gene expression within a separate population of autistic cases, suggesting that the signature of genomic variation may also be detectable in blood-based transcriptional profiles. This cross-validation with gene expression data from individuals with autism coupled with the enrichment within autism-related neurological disorders supported the possibility that the mutations play important roles in the onset of autism and should be given priority for further study. Our work provides new leads into the genetic underpinnings of autism and highlights the importance of reanalysis of genomic studies of complex disease using prior knowledge of genetic organization.
REVIEW | doi:10.20944/preprints202009.0672.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: iPSC; hematopoiesis; developmental biology; anemia; thrombosis; immunodeficiency; cancer
Online: 27 September 2020 (08:39:30 CEST)
Human induced pluripotent stem cell (iPSC)-based model systems can be used to produce blood cells for the study of both hematologic and non-hematologic disorders. This commentary discusses recent advances that have utilized iPSC-derived red blood cells, megakaryocytes, myeloid cells, and lymphoid cells to model hematopoietic disorders. In addition, we review recent studies that have defined how microglial cells differentiated from iPSC-derived monocytes impact neurodegenerative disease. Related translational insights highlight the utility of iPSC models for studying pathologic anemia, bleeding, thrombosis, autoimmunity, immunodeficiency, blood cancers, and neurodegenerative disease such as Alzheimer’s.
ARTICLE | doi:10.20944/preprints201912.0183.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Bioinformatics, Cancer, Genomics, Computational Biology, RNA sequencing, TCGA
Online: 13 December 2019 (10:57:29 CET)
This study aimed to rank cancers by the strength of relationship between comprehensive mRNA expression of the most harmful or protective genes and patient survival. Using TCGA dataset including RNA-SEQ and clinical data, we investigated not only gene specific prognostic availability, but also comprehensive prognostic availability of prognostic genes filtered by cox coefficient, and ranked cancers by specially designed prognostic indicator. Through Kaplan-Meier plots, we checked that cancers vary in the strength of influence of prognostic genes, and they follow as the rank. Developing treatment with method to reduce or increase expression of biomarkers for specific cancer which ranked bottom, it would be not efficient in high probability. The results of this study can be a scientific evidence for that.
ARTICLE | doi:10.20944/preprints201907.0043.v1
Subject: Computer Science And Mathematics, Applied Mathematics Keywords: Network biology; LINE; lncRNA; protein; miRNA; Drug; disease
Online: 2 July 2019 (11:42:26 CEST)
The key issue in the post-genomic era is how to systematically describe the association between small molecule transcripts or translations inside cells. With the rapid development of high-throughput “omics” technologies, the achieved ability to detect and characterize molecules with other molecule targets opens up the possibility of investigating the relationships between different molecules from a global perspective. In this article, a Molecular Associations Network(MAN) is constructed and comprehensively analyzed by integrating the associations among miRNA, lncRNA, protein, drug, and disease, in which any kind of potential associations can be predicted. More specifically, each node in MAN can be represented as a vector by combining two kinds of information including the attributes of the node itself (e.g. sequences of ncRNAs and proteins, semantics of diseases and molecular fingerprints of drugs) and the manner of the node in the complex network (associations with other nodes). Random Forest classifier is trained to classify and predict new interactions or associations between biomolecules. In the experiment, the proposed method achieves a superb performance with 0.9735 AUC in 5-fold cross-validation, which show that the proposed method can provide new insight for exploration of the molecular mechanisms of disease and valuable clues for disease treatment.
REVIEW | doi:10.20944/preprints201708.0093.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: bacterial pathogens; host-pathogen interaction; infection biology; omics
Online: 27 August 2017 (11:18:27 CEST)
By providing useful tools to study host-pathogen interactions, next-generation omics has recently enabled the study of gene expression changes in both pathogen and infected host simultaneously. However, since great discriminative power is required to study pathogen and host simultaneously throughout the infection process, the depth of quantitative gene expression profiling has proven to be unsatisfactory when focusing on bacterial pathogens, thus preferentially requiring specific strategies or the development of novel methodologies based on complementary omics approaches. In this review, we focus on the difficulties encountered when making use of omics approaches to study bacterial pathogenesis. Besides, we review different omics strategies (i.e. transcriptomics, proteomics and secretomics) and their applications for studying interactions of pathogens with their host.
ARTICLE | doi:10.20944/preprints202309.1758.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: membrane pump theory; membrane potential; cell shape; biophysics; biology
Online: 26 September 2023 (11:32:12 CEST)
Membrane potential generation and maintenance are fundamental parts of membrane theory. However, since its inception, theories and assumptions have remained simple, whereas the amount of knowledge available has only grown. Unfortunately, this simplification and reductionism lead to its loss of validity on both microscopic and macroscopic scales. This article shows that assumptions made outside the context of factual reality lead to contradictions that cannot be compared with science. Membrane theory must be thoroughly revised, taking into account all forgotten and unanswered assumptions and questions to conform to facts and science to maintain credibility.
ARTICLE | doi:10.20944/preprints202308.0041.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: entropy generation; control; elasticities; flow; optimality; physiology; biology; thermodynamics
Online: 1 August 2023 (10:41:02 CEST)
Living beings are composite thermodynamic systems in non-equilibrium conditions. Within this context, there are a number of thermodynamic potential differences (forces) between them and the surroundings, as well as internally. These forces lead to flows, which, ultimately, are essential to life itself. Living beings are under the pressures of natural selection, thus are biological flows as well. At the same time, the maintenance of homeostatic conditions, the tenet of physiology, demands regulation of these flows by control of variables. However, due to the very nature of these systems, regulation of flows and control of variables become entangled in closed loops. Therefore, the search for adaptation in flows takes a different path than the search for adaptation in morphological traits. Being at the roots of transfer processes, thermodynamic criteria turn out to be as natural physical candidates. Likewise, being at the roots of physiology, control turns out to be as a natural biological candidate in that path. Here we show how to combine entropy generation, with respect to a generalized process, and control of parameters (in such a generalized process) in order to create a criterium of optimal ways to regulate changes in generalized flows.
REVIEW | doi:10.20944/preprints202306.1281.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: microcirculation; peripheral circulation; remodelling; small resistance arteries; vascular biology
Online: 19 June 2023 (04:11:00 CEST)
Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases as well as microvascular eye diseases. Established hypertension leads to chronic vasoconstriction of small arteries as well as to decreased lumen diameter and thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was first demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alteration in small resistance arteries; however microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events, possessing, therefore, a prognostic relevance. New, non-invasive techniques, such as Scanning Laser Doppler Flowmetry or Adaptive Optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in term of cardio- and cerebrovascular events. A rarefaction of capillary network has also been reported in hypertension which may contribute to flow reduction and impairment in oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might concur to microvascular angina, stroke, and renal dysfunction. In addition, they could be a marker useful in monitoring the beneficial effect of antihypertensive treatment. Also conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. The review will address the possible relations between structural microvascular alterations and hypertension-mediated organ damage and their potential improvement with antihypertensive treatment.
REVIEW | doi:10.20944/preprints202306.0849.v1
Subject: Medicine And Pharmacology, Hematology Keywords: Molecular biology; infectious diseases; clinical diagnostic; early detection; prognosis
Online: 12 June 2023 (14:31:24 CEST)
Epigenetic alterations are heritable and enduring modifications in gene expression that play a pivotal role in immune evasion. These include alterations to noncoding RNA, DNA methylation, and histone modifications. DNA methylation plays a crucial role in normal cell growth and development but alterations in methylation patterns such as hypermethylation or hypomethylation can enable tumor and viral cells to evade host immune responses. Histone modifications can also inhibit immune responses by promoting the expression of genes involved in suppressing normal immune function. In the case of T-cell lymphoma, adult T-cell Lymphomas (ALT) also undergo immune evasion through the exceptional function of its accessory and regulatory genes. Epigenetic therapies are emerging as a promising adjunct to traditional immunotherapy and chemotherapy regimens. Clinical trials are currently investigating the use of epigenetic therapies in combination with immunotherapies and chemotherapies for more effective treatment of ATL and other cancers. This review highlights epigenetic alterations that are widely found in T cell malignancies.
REVIEW | doi:10.20944/preprints202305.1725.v1
Subject: Medicine And Pharmacology, Hematology Keywords: Molecular biology; infectious diseases; clinical diagnostic; early detection; prognosis
Online: 25 May 2023 (03:34:18 CEST)
Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic re-sistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating anti-biotic efficacy and resistance. This review delves into the intricate relationship between gut mi-crobiota, antibiotic therapy, and resistance, and discusses the potential applications of gut mi-crobiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demon-strated the potential for tailored antibiotic regimens that minimize collateral damage to com-mensal bacteria and reduce the risk of resistance. Adjuvant therapies such as probiotics, prebi-otics, and synbiotics have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field including the need for standardized methodologies, ethical considerations, and interdisci-plinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.
ARTICLE | doi:10.20944/preprints202302.0369.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: cell biology; protein sorting; nuclear translocation; protein domain; WAC
Online: 22 February 2023 (02:37:35 CET)
Dysfunction of the WW domain-containing adaptor with coiled-coil, WAC, gene underlies a rare autosomal dominant disorder, DeSanto-Shinawi syndrome (DESSH). DESSH is associated with facial dysmorphia, hypotonia, and cognitive alterations, including attention deficit hyperactivity disorder and autism. How the WAC protein localizes and functions in neural cells is critical to understanding its role during development. To understand the genotype-phenotype role of WAC, we developed a knowledgebase of WAC expression, evolution, human genomics, and structural/motif analysis combined with human protein domain deletions to assess how conserved domains guide cellular distribution. Then assessed in a cell type implicated in DESSH, cortical GABAergic neurons. WAC contains conserved charged amino acids, phosphorylation signals, and enriched nuclear motifs, suggesting a role in cellular signaling and gene transcription. Human DESSH variants are found within these regions. We also discovered and tested a nuclear localaization domain that impacts the cellular distribution of the protein. These data provide new insights into the potential roles of this critical developmental gene, establishing a platform to assess further translational studies, including the screening of missense genetic variants in WAC. Moreover, these studies are essential for understanding the role of human WAC variants in more diverse neurological phenotypes, including autism spectrum disorder.
ARTICLE | doi:10.20944/preprints202103.0197.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Systems biology; cervical cancer; prognostic biomarker; differentially expressed genes.
Online: 5 March 2021 (21:25:47 CET)
Nowadays, cervical cancer (CC) is treated as the leading cancer among women throughout the world. Despite effective vaccination and improved surgery and treatment, CC remains its fatality rate about half of the infected populations globally. The major screening biomarkers and therapeutic target identification have now become a global concern. The present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from the transcriptomic profiling. Initially, we have identified 76 of each up-regulated and down-regulated gene from a total of 4,643 differentially expressed genes. The up-regulatory genes are mainly concentrating on immune-inflammatory response and the down-regulatory genes are on receptor binding and gamma-glutamyltransferase. The involved pathways associated with these genes were also assessed through pathway enrichment and they were mainly focused on different cancer pathways, immunoresponse, and cell cycle pathways. After the subsequent enrichment of these genes, we have identified 12 hub genes, which play a crucial role in CC. Furthermore, the survival of the hub genes was also assessed, and among them, finally, CXCR4 has identified as one of the most potential differentially expressed gene that might play a vital role to the survival of CC patients. Thus CXCR4 could be used as a prognostic biomarker and development of a drug target for CC.
REVIEW | doi:10.20944/preprints202010.0041.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Coronavirus, SARS-CoV-2, Pandemics, Molecular biology, Immunity, Pathology
Online: 2 October 2020 (13:24:16 CEST)
In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.
ARTICLE | doi:10.20944/preprints202006.0212.v1
Subject: Physical Sciences, Condensed Matter Physics Keywords: neural synchronization; consciousness; quantum biology; brain dynamics; brain connectivity
Online: 17 June 2020 (09:29:28 CEST)
One of the biggest queries in cognitive sciences is the emergence of consciousness from matter. Modern neurobiological theories of consciousness propose that conscious experience is the result of interactions between large-scale neuronal networks in the brain, traditionally described within the realm of classical physics. Here, we propose a generalized connectionist framework in which the emergence of “conscious networks” is not exclusive of large brain areas, but can be identified in sub-cellular networks exhibiting non-trivial quantum phenomena. The essential feature of such networks is the existence of strong correlations in the system (classical or quantum coherence) and the presence of an optimal point at which the system’s complexity is maximized, expressed either by maximization of the information content in large scale functional networks or by achieving optimal efficiency through the quantum Goldilock effect.
ARTICLE | doi:10.20944/preprints202003.0339.v1
Subject: Environmental And Earth Sciences, Remote Sensing Keywords: ALS; forest ecology; forest structure; NEON; macrosystems biology; TLS
Online: 23 March 2020 (06:42:29 CET)
Structural diversity is a key feature of forest ecosystems that influences ecosystem functions from local to macroscales. The ability to measure structural diversity in forests with varying ecological composition and management history can improve the understanding of linkages between forest structure and ecosystem functioning. Terrestrial LiDAR has often been used to provide a detailed characterization of structural diversity at local scales, but it is largely unknown whether these same structural features are detectable using aerial LiDAR data that are available across larger spatial scales. We used univariate and multivariate analyses to quantify cross-compatibility of structural diversity metrics from terrestrial versus aerial LiDAR in seven National Ecological Observatory Network sites across the eastern USA. We found strong univariate agreement between terrestrial and aerial LiDAR metrics of canopy height, openness, internal heterogeneity, and leaf area, but found marginal agreement between metrics that describe heterogeneity of the outer most layer of the canopy. Terrestrial and aerial LiDAR both demonstrated the ability to distinguish forest sites from structural diversity metrics in multivariate space, but terrestrial LiDAR was able to resolve finer-scale detail within sites. Our findings indicate that aerial LiDAR can be of use in quantifying broad-scale variation in structural diversity across macroscales.
CONCEPT PAPER | doi:10.20944/preprints202002.0182.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: sustainable development; plant sciences; ecology; conservation; urbanism; synthetic biology
Online: 14 February 2020 (02:57:11 CET)
Increasingly, architects are looking towards nature to design more sustainable, efficient cities to reduce the environmental impact of urban life. At the moment, plants are incorporated into urban design for conservation or aesthetic reasons. Here, I argue plants can be rationally designed into synthetic systems based on chemical and other functional traits to increase the stability of urban infrastructure, protect native biodiversity, and promote human health while meeting key UN Sustainable Development Goals.
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cysteine oxidation redox systems biology proteomics signaling EGFR cryptic
Online: 10 April 2019 (10:07:12 CEST)
Significance: Cellular redox processes are highly interconnected, yet not in equilibrium, and governed by a wide range of biochemical parameters. Technological advances continue refining how specific redox processes are regulated, but broad understanding of the dynamic interconnectivity between cellular redox modules remains limited. Systems biology investigates multiple components in complex environments and can provide integrative insights into the multi-faceted cellular redox state. This review describes the state of the art in redox systems biology as well as provides an updated perspective and practical guide for harnessing thousands of cysteine sensors in the redoxome for multi-parameter characterization of cellular redox networks. Recent Advances: Redox systems biology has been applied to genome-scale models and large public datasets, challenged common conceptions and provided new insights that complement reductionist approaches. Advances in public knowledge and user-friendly tools for proteome-wide annotation of cysteine sentinels can now leverage cysteine redox proteomics datasets to provide spatial, functional, and protein structural information. Critical Issues: Careful consideration of the analytical approaches is needed to broadly characterize the systems level properties of redox signaling networks and be experimentally feasible. The cysteine redoxome is an informative focal point since it integrates many aspects of redox biology. The mechanisms and redox modules governing cysteine redox regulation, cysteine oxidation assays, proteome-wide annotation of the biophysical and biochemical properties of individual cysteines, and their clinical application are discussed. Future Directions: Investigating the cysteine redoxome at a systems level will uncover new insights into the mechanisms of selectivity and context-dependence of redox signaling networks.
ARTICLE | doi:10.20944/preprints201904.0011.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: DNA sequence; helix; nucleotide frequencies; DNA epi-chains; helical antennas; Fröhlich's theory; long-range coherence; epigenetics; quantum biology; binary representation
Online: 14 May 2019 (06:22:48 CEST)
One of creators of quantum mechanics P. Jordan in his work on quantum biology claimed that life's missing laws were the rules of chance and probability of the quantum world. The article presents author’s results of studying frequencies (or probabilities) of nucleotides on so-called epi-chains of long DNA sequences of various eukaryotic and prokaryotic genomes. DNA epi-chains are algorithmically constructed subsequencies of DNA nucleotide sequences. According to the algorithm of construction of any epi-chain of the order n, the epi-chain is such nucleotide subsequence, in which the numerations of adjacent nucleotides differ by natural number n (n = 1, 2, 3, 4,…). Correspondingly each epi-chain of order n ≥ 2 contains n times less nucleotides than the original DNA sequence. The presented results unexpectedly discover that in long single-stranded and double-stranded DNA of any tested genome its DNA epi-chains of different orders n (values n are not too large) have practically identical frequencies (or probabilities) of each kind of nucleotides. These data allow considering DNA as a regular rich set of epi-chains, which can play a certain role in genetic and epigenetic phenomena as the author belives. Appropriate rules of nucleotide frequencies on epi-chains of long DNA sequences are formulated for further their tests on a wider set of genomes. These results testify on existence of long-range coherence in long DNA and remind the Fröhlich's theory of long-range coherence in biological systems. The phenomenological data are discussed from different standpoints: the DNA double helices and helical antennas with circular polarizations of electromagnetic waves; relations with the Fröhlich's theory; numerical analysis of DNA epi-chains under binary representations of nucleotides. Results are useful for developing quantum and algebraic biology.
ARTICLE | doi:10.20944/preprints201811.0478.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Japanese encephalitis virus; drug repurposing; systems biology; antiviral agents
Online: 20 November 2018 (04:54:48 CET)
Japanese encephalitis is a zoonotic disease caused by Japanese encephalitis virus (JEV). It is mainly epidemic in Asia with an estimated 69,000 cases occurring per year. However, no approved agents are available for the treatment of JEV infection, and existing vaccines cannot resist various types of JEV strains. Drug repurposing is a new concept for finding new indication of existing drugs, and recently, it has been used to discover new antiviral agents. Identifying host proteins involved in the progress of JEV infection and using these proteins as targets are the center of drug repurposing for JEV infection. In this study, based on the gene expression data of JEV infection and the phenome-wide association study (PheWAS) data, we identified 286 genes participating in the progress of JEV infection using the systems biology methods. The enrichment analysis of these genes suggested that the genes identified by our methods were predominantly related to viral infection pathways and immune response-related pathways. We found that bortezomib which can target these genes may have potential effect on the treatment of JEV infection. Subsequently, we evaluated the antiviral activity of bortezomib using the JEV-infected mice model. The results showed that bortezomib can lower JEV-induced lethality in mice, alleviate suffering in JEV-infected mice and reduce the damage in brains caused by JEV infection. This work provides a new method for the development of antiviral agents.
REVIEW | doi:10.20944/preprints201806.0451.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: aroma; bioflavour; Saccharomyces cerevisiae; synthetic biology; yeast; Yeast 2.0
Online: 27 June 2018 (15:24:02 CEST)
Abstract: Yeast – especially Saccharomyces cerevisiae – have long been a preferred workhorse for the production of numerous recombinant proteins and other metabolites. S. cerevisiae is a noteworthy aroma compound producer, and has also been exploited to produce foreign bioflavour compounds. In the past few years, important strides have been made in unlocking the key elements in the biochemical pathways involved in the production of many aroma compounds. The expression of these biochemical pathways in yeast often involves the manipulation of the host strain to direct the flux towards certain precursors needed for the production of the given aroma compound. This review highlights recent advances in the bioengineering of yeast – including S. cerevisiae – to produce aroma compounds and bioflavours. To capitalise on recent advances in synthetic yeast genomics, this review presents yeast as a significant producer of bioflavours in a fresh context and proposes new directions for combining engineering and biology principles to improve the yield of targeted aroma compounds.
ARTICLE | doi:10.20944/preprints201803.0039.v1
Subject: Biology And Life Sciences, Other Keywords: systems biology; probabilistic modelling; experimenter effect; quantum-like correlations
Online: 6 March 2018 (03:35:12 CET)
Background: Benveniste’s biology experiments suggested the existence of molecular-like effects without molecules (“memory of water”). In this article, it is proposed that these disputed experiments could have been the consequence of a previously unnoticed and non-conventional experimenter effect. Methods: A probabilistic modelling is built in order to describe an elementary laboratory experiment. A biological system is modelled with two possible states (“resting” and “activated”) and exposed to two experimental conditions labelled “control” and “test”, but both biologically inactive. The modelling takes into account not only the biological system, but also the experimenters. In addition, an outsider standpoint is adopted to describe the experimental situation. Results: A classical approach suggests that, after experiment completion, the “control” and “test” labels of biologically-inactive conditions should be both associated with “resting” state (i.e. no significant relationship between labels and system states). However, if the fluctuations of the biological system are also considered, a quantum-like relationship emerges and connects labels and system states (analogous to a biological “effect” without molecules). Conclusions: No hypotheses about water properties or other exotic explanations are needed to describe Benveniste’s experiments, including their unusual features. This modelling could be extended to other experimental situations in biology, medicine and psychology.
ARTICLE | doi:10.20944/preprints202311.0819.v1
Subject: Biology And Life Sciences, Virology Keywords: bacteriophage; virion structure; Lactococcus; structural biology; Alphafold; P335; TP901-1
Online: 13 November 2023 (12:05:35 CET)
Bacteria are engaged in a constant battle against preying viruses, called bacteriophages (or phag-es). These remarkable nano-machines pack and store their genomes in a capsid and inject it into the cytoplasm of their bacterial prey following specific adhesion to the host cell surface. Tailed phages possessing dsDNA genomes are the most abundant phages in the bacterial virosphere, particularly those with long, non-contractile tails. All tailed phages possess a nano-device at their tail tip that specifically recognizes and adheres to a suitable host cell surface receptor, being pro-teinaceous and/or saccharidic. Adhesion devices of tailed phages infecting Gram-positive bacte-ria are highly diverse and, for the majority, remain poorly understood. Their long, flexible and multi-domain encompassing tail limits experimental approaches to determine their complete structure. We have previously shown that the recently developed protein structure prediction program AlphaFold2 can overcome this limitation by predicting the structures of phage adhesion devices with confidence. Here, we extend this approach and employ AlphaFold2 to determine the structure of a complete phage, the lactococcal P335 phage TP901-1. Herein we report the structures of its capsid and neck, its extended tail, and the complete adhesion device, the baseplate, which was previously partially determined by X-ray crystallography.
REVIEW | doi:10.20944/preprints202308.1386.v2
Subject: Biology And Life Sciences, Biophysics Keywords: membrane proteins; cryo-electron microscopy; detergents; nanodiscs; amphipols; structural biology
Online: 22 September 2023 (13:10:51 CEST)
Single-particle cryo-electron microscopy (cryo-EM SPA) has recently emerged as an exceptionally well-suited technique for determining the structure of membrane proteins (MPs). Indeed, in the last years, it was observed a huge increase in the number of MPs solved by cryo-EM SPA at a resolution better than 3.0 Å in the Protein Data Bank (PDB). However, sample preparation remains a significant challenge in the field. Here, we evaluated in the MPs solved by cryo-EM SPA deposited in the PDB in the last two years at a resolution below 3.0 Å the most critical parameters for sample preparation: i) the surfactant used for protein extraction from the membrane, ii) the surfactant, amphiphiles, nanodiscs or other molecules present in the vitrification step, iii) the vitrification method employed, and iv) the type of grids used. The aim is not to provide a definitive answer on the optimal sample conditions for cryo-EM SPA of MPs, but rather assess the current trends in the MP structural biology community towards obtaining high-resolution cryo-EM structures.
ARTICLE | doi:10.20944/preprints202308.0171.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Streptococcus pneumoniae; Influenza (H1N1) virus; computational biology; Blastn; DAVID; NDEx
Online: 2 August 2023 (10:08:44 CEST)
Aim: Streptococcus pneumoniae and influenza H1N1 virus are common organisms associated with human infections. These infections could play a significant role in immune regulation. The study was performed to analyse the genome sequences of these organisms with human genome and study its functional significance. Methods: The study was performed to analyse the overlapping of genome sequences in Streptococcus pneumoniae and Influenza (H1N1) virus against human genome sequences by BLASTn sequence analysis. The alignments are studied against the corresponding genes for their functional significance with DAVID and NDEx software.Results: Several hits or overlapping nucleotide segments were identified. Between streptococcus and homo sapiens 287 overlaps were identified, and among influenza and homo sapiens 124 hits were identified. A wide range of functional significance of these genes were identified, and the results are presented in this study. The results show insights into functional pathways and biological activities associated with the respective vaccinations or infections by these microorganisms. Conclusion: The common organisms like Streptococcus pneumoniae and Influenza H1N1 virus actively interact with the immune system and result in a wide range of immune regulations.
ARTICLE | doi:10.20944/preprints202307.0325.v1
Subject: Physical Sciences, Condensed Matter Physics Keywords: quantum decoherence, macroscopic quantum mechanics, high temperature superconductivity, quantum biology
Online: 5 July 2023 (13:51:34 CEST)
We consider new insights into the origin and nature of pointer states and their role in wave function collapse in macroscopic quantum coherence. The work includes new theory of quantum coherence underpinned by turbulence, generated by a field of pointer states in the form of recirculating vortices (toroids), interconnected via a vortex cascade. Decoherence occurs when the interconnected field of vortices between pointer states is disrupted by external forces, leading to their localisation. The applicability of this work is considered in addressing unresolved questions in high temperature superconductivity and macroscopic quantum processes in biological systems. We also consider its implications for our understanding of intrinsic spin and pointer states within the standard "point source" representation of a quantum particle, which intuitively requires a more complexed description.
ARTICLE | doi:10.20944/preprints202208.0170.v1
Subject: Computer Science And Mathematics, Applied Mathematics Keywords: neuron; astrocyte; network; short-term memory; spatial frequency; computational biology
Online: 9 August 2022 (04:04:31 CEST)
Working memory refers to the capability of the nervous system to selectively retain short-term memories in an active state. The long-standing viewpoint is that neurons play an indispensable role and working memory is encoded by synaptic plasticity. Furthermore, some recent studies have shown that calcium signaling assists the memory processes and the working memory might be affected by the astrocyte density. Over the last few decades, growing evidence has also revealed that astrocytes exhibit diverse coverage of synapses which are considered to participate in neuronal activities. However, very little effort has yet been made to attempt to shed light on the potential correlations between these observations. Hence, in this article we will leverage a computational neuron-astrocyte model to study the short-term memory performance subject to various astrocytic coverage and we will demonstrate that the short-term memory is susceptible to this factor. Our model may also provide plausible hypotheses for the various sizes of calcium events as they are reckoned to be correlated with the astrocytic coverage.
REVIEW | doi:10.20944/preprints202108.0232.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: Cyperus exculentus; Neglected/Underutilized Crop species; Biology; Uses; Production constraints
Online: 10 August 2021 (12:33:44 CEST)
Food security relies mainly on a few major crop such as wheat, maize, rice and yam. Many of the cultivated plant such as Cyperus exculentus are still considered invasive plants and are neglected and underutilized. In the perspective to valorization of the species, this systematic review aimed at identifying the biology, production constraints and uses of tigernut for future research directions. Extensive searches were carried out and studies were screened and extracted using established systematic review methods. A total of 175 papers met the inclusion criteria. Approximately 52% and 21.71% of the studies were undertaken in Europe and Africa respectively. Most of the papers reviewed for the study were published between [2010-2015[. The review highlighted the critical research gaps in genetic diversity using SSR makers and evolutionary biology. Further, production constraints and solution approaches for the promotion of the species were the other gaps identified in the reviewed studies. Production constraints were specifically related to the insufficient mineral fertilizers and difficult in harvesting. Tigernut is used in more fields such as food, medicinal, cosmetic, biofuel and fishing and fish breeding. Such investigations would help in decision-making and elaboration of breeding strategies, and advancing steps towards sustainable use of the species.
REVIEW | doi:10.20944/preprints202103.0416.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; CoVID-19 Dignosis; CoVID-19 Chemistry & Biology
Online: 16 March 2021 (11:54:28 CET)
CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.
ARTICLE | doi:10.20944/preprints202102.0623.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: history of biology; history of zoology; taxonomy; biological nomenclature; metazoans
Online: 26 February 2021 (15:32:17 CET)
The great Greek philosopher Aristotle (384–322 BCE) is almost unanimously acclaimed as the founder of zoology. There is a consensus that he was interested in attributes of animals, but whether or not he tried to develop a zoological taxonomy remains controversial. Fürst von Lieven and Humar compiled a data matrix and showed, through a parsimony analysis published in 2008, that these data produced a hierarchy that matched several taxa recognized by Aristotle. However, their analysis leaves some questions unanswered because random data can sometimes yield fairly resolved trees. In this study, we update the scores of many cells and add four new characters to the data matrix (147 taxa scored for 161 characters) and quote passages from Aristotle’s Historia animalium to justify these changes. We confirm the presence of a phylogenetic signal in these data through a test using skewness in length distribution of a million random trees, which shows that many of the characters discussed by Aristotle were systematically relevant. Our parsimony analyses on the updated matrix recover far more trees than reported by Fürst von Lieven and Humar, but their consensus includes many taxa that Aristotle recognized and apparently named for the first time, such as selachē (selachians) and dithyra (Bivalvia). This study suggests that even though taxonomy was clearly not Aristotle’s chief interest in Historia animalium, it was probably among his secondary interests. These results may pave the way for further taxonomic studies in Aristotle’s zoological writings in general. Despite being almost peripheral to Aristotle’s writings, his taxonomic contributions are clearly major achievements.
REVIEW | doi:10.20944/preprints202101.0151.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: complement system; proteolytic cascade; convertase; inhibitor; structural biology; molecular mechanism
Online: 8 January 2021 (11:54:36 CET)
The complement system is part of the innate immune response, where it provides immediate protection from infectious agents and plays a fundamental role in homeostasis. Complement dysregulation occurs in several diseases, where the tightly regulated proteolytic cascade turns offensive. Prominent examples are atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria and Alzheimer’s disease. Therapeutic intervention targeting complement activation may allow treatment of such debilitating diseases. In this review, we describe a panel of complement targeting nanobodies that allow modulation at different steps of the proteolytic cascade, from the activation of the C1 complex in the classical pathway to formation of the C5 convertase in the terminal pathway. Thorough structural and functional characterization has provided a deep mechanistic understanding of the mode of inhibition for each of the nanobodies. These complement specific nanobodies are novel powerful probes for basic research and offer new opportunities for in vivo complement modulation.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: reproductive health; infertility; big data; Machine Learning; AI; Systems Biology
Online: 18 November 2020 (13:51:46 CET)
Advances in machine learning (ML) and artificial intelligence (AI) are transforming the way we treat patients in ways not even imagined a few years ago. Cancer research is at the forefront of this movement. Infertility, though not a life-threatening condition, affects around 15% of couples trying for a pregnancy. Increasing availability of large datasets from various sources creates an opportunity to introduce ML and AI into infertility prevention and treatment. At present in the field of assisted reproduction, very little is done in order to prevent infertility from arising, with the main focus put on treatment when often advanced maternal age and low ovarian reserve make it very difficult to conceive. A shift from this disease-centric model to a health centric model in infertility is already taking place with more emphasis on the patient as an active participator in the process. Poor quality and incomplete data as well as biological variability remain the main limitations in the widespread and reliable implementation of AI in the field of reproductive medicine. That said, one of the areas where this technology managed to find a foothold is identification of developmentally competent embryos. More work is required however to learn about ways to improve natural conception, the detection and diagnosis of infertility, and improve assisted reproduction treatments (ART) and ultimately, develop clinically useful algorithms able to adjust treatment regimens in order to assure a successful outcome of either fertility preservation or infertility treatment. Progress in genomics, digital technologies and advances in integrative biology has had a tremendousimpact on research and clinical medicine. With the rise of ‘big data’, artificial intelligence, and the advances in molecular profiling, there is an enormous potential to transform not only scientific research progress, but also clinical decision making towards predictive, preventive, and personalized medicine. In the field of reproductive health, there is now an exciting opportunity to leverage these technologies and develop more sophisticated approaches to diagnose and treat infertility disorders. In this review, we present a comprehensive analysis and interpretation of different innovation forces that are driving the emergence of a system approach to the infertility sector. Here we discuss recent influential work and explore the limitations of the use of Machine Learning models in this rapidly developing area.
REVIEW | doi:10.20944/preprints202009.0004.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: metabolomics; vaccines; infections; integrative metabolomics; systems biology; diagnosis; response detection
Online: 1 September 2020 (10:25:03 CEST)
Approaches to identification of metabolites have progressed from early biochemical pathway evaluation to modern high dimensional metabolomics which is a powerful tool to identify and characterize biomarkers of health and disease. While traditionally considered relevant in the context of classic metabolic diseases, immunometabolism has emerged as an important area of study as leukocytes generate key metabolites important to innate and adaptive immunity. Herein we discuss the metabolomic signatures and pathways perturbed during infection as well as vaccination. For example, changes in lipid and amino acid pathways (e.g., tryptophan, serine, and threonine) have been noted during infection while carbohydrate and bile acid pathways have shift upon vaccination. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying host response to infection and vaccination, and its integration with other systems biology platforms will add further impact to our studies of health and disease.
Subject: Biology And Life Sciences, Biophysics Keywords: computational molecular biology, biochemistry, quantum computing, hybrid quantum-classical algorithms
Online: 24 August 2020 (09:37:44 CEST)
Chemistry has been viewed as one of the most fruitful near-term applications to science of quantum computing. Recent work in transitioning classical algorithms to a quantum computer has led to great strides in improving quantum algorithms and illustrating their quantum advantage. Much less effort has been placed on how one finishes these calculations by using the results from the quantum computer (on the active region of the molecule) and embeds them back into the remainder of the molecule in order to determine the properties of the entire molecule. Such strategies are critical if one wants to expand the focus to biochemical molecules that contain active regions that cannot be properly explained with classical algorithms on classical computers. While we do not solve this problem here, we provide an overview of where the field is going to enable such problems to be tackled in the future.
REVIEW | doi:10.20944/preprints202008.0234.v1
Subject: Chemistry And Materials Science, Applied Chemistry Keywords: Photosynthesis; Photoelectrochemical Devices; Biohybrid; Synthetic Biology; Photochemistry; Photoelectrochemistry; Hydrogen Evolution
Online: 10 August 2020 (04:20:58 CEST)
Abstract: The biological process of photosynthesis was critical in catalyzing the oxygenation of Earth’s atmosphere 2.5 billion years ago, changing the course of development of life on Earth. Recently, the fields of applied and synthetic photosynthesis have utilized the light-driven protein-pigment supercomplexes central to photosynthesis for the photocatalytic production of fuel and other various valuable products. The reaction center Photosystem I is of particular interest in applied photosynthesis due to its high stability post-purification, non-geopolitical limitation, and its ability to generate the greatest reducing power found in Nature. These remarkable properties have been harnessed for the photocatalytic production of a number of valuable products in the applied photosynthesis research field. These primarily include photocurrents and molecular hydrogen as fuels. The use of artificial reaction centers to generate substrates and reducing equivalents to drive non-photoactive enzymes for valuable product generation has been a long-standing area of interest of the synthetic photosynthesis research field. In this review, we cover advances in these areas and further speculate synthetic and applied photosynthesis as photocatalysts for the generation of valuable products.
REVIEW | doi:10.20944/preprints202007.0123.v1
Subject: Computer Science And Mathematics, Mathematical And Computational Biology Keywords: causal interactions; databases; interoperability; biological pathway; logical modeling; computational biology
Online: 7 July 2020 (09:50:40 CEST)
Causal molecular interactions represent key building blocks used in computational modeling, where they facilitate the assembly of regulatory networks. These regulatory networks can then be used to predict biological and cellular behavior by system perturbations and in silico simulations. Today, broad sets of these interactions are being made available in a variety of biological knowledge resources. Moreover, different visions, based on distinct biological interests, have led to the development of multiple ways to describe and annotate causal molecular interactions. Therefore, data users can find it challenging to efficiently explore resources of causal interaction and to be aware of recorded contextual information that ensures valid use of the data. This manuscript presents a review of public resources collecting causal interactions and the different views they convey, together with a thorough description of the export formats established to store and retrieve these interactions. Our goal is to raise awareness amongst the targeted audience, i.e., logical modelers, but also any scientist interested in molecular causal interactions, about existing data resources and how to get familiar with them.
ARTICLE | doi:10.20944/preprints202004.0008.v1
Subject: Biology And Life Sciences, Biophysics Keywords: bottom-up synthetic biology; motor proteins; pattern formation; self-organization
Online: 2 April 2020 (04:02:53 CEST)
Cortical actomyosin flows, among other mechanisms, scale up spontaneous symmetry breaking and thus play pivotal roles in cell differentiation, division, and motility. According to many model systems, myosin motor-induced local contractions of initially isotropic actomyosin cortices are nucleation points for generating cortical flows. However, the positive feedback mechanisms by which spontaneous contractions can be amplified towards large-scale directed flows remain mostly speculative. To investigate such a process on spherical surfaces, we reconstituted and confined initially isotropic minimal actomyosin cortices to the interfaces of emulsion droplets. The presence of ATP leads to myosin-induced local contractions that self-organize and amplify into directed, large-scale actomyosin flows. By combining our experiments with theory, we found that the feedback mechanism leading to a coordinated, directional motion of actomyosin clusters can be described as asymmetric cluster vibrations, caused by intrinsic non-isotropic ATP consumption, in conjunction with spatial confinement. By tracking individual actomyosin clusters, we identified fingerprints of vibrational states as the basis of directed motions. These vibrations may represent a generic key driver of directed actomyosin flows under spatial confinement in vitro and in living systems.