Conceptual modelling for life sciences based on systemist foundations.

BACKGROUND: All aspects of our society, including the life sciences, need a mechanism for people working within them to represent the concepts they employ to carry out their research. For the information systems being designed and developed to support researchers and scientists in conducting their work, conceptual models of the relevant domains are usually designed as both blueprints for a system being developed and as a means of communication between the designer and developer. Most conceptual modelling concepts are generic in the sense that they are applied with the same understanding across many applications. Problems in the life sciences, however, are especially complex and important, because they deal with humans, their well-being, and their interactions with the environment as well as other organisms. RESULTS: This work proposes a "systemist" perspective for creating a conceptual model of a life scientist's problem. We introduce the notion of a system and then show how it can be applied to the development of an information system for handling genomic-related information. We extend our discussion to show how the proposed systemist perspective can support the modelling of precision medicine. CONCLUSION: This research recognizes challenges in life sciences research of how to model problems to better represent the connections between physical and digital worlds. We propose a new notation that explicitly incorporates systemist thinking, as well as the components of systems based on recent ontological foundations. The new notation captures important semantics in the domain of life sciences. It may be used to facilitate understanding, communication and problem-solving more broadly. We also provide a precise, sound, ontologically supported characterization of the term "system," as a basic construct for conceptual modelling in life sciences.

Biotechnology in India: An Analysis of 'Biotechnology Industry Research Assistance Council' (BIRAC)-Supported Projects.

A comprehensive analysis of 2165 projects funded by India's Department of Biotechnology since 2005 through private-public partnerships, and as of 2012 through the 'Biotechnology Industry Research Assistance Council (BIRAC)' until BIRAC's tenth anniversary at the end of March 2022 reveals details of the science and technology underpinning past and current biotechnology research and development projects in the country. They are led by human healthcare projects (74.9 % overall), of which medical technology (58.7 %) and therapeutics (24.5 %) are the main drivers, ahead of vaccines (4.3 %), regenerative medicine (3.9 %), public health (3.5 %) and others (5.1 %). Agricultural projects (15.2 % overall) have mainly been driven by plant breeding and cloning (24.6 %), animal biotechnology (20.4 %), agri-informatics (13.4 %), aquaculture (6.1 %), and (bio)fertilizers (4.3 %). The key components of industrial biotechnology (9.9 % overall) have been fine chemicals (44.7 %), environmental projects (23.3 %), clean energy (18.1 %) and industrial enzymes (12.1 %). Analysis of the projects funded pre- versus post-2017, compared to the distribution of equity funding as of early 2022 identifies trends in terms of growth areas and locations of industrial biotechnology projects and activities in India.

How to teach life sciences students about dual-use research-a view from the field.

To reduce biological risks, raising awareness for dual-use issues already at the level of university education is essential. Currently, most life sciences education programs do not incorporate biosecurity and dual-use in their regular curricula. Consequently, the responsibility rests with individual lecturers and depends on their initiative to incorporate dual-use topics into teaching activities. Students interested in biosecurity and dual-use topics often only have the option to educate themselves in external or online courses. Here, we provide practical guidance on how to initiate and integrate a dual-use education program within the curriculum and provide a selection of existing teaching materials. In addition, we suggest key learning objectives to guide the planning of dual-use courses. Different course formats like lectures, seminars, or stand-alone events are discussed regarding their advantages, disadvantages, and suitability for conveying the learning objectives to different educational stages and audiences. As a minimum, we recommend the incorporation of dual-use issues into at least one mandatory course. Ideally, students should additionally participate in in-depth seminars, which can be voluntary and offered in cooperation with external organisations.

Pandemic-Era Digital Education: Insights from an Undergraduate Medical Programme.

The undergraduate medical programme at Newcastle University (NU) includes a fundamental 'Essentials of Medical Practice' (EOMP) phase comprising the first 2 years of study. This period is designed to support entrants in their transition from further education into the advanced study and practice of clinical medicine. The anatomical sciences of gross anatomy, histology and embryology, and life sciences including physiology, pharmacology and genetics are key disciplines taught within the integrated case-based EOMP curriculum. Learners apply basic science knowledge to clinical scenarios during training in practical examination, communication and reasoning skills. Within the modern pedagogic landscape, the development and introduction of technology-enhanced learning strategies have enhanced the provision of remote learning resources in pre-clinical education. However, the emergence of COVID-19 has resulted in widespread technological challenges for educators and learners, and has raised pedagogic, logistical and ethical concerns. Nonetheless, the pandemic has produced favourable conditions for the creation of valuable digital visualisation strategies for learning and teaching, and for developing and modernising universal approaches to remote education. Here, we describe our technology-enhanced adaptations to COVID-19 across the domains of teaching, learning and academic support for pre-clinical learners studying basic life sciences and clinical skills. Moreover, we outline research-informed digital visualisation solutions to pandemic-era challenges and reflect upon experiences gained within our own educational context. In doing so, we provide insights into the impacts and successes of our interventions. While providing a record of unprecedented contemporary circumstances, we also aim to utilise our observations and experiences of COVID-19 pedagogy when developing ongoing strategies for delivering curricula and futureproofing educational practice.

Application of the Nicoya OpenSPR to Studies of Biomolecular Binding: A Review of the Literature from 2016 to 2022.

The Nicoya OpenSPR is a benchtop surface plasmon resonance (SPR) instrument. As with other optical biosensor instruments, it is suitable for the label-free interaction analysis of a diverse set of biomolecules, including proteins, peptides, antibodies, nucleic acids, lipids, viruses, and hormones/cytokines. Supported assays include affinity/kinetics characterization, concentration analysis, yes/no assessment of binding, competition studies, and epitope mapping. OpenSPR exploits localized SPR detection in a benchtop platform and can be connected with an autosampler (XT) to perform automated analysis over an extended time period. In this review article, we provide a comprehensive survey of the 200 peer-reviewed papers published between 2016 and 2022 that use the OpenSPR platform. We highlight the range of biomolecular analytes and interactions that have been investigated using the platform, provide an overview on the most common applications for the instrument, and point out some representative research that highlights the flexibility and utility of the instrument.

Strategies for Mitigating Commercial Sensor Chip Variability with Experimental Design Controls.

Surface plasmon resonance (SPR) is a popular real-time technique for the measurement of binding affinity and kinetics, and bench-top instruments combine affordability and ease of use with other benefits of the technique. Biomolecular ligands labeled with the 6xHis tag can be immobilized onto sensing surfaces presenting the Ni2+-nitrilotriacetic acid (NTA) functional group. While Ni-NTA immobilization offers many advantages, including the ability to regenerate and reuse the sensors, its use can lead to signal variability between experimental replicates. We report here a study of factors contributing to this variability using the Nicoya OpenSPR as a model system and suggest ways to control for those factors, increasing the reproducibility and rigor of the data. Our model ligand/analyte pairs were two ovarian cancer biomarker proteins (MUC16 and HE4) and their corresponding monoclonal antibodies. We observed a broad range of non-specific binding across multiple NTA chips. Experiments run on the same chips had more consistent results in ligand immobilization and analyte binding than experiments run on different chips. Further assessment showed that different chips demonstrated different maximum immobilizations for the same concentration of injected protein. We also show a variety of relationships between ligand immobilization level and analyte response, which we attribute to steric crowding at high ligand concentrations. Using this calibration to inform experimental design, researchers can choose protein concentrations for immobilization corresponding to the linear range of analyte response. We are the first to demonstrate calibration and normalization as a strategy to increase reproducibility and data quality of these chips. Our study assesses a variety of factors affecting chip variability, addressing a gap in knowledge about commercially available sensor chips. Controlling for these factors in the process of experimental design will minimize variability in analyte signal when using these important sensing platforms.

Editorial introduction: Biomedicine and life sciences as a challenge to human temporality.

Bringing together scholars from philosophy, bioethics, law, sociology, and anthropology, this topical collection explores how innovations in the field of biomedicine and the life sciences are challenging and transforming traditional understandings of human temporality and of the temporal duration, extension and structure of human life. The contributions aim to expand the theoretical debate by highlighting the significance of time and human temporality in different discourses and practical contexts, and developing concrete, empirically informed, and culturally sensitive perspectives. The collection is structured around three main foci: the beginning of life, the middle of life, and later life. This structure facilitates an in-depth examination of specific technological and biographical contexts and at the same time allows an overarching comparison of relevant similarities and differences between life phases and fields of application.

Colonial rodent control in Tanganyika and the application of ecological frameworks.

ABSTRACTAt the end of the 1920s, Tanganyika Territory experienced several serious rodent outbreaks that threatened cotton and other grain production. At the same time, regular reports of pneumonic and bubonic plague occurred in the northern areas of Tanganyika. These events led the British colonial administration to dispatch several studies into rodent taxonomy and ecology in 1931 to determine the causes of rodent outbreaks and plague disease, and to control future outbreaks. The application of ecological frameworks to the control of rodent outbreaks and plague disease transmission in colonial Tanganyika Territory gradually moved from a view that prioritised 'ecological interrelations' among rodents, fleas and people to one where those interrelations required studies into population dynamics, endemicity and social organisation in order to mitigate pests and pestilence. This shift in Tanganyika anticipated later population ecology approaches on the African continent. Drawing on sources from the Tanzania National Archives, this article offers an important case study of the application of ecological frameworks in a colonial setting that anticipated later global scientific interest in studies of rodent populations and rodent-borne disease ecologies.

Circulation as a Visual Practice.

This special issue looks at some of the ways that images are adopted, co-opted, and adapted in the life sciences and beyond. It brings together papers that investigate the role of visualization in scientific knowledge-production with contributions that focus on the distribution and dissemination of knowledge to a broader audience. A commentary provides a critical perspective. In this editorial we introduce circulation as a practice to better understand scientific images. Along two themes, we highlight connections across the papers. First, the social life of scientific representation follows the contexts, settings, and spaces through which images circulate. Second, authorship, expertise, and trust inform the capacity and the failure of images to circulate. Altogether, this volume raises a set of new questions about circulation as practice in the historiography of images in the life sciences.

New Opportunities for the Utilization of the Sulfoximine Group in Medicinal Chemistry from the Drug Designer's Perspective.

Extension of the medicinal chemistry toolbox is in the vital interest of drug designers. However, the diffusion of an innovation can be a lengthy process. Along these lines, it took almost 70 years before the use of the sulfoximine group reached a critical mass in medicinal chemistry. Even though interest in this versatile functional group has increased exponentially in recent years, there is ample room for further innovative applications. This Review highlights emerging trends and opportunities for drug designers for the utilization of the sulfoximine group in medicinal chemistry, such as in the construction of complex molecules, proteolysis targeting chimeras (PROTACs), antibody-drug conjugates (ADCs) and novel warheads for covalent inhibition.

Genetic epidemiology of human neutrophil antigen variants suggests significant global variability.

Human neutrophil antigens possess significant clinical implications especially in the fields of transfusion and transplantation medicine. Efforts to estimate the prevalence of genetic variations underpinning the antigenic expression are emerging. However, there lacks a precise capture of the global frequency profiles. Our article emphasizes the potential utility of maintaining an organized online repository of evidence on neutrophil antigen-associated genetic variants from published literature and reports. This, in our opinion, is an emerging area and would significantly benefit from the awareness and understanding of population-level diversities.

Mass Spectrometry in Proteomics: Technologies, Methods, and Research Applications for the Life Sciences.

Mass spectrometry is a powerful tool in the hand of life science researchers, who constantly develop and apply new methods for the investigation of biomolecules, such as proteins, peptides, metabolites, lipids, and glycans. In this review, we will discuss the importance of mass spectrometry for the life science sector, with a special focus on the most relevant current applications in the field of proteomics. Moreover, we will comment on the factors that research groups should consider when setting up a mass spectrometry laboratory, and on the fundamental role played by academic core facilities and industrial service providers.

"How Many Individuals Consider Themselves to Be Cell Biologists but Are Informed by the Journal That Their Work Is Not Cell Biology".

What can we gain from co-analyzing experimental cultures, regionalization, and disciplinary phenomena of late twentieth century life sciences under our historiographic looking glass? This essay investigates the potential of such a strategy for the case of cell biology after 1960. By merging perspectives from historical epistemology inspired by the work of Hans-Jörg Rheinberger with a focus on boundary work in the realm of scientific publishing, community building, and disciplinary norms, a set of understudied scientific practices is exposed. These practices, historically subsumed under the label descriptive, have been as central in cell biology as hypothesis-driven research aiming at mechanistic explanations of cellular function. Against the background of an increasing molecular-mechanistic imperative in cell biology since the late 1960s, knowledge from descriptive practices was often judged as having low value but was nonetheless frequently cited and considered essential. Investigating the underlying epistemic practices and their interactions with disciplinary gatekeeping phenomena (as policed by journals and learned societies) provides historiographic access to the plurality of experimental cultures of cell biology, scattered into many interdisciplinary research fields-with some of them only partially engaged with mechanistic questions.

"Be Healthy as a Fish" educational program - Presenting how zebrafish can improve our understanding of human diseases.

While mice and rats are still the most common choices for modeling human diseases, the use of zebrafish (Danio rerio) is becoming increasingly popular. In response to this growing potential, the International Institute of Molecular and Cell Biology in Warsaw (IIMCB) decided to introduce the Be Healthy as a Fish campaign in 2014. The program aims to educate school children on how the zebrafish can be used as a model organism to help scientists understand the way the human body works. Interactive workshops with the use of modern research equipment are part of the educational campaign, which also includes a short animated movie and a booklet. To make the program understandable and interesting for young audience, all of the materials and teaching aids were consulted with the Centre for Innovative Bioscience Education (BioCEN, Warsaw, Poland), whose mission is to popularize biology in society, especially through workshops for students and their teachers. As of October 31, 2018, nearly 900 primary school students participated in workshops. Nearly 2600 viewers have watched the movie on YouTube channel and more than 11,000 people received the book.

Life sciences and mass spectrometry: some personal reflections.

Molecular analysis of biological systems by mass spectrometry was in focus of technological developments in the second half of the 20th century, in which the issues of chemical identification of high molecular diversity by biophysical instrumental methods appeared as a mission impossible. By developing dialogs between researchers dealing with life sciences and medicine on one side and technology developers on the other, new horizons toward deciphering, identifying and quantifying of complex systems became a reality. Contributions toward this goal can be today considered as pioneering efforts delivered by a number of researchers, including generations of motivated students and associates.

Where to search top-K biomedical ontologies?

MOTIVATION: Searching for precise terms and terminological definitions in the biomedical data space is problematic, as researchers find overlapping, closely related and even equivalent concepts in a single or multiple ontologies. Search engines that retrieve ontological resources often suggest an extensive list of search results for a given input term, which leads to the tedious task of selecting the best-fit ontological resource (class or property) for the input term and reduces user confidence in the retrieval engines. A systematic evaluation of these search engines is necessary to understand their strengths and weaknesses in different search requirements. RESULT: We have implemented seven comparable Information Retrieval ranking algorithms to search through ontologies and compared them against four search engines for ontologies. Free-text queries have been performed, the outcomes have been judged by experts and the ranking algorithms and search engines have been evaluated against the expert-based ground truth (GT). In addition, we propose a probabilistic GT that is developed automatically to provide deeper insights and confidence to the expert-based GT as well as evaluating a broader range of search queries. CONCLUSION: The main outcome of this work is the identification of key search factors for biomedical ontologies together with search requirements and a set of recommendations that will help biomedical experts and ontology engineers to select the best-suited retrieval mechanism in their search scenarios. We expect that this evaluation will allow researchers and practitioners to apply the current search techniques more reliably and that it will help them to select the right solution for their daily work. AVAILABILITY: The source code (of seven ranking algorithms), ground truths and experimental results are available at https://github.com/danielapoliveira/bioont-search-benchmark.

Cryo-FIB preparation of whole cells and tissue for cryo-TEM: use of high-pressure frozen specimens in tubes and planchets.

The desire to study macromolecular complexes within their cellular context requires the ability to produce thin samples suitable for cryo-TEM (cryo-transmission electron microscope) investigations. In this paper, we discuss two similar approaches, which were developed independently in Utrecht (the Netherlands) and Albany (USA). The methods are particularly suitable for both tissue samples and cell suspensions prepared by a high-pressure freezer (HPF). The workflows are explained with particular attention to potential pitfalls, while underlying principles are highlighted ('why to do so'). Although both workflows function with a high success rate, full execution requires considerable experience and remains demanding. In addition, throughput is low. We hope to encourage other research groups worldwide to take on the challenge of improving the HPF- cryo-FIB-SEM - cryo-TEM workflow. We discuss a number of suggestions to this end. LAY DESCRIPTION: Life is ultimately dictated by the interaction of molecules in our bodies. Highly complex equipment is being used and further developed to study these interactions. The present paper describes methods to prepare small, very thin lamellae (area of 5×5 µm2 , thickness 50-300 nm) of a cell to be studied in a cryo-transmission electron microscope (cryo-TEM). Special care must be taken to preserve the natural state of molecules in their natural environment. In the case of cryo-TEM, the samples must be frozen and kept frozen to be compatible with the vacuum conditions in the microscope. The frozen condition imposes technical challenges which are addressed. Two approaches to obtain the thin lamellae are described. Both make use of a focused ion beam (FIB) microscope. The FIB allows removal of material with nanometre precision by focusing a beam of ionised atoms (gallium ions) onto the sample. Careful control of the FIB allows cutting out of the required thin lamellae. In both strategies, the thin lamellae remain attached to the original sample, and the ensemble of sample with section and sample holder is transported from the FIB microscope to the TEM while being kept frozen.

Mapping the biomedical sciences using Medical Subject Headings: a comparison between MeSH co-assignments and MeSH citation pairs.

OBJECTIVE: This study compares two maps of biomedical sciences using Medical Subject Headings (MeSH) term co-assignments versus MeSH terms of citing/cited articles and reveals similarities and differences between the two approaches. METHODS: MeSH terms assigned to 397,475 journal articles published in 2015, as well as their 4,632,992 cited references, were retrieved from Web of Science and MEDLINE databases, respectively, which formed over 7 million MeSH co-assignments and nearly 18 million direct citation pairs. We generated six network visualizations of biomedical science at three levels using Gephi software based on these MeSH co-assignments and citation pairs. RESULTS: The MeSH co-assignment map contained more nodes and edges, as MeSH co-assignments cover all medical topics discussed in articles. By contrast, the MeSH citation map contained fewer but larger nodes and wider edges, as citation links indicate connections to two similar medical topics. CONCLUSION: These two types of maps emphasize different aspects of biomedical sciences, with MeSH co-assignment maps focusing on the relationship between topics in different categories and MeSH direct citation maps providing insights into relationships between topics in the same or similar category.

Seeing clearly through COVID-19: current and future questions for the history and philosophy of the life sciences.

The role of a journal like HPLS during the novel coronavirus pandemic should serve as a means for scholars in different fields and professions to consider historically and critically what is happening as it unfolds. Surely it cannot tackle all the possible issues related to the pandemic, in particular to the COVID-19 pandemic, but it does have a responsibility to foster the best possible dialogue about the various issues related to the history and philosophy of the life sciences, and thus to solicit contributions from potential authors working in different parts of the world and belonging to different cultural traditions. Only a real plurality of perspectives should allow for a better, large-scale comprehension of what the COVID-19 pandemic is.

Unlocking the efficiency of genomics laboratories with robotic liquid-handling.

In research and clinical genomics laboratories today, sample preparation is the bottleneck of experiments, particularly when it comes to high-throughput next generation sequencing (NGS). More genomics laboratories are now considering liquid-handling automation to make the sequencing workflow more efficient and cost effective. The question remains as to its suitability and return on investment. A number of points need to be carefully considered before introducing robots into biological laboratories. Here, we describe the state-of-the-art technology of both sophisticated and do-it-yourself (DIY) robotic liquid-handlers and provide a practical review of the motivation, implications and requirements of laboratory automation for genome sequencing experiments.