Biological Innovations Research Articles

Evolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum

Evolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum

Genetic Variation, Polyploidy, Hybridization Influencing the Aroma Profiles of Rosaceae Family.

The fragrance and aroma of Rosaceae plants are complex traits influenced by a multitude of factors, with genetic variation standing out as a key determinant which is largely impacted by polyploidy. Polyploidy serves as a crucial evolutionary mechanism in plants, significantly boosting genetic diversity and fostering speciation. This review focuses on the Rosaceae family, emphasizing how polyploidy influences the production of volatile organic compounds (VOCs), which are essential for the aromatic characteristics of economically important fruits like strawberries, apples, and cherries. The review delves into the biochemical pathways responsible for VOC biosynthesis, particularly highlighting the roles of terpenoids, esters alcohols, aldehydes, ketones, phenolics, hydrocarbons, alongside the genetic mechanisms that regulate these pathways. Key enzymes, such as terpene synthases and alcohol acyltransferases, are central to this process. This review further explores how polyploidy and hybridization can lead to the development of novel metabolic pathways, contributing to greater phenotypic diversity and complexity in fruit aromas. It underscores the importance of gene dosage effects, isoenzyme diversity, and regulatory elements in determining VOC profiles. These findings provide valuable insights for breeding strategies aimed at improving fruit quality and aligning with consumer preferences. Present review not only elucidates the complex interplay between genomic evolution and fruit aroma but also offers a framework for future investigations in plant biology and agricultural innovation.

Restoring protein glycosylation with GlycoShape

Despite ground-breaking innovations in experimental structural biology and protein structure prediction techniques, capturing the structure of the glycans that functionalize proteins remains a challenge. Here we introduce GlycoShape (https://glycoshape.org), an open-access glycan structure database and toolbox designed to restore glycoproteins to their native and functional form in seconds. The GlycoShape database counts over 500 unique glycans so far, covering the human glycome and augmented by elements from a wide range of organisms, obtained from 1 ms of cumulative sampling from molecular dynamics simulations. These structures can be linked to proteins with a robust algorithm named Re-Glyco, directly compatible with structural data in open-access repositories, such as the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) and AlphaFold Protein Structure Database, or own. The quality, performance and broad applicability of GlycoShape is demonstrated by its ability to predict N-glycosylation occupancy, scoring a 93% agreement with experiment, based on screening all proteins in the PDB with a corresponding glycoproteomics profile, for a total of 4,259 N-glycosylation sequons.

Evolution of Sensory Receptors.

Sensory receptors are at the interface between an organism and its environment and thus represent key sites for biological innovation. Here, we survey major sensory receptor families to uncover emerging evolutionary patterns. Receptors for touch, temperature, and light constitute part of the ancestral sensory toolkit of animals, often predating the evolution of multicellularity and the nervous system. In contrast, chemoreceptors exhibit a dynamic history of lineage-specific expansions and contractions correlated with the disparate complexity of chemical environments. A recurring theme includes independent transitions from neurotransmitter receptors to sensory receptors of diverse stimuli from the outside world. We then provide an overview of the evolutionary mechanisms underlying sensory receptor diversification and highlight examples where signatures of natural selection are used to identify novel sensory adaptations. Finally, we discuss sensory receptors as evolutionary hotspots driving reproductive isolation and speciation, thereby contributing to the stunning diversity of animals.

Single-Molecule Bioelectronic Sensors with AI-Aided Data Analysis: Convergence and Challenges.

Single-molecule bioelectronic sensing, a groundbreaking domain in biological research, has revolutionized our understanding of molecules by revealing deep insights into fundamental biological processes. The advent of emergent technologies, such as nanogapped electrodes and nanopores, has greatly enhanced this field, providing exceptional sensitivity, resolution, and integration capabilities. However, challenges persist, such as complex data sets with high noise levels and stochastic molecular dynamics. Artificial intelligence (AI) has stepped in to address these issues with its powerful data processing capabilities. AI algorithms effectively extract meaningful features, detect subtle changes, improve signal-to-noise ratios, and uncover hidden patterns in massive data. This review explores the synergy between AI and single-molecule bioelectronic sensing, focusing on how AI enhances signal processing and data analysis to boost accuracy and reliability. We also discuss current limitations and future directions for integrating AI, highlighting its potential to advance biological research and technological innovation.

The dimensions of ‘forensic biosecurity’ in genetic and facial contexts

This article seeks to examine the co-productions of security and emerging technologies in the two contexts of forensic genetics and forensic facial identification. These surfacing co-productions, deemed here as ‘forensic biosecurity’, are evolving rapidly in both theoretical and practical terms. Definitions and conceptualisations of security are contingent and multiple, impacting forensic biological techniques and innovations in both predictable and unpredictable ways. The military, counter-terrorism, law enforcement, immigration, customs, border patrol, mass disasters, cold case reviews, health, defence, private security, and biometric applications are just a few of the many security environments where forensic biological techniques are applied. The continual development of variations in forensic genetics and facial identification renders a futher blurring of traditional evidence with that of intelligence. Drawing in particular from Joly’s (in: S. Hilgartner, C. Miller, and R. Hagendijk (eds) Science and democracy: Making knowledge and making power in the biosciences and beyond, Taylor and Francis, London, 2015) work on emerging technologies, forensic biosecurity is analysed from a science and technology studies (STS) perspective. An emerging technology in the initial stages is thought to be highly flexible with the potential impacts on society and criminal justice being possibly difficult to predict. Once the science and/or technology has become entrenched and mainstream, it may be difficult to change. The enthusiasm portrayed by law enforcement and security agencies regarding emerging technologies, shows that it is important to remain somewhat cautious about the proliferation of these techniques. While such science and technologies appear to be effective and innovative in the present, it is difficult to accurately forecast or predict the future consequences of such innovations.

Innovations in computational biology: RECOMB 2024 Special Issue

Innovations in computational biology: RECOMB 2024 Special Issue

Sustainability through Biomimicry: A Comprehensive Review of Bionic Design Applications.

The research objective of this paper is to examine the role of bionic design in advancing sustainable development within industrial design by outlining its theoretical framework; analyzing its applications in morphological, functional, and material aspects; identifying current challenges; and projecting future trends toward eco-integration, resource efficiency, and technological innovation. First, the definition, development history, and theoretical basis of the sustainable development of bionic design are outlined. Secondly, the application of bionic design in sustainable industrial design is analyzed in depth, including the application of morphological bionic design in exploring the combination of nature and innovation, the role of functional bionic design in integrating biological function and product innovation, and the harmonious unification of material bionic and environmental friendliness. Finally, it points out the current challenges faced by bionic design, such as barriers in design practice and market acceptance issues, and looks forward to the sustainable development trend of bionic design, including eco-integration, resource efficiency enhancement, technological innovation, integrated application, etc., to provide new ideas and impetus for the sustainable development of the industrial design field in the future.

Reconstructing Early Microbial Life.

For more than 3.5 billion years, life experienced dramatic environmental extremes on Earth. These include shifts from oxygen-less to overoxygenated atmospheres and cycling between hothouse conditions and global glaciations. Meanwhile, an ecological revolution took place. Earth evolved from one dominated by microbial life to one containing the plants and animals that are most familiar today. Many key cellular features evolved early in the history of life, collectively defining the nature of our biosphere and underpinning human survival. Recent advances in molecular and evolutionary biology have profoundly deepened our understanding of the origin and evolution of microbes across deep time. However, the incorporation of molecular genetics, population biology, and evolutionary biology approaches into the study of Precambrian biota remains a significant challenge. This review synthesizes our current knowledge of early microbial life with an emphasis on ancient metabolisms. It also outlines the foundations of an emerging interdisciplinary area that integrates microbiology, paleobiology, and evolutionary synthetic biology to reconstruct ancient biological innovations.

Three enzymes governed the rise of O2 on Earth

Current views of O2 accumulation in Earth history depict three phases: The onset of O2 production by ∼2.4 billion years ago; 2 billion years of stasis at ∼1 % of modern atmospheric levels; and a rising phase, starting about 500 million years ago, in which oxygen eventually reached modern values. Purely geochemical mechanisms have been proposed to account for this tripartite time course of Earth oxygenation. In particular the second phase, the long period of stasis between the advent of O2 and the late rise to modern levels, has posed a puzzle. Proposed solutions involve Earth processes (geochemical, ecosystem, day length). Here we suggest that Earth oxygenation was not determined by geochemical processes. Rather it resulted from emergent biological innovations associated with photosynthesis and the activity of only three enzymes: 1) The oxygen evolving complex of cyanobacteria that makes O2; 2) Nitrogenase, with its inhibition by O2 causing two billion years of oxygen level stasis; 3) Cellulose synthase of land plants, which caused mass deposition and burial of carbon, thus removing an oxygen sink and therefore increasing atmospheric O2. These three enzymes are endogenously produced by, and contained within, cells that have the capacity for exponential growth. The catalytic properties of these three enzymes paved the path of Earth's atmospheric oxygenation, requiring no help from Earth other than the provision of water, CO2, salts, colonizable habitats, and sunlight.

Pan-Evo: The Evolution of Information and Biology's Part in This.

Many people wonder whether biology, including humans, will benefit or experience harm from new developments in information such as artificial intelligence (AI). Here, it is proposed that biological and non-biological information might be components of a unified process, 'Panevolution' or 'Pan-Evo', based on four basic operations-innovation, transmission, adaptation, and movement. Pan-Evo contains many types of variable objects, from molecules to ecosystems. Biological innovation includes mutations and behavioural changes; non-biological innovation includes naturally occurring physical innovations and innovation in software. Replication is commonplace in and outside biology, including autocatalytic chemicals and autonomous software replication. Adaptation includes biological selection, autocatalytic chemicals, and 'evolutionary programming', which is used in AI. The extension of biological speciation to non-biological information creates a concept called 'Panspeciation'. Panevolution might benefit or harm biology, but the harm might be minimal if AI and humans behave intelligently because humans and the machines in which an AI resides might split into vastly different environments that suit them. That is a possible example of Panspeciation and would be the first speciation event involving humans for thousands of years. This event will not be particularly hostile to humans if humans learn to evaluate information and cooperate better to minimise both human stupidity and artificial simulated stupidity (ASS-a failure of AI).

Legal Challenges for Synthetic Biology Innovation

Legal Challenges for Synthetic Biology Innovation

The Human Developing Cerebral Cortex Is Characterized by an Elevated De Novo Expression of Long Noncoding RNAs in Excitatory Neurons.

The outstanding human cognitive capacities are computed in the cerebral cortex, a mammalian-specific brain region and the place of massive biological innovation. Long noncoding RNAs have emerged as gene regulatory elements with higher evolutionary turnover than mRNAs. The many long noncoding RNAs identified in neural tissues make them candidates for molecular sources of cerebral cortex evolution and disease. Here, we characterized the genomic and cellular shifts that occurred during the evolution of the long noncoding RNA repertoire expressed in the developing cerebral cortex and explored putative roles for these long noncoding RNAs in the evolution of the human brain. Using transcriptomics and comparative genomics, we comprehensively annotated the cortical transcriptomes of humans, rhesus macaques, mice, and chickens and classified human cortical long noncoding RNAs into evolutionary groups as a function of their predicted minimal ages. Long noncoding RNA evolutionary groups showed differences in expression levels, splicing efficiencies, transposable element contents, genomic distributions, and transcription factor binding to their promoters. Furthermore, older long noncoding RNAs showed preferential expression in germinative zones, outer radial glial cells, and cortical inhibitory (GABAergic) neurons. In comparison, younger long noncoding RNAs showed preferential expression in cortical excitatory (glutamatergic) neurons, were enriched in primate and human-specific gene co-expression modules, and were dysregulated in neurodevelopmental disorders. These results suggest different evolutionary routes for older and younger cortical long noncoding RNAs, highlighting old long noncoding RNAs as a possible source of molecular evolution of conserved developmental programs; conversely, we propose that the de novo expression of primate- and human-specific young long noncoding RNAs is a putative source of molecular evolution and dysfunction of cortical excitatory neurons, warranting further investigation.

Sustaining competition for biosimilars on the pharmacy benefit: Use it or lose it.

Congress passed the Biologic Price Competition and Innovation Act of 2009, specifically to offer market competition as a counterweight to the rising costs of biologic medicines. As of April 15, 2024, 49 biosimilars have been approved by the US Food and Drug Administration in 15 biologic categories. Biosimilar competition has been undeniably successful: Through 2022, biosimilars have saved the US health system $23.6 billion, without significant care disruption or reduced quality. Through 2023, adalimumab biosimilar competition has added an additional $6.5 billion to this total, primarily through greater rebates from the reference manufacturer. Despite launching at discounts as great as 85%, adalimumab biosimilars have not been given preferred formulary positioning in the vast majority of cases and have thus gained only 3% of market share through 2023, largely because of payers' and pharmacy benefit managers' preference for rebates over discounts. This situation may negatively influence future biosimilar development, posing a threat to a biosimilar pipeline that represents hundreds of billions in savings over the next 10 years.

Social and biological innovations are essential to deliver transformative forest biotechnologies.

Forests make immense contributions to societies in the form of ecological services and sustainable industrial products. However, they face major challenges to their viability and economic use due to climate change and growing biotic and economic threats, for which recombinant DNA (rDNA) technology can sometimes provide solutions. But the application of rDNA technologies to forest trees faces major social and biological obstacles that make its societal acceptance a 'wicked' problem without straightforward solutions. We discuss the nature of these problems, and the social and biological innovations that we consider essential for progress. As case studies of biological challenges, we focus on studies of modifications in wood chemistry and transformation efficiency. We call for major innovations in regulations, and the dissolution of method-based market barriers, that together could lead to greater research investments, enable wide use of field studies, and facilitate the integration of rDNA-modified trees into conventional breeding programs. Without near-term adoption of such innovations, rDNA-based solutions will be largely unavailable to help forests adapt to the growing stresses from climate change and the proliferation of forest pests, nor will they be available to provide economic and environmental benefits from expanded use of wood and related bioproducts as part of an expanding bioeconomy.

Quantitative evaluation of the medicine innovation policy in China: based on the PMC-Index model.

Medicine innovation is crucial in promoting the sustainable development of medicine undertakings, which has significant economic and social benefits. China is the main force in global medicine consumption, with a huge demand for innovative medicines. Thus, the Chinese government releases a series of policies aimed at providing scientific and reasonable guidance for medicine innovation. However, there is inadequate quantitative evaluation and comparison of various medicine innovation policies in the existing studies. This paper adopts the approach of text mining and the Policy Modeling Consistency Index (PMC-Index) model to construct an evaluation system and then quantitatively evaluates and compares the traditional Chinese medicine innovation policies (TCMIPs), the biological medicine innovation policies (BMIPs), and the multiple medicine innovation policies (MMIPs) in China. The results indicate that: (1) The three types of drug innovation policies have similarities in content and goal through comparative analysis of high-frequency words, while they also have their own characteristics. (2) The average PMC-Index of 29 TCMIPs is 5.77, which has the highest policy bad rate (21%); the average PMC-Index of 12 BMIPs is 6.21, which has the highest policy good rate (92%); moreover, the average PMC-Index of 35 MMIPs is 6.06, which has the highest policy excellence rate (26%). (3) The BMIPs, MMIPs, and TCMIPs have similar scores on policy object, policy orientation, policy timeliness, policy evaluation, and policy accessibility, while they differ significantly mainly on policy nature, incentive method, policy function, policy issuing agency, and policy instrument. This study contributes to a comprehensive understanding of medicine innovation policies in China, in order to provide theoretical support for future policy formulation and optimization in the medicine industry. Moreover, we expand the application scenarios of policy diffusion theory.

CRISPR/Cas9 gene targeting plus nanopore DNA sequencing with the plasmid pBR322 in the classroom.

Both nanopore-based DNA sequencing and CRISPR/Cas-based gene editing represent groundbreaking innovations in molecular biology and genomics, offering unprecedented insights into and tools for working with genetic information. For students, reading, editing, and even writing DNA will be part of their everyday life. We have developed a laboratory procedure that includes (i) the biosynthesis of a guide RNA for, (ii) targeting Cas9 to specifically linearize the pBR322 plasmid, and (iii) the identification of the cutting site through nanopore DNA sequencing. The protocol is intentionally kept simple and requires neither living organisms nor biosafety laboratories. We divided the experimental procedures into separate activities to facilitate customization. Assuming access to a well-equipped molecular biology laboratory, an initial investment of approximately $2,700 is necessary. The material costs for each experiment group amount to around $130. Furthermore, we have developed a freely accessible website (https://dnalesen.hs-mittweida.de) for sequence read analysis and visualization, lowering the required computational skills to a minimum. For those with strong computational skills, we provide instructions for terminal-based data processing. With the presented activities, we aim to provide a hands-on experiment that engages students in modern molecular genetics and motivates them to discuss potential implications. The complete experiment can be accomplished within half a day and has been successfully implemented by us at high schools, in teacher training, and at universities. Our tip is to combine CRISPR/Cas gene targeting with nanopore-based DNA sequencing. As a tool, we provide a website that facilitates sequence data analysis and visualization.

Cold Spring Harbor Laboratory Courses in Phage and Bacterial Genetics: A Catalyst for Innovation in Molecular Biology, Genetics, and Microbiology.

The ability to answer complex scientific questions depends on the experimental methods available. New methods often allow scientists to answer questions that were previously intractable, leading to discoveries that often dramatically change a field. Beginning with Max Delbrück's famous summer phage course at Cold Spring Harbor Laboratory in 1945, the Phage, Bacterial Genetics, and Advanced Bacterial Genetics courses have provided hands-on experiences to generations of scientists that facilitated the broad adoption of new experimental methods into laboratories around the world. These methods have led to discoveries that changed the way we think about genetics, bacteria, and viruses, transforming our understanding of biology. The impact of these courses has been further amplified by published laboratory manuals that provide detailed protocols for the evolving experimental toolkit. These courses catalyzed intensive and critical discourse about ideas that were previously intractable and provided novel experimental approaches to answer new questions-a process that epitomizes Thomas Kuhn's concepts of Scientific Revolution, spinning off the new field of Molecular Biology and dramatically changing the field of microbiology.

De novo assembling a high-quality genome sequence of Amur grape (Vitis amurensis Rupr.) gives insight into Vitis divergence and sex determination.

To date, there has been no high-quality sequence for genomes of the East Asian grape species, hindering biological and breeding efforts to improve grape cultivars. This study presents ~522Mb of the Vitis amurensis (Va) genome sequence containing 27 635 coding genes. Phylogenetic analysis indicated that Vitis riparia (Vr) may have first split from the other two species, Va and Vitis vinifera (Vv). Divergent numbers of duplicated genes reserved among grapes suggests that the core eudicot-common hexaploidy (ECH) and the subsequent genome instability still play a non-negligible role in species divergence and biological innovation. Prominent accumulation of sequence variants might have improved cold resistance in Va, resulting in a more robust network of regulatory cold resistance genes, explaining why it is extremely cold-tolerant compared with Vv and Vr. In contrast, Va has preserved many fewer nucleotide binding site (NBS) disease resistance genes than the other grapes. Notably, multi-omics analysis identified one trans-cinnamate 4-monooxygenase gene positively correlated to the resveratrol accumulated during Va berry development. A selective sweep analysis revealed a hypothetical Va sex-determination region (SDR). Besides, a PPR-containing protein-coding gene in the hypothetical SDR may be related to sex determination in Va. The content and arrangement order of genes in the putative SDR of female Va were similar to those of female Vv. However, the putative SDR of female Va has lost one flavin-containing monooxygenase (FMO) gene and contains one extra protein-coding gene uncharacterized so far. These findings will improve the understanding of Vitis biology and contribute to the improvement of grape breeding.

Innovative approaches to enhance high-LETd tumor targeting in carbon ion radiotherapy

PurposeTo present novel approaches in particle therapy that could result in an improvement of patient outcome.MethodsTechnological/planning and biological innovations could bring particle therapy into a new area of precision medicine. However, several hurdles have to be overcome in order to transform these R&D opportunities into clinical advantages. In this contribution, we summarize the potential advantages of novel tumor targeting, through high-LETd boosting strategies with carbon ions, over standard IMPT: LETd-optimization for IMPT plan, IMPTLET, and spot-scanning hadron arc (SHArc) therapy. Two patient cases are presented to showcase the benefit: a pancreatic cancer patient (PATA) and a recurrent glioblastoma patient (PATB).ResultsFor both patients, the prescription dose and target/organs at risk (OARs) optimization goals were reached for the three techniques. In standard IMPT, the maximum LETd is placed outside of the target volume and extends into normal tissues. For the gross target volume (GTV), mean LETd values were, on average, around ∼40–60 keV/µm. IMPTLET allowed an increase in the GTV minimum LETd from 38.4 keV/µm to 48.6 keV/µm, and from 55.1 to 87.1 keV/µm, for PATA and PATB, respectively. SHArc led to an enhancement of the maximum LETd in the GTV up to at least 125 keV/µm, while the minimum GTV LETd were 47.2 keV/µm and 46.1 keV/µm, respectively. For PATA, SHArc lowers the maximum LETd in the gastrointestinal tract to 47.5 keV/µm compared to 88.0 keV/µm and 83.0 keV/µm found for the IMPT and IMPTLET plans, respectively.ConclusionsMany technological and biological innovations could enhance our current clinical approach. Following the current success of the IMPTLET introduction in clinic, SHARc will represent an interesting clinical option in carbon ion therapy.