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The relevant and correct prescribing of medical biology is a major public health issue. Correct prescribing is a legal obligation under article L6211-8 of the French Public Health Code and is an integral part of the biologist's daily work, already specified in the 2012 (section 4.7) and 2022 (section 5.3.3) versions of the NF EN ISO 15189 standard. COFRAC document SH REF 02 v08 specifies the requirements for consultancy services. The adaptation of the prescriptions is a revision of the contract with the prescriber, which makes it possible to optimize patient care and ensure the satisfaction of the laboratory users. Although essential, accurate prescribing is time consuming. "Chronophage" is the term that has been used for almost a decade. At present, the work of biologists in this area is not valued. In fact, there is no evaluation system to highlight this regulation control activity. To date, no work has been published to estimate this time, this chronophagy, and to evaluate its impact. Cost measurement using Time-Driven Activity-Based Costing (TDABC), a variant of Activity-Based Costing (ABC), is based on a process approach. The main contribution of TDABC is that it uses a single cost driver: time. Serum immunofixation is a test used to confirm and monitor plasma cell dyscrasias, the archetype of which is multiple myeloma. The learned societies and the IMWG provide explicit diagnostic criteria, but the guidelines do not address the frequency of follow-up. In particular, the frequency of repeat and follow-up serum immunofixation remains unaddressed from an evidence-based medicine perspective. This work has made it possible to highlight the savings made between 1st January and 31th August 2023 thanks to the involvement of the biologist and to highlight his essential role in the process of controlling the overall expenditure (reagents, human resources, time and money) in the specialized biochemistry sector (bench: proteins) and to strengthen the role of the biologist within the institution. The various players in the healthcare sector - prescribing physicians, biologists, hospital administrators and, last but not least, patients - all have an essential role to play in maximizing value for patients and in the healthcare economy.

As part of this special issue on physics and biology, we invited several leading experts that bridge these disciplines to provide their views on the reciprocal contributions of each field and the benefits and challenges of working across physics and biology: introduction provided by Wallace Marshall., Competing Interests: Declaration of interests W.M., A.F., C.-P.H., A.M., C.M.N., X.T. and A.Y. are all advisory board members of Current Biology. All other authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Three-dimensional (3D) printing promises a revolution in laboratory creativity by enabling rapid prototyping, broader availability of scientific apparatuses, and transformative scientific workflows. We believe all chemistry and biology laboratories should equip themselves with one or more 3D printers and a critical mass of scientists trained to operate them. This overview surveys the techniques, intricacies, and pitfalls associated with 3D printing of functional parts, including measurements, computer-aided design, slicing, limitations of 3D printing, troubleshooting, tips for tricky filaments, and 3D printer maintenance. A flow cells are essential tools in chemistry and biology laboratories, we discuss techniques relevant to the construction of watertight 3D-printed parts. Finally, we articulate a set of principles required for reporting 3D-printed innovations to improve the field's reproducibility and encourage iterative improvements by other scientists. Ideally, authors, peer reviewers, and editors will adopt these principles. We hope these protocols inspire a new generation of publications applying 3D printing in chemistry and biology-especially highly reproducible inventions with the requisite detail and associated documentation. Such reports will facilitate broad adoption and creative iteration of the most innovative designs, thus accelerating discovery in chemistry and biology. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC., (© 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.)

The concept of performance has gradually become established in health policies. Presented as necessary and positive, it is often reduced to efficiency, which results in policies and management styles aimed at optimisation. While they are supposed to guarantee the sustainability of our healthcare systems, these practices have made them fragile. Insights from the life sciences help us understand why. Indeed, biologists observe that living beings do not prioritise optimisation but robustness. To cope with fluctuations, a robust organisation operates with redundancies, apparent waste, heterogeneity, organised fluctuations, slowness, and hesitation. It functions sub-optimally. This article offers a theoretical reflection and management directions for more robust healthcare systems., (© 2024 John Wiley & Sons Ltd.)

ConspectusChemical synthesis as a tool to control the structure and properties of matter is at the heart of chemistry─from the synthesis of fine chemicals and polymers to drugs and solid-state materials. But as the field evolves to tackle larger and larger molecules and molecular complexes, the traditional tools of synthetic chemistry become limiting. In contrast, Mother Nature has developed very different strategies to create the macromolecules and molecular systems that make up the living cell. Our focus has been to ask whether we can use the synthetic strategies and machinery of Mother Nature, together with modern chemical tools, to create new macromolecules, and even whole organisms with properties not existing in nature. One such example involves reprogramming the complex, multicomponent machinery of ribosomal protein synthesis to add new building blocks to the genetic code, overcoming a billion-year constraint on the chemical nature of proteins. This methodology exploits the concept of bioorthogonality to add unique codons, tRNAs and aminoacyl-tRNA synthetases to cells to encode amino acids with physical, chemical and biological properties not found in nature. As a result, we can make precise changes to the structures of proteins, much like those made by chemists to small molecules and beyond those possible by biological approaches alone. This technology has made it possible to probe protein structure and function in vitro and in vivo in ways heretofore not possible, and to make therapeutic proteins with enhanced pharmacology. A second example involves exploiting the molecular diversity of the humoral immune system together with synthetic transition state analogues to make catalytic antibodies, and then expanding this diversity-based strategy (new to chemists at the time) to drug discovery and materials science. This work ushered in a new nature-inspired synthetic strategy in which large libraries of natural or synthetic molecules are designed and then rationally selected or screened for new function, increasing the efficiency by which we can explore chemical space for new physical, chemical and biological properties. A final example is the use of large chemical libraries, robotics and high throughput phenotypic cellular screens to identify small synthetic molecules that can be used to probe and manipulate the complex biology of the cell, exemplified by druglike molecules that control cell fate. This approach provides new insights into complex biology that complements genomic approaches and can lead to new drugs that act by novel mechanisms of action, for example to selectively regenerate tissues. These and other advances have been made possible by using our knowledge of molecular structure and reactivity hand in hand with our understanding of and ability to manipulate the complex machinery of living cells, opening a new frontier in synthesis. This Account overviews the work in my lab and with our collaborators, from our early days to the present, that revolves around this central theme.

When you take the time to observe another organism, there is a sort of gravity that can take hold, a mixture of curiosity and connection that expands and strengthens the more you interact with that organism. Yet, in research, a connection with one's study organism can, at times, feel countercultural. Study organisms are sometimes viewed more as tools to conveniently study biological questions. Here, we explicitly highlight the importance of organism-centered research not only in scientific discovery, but also in conservation and in the communication and perception of science., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Over 160 years after Darwin and 70 years after the discovery of DNA, two fundamental questions of biology remain unanswered: What differentiates the living from the nonliving? How can mechanistic and finalistic or holistic biology be unified? Niels Bohr introduced a concept of complementarity in quantum physics and based on the paradox of light as a simultaneous wave and particle, conjectured that a similar concept might exist in biology that would solve the paradox of life originating from the nonliving. Bohr proposed that two mutually exclusive-independent observations may be necessary to explain a phenomenon and provided support to Immanuel Kant's idea that the "purposive" behaviour of organisms could only be explained in teleological terms and that mechanical and teleological approaches were necessary and complementary to explain biology. We present a concept of complementarity whereby biochemical pathways or cellular channels for the flow of information are simultaneously complex and redundant and complexity and redundancy complement each other. The postulates of biological complementarity are that (1) it was an essential condition in the origin of life; (2) it provided physiological flexibility that allowed organisms to mount self-protection response and complexity to evolve in the face of deleterious mutations before the evolution of bi-parental sex; (3) it laid the foundation for the evolution of a choice of response when confronted with threat; and (4) it applies to all levels of biological organizations and, thus, can serve as a basis for the unification of mechanistic and holistic biology. It is proposed that teleology is simultaneously constitutive and heuristic: constitutive because organisms' "purposive" behaviours are adaptive and are grounded in mechanism (complexity and redundancy), and heuristic because with our finite cognition and our goal-oriented (humans alone are aware of "tomorrow") and anthropomorphic pre-disposition, teleology will remain useful as a guide to our making sense of the world, even how to ask a meaningful question., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Advances in DNA sequencing and machine learning are providing insights into protein sequences and structures on an enormous scale 1 . However, the energetics driving folding are invisible in these structures and remain largely unknown 2 . The hidden thermodynamics of folding can drive disease 3,4 , shape protein evolution 5-7 and guide protein engineering 8-10 , and new approaches are needed to reveal these thermodynamics for every sequence and structure. Here we present cDNA display proteolysis, a method for measuring thermodynamic folding stability for up to 900,000 protein domains in a one-week experiment. From 1.8 million measurements in total, we curated a set of around 776,000 high-quality folding stabilities covering all single amino acid variants and selected double mutants of 331 natural and 148 de novo designed protein domains 40-72 amino acids in length. Using this extensive dataset, we quantified (1) environmental factors influencing amino acid fitness, (2) thermodynamic couplings (including unexpected interactions) between protein sites, and (3) the global divergence between evolutionary amino acid usage and protein folding stability. We also examined how our approach could identify stability determinants in designed proteins and evaluate design methods. The cDNA display proteolysis method is fast, accurate and uniquely scalable, and promises to reveal the quantitative rules for how amino acid sequences encode folding stability., (© 2023. The Author(s).)

Mapping gene networks requires large amounts of transcriptomic data to learn the connections between genes, which impedes discoveries in settings with limited data, including rare diseases and diseases affecting clinically inaccessible tissues. Recently, transfer learning has revolutionized fields such as natural language understanding 1,2 and computer vision 3 by leveraging deep learning models pretrained on large-scale general datasets that can then be fine-tuned towards a vast array of downstream tasks with limited task-specific data. Here, we developed a context-aware, attention-based deep learning model, Geneformer, pretrained on a large-scale corpus of about 30 million single-cell transcriptomes to enable context-specific predictions in settings with limited data in network biology. During pretraining, Geneformer gained a fundamental understanding of network dynamics, encoding network hierarchy in the attention weights of the model in a completely self-supervised manner. Fine-tuning towards a diverse panel of downstream tasks relevant to chromatin and network dynamics using limited task-specific data demonstrated that Geneformer consistently boosted predictive accuracy. Applied to disease modelling with limited patient data, Geneformer identified candidate therapeutic targets for cardiomyopathy. Overall, Geneformer represents a pretrained deep learning model from which fine-tuning towards a broad range of downstream applications can be pursued to accelerate discovery of key network regulators and candidate therapeutic targets., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Most mathematical modeling in biology relies either implicitly or explicitly on the epistemology of physics. The underlying conception is that the historicity of biological objects would not matter to understand a situation here and now, or, at least, historicity would not impact the method of modeling. We analyze that it is not the case with concrete examples. Historicity forces a conceptual reconfiguration where equations no longer play a central role. We argue that all observations depend on objects defined by their historical origin instead of their relations as in physics. Therefore, we propose that biological variations and historicity come first, and regularities are constraints with limited validity in biology. Their proper theoretical and empirical use requires specific rationales., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Mitochondria are maternally inherited organelles that play critical tissue-specific roles, including hormone synthesis and energy production, that influence human development, health, and aging. However, whether mitochondria from women and men exhibit consistent biological differences remains unclear, representing a major gap in knowledge. This meta-analysis systematically examined four domains and six subdomains of mitochondrial biology (total 39 measures), including mitochondrial content, respiratory capacity, reactive oxygen species (ROS) production, morphometry, and mitochondrial DNA copy number. Standardized effect sizes (Hedge's g) of sex differences were computed for each measure using data in 2258 participants (51.5% women) from 50 studies. Only two measures demonstrated aggregate binary sex differences: higher mitochondrial content in women's WAT and isolated leukocyte subpopulations (g = 0.20, χ 2 p = .01), and higher ROS production in men's skeletal muscle (g = 0.49, χ 2 p < .0001). Sex differences showed weak to no correlation with age or BMI. Studies with small sample sizes tended to overestimate effect sizes (r = -.17, p < .001), and sex differences varied by tissue examined. Our findings point to a wide variability of findings in the literature concerning possible binary sex differences in mitochondrial biology. Studies specifically designed to capture sex- and gender-related differences in mitochondrial biology are needed, including detailed considerations of physical activity and sex hormones., (© 2022 Federation of American Societies for Experimental Biology.)

Cells can maintain their homeostasis in a noisy environment since their signaling pathways can filter out noise somehow. Several network motifs have been proposed for biological noise filtering and, among these, feed-forward loops have received special attention. Specific feed-forward loops show noise reducing capabilities, but we notice that this feature comes together with a reduced signal transducing performance. In posttranslational signaling pathways feed-forward loops do not function in isolation, rather they are coupled with other motifs to serve a more complex function. Feed-forward loops are often coupled to other feed-forward loops, which could affect their noise-reducing capabilities. Here we systematically study all feed-forward loop motifs and all their pairwise coupled systems with activation-inactivation kinetics to identify which networks are capable of good noise reduction, while keeping their signal transducing performance. Our analysis shows that coupled feed-forward loops can provide better noise reduction and, at the same time, can increase the signal transduction of the system. The coupling of two coherent 1 or one coherent 1 and one incoherent 4 feed-forward loops can give the best performance in both of these measures., Competing Interests: The authors have declared that no competing interests exist.

The recent deluge of genome-wide technologies for the mapping of the epigenome and resulting data in cancer samples has provided the opportunity for gaining insights into and understanding the roles of epigenetic processes in cancer. However, the complexity, high-dimensionality, sparsity, and noise associated with these data pose challenges for extensive integrative analyses. Machine Learning (ML) algorithms are particularly suited for epigenomic data analyses due to their flexibility and ability to learn underlying hidden structures. We will discuss four overlapping but distinct major categories under ML: dimensionality reduction, unsupervised methods, supervised methods, and deep learning (DL). We review the preferred use cases of these algorithms in analyses of cancer epigenomics data with the hope to provide an overview of how ML approaches can be used to explore fundamental questions on the roles of epigenome in cancer biology and medicine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This essay aims to define the origin, expansion, and evolution of living matter. The first formations, identified as remains, fossils, traces etc. of life are almost as old as the Earth itself. During four billion years, life on the Earth has continuously existed and been implemented in the range of conditions, ensuring the liquid state of water. During the entire period of life existence, its evolution was proceeding with the tendency of multidirectionality, after each catastrophe tending to the diversity and vastness of distribution, and all the currently living species, regardless of their complexity, have the same evolutionary age. The property of reproductive surplus (multiplication) is inherent in all the living matter. The reproduction of all the living matter is implemented via the "development" - a process of continuous occurrence of something new that did not exist in the previous moment in the reproduced individual at each specific moment of time with the tendency towards the reproduction of a "copy". In its fundamental basis, Life is based on a programme, its material support is implemented and exists not in the field of causative-consecutive events, but in the field of programmed-causative-consecutive events. This predetermines the "biology laws", the behaviour of the material constituent of Life at each time period, and the future of the material constituent of life., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the philosophy of science, we can consider debates about the nature of non-causal explanations in general (e.g. Reutlinger, Saatsi 2018; Lange 2017) and then especially those in the life sciences (e.g. Huneman, 2018; Kostić 2020). These debates are accompanied by the development of a new mechanism that is becoming the major response to the nature of scientific explanation in the life sciences (e.g. Craver, Darden 2013; Craver 2006); and also by the development of a design explanation (e.g. Eck, Mennes 2016) that represents a modern variant of a functional explanation. In this paper, we will methodically: 1. evaluate the plurality of explanatory strategies in contemporary science (chapter 2). 2. describe the mechanical philosophy and mechanistic explanation (Glennan 2016; Craver, Darden 2013, etc.) (chapter 3). 3. explicate the role of mechanisms in code biology (Barbieri 2015, 2002, etc.) and its relation to the new mechanism (chapter 4). 4. fulfill the main goal of the paper - to apply mechanistic explanations in code biology (Barbieri 2019, etc.) and to apply their suitability for this scientific domain (chapter 5)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The protracted COVID 19 pandemic may indicate failures of scientific methodologies. Hoping to facilitate the evaluation and/or update of methods relevant in Biomedicine, several aspects of scientific processes are here explored. First, the background is reviewed. In particular, eight topics are analyzed: (i) the history of Higher Education models in reference to the pursuit of science and the type of student cognition pursued, (ii) whether explanatory or actionable knowledge is emphasized depending on the well- or ill-defined nature of problems, (iii) the role of complexity and dynamics, (iv) how differences between Biology and other fields influence methodologies, (v) whether theory, hypotheses or data drive scientific research, (vi) whether Biology is reducible to one or a few factors, (vii) the fact that data, to become actionable knowledge, require structuring, and (viii) the need of inter-/trans-disciplinary knowledge integration. To illustrate how these topics interact, a second section describes four temporal stages of scientific methods: conceptualization, operationalization, validation and evaluation. They refer to the transition from abstract (non-measurable) concepts (such as 'health') to the selection of concrete (measurable) operations (such as 'quantification of ́anti-virus specific antibody titers'). Conceptualization is the process that selects concepts worth investigating, which continues as operationalization when data-producing variables viewed to reflect critical features of the concepts are chosen. Because the operations selected are not necessarily valid, informative, and may fail to solve problems, validations and evaluations are critical stages, which require inter/trans-disciplinary knowledge integration. It is suggested that data structuring can substantially improve scientific methodologies applicable in Biology, provided that other aspects here mentioned are also considered. The creation of independent bodies meant to evaluate biologically oriented scientific methods is recommended., (Copyright © 2021. Published by Elsevier Inc.)

Organ-on-a-chip (OOC) platforms involve the miniaturization of cell culture systems and enable a variety of novel experimental approaches. These range from modeling the independent effects of biophysical forces on cells to screening novel drugs in multi-organ microphysiological systems, all within microscale devices. As in living systems, the incorporation of vascular structure is a key feature common to almost all organ-on-a-chip systems. In this review we highlight recent advances in organ-on-a-chip technologies with a focus on the vasculature. We first present the developmental process of the blood vessels through which vascular cells assemble into networks and remodel to form complex vascular beds under flow. We then review self-assembled vascular models and flow systems for the study of vascular development and biology as well as pre-patterned vascular models for the generation of perfusable microvessels for modeling vascular and tissue function. We finally conclude with a perspective on developing future OOC approaches for studying different aspects of vascular biology. We highlight the fit for purpose selection of OOC models towards either simple but powerful testbeds for therapeutic development, or complex vasculature to accurately replicate human physiology for specific disease modeling and tissue regeneration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In acute coronary syndrome (ACS) patients, restoring epicardial culprit vessel patency and flow with percutaneous coronary intervention or coronary artery bypass grafting has been the mainstay of treatment for decades. However, there is an emerging understanding of the crucial role of coronary microcirculation in predicting infarct burden and subsequent left ventricular remodelling, and the prognostic significance of coronary microvascular obstruction (MVO) in mortality and morbidity. This review will elucidate the multifaceted and interconnected pathophysiological processes which underpin MVO in ACS, and the various diagnostic modalities as well as challenges, with a particular focus on the invasive but specific and reproducible index of microcirculatory resistance (IMR). Unfortunately, a multitude of purported therapeutic strategies to address this unmet need in cardiovascular care, outlined in this review, have so far been disappointing with conflicting results and a lack of hard clinical end-point benefit. There are however a number of exciting and novel future prospects in this field that will be evaluated over the coming years in large adequately powered clinical trials, and this review will briefly appraise these.

Bacterial infections of the cornea, or bacterial keratitis (BK), are notorious for causing rapidly fulminant disease and permanent vision loss, even among treated patients. In the last sixty years, dramatic upward trajectories in the frequency of BK have been observed internationally, driven in large part by the commercialization of hydrogel contact lenses in the late 1960s. Despite this worsening burden of disease, current evidence-based therapies for BK - including broad-spectrum topical antibiotics and, if indicated, topical corticosteroids - fail to salvage vision in a substantial proportion of affected patients. Amid growing concerns of rapidly diminishing antibiotic utility, there has been renewed interest in urgently needed novel treatments that may improve clinical outcomes on an individual and public health level. Bridging the translational gap in the care of BK requires the identification of new therapeutic targets and rational treatment design, but neither of these aims can be achieved without understanding the complex biological processes that determine how bacterial corneal infections arise, progress, and resolve. In this chapter, we synthesize the current wealth of human and animal experimental data that now inform our understanding of basic BK pathophysiology, in context with modern concepts in ocular immunology and microbiology. By identifying the key molecular determinants of clinical disease, we explore how novel treatments can be developed and translated into routine patient care., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The widespread failure of anthelmintic drugs against nematodes of veterinary interest requires novel control strategies. Selective treatment of the most susceptible individuals could reduce drug selection pressure but requires appropriate biomarkers of the intrinsic susceptibility potential. To date, this has been missing in livestock species. Here, we selected Welsh ponies with divergent intrinsic susceptibility (measured by their egg excretion levels) to cyathostomin infection and found that their divergence was sustained across a 10-year time window. Using this unique set of individuals, we monitored variations in their blood cell populations, plasma metabolites and faecal microbiota over a grazing season to isolate core differences between their respective responses under worm-free or natural infection conditions. Our analyses identified the concomitant rise in plasma phenylalanine level and faecal Prevotella abundance and the reduction in circulating monocyte counts as biomarkers of the need for drug treatment (egg excretion above 200 eggs/g). This biological signal was replicated in other independent populations. We also unravelled an immunometabolic network encompassing plasma beta-hydroxybutyrate level, short-chain fatty acid producing bacteria and circulating neutrophils that forms the discriminant baseline between susceptible and resistant individuals. Altogether our observations open new perspectives on the susceptibility of equids to strongylid infection and leave scope for both new biomarkers of infection and nutritional intervention., (© 2021. The Author(s).)

This paper discusses, from a mathematician's point of view, the thesis formulated by Israel Gelfand, one of the greatest mathematicians of the 20th century, and one of the pioneers of mathematical biology, about the unreasonable ineffectiveness of mathematics in biology as compared with the obvious success of mathematics in physics. The author discusses the limitations of the mainstream mathematics of today when it is used in biology. He suggests that some emerging directions in mathematics have potential to enhance the role of mathematics in biology., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Over the last few years, cryo electron microscopy has become the most important method in structural biology. While 80% of deposited maps are from single particle analysis, electron tomography has grown to become the second most important method. In particular sub-tomogram averaging has matured as a method, delivering structures between 2 and 5 Å from complexes in cells as well as in vitro complexes. While this resolution range is not standard, novel developments point toward a promising future. Here, we provide a guide for the workflow from sample to structure to gain insight into this emerging field.

The biogeographic contributions of Léon Croizat (1894-1982) and the conflictive relationships with his intellectual descendants and critics are analysed. Croizat's panbiogeography assumed that vicariance is the most important biogeographic process and that dispersal does not contribute to biogeographic patterns. Dispersalist biogeographers criticized or avoided mentioning panbiogeography, especially in the context of the "hardening" of the Modern Synthesis. Researchers at the American Museum of Natural History associated panbiogeography with Hennig's phylogenetic systematics, creating cladistic biogeography. On the other hand, a group of New Zealand biologists formalized Croizat's original concepts and soon began arguing with cladistic biogeographers over the relative merits of their approaches. In Latin America, panbiogeography and cladistic biogeography were incorporated as parts of an integrative approach. A recent development, molecular panbiogeography, is based on the use of molecular phylogenetic data. The current practice shows that some authors insist on considering panbiogeography as the only appropriate approach and vicariance as the only relevant process, whereas others accept Croizat's dictum "Earth and life evolve together" as a useful guide to understanding broad, general patterns, but recognize that dispersal also contributes substantially to biotic assembly. The framework of integrative pluralism allows to explain the complexities of the biogeographic processes involved in biotic assembly without the need of unification on a large scale. This historical analysis intersects with the existing historiography of the Modern Synthesis and may provide some insights on the dynamics of integrative pluralism, which may be especially relevant in the current development of the Extended Synthesis.

Tumor cells metastasize to distant organs through a complex series of events that are driven by tumor intrinsic and extrinsic factors. In particular, non-malignant stromal cells, including immune cells, modify tumor metastatic behavior. Of these cells, tumor-associated innate immune cells, particularly macrophages and neutrophils, suppress the cytotoxic activity of innate and adaptive killer cells and interact with tumor cells to promote their growth and malignancy. These findings in mouse cancer models suggest that targeting these sub-populations of immune cells holds therapeutic promise in treating metastatic disease. In this review, we describe the origin and role of the macrophages, neutrophils, and their progenitors in the metastatic cascade and suggest strategies that might enhance cancer therapy., Competing Interests: Declaration of interests J.W.P. is a founder of, has equity in, and is a consultant for "Macomics, Ltd.," an immunooncology company. J.W.P. has filed patents for some molecules discussed briefly in the review., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual's repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists., Competing Interests: Declaration of interests An institutional affiliation (Nanfang Hospital, Southern Medical University, Guangzhou 510515, China) has patents on library preparation methods for HTS sequencing (China patents CN201910468844.1, CN201910468845.6, and CN201910468857.9). The authors declare no other competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Critical to viral infection are the multiple interactions between viral proteins and host-cell counterparts. The first such interaction is the recognition of viral envelope proteins by surface receptors that normally fulfil other physiological roles, a hijacking mechanism perfected over the course of evolution. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), has successfully adopted this strategy using its spike glycoprotein to dock on the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2). The crystal structures of several SARS-CoV-2 proteins alone or in complex with their receptors or other ligands were recently solved at an unprecedented pace. This accomplishment is partly due to the increasing availability of data on other coronaviruses and ACE2 over the past 18 years. Likewise, other key intervening actors and mechanisms of viral infection were elucidated with the aid of biophysical approaches. An understanding of the various structurally important motifs of the interacting partners provides key mechanistic information for the development of structure-based designer drugs able to inhibit various steps of the infective cycle, including neutralizing antibodies, small organic drugs, and vaccines. This review analyzes current progress and the outlook for future structural studies.

In this paper, I discuss the neo-Aristotelian approaches, which usually reinterpret Aristotle's ideas on form and/or borrow the notion of formal cause without engaging with the broader implications of Aristotle's metaphysics. In opposition to these approaches, I claim that biosemiotics can propose an alternative view on life's form. Specifically, I examine the proposals to replace the formal cause with gene-centrism, functionalism, and structuralism. After critically addressing these approaches, I discuss the problems of reconciling Aristotelianism with the modern view of life's organization. I claim that the notion of the final cause proposes a cosmological hierarchy and that this is the main problem with applying the formal cause to biology. An alternative categorization of conceptualizing life's form involves (1) the processual identity, (2) relational property clusters, and (3) context-dependent transmission of representational units. The third category points to a semiotic basis of the form of life. In this context, I offer to readjust the focus of the problem of matter-form duality by pointing out that form is primarily an issue of the subject-object relation. Biosemiotics helps to understand the constructive role of symbolic representation in living systems, which is crucial to extend the analysis of the form from cognitive representations to external phenomena. Emergence of subjectivity and perspectivity of interactions are key elements to bridge the form and actual processes within a non-hylomorphic account. To demonstrate transitions from the physical influence of shapes to the organic recognition of forms, I address the biological studies on the synchronization of coincidental inputs and enzyme specificity.

Serial Endosymbiosis Theory, or SET, was conceived and developed by Lynn Margulis, to explain the greatest discontinuity in the history of life, the origin of eukaryotic cells. Some predictions of SET, namely the origin of mitochondria and chloroplasts, withstood the test of the most recent evidence from a variety of disciplines including phylogenetics, biochemistry, and cell biology. Even though some other predictions fared less well, SET remains a seminal theory in biology. In this paper, I focus on two aspects of SET. First, using the concept of "universal symbiogenesis", developed by Freeman Dyson to search for commonalities in astronomy and biology, I propose that SET can be extended beyond eukaryogenesis. The extension refers to the possibility that even prokaryotic organisms, themselves subject to the process of symbiogenesis in SET, could have emerged symbiotically. Second, I contrast a recent "viral eukaryogenesis" hypothesis, according to which the nucleus evolved from a complex DNA virus, with a view closer to SET, according to which the nucleus evolved through the interplay of the archaeal host, the eubacterial symbiont, and a non-LTR transposon, or telomerase. Viruses joined in later, through the process of viral endogenization, to shape eukaryotic chromosomes in the process of karyotype evolution. These two proposals based on SET are a testament to its longevity as a scientific theory., (Copyright © 2021 Elsevier B.V. All rights reserved.)

For years, the renin-angiotensin system (RAS) has been perceived as a system whose role is to primarily modulate the functioning of the cardiovascular system. Years of research into the role of RAS have provided the necessary data to confirm that the role of RAS is very complex and not limited to the cardiovascular system. The presence of individual elements of the renin-angiotensin (RA) system allows to control many processes, ranging from the memorization to pro-cancer processes. Maintaining the proportions between the individual axes of the RA system allows for achieving a balance, often called homeostasis. Thus, any disturbance in the expression or activity of individual RAS elements leads to pathophysiological processes.

The emergence of bioorthogonal reactions has greatly advanced research in the fields of biology and medicine. They are not only valuable for labeling, tracking, and understanding biomolecules within living organisms, but also important for constructing advanced bioengineering and drug delivery systems. As the systems studied are increasingly complex, the simultaneous use of multiple bioorthogonal reactions is equally desirable. In this review, we take a look at the different bioorthogonal reactions that have recently been developed, the methods of cellular incorporation and the strategies to create orthogonality within the bioorthogonal landscape., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Novel ibuprofen derivatives 1-19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2-19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, 1 H-, and 13 C-NMR spectroscopic techniques. The synthetic molecules 1-19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC 50  = 2.96-178 μM as compared to the standard thiourea (IC 50  = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2-4, 6, 7, 9, 11-15, 17, and 18 demonstrated remarkable inhibitory activity with IC 50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC 50 value of 37.3 ± 0.41 μM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure-activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme.

N-Acyl imidazoles are unique electrophiles that exhibit moderate reactivity, relatively long-half life, and high solubility in water. Thanks to their tunable reactivity and chemical selectivity, the application of N-acyl imidazole derivatives has launched to a number of chemical biology researches, which include chemical synthesis of peptide/protein, chemical labeling of native proteins of interest (POIs), and structural analysis and functional manipulation of RNAs. Since proteins and RNAs play pivotal roles in numerous biological events in all living organisms, the methods that enable the chemical modification of endogenously existing POIs and RNAs in live cells may offer a variety of opportunities not only for fundamental scientific study but also for biotechnology and drug development. In this review, we discuss the recent progress of N-acyl imidazole chemistry that contributes to the chemical labeling and functional control of endogenous proteins and RNAs under multimolecularly crowded biological conditions of live cells., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Activated complement component C4 (C4b) is the nonenzymatic component of the classical pathway (CP) convertases of the complement system. Preparation of C4 and C4b samples suitable for structural biology studies is challenging due to low yields and complexity of recombinant C4 production protocols reported so far and heterogeneity of C4 in native sources. Here we present a purification protocol for human C4 and describe sample preparation methods for structural investigation of C4 and its complexes by crystallography, small angle X-ray scattering, and electron microscopy.

The medical and university department of biology pathology at Henri Mondor hospital in Créteil has been engaged in an NF EN ISO 15189 accreditation process since 2014. One of the elements of this process concerns the quality of handling of samples and their transportation to laboratories, including the implementation place requires fighting against pre-examination non-conformities, which are the source of many dysfunctions. The pre-examination group has implemented several actions in a targeted care service. Thanks to these, the rate of non-conformities has halved in 18 months. In parallel, a work project targeting student nurses on internship was born to follow up on the results of a statistical study carried out by the pre-examination group on non-conformities. The objective of the project was to include nursing students on internship in a full support course on good sampling practices and pre-analytical non-conformities. This was based on the realization of two knowledge quizzes (before and after training), theoretical training, and visits to several laboratories. This study lasted 10 months with the participation of 37 students. The results showed a marked improvement in knowledge of pre-analytics as well as total satisfaction of all students. Our approach has helped to better understand the needs of laboratories and demonstrates the usefulness of training students in good sampling practices in order to ensure better patient care as well as an improvement in their comfort and well-being.

Ethnobiology has emerged as an important transdisciplinary field that addresses the epistemic and political value of Traditional Ecological Knowledge (TEK) through an integration of biological and social sciences. In North and Latin America, ethnobiology encompasses a diversity of approaches towards TEK but there is no consensus on how TEK relates to biological and anthropological research. The aim of this article is to develop an account that helps to map integration strategies in ethnobiological approaches in North and Latin America that jointly embrace biology, anthropology, and TEK. Borrowing the notion of 'styles of reasoning' and the framework of integrative pluralism from philosophy of science, we argue that ethnobiologists across the Americas have developed heterogeneous research programs. At the same time, we argue that these styles of reasoning tend to converge in prioritizing biological perspectives and are often limited in their understandings of cultural practices due to a lack of substantive ethnographic methods., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The founders of Hereditas envisioned that race biology would be a major subject that had social applications with utmost importance in the near future. Anthropometrics was in this context understood to be the pure and eugenics the applied science. Sweden had a long tradition in physical anthropometry. Herman Lundborg, member of the advisory board of Hereditas, united the anthropometric and eugenic approaches in a synthesis. He was the first head of the Institute for Race Biology in Sweden. The contents of Hereditas reflect the development of race biology in the Nordic countries., Conclusions: The initial enthusiasm for applied race biology did not last long. In the 1920's Hereditas carried papers on both physical anthropology and eugenics. Most paper dealt, however, with human genetics without eugenic content. Two papers, published in 1921 and 1939 show how the intellectual climate had changed from positive to negative. Finally only human genetics prevailed as the legitimate study of the human race or humankind. A belated defense of eugenics published in 1951 did not help; geneticists had abandoned anthropometrics for good around the year 1940 and eugenics about a decade later. In spite of that, eugenic legislation was amended astonishingly late, in the 1970's. The development was essentially similar in all Nordic countries.

In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous membraneless organelles assembled via liquid-liquid phase separation (LLPS), known as condensates, also facilitate compartmentalization of cellular functions. Emerging evidence shows that these two organelle types interact in many biological processes. Membranes modulate the biogenesis and dynamics of phase-separated condensates by serving as assembly platforms or by forming direct contacts. Phase separation of membrane-associated proteins participates in various trafficking events, such as clustering of vesicles for temporally controlled fusion and storage, and transport of membraneless condensates on membrane-bound organelles. Phase separation also acts in cargo trafficking pathways by sorting and docking cargos for translocon-mediated transport across membranes, by shuttling cargos through the nuclear pore complex, and by triggering the formation of surrounding autophagosomes for delivery to lysosomes. The coordinated actions of membrane-bound and membraneless organelles ensure spatiotemporal control of various cellular functions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The historical reliance of biological research on the use of animal models has sometimes made it challenging to address questions that are specific to the understanding of human biology and disease. But with the advent of human organoids - which are stem cell-derived 3D culture systems - it is now possible to re-create the architecture and physiology of human organs in remarkable detail. Human organoids provide unique opportunities for the study of human disease and complement animal models. Human organoids have been used to study infectious diseases, genetic disorders and cancers through the genetic engineering of human stem cells, as well as directly when organoids are generated from patient biopsy samples. This Review discusses the applications, advantages and disadvantages of human organoids as models of development and disease and outlines the challenges that have to be overcome for organoids to be able to substantially reduce the need for animal experiments.

Super-resolution microscopy can reveal the subtle biological processes hidden behind the optical diffraction barrier. Plasmonics is a key nanophotonic that combines electronics and photonics through the interaction of light with the metallic nanostructure. In this review, we survey the recent progresses on plasmonic-assisted super-resolution microscopy. The strong electromagnetic field enhancement trapped near metallic nanostructures offers a unique opportunity to manipulate the illumination scheme for overcoming the diffraction limit. Plasmonic nanoprobes, exploited as surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence nanoparticles, are a major category of contrast agent in super-resolution microscopy. The outstanding challenges, future developments, and potential biological applications are also discussed., (Copyright © 2020. Published by Elsevier Ltd.)