Innovation, conservation, and repurposing of gene function in root cell type development.

Plant species have evolved myriads of solutions, including complex cell type development and regulation, to adapt to dynamic environments. To understand this cellular diversity, we profiled tomato root cell type translatomes. Using xylem differentiation in tomato, examples of functional innovation, repurposing, and conservation of transcription factors are described, relative to the model plant Arabidopsis. Repurposing and innovation of genes are further observed within an exodermis regulatory network and illustrate its function. Comparative translatome analyses of rice, tomato, and Arabidopsis cell populations suggest increased expression conservation of root meristems compared with other homologous populations. In addition, the functions of constitutively expressed genes are more conserved than those of cell type/tissue-enriched genes. These observations suggest that higher order properties of cell type and pan-cell type regulation are evolutionarily conserved between plants and animals.

Biomedical Research Goes Viral: Dangers and Opportunities.

Researchers around the globe have been mounting, accelerating, and redeploying efforts across disciplines and organizations to tackle the SARS-CoV-2 outbreak. However, humankind continues to be afflicted by numerous other devastating diseases in increasing numbers. Here, we outline considerations and opportunities toward striking a good balance between maintaining and redefining research priorities.

Engineering a Biological Revolution.

The new field of synthetic biology promises to change health care, computer technology, the production of biofuels, and more. Students participating in the International Genetically Engineered Machine (iGEM) competition are on the front lines of this revolution.

Papers and patents are becoming less disruptive over time.

Theories of scientific and technological change view discovery and invention as endogenous processes1,2, wherein previous accumulated knowledge enables future progress by allowing researchers to, in Newton's words, 'stand on the shoulders of giants'3-7. Recent decades have witnessed exponential growth in the volume of new scientific and technological knowledge, thereby creating conditions that should be ripe for major advances8,9. Yet contrary to this view, studies suggest that progress is slowing in several major fields10,11. Here, we analyse these claims at scale across six decades, using data on 45 million papers and 3.9 million patents from six large-scale datasets, together with a new quantitative metric-the CD index12-that characterizes how papers and patents change networks of citations in science and technology. We find that papers and patents are increasingly less likely to break with the past in ways that push science and technology in new directions. This pattern holds universally across fields and is robust across multiple different citation- and text-based metrics1,13-17. Subsequently, we link this decline in disruptiveness to a narrowing in the use of previous knowledge, allowing us to reconcile the patterns we observe with the 'shoulders of giants' view. We find that the observed declines are unlikely to be driven by changes in the quality of published science, citation practices or field-specific factors. Overall, our results suggest that slowing rates of disruption may reflect a fundamental shift in the nature of science and technology.

Assembly theory explains and quantifies selection and evolution.

Scientists have grappled with reconciling biological evolution1,2 with the immutable laws of the Universe defined by physics. These laws underpin life's origin, evolution and the development of human culture and technology, yet they do not predict the emergence of these phenomena. Evolutionary theory explains why some things exist and others do not through the lens of selection. To comprehend how diverse, open-ended forms can emerge from physics without an inherent design blueprint, a new approach to understanding and quantifying selection is necessary3-5. We present assembly theory (AT) as a framework that does not alter the laws of physics, but redefines the concept of an 'object' on which these laws act. AT conceptualizes objects not as point particles, but as entities defined by their possible formation histories. This allows objects to show evidence of selection, within well-defined boundaries of individuals or selected units. We introduce a measure called assembly (A), capturing the degree of causation required to produce a given ensemble of objects. This approach enables us to incorporate novelty generation and selection into the physics of complex objects. It explains how these objects can be characterized through a forward dynamical process considering their assembly. By reimagining the concept of matter within assembly spaces, AT provides a powerful interface between physics and biology. It discloses a new aspect of physics emerging at the chemical scale, whereby history and causal contingency influence what exists.

Early contact between late farming and pastoralist societies in southeastern Europe.

Archaeogenetic studies have described two main genetic turnover events in prehistoric western Eurasia: one associated with the spread of farming and a sedentary lifestyle starting around 7000-6000 BC (refs. 1-3) and a second with the expansion of pastoralist groups from the Eurasian steppes starting around 3300 BC (refs. 4,5). The period between these events saw new economies emerging on the basis of key innovations, including metallurgy, wheel and wagon and horse domestication6-9. However, what happened between the demise of the Copper Age settlements around 4250 BC and the expansion of pastoralists remains poorly understood. To address this question, we analysed genome-wide data from 135 ancient individuals from the contact zone between southeastern Europe and the northwestern Black Sea region spanning this critical time period. While we observe genetic continuity between Neolithic and Copper Age groups from major sites in the same region, from around 4500 BC on, groups from the northwestern Black Sea region carried varying amounts of mixed ancestries derived from Copper Age groups and those from the forest/steppe zones, indicating genetic and cultural contact over a period of around 1,000 years earlier than anticipated. We propose that the transfer of critical innovations between farmers and transitional foragers/herders from different ecogeographic zones during this early contact was integral to the formation, rise and expansion of pastoralist groups around 3300 BC.

Remote collaboration fuses fewer breakthrough ideas.

Theories of innovation emphasize the role of social networks and teams as facilitators of breakthrough discoveries1-4. Around the world, scientists and inventors are more plentiful and interconnected today than ever before4. However, although there are more people making discoveries, and more ideas that can be reconfigured in new ways, research suggests that new ideas are getting harder to find5,6-contradicting recombinant growth theory7,8. Here we shed light on this apparent puzzle. Analysing 20 million research articles and 4 million patent applications from across the globe over the past half-century, we begin by documenting the rise of remote collaboration across cities, underlining the growing interconnectedness of scientists and inventors globally. We further show that across all fields, periods and team sizes, researchers in these remote teams are consistently less likely to make breakthrough discoveries relative to their on-site counterparts. Creating a dataset that allows us to explore the division of labour in knowledge production within teams and across space, we find that among distributed team members, collaboration centres on late-stage, technical tasks involving more codified knowledge. Yet they are less likely to join forces in conceptual tasks-such as conceiving new ideas and designing research-when knowledge is tacit9. We conclude that despite striking improvements in digital technology in recent years, remote teams are less likely to integrate the knowledge of their members to produce new, disruptive ideas.

Innovative Homo sapiens behaviours 105,000 years ago in a wetter Kalahari.

The archaeological record of Africa provides the earliest evidence for the emergence of the complex symbolic and technological behaviours that characterize Homo sapiens1-7. The coastal setting of many archaeological sites of the Late Pleistocene epoch, and the abundant shellfish remains recovered from them, has led to a dominant narrative in which modern human origins in southern Africa are intrinsically tied to the coast and marine resources8-12, and behavioural innovations in the interior lag behind. However, stratified Late Pleistocene sites with good preservation and robust chronologies are rare in the interior of southern Africa, and the coastal hypothesis therefore remains untested. Here we show that early human innovations that are similar to those dated to around 105 thousand years ago (ka) in coastal southern Africa existed at around the same time among humans who lived over 600 km inland. We report evidence for the intentional collection of non-utilitarian objects (calcite crystals) and ostrich eggshell from excavations of a stratified rockshelter deposit in the southern Kalahari Basin, which we date by optically stimulated luminescence to around 105 ka. Uranium-thorium dating of relict tufa deposits indicates sporadic periods of substantial volumes of fresh, flowing water; the oldest of these episodes is dated to between 110 and 100 ka and is coeval with the archaeological deposit. Our results suggest that behavioural innovations among humans in the interior of southern Africa did not lag behind those of populations near the coast, and that these innovations may have developed within a wet savannah environment. Models that tie the emergence of behavioural innovations to the exploitation of coastal resources by our species may therefore require revision.

A blueprint for cancer screening and early detection: Advancing screening's contribution to cancer control.

From the mid-20th century, accumulating evidence has supported the introduction of screening for cancers of the cervix, breast, colon and rectum, prostate (via shared decisions), and lung. The opportunity to detect and treat precursor lesions and invasive disease at a more favorable stage has contributed substantially to reduced incidence, morbidity, and mortality. However, as new discoveries portend advancements in technology and risk-based screening, we fail to fulfill the greatest potential of the existing technology, in terms of both full access among the target population and the delivery of state-of-the art care at each crucial step in the cascade of events that characterize successful cancer screening. There also is insufficient commitment to invest in the development of new technologies, incentivize the development of new ideas, and rapidly evaluate promising new technology. In this report, the authors summarize the status of cancer screening and propose a blueprint for the nation to further advance the contribution of screening to cancer control.

Faculty as catalysts for training new inventors: Differential outcomes for male and female PhD students.

STEM PhDs are a critical source of human capital in the economy, contributing to commercial as well as academic science. We examine whether STEM PhD students become new inventors (file their first patent) during their doctoral training at the top 25 U.S. universities (by patenting). We find that 4% of PhDs become new inventors. However, among PhDs of faculty who are themselves top (prolific) inventors, this figure rises to 23%. These faculty train 44% of all the new inventor PhDs by copatenting with their advisees. We also explore whether new inventor PhDs are equally distributed by gender. In our university sample, the female share of new inventors is 9% points (pp) lower than the female share of PhDs. Several channels contribute to this: First, female PhDs are less likely to be trained by top inventor advisors (TIs) than male PhDs. Second, they are less likely to be trained by (the larger number of) male top inventors: The estimated gap in the female % of PhDs between female and male TIs is 7 to 9 pp. Third, female PhDs (supervised by top inventors and especially by other faculty) have a lower probability of becoming new inventors relative to their male counterparts. Notably, we find that male and female top inventors have similar rates of transforming their female advisees into new inventors at 4 to 8 pp lower (17 to 26% lower rate) than for male advisees. The gap remains at 4 pp comparing students of the same advisor and controlling for thesis topic.

Can the SBIR and STTR programs advance research goals?

With diminishing grant support for traditional funding in immunology, can the small-business program leverage a research program? The small-business grants programs offered by the US National Institutes of Health and other organizations support high-risk, early-stage technology commercialization at small businesses.

Quantifying the dynamics of failure across science, startups and security.

Human achievements are often preceded by repeated attempts that fail, but little is known about the mechanisms that govern the dynamics of failure. Here, building on previous research relating to innovation1-7, human dynamics8-11 and learning12-17, we develop a simple one-parameter model that mimics how successful future attempts build on past efforts. Solving this model analytically suggests that a phase transition separates the dynamics of failure into regions of progression or stagnation and predicts that, near the critical threshold, agents who share similar characteristics and learning strategies may experience fundamentally different outcomes following failures. Above the critical point, agents exploit incremental refinements to systematically advance towards success, whereas below it, they explore disjoint opportunities without a pattern of improvement. The model makes several empirically testable predictions, demonstrating that those who eventually succeed and those who do not may initially appear similar, but can be characterized by fundamentally distinct failure dynamics in terms of the efficiency and quality associated with each subsequent attempt. We collected large-scale data from three disparate domains and traced repeated attempts by investigators to obtain National Institutes of Health (NIH) grants to fund their research, innovators to successfully exit their startup ventures, and terrorist organizations to claim casualties in violent attacks. We find broadly consistent empirical support across all three domains, which systematically verifies each prediction of our model. Together, our findings unveil detectable yet previously unknown early signals that enable us to identify failure dynamics that will lead to ultimate success or failure. Given the ubiquitous nature of failure and the paucity of quantitative approaches to understand it, these results represent an initial step towards the deeper understanding of the complex dynamics underlying failure.

Science shines in a new virtual SY-Stem.

The third 'Symposium for the Next Generation of Stem Cell Research' (SY-Stem) was held virtually on 3-5 March 2021, having been cancelled in 2020 due to the COVID-19 pandemic. As in previous years, the meeting highlighted the work of early career researchers, ranging from postgraduate students to young group leaders working in developmental and stem cell biology. Here, we summarize the excellent work presented at the Symposium, which covered topics ranging from pluripotency, species-specific aspects of development and emerging technologies, through to organoids, single-cell technology and clinical applications.

The Future of Durable Mechanical Circulatory Support: Emerging Technological Innovations and Considerations to Enable Evolution of the Field.

The field of durable mechanical circulatory support (MCS) has undergone an incredible evolution over the past few decades, resulting in significant improvements in longevity and quality of life for patients with advanced heart failure. Despite these successes, substantial opportunities for further improvements remain, including in pump design and ancillary technology, perioperative and postoperative management, and the overall patient experience. Ideally, durable MCS devices would be fully implantable, automatically controlled, and minimize the need for anticoagulation. Reliable and long-term total artificial hearts for biventricular support would be available; and surgical, perioperative, and postoperative management would be informed by the individual patient phenotype along with computational simulations. In this review, we summarize emerging technological innovations in these areas, focusing primarily on innovations in late preclinical or early clinical phases of study. We highlight important considerations that the MCS community of clinicians, engineers, industry partners, and venture capital investors should consider to sustain the evolution of the field.

Empowering grassroots innovation to accelerate biomedical research.

The purpose of biomedicine is to serve society, yet its hierarchical and closed structure excludes many citizens from the process of innovation. We propose a collection of reforms to better integrate citizens within the research community, reimagining biomedicine as more participatory, inclusive, and responsive to societal needs.

Innovating in a bioimaging core through instrument development.

Developing devices and instrumentation in a bioimaging core facility is an important part of the innovation mandate inherent in the core facility model but is a complex area due to the required skills and investments, and the impossibility of a universally applicable model. Here, we seek to define technological innovation in microscopy and situate it within the wider core facility innovation portfolio, highlighting how strategic development can accelerate access to innovative imaging modalities and increase service range, and thus maintain the cutting edge needed for sustainability. We consider technology development from the perspective of core facility staff and their stakeholders as well as their research environment and aim to present a practical guide to the 'Why, When, and How' of developing and integrating innovative technology in the core facility portfolio. Core facilities need to innovate to stay up to date. However, how to carry out the innovation is not very obvious. One area of innovation in imaging core facilities is the building of optical setups. However, the creation of optical setups requires specific skill sets, time, and investments. Consequently, the topic of whether a core facility should develop optical devices is discussed as controversial. Here, we provide resources that should help get into this topic, and we discuss different options when and how it makes sense to build optical devices in core facilities. We discuss various aspects, including consequences for staff and the relation of the core to the institute, and also broaden the scope toward other areas of innovation.