Revolution In Biology Research Articles

The 'Omics Revolution in CHO Biology: Roadmap to Improved CHO Productivity.

Chinese hamster ovary (CHO) cell physiology understanding has advanced very rapidly in the past few years with incredible improvements in long-read sequencing, improved resolution, and increased computational power. Multiple parental lines have been sequenced and the resultant pan-genome can be leveraged to increase our understanding of the diverse pathways CHO cells can take to get high-productivity phenotypes. The same improvements in workflows have complemented transcriptomic studies. Microfluidics and label-free innovations have further increased the sensitivity and accuracy of proteomic methods, while also making proteomics more accessible. In this 'omics era, high-throughput screening methods, sophisticated informatic tools, and models continually drive major innovations in cell line development and process engineering. This review describes the various recent achievements in 'omics techniques and their application to improve recombinant protein expression from CHO cell lines.

The legacy and evolvability of Pere Alberch's ideas.

Pere Alberch played a pivotal role in shaping the field of evolutionary developmental biology during the 1980s and 1990s. Whereas initially his contributions were sidelined by the empirical advancements of the molecular revolution in developmental and evolutionary biology, his theoretical insights have left a lasting impact on the discipline. This article provides a comprehensive review of the legacy and evolvability of Alberch's ideas in contemporary evo-devo, which included the study of morphogenesis as the proper level of developmental causation, the interplay between developmental constraints and natural selection, the epistemic role of teratologies, the origin of evolutionary novelties and the concept of evolvability.

Ethical aspects associated with genome alteration techniques applied to animal reproduction research.

The revolution in biology triggered by the different genome-editing tools has of course arrived to the research field of animal reproduction. Yeast meganucleases, zinc-finger nucleases, TALEN and, particularly, the several generations of CRISPR tools have landed in animal reproduction thereby providing novel strategies to optimize or modify some of the features and capabilities of the recipient animals. All these genome-editing proposals and activities are associated with ethical considerations regarding how those planned genome alterations might affect important animal welfare issues. The ethical dimension of all these genome editing must be seriously considered. Hence, all ethical aspects bound to any given genome-edited allele in animals should be discussed in order to ensure that we are maximizing benefits and reducing any potential risk or negative considerations of these modifications. In this review, I will summarize some of the experiments reported aiming to investigate or improve animal reproduction and I will address the ethics issues that should also be considered.

World Futures Day 2023 Global futures agenda by The Millennium Project

World Futures Day (WFD), the 24 h round-the-world participatory method hosted every year by The Millennium Project and others on March 1, stimulates conversations and collective intelligence on possible futures. The 2023 edition marked its tenth anniversary. The 2023 Global futures agenda coming out from the data analysis is composed of four main clusters, each listing future oriented topics and related contents. Cluster 1, Complex solutions for complex problems, includes topics such as Environmental regeneration, Predictable food systems, Energy transition, Homo Galaxia, and Synergetic relations for peace. Cluster 2, A hyper-technological humanity, includes topics such as A biological revolution, New definitions of truth, An emotional AGI, A conscious AGI, and AGI governance. Cluster 3, Education and learning for a better future, includes topics such as Intelligent agent teachers, Intergenerational storytelling, and A cultural shift to self-actualization. Cluster 4, Improving global foresight, includes topics such as Futurists as a contradiction, A new leadership agenda, Futures shapers, The power of stories, Judging trillions of scenarios, Committees and summits for the future. After discussing some changes in the contents addressed over the years and some potential next steps for the research on WFD, the conclusions report that one key takeaway from WFD 2023 is that we have a vital need for pragmatic hope.

An Erratic Path Toward Discovery

Through a series of accidents of history, my career began just when the revolution in molecular biology was taking place. The allure of molecular biology attracted me to exploiting tumor viruses as experimental models of the nucleic acid metabolism of cells. The fact that these viruses cause cancer was incidental but eventually led to an interest in cancer pathogenesis, exploiting them to understand the mechanisms of cell transformation. This made it possible to test the speculation that cell transformation derived from the mutation of cellular genes and that cancer cell behavior is driven by the actions of resulting mutant alleles of these genes. In 1979, we showed that cells that had been transformed by 3-methylcholanthrene carried a mutant oncogenic allele. This work progressed so that by 1982 my research group and others demonstrated that human bladder carcinoma cells carried a point-mutated RAS oncogene, providing a direct proof of the mutational theory of cancer pathogenesis.

Tectonic trigger to the first major extinction of the Phanerozoic: The early Cambrian Sinsk event.

The Cambrian explosion, one of the most consequential biological revolutions in Earth history, occurred in two phases separated by the Sinsk event, the first major extinction of the Phanerozoic. Trilobite fossil data show that Series 2 strata in the Ross Orogen, Antarctica, and Delamerian Orogen, Australia, record nearly identical and synchronous tectono-sedimentary shifts marking the Sinsk event. These resulted from an abrupt pulse of contractional supracrustal deformation on both continents during the Pararaia janeae trilobite Zone. The Sinsk event extinction was triggered by initial Ross/Delamerian supracrustal contraction along the edge of Gondwana, which caused a cascading series of geodynamic, paleoenvironmental, and biotic changes, including (i) loss of shallow marine carbonate habitats along the Gondwanan margin; (ii) tectonic transformation to extensional tectonics within the Gondwanan interior; (iii) extrusion of the Kalkarindji large igneous province; (iv) release of large volumes of volcanic gasses; and (v) rapid climatic change, including incursions of marine anoxic waters and collapse of shallow marine ecosystems.

Convergence of Surface-Enhanced Raman Scattering with Molecular Diagnostics: A Perspective on Future Directions.

Molecular diagnostics (MD) is widely employed in multiple scientific disciplines, such as oncology, pathogen detection, forensic investigations, and the pharmaceutical industry. Techniques such as polymerase chain reaction (PCR) revolutionized the rapid and accurate identification of nucleic acids (DNA, RNA). More recently, CRISPR and its CRISPR-associated protein (Cas) have been a ground-breaking discovery that is the latest revolution in molecular biology, including MD. Surface-enhanced Raman scattering (SERS) is a very attractive alternative to fluorescence as the currently most widely used optical readout in MD. In this Perspective, milestones in the development of MD, SERS-PCR, and next-generation approaches to MD, such as Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) and DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR), are briefly summarized. Our perspective on the future convergence of SERS with MD is focused on SERS-based CRISPR/Cas (SERS-CRISPR) since we anticipate many promising applications in this rapidly emerging field. We predict that major future developments will exploit the advantages of real-time monitoring with the superior brightness, photostability, and spectral multiplexing potential of SERS nanotags in an automated workflow for rapid assays under isothermal, amplification-free conditions.

Novel Immunopharmacological Drugs for the Treatment of Allergic Diseases.

The exponential rise in the prevalence of allergic diseases since the mid-twentieth century has led to a genuine public health emergency and has also fostered major progress in research on the underlying mechanisms and potential treatments. The management of allergic diseases benefits from the biological revolution, with an array of novel immunomodulatory therapeutic and investigational tools targeting players of allergic inflammation at distinct pathophysiological steps. Prominent examples include therapeutic monoclonal antibodies against cytokines, alarmins, and their receptors, as well as small-molecule modifiers of signal transduction mainly mediated by Janus kinases and Bruton's tyrosine kinases. However, the first-line therapeutic options have yet to switch from symptomatic to disease-modifying interventions. Here we present an overview of available drugs in the context of our current understanding of allergy pathophysiology, identify potential therapeutic targets, and conclude by providing a selection of candidate immunopharmacological molecules under investigation for potential future use in allergic diseases.

Recent advances in protein conformation sampling by combining machine learning with molecular simulation

Abstract The rapid advancement and broad application of machine learning (ML) have driven a groundbreaking revolution in computational biology. One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improving the sampling efficiency of the vast conformational space of large biomolecules. This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape. We first highlight the recent development of ML-aided enhanced sampling methods, including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential, or facilitate the exploration of the unsampled region of the energy landscape. Further, we review the development of autoencoder based methods which combine molecular simulations and deep learning to expand the search of protein conformations. Lastly, we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights. Collectively, this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.

Protein click chemistry and its potential for medical applications.

A revolution in chemical biology occurred with the introduction of click chemistry. Click chemistry plays an important role in protein chemistry modifications, providing specific, sensitive, rapid, and easy-to-handle methods. Under physiological conditions, click chemistry often overlaps with bioorthogonal chemistry, defined as reactions that occur rapidly and selectively without interfering with biological processes. Click chemistry is used for the posttranslational modification of proteins based on covalent bond formations. With the contribution of click reactions, selective modification of proteins would be developed, representing an alternative to other technologies in preparing new proteins or enzymes for studying specific protein functions in different biological processes. Click-modified proteins have potential in diverse applications such as imaging, labeling, sensing, drug design, and enzyme technology. Due to the promising role of proteins in disease diagnosis and therapy, this review aims to highlight the growing applications of click strategies in protein chemistry over the last two decades, with a special emphasis on medicinal applications.

Viewing 3D spatial biology with highly-multiplexed Raman imaging: from spectroscopy to biotechnology.

Understansding complex biological systems requires the simultaneous characterization of a large number of interacting components in their native 3D environment with high spatial resolution. Highly-multiplexed Raman imaging is an emerging general strategy for detecting biomarkers with scalable multiplexity and ultra-sensitivity based on a series of stimulated Raman scattering (SRS) techniques. Here we review recent advances in highly-multiplexed Raman imaging and how they contribute to the technological revolution in 3D spatial biology, focusing on the developmental pathway from spectroscopy study to biotechnology invention. We envision highly-multiplexed Raman imaging is taking off, which will greatly facilitate our understanding in biological and medical research fields.

Thinking process templates for constructing data stories with SCDNEY

Background Globally, scientists now have the ability to generate a vast amount of high throughput biomedical data that carry critical information for important clinical and public health applications. This data revolution in biology is now creating a plethora of new single-cell datasets. Concurrently, there have been significant methodological advances in single-cell research. Integrating these two resources, creating tailor-made, efficient, and purpose-specific data analysis approaches can assist in accelerating scientific discovery. Methods We developed a series of living workshops for building data stories, using Single-cell data integrative analysis (scdney). scdney is a wrapper package with a collection of single-cell analysis R packages incorporating data integration, cell type annotation, higher order testing and more. Results Here, we illustrate two specific workshops. The first workshop examines how to characterise the identity and/or state of cells and the relationship between them, known as phenotyping. The second workshop focuses on extracting higher-order features from cells to predict disease progression. Conclusions Through these workshops, we not only showcase current solutions, but also highlight critical thinking points. In particular, we highlight the Thinking Process Template that provides a structured framework for the decision-making process behind such single-cell analyses. Furthermore, our workshop will incorporate dynamic contributions from the community in a collaborative learning approach, thus the term ‘living’.

Aedes-borne orthoflavivirus infections in neotropical primates - Ecology, susceptibility, and pathogenesis.

Arboviral diseases comprise a group of important infectious diseases imposing a heavy burden to public health in many locations of the world. Orthoflaviviruses are viruses belonging to the genus Orthoflavivirus; this genus includes some of the most relevant arboviruses to human health. Orthoflaviviruses can infect several different hosts, with some species being transmitted in cycles involving birds and anthropophilic mosquitoes and others transmitted between mammals and mostly Aedes sp. mosquitoes. Some of the most important sylvatic reservoirs of orthoflaviviruses are non-human primates (NHPs). Many flaviviruses that infect NHPs in nature have the potential to cause epidemics in humans, as has been observed in the cases of Orthoflavivirus denguei (dengue virus - DENV), Orthoflavivirus flavi (yellow fever virus - YFV), and Orthoflavivirus zikaense (Zika virus - ZIKV). In this minireview, we discuss important aspects regarding history, ecology involving NHP, distribution, disease outcome, and pathogenesis of these three major orthoflaviviruses that affect humans and NHP and relate this information to the potential of using NHP as experimental models. In addition, we suggest some orthoflaviviruses that could be better investigated, both in nature and in experimental studies, in light of the recent revolution in molecular biology.

Mental Health's Stalled (Biological) Revolution: Its Origins, Aftermath & Future Opportunities

Abstract The 1980s, by common consensus, saw a big and remarkably rapid pivot away from previously dominant psychoanalytic and social science perspectives in American psychiatry and toward a so-called medical model foregrounding biology and the brain. The standard understanding is that this happened because, after years of wandering lost in a Freudian desert, the field had finally gained some fundamental new biological understandings of mental illness. The standard understanding is wrong. Nothing of sudden significance had happened on the biological front. There had been no major scientific or therapeutic breakthroughs. Why, then, did the field really pivot? This essay aims to explain. The answer is important, not least because choices made back then have directly shaped the fraught world of psychiatry with which we live today.

Animus: human-embodied animals

We review recent research to introduce human brain organoids into the brains of infant rats. This research shows these organoids integrate and function to affect behaviour in rats. We argue...

Osteocalcin: A new phenomenon for type 2 diabetes and obesity

<b>Objectives: </b>The molecular biology revolution has emerged with the determination that bone tissue is an endocrine organ that regulates many physiological processes, and osteocalcin (OCN), an osteoblast-derived protein that provides endocrine control, is a hormone that regulates glucose and energy homeostasis. By controlling gene expression in β-cells and adipocytes, OCN improves glucose intolerance, obesity, and insulin expression. In addition, OCN stimulates the secretion of adiponectin, a molecule that increases fatty acid oxidation and insulin secretion and sensitivity in adipose tissue and reduces adipose tissue accumulation. Recent research suggests that serum OCN increases the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein-1 (UCP1) genes, which play a role in thermogenesis in brown adipose tissue, it also affects insulin sensitivity by increasing adiponectin expression in white adipose tissue. OCN the target gene of insulin, and resting energy expenditure and mitochondrial biogenesis. With all these effects, OCN is a protein that has recently been found to be associated with diabetes and obesity components.<br /> <b>Conclusions: </b>This review aims to present an overview of understanding the interaction of OCN produced by osteoblasts with insulin, glucose metabolism, adipose tissue, skeletal and muscle tissue, and appetite metabolism in understanding the endocrine functions of bone. In addition, it was conducted to examine the role of OCN in energy metabolism and to evaluate the relationship of energy metabolism pathways affected by OCN with non-communicable chronic diseases such as type 2 diabetes mellitus and obesity.

Fifty years of DIPG: looking at the future with hope.

Diffuse intrinsic pontine glioma (DIPG) is a primary brainstem tumor of childhood that carries a dismal prognosis, with median survival of less than 1year. Because of the brain stem location and pattern of growth within the pons, Dr. Harvey Cushing, the father of modern neurosurgery, urged surgical abandonment. Such a dismal prognosis remained unchanged for decades, coupled with a lack of understanding of tumor biology and an unchanging therapeutic panorama. Beyond palliative external beam radiation therapy, no therapeutic approach has been widely accepted. In the last one to two decades, however, increased tissue availability, an improving understanding of biology, genetics, and epigenetics have led to the development of novel therapeutic targets. In parallel with this biological revolution, new methods intended to enhance drug delivery into the brain stem are contributing to a surge of exciting experimental therapeutic strategies.

Multisite transformation in Neisseria gonorrhoeae: insights on transformations mechanisms and new genetic modification protocols.

Natural transformation, or the uptake of naked DNA from the external milieu by bacteria, holds a unique place in the history of biology. This is both the beginning of the realization of the correct chemical nature of genes and the first technical step to the molecular biology revolution that sees us today able to modify genomes almost at will. Yet the mechanistic understanding of bacterial transformation still presents many blind spots and many bacterial systems lag behind power horse model systems like Escherichia coli in terms of ease of genetic modification. Using Neisseria gonorrhoeae as a model system and using transformation with multiple DNA molecules, we tackle in this paper both some aspects of the mechanistic nature of bacterial transformation and the presentation of new molecular biology techniques for this organism. We show that similarly to what has been demonstrated in other naturally competent bacteria, Neisseria gonorrhoeae can incorporate, at the same time, different DNA molecules modifying DNA at different loci within its genome. In particular, co-transformation of a DNA molecule bearing an antibiotic selection cassette and another non-selected DNA piece can lead to the integration of both molecules in the genome while selecting only through the selective cassette at percentages above 70%. We also show that successive selections with two selection markers at the same genetic locus can drastically reduce the number of genetic markers needed to do multisite genetic modifications in Neisseria gonorrhoeae. Despite public health interest heightened with the recent rise in antibiotic resistance, the causative agent of gonorrhea still does not possess a plethora of molecular techniques. This paper will extend the techniques available to the Neisseria community while providing some insights into the mechanisms behind bacterial transformation in Neisseria gonorrhoeae. We are providing a suite of new techniques to quickly obtain modifications of genes and genomes in the Neisserial naturally competent bacteria.

Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors

G-protein coupled receptors (GPCRs) are versatile signaling proteins that regulate key physiological processes in response to a wide variety of extracellular stimuli. The last decade has seen a revolution in the structural biology of clinically important GPCRs. Indeed, the improvement in molecular and biochemical methods to study GPCRs and their transducer complexes, together with advances in cryo-electron microscopy, NMR development, and progress in molecular dynamic simulations, have led to a better understanding of their regulation by ligands of different efficacy and bias. This has also renewed a great interest in GPCR drug discovery, such as finding biased ligands that can either promote or not promote specific regulations. In this review, we focus on two therapeutically relevant GPCR targets, the V2 vasopressin receptor (V2R) and the mu-opioid receptor (µOR), to shed light on the recent structural biology studies and show the impact of this integrative approach on the determination of new potential clinical effective compounds.

A Kuhnian revolution in molecular biology: Most genes in complex organisms express regulatory RNAs.

Thomas Kuhn described the progress of science as comprising occasional paradigm shifts separated by interludes of 'normal science'. The paradigm that has held sway since the inception of molecular biology is that genes (mainly) encode proteins. In parallel, theoreticians posited that mutation is random, inferred that most of the genome in complex organisms is non-functional, and asserted that somatic information is not communicated to the germline. However, many anomalies appeared, particularly in plants and animals: the strange genetic phenomena of paramutation and transvection; introns; repetitive sequences; a complex epigenome; lack of scaling of (protein-coding) genes and increase in 'noncoding' sequences with developmental complexity; genetic loci termed 'enhancers' that control spatiotemporal gene expression patterns during development; and a plethora of 'intergenic', overlapping, antisense and intronic transcripts. These observations suggest that the original conception of genetic information was deficient and that most genes in complex organisms specify regulatory RNAs, some of which convey intergenerational information. Also see the video abstract here: https://youtu.be/qxeGwahBANw.