Constructing combinatorially complete species assemblages is often necessary to dissect the complexity of microbial interactions and to find optimal microbial consortia. At the moment, this is accomplished through either painstaking, labor-intensive liquid handling procedures, or through the use of state-of-the-art microfluidic devices. Here, we present a simple, rapid, low-cost, and highly accessible liquid handling methodology for assembling all possible combinations of a library of microbial strains, which can be implemented with basic laboratory equipment. To demonstrate the usefulness of this methodology, we construct a combinatorially complete set of consortia from a library of eight <i>Pseudomonas aeruginosa</i> strains, and empirically measure the community-function landscape of biomass productivity, identify the highest-yield community, and dissect the interactions that lead to its optimal function. This easy-to-implement, inexpensive methodology will make the assembly of combinatorially complete microbial consortia easily accessible for all laboratories.
Science Journals
This Perspective discusses the importance of the US Food and Drug Administration’s draft guidance on the use of bayesian methods in clinical trials because it underscores its commitment to modernizing clinical research.
Listen to the JAMA Editor’s Summary for an overview and discussion of the important articles appearing in JAMA.
<p>by Anthony M. Bonacolta, Tristan Kravitz, Rocío Mozo, Lydia J. Baker, Rachael M. Heuer, Martin Grosell, Javier del Campo</p>
Marine fish play a significant yet understudied role in the oceanic carbon cycle through the production of magnesium-rich calcium carbonate (CaCO<sub>3</sub>) precipitates known as ichthyocarbonates. These deposits form in the gut of marine teleost fish in response to salinity, serving as part of their osmoregulation strategy. Through this, marine fish may contribute as much as 9.04 Pg of CaCO<sub>3</sub> per year in global new carbonate production, being equivalent to or potentially higher than the production by coccolithophores and pelagic foraminifera. Despite their ecological relevance, the biological mechanisms driving ichthyocarbonate precipitation remain to be fully resolved. Intriguingly, bacteria are consistently found in intimate association with ichthyocarbonate precipitates. Given the widespread capacity of prokaryotes to mediate CaCO₃ precipitation, this association points to a previously unexplored microbial contribution to the process. To investigate the potential role of bacteria in ichthyocarbonate production, we subjected Gulf toadfish (<i>Opsanus beta</i>) to salinity treatments common to their native range and known to elicit changes in CaCO<sub>3</sub> precipitation. To assess the respective contributions of the host and its microbiota to ichthyocarbonate formation in the gut, we characterized the microbiome across the toadfish gut and performed meta-transcriptomic analysis. Across the toadfish gut, we identify a high abundance of vibrios associated with ichthyocarbonates with the metabolic potential for CaCO<sub>3</sub> precipitation. Specifically, we observe the expression of the transcriptional activator of urease (<i>ureR</i>) by <i>Photobacterium damselae</i> subsp<i>. damselae,</i> which can induce the precipitation of CaCO<sub>3</sub> via the production of bicarbonate. We demonstrate that CaCO₃ precipitation …
An endogenous circadian clock controls many of the behavioral traits of <i>Drosophila melanogaster</i>. This ‘clock’ relies on the activity of interconnected clusters of neurons that harbor the clock machinery. The hierarchy among clusters involved in the control of rest-activity cycles has been extensively studied. Sexually dimorphic behaviors, on the other hand, have received less attention. Even though egg-laying, a female characteristic behavior, has been shown to be rhythmic, it remains largely unexplored possibly due to methodological constraints. The current study provides the first steps towards determining the neural substrates underlying the circadian control of egg-laying. We show that, whereas the lateral ventral neurons (LNvs) and the dorsal neurons (DNs) are dispensable, the lateral dorsal neurons (LNds) are necessary for rhythmic egg-laying. Systematically probing the <i>Drosophila</i> connectome for contacts between circadian clusters and oviposition-related neurons, we found no evidence of direct connections between LNvs or DNs and neurons recruited during oviposition. Conversely, we did find bidirectional connections between two Cryptochrome (Cry) expressing LNd (Cry + LNds) and oviposition-related neurons. Taken together, these results reveal that Cry + LNd neurons have a leading role in the control of the egg-laying rhythm in <i>Drosophila</i> females.
The ability to record the real-time activity of specialized neurons in the brains of female mice is providing new insights into the hormonal control of ovulation.
A large fraction of newly transcribed RNA is degraded in the nucleus, but nuclear mRNA degradation pathways remain largely understudied. The yeast nuclear endoribonuclease Rnt1 has a well-characterized role in the maturation of many ncRNA precursors. However, the scope and consequence of its function in mRNA degradation pathways are much less defined. Here, we take a whole-transcriptome approach to identify Rnt1 cleavage sites throughout the yeast transcriptome in vivo, at single-nucleotide resolution. We discover previously unknown Rnt1 cleavage sites in many protein-coding regions and find that the sequences and structures necessary for cleavage mirror those required for the cleavage of known targets. We show that the nuclear localization of Rnt1 functions as an additional layer of target selection control, and that cleaved mRNAs are likely exported to the cytoplasm to be degraded by Xrn1. Further, we find that several cleavage products are much more abundant in our degradome sequencing libraries than decapping products, and strikingly, mutations in one Rnt1 target, <i>YDR514C</i>, suppress the growth defect of an <i>RNT1</i> deletion. Overexpression of <i>YDR514C</i> results in slow growth, further suggesting that Rnt1 may limit the expression of <i>YDR514C</i> to maintain proper cell growth. This study uncovers a broader target range and function for the well-known RNase III enzyme.
The greatest mass extinction at the end of the Permian, ca. 252 million years ago, led to a tropical dead zone on land and sea. The speed of recovery of life has been debated, whether fast or slow, and terrestrial ecosystems are much less understood than marine. Here, we show fast reestablishment of riparian ecosystems in low-latitude North China as little as ~2 million years after the end-Permian mass extinction. The initial ichnoassemblages in shallow lacustrine and fluvial facies of late Smithian age are monospecific, devoid of infaunalization, with apparent size reduction. In the following Spathian, relatively complex, multi-level, structured riverain ecosystems had been rebuilt including medium-sized carnivores, plant stems, root traces, increased ichnological complexity, and significantly increased infaunalization. Specifically, burrowing behavior had re-emerged as a key life strategy not only to minimize stressful climatic conditions, but possibly to escape predation.
The ion channel (IC) genes encoded in the human genome play fundamental roles in cellular functions and disease, and are one of the largest classes of druggable proteins. However, limited knowledge of the diverse molecular and cellular functions carried out by ICs presents a major bottleneck in developing selective chemical probes for modulating their functions in disease states. The wealth of sequence data available on ICs from diverse organisms provides a valuable source of untapped information for illuminating the unique modes of channel regulation and functional specialization. However, the extensive diversification of IC sequences and the lack of a unified resource present a challenge in effectively using existing data for IC research. Here, we perform integrative mining of available sequence, structure, and functional data on 419 human ICs across disparate sources, including extensive literature mining by leveraging advances in LLMs to annotate and curate the full complement of the ‘channelome’. We employ a well-established orthology inference approach to identify and extend the IC orthologs across diverse organisms to above 48,000. We show that the depth of conservation and taxonomic representation of IC sequences can further be translated to functional similarities by clustering them into functionally relevant groups, which can be used for downstream functional prediction on understudied members. We demonstrate this by delineating co-conserved patterns characteristic of the understudied family of the calcium homeostasis modulator (CALHM) family of ICs. Through mutational analysis of co-conserved residues altered in human diseases and electrophysiological studies, we show that these evolutionarily constrained residues play an important role in channel gating functions. Thus, by providing new tools and resources for performing large comparative analyses on ICs, this study addresses the unique needs of the IC community and provides the groundwork for acceler…
The rapid evolution of SARS-CoV-2 and other respiratory RNA viruses limits the success of current vaccines and antibody-based therapies. Engineered decoy receptors based on soluble angiotensin-converting enzyme 2 (sACE2) offer promising alternatives but show limited clinical success. This study conducted functional and mechanistic analyses using an optimized sACE2 mutant fused to human IgG1 Fc (B5-D3) as a representative, revealing redirection of virus–decoy complexes from epithelial infection to lysosomal degradation in phagocytes beyond viral neutralization. Intranasal prophylactic delivery of B5-D3 confers complete protection in SARS-CoV-2-infected K18-hACE2 mice, regardless of age. Abrogation of Fc effector functions compromises antiviral protection, indicating that Fc-mediated uptake of virus–decoy complexes is critical. Transcriptomic analysis suggests that B5-D3 induces early immune activation in the lungs of infected mice. Bio-distribution and flow cytometry reveal selective targeting of airway phagocytes. In vitro assays confirm lysosomal degradation of virus–decoy complexes by macrophages without productive infection. These findings reveal a distinct antiviral mechanism via phagocytic clearance, supporting refined regimens for decoy treatments against SARS-CoV-2 and potentially other respiratory viruses.
Neutrophils are short-lived cells of the innate immune system that play numerous roles in defense against infection, regulation of immune responses, tissue damage and repair, autoimmunity, and other non-communicable diseases. Understanding neutrophil function at a mechanistic level has been hampered by the difficulty of working with primary neutrophils, which die rapidly upon isolation, and the relative paucity of neutrophil cell lines. Here, we report the creation of a Cas9+ER-Hoxb8 neutrophil progenitor cell line that enables both forward and reverse genetic analysis of neutrophils. By editing progenitors via transduction with sgRNAs and then withdrawing estrogen, Cas9-edited neutrophils are produced with high efficiency. Importantly, neutrophil differentiation of edited progenitors occurs both <i>in vitro</i> in cell culture and when transferred into murine recipients. To demonstrate the utility of Cas9+ER-Hoxb8 progenitors for forward genetics, we performed a pooled CRISPR screen to identify factors required for survival during neutrophil differentiation. This screen identified hundreds of genes, including <i>Cebpe</i>, a transcription factor known to be required for neutrophil differentiation from pre-neutrophils to immature neutrophils. Using this progenitor cell line, we confirmed that <i>Cebpe</i> is required for neutrophil differentiation <i>in vivo</i>, validating the utility of this line for studying <i>in vivo</i> phenotypes. The screen also identified all components of the WASH complex as being required for neutrophil differentiation, extending its known role in hematopoietic stem cell differentiation to later stages of neutrophil development. Taken together, this resource enables the analysis of the role of neutrophils in numerous disease states using genetics for the first time.
20 years ago, The Lancet published an Editorial on reviving research into psychedelics for mental health conditions, observing that “the blanket ban on psychedelic drugs enforced in many countries continues to hinder safe and controlled investigation, in a medical environment, of their potential benefits”. The Lancet of 2006 could not have foreseen that one day a president of the USA would sign an executive order aiming to “dramatically accelerate access to new medical research and treatments based on psychedelic drugs”.
Complicated urinary tract infections (cUTIs) and acute pyelonephritis remain major causes of hospitalisation worldwide and contribute substantially to antibiotic consumption and health-care costs.1 The increasing prevalence of antibiotic resistance among Gram-negative bacterial pathogens, particularly extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant bacteria has made effective treatment increasingly challenging.2
Vaccines remain one of the most impactful and cost-effective public health interventions. Decades of evidence from randomised controlled trials and epidemiological studies have shown the impact of vaccines on population health following the introduction and scale-up of immunisation programmes.1 As the incidence of previously debilitating vaccine-preventable childhood diseases diminishes due to vaccination efforts, the perceived importance of immunisation could become less evident to the public. Amid rising vaccine hesitancy and the spread of misinformation, it is increasingly important to continue demonstrating the tangible impact of vaccines globally.
Autologous stem-cell transplantation (ASCT) has remained central to the care of younger patients with mantle cell lymphoma since the publication of the first European Mantle Cell Lymphoma Network trial in 2005.1 Its role is now firmly challenged in The Lancet by results of the TRIANGLE study from Martin Dreyling and colleagues.2
Memories resurface. An unfamiliar virus. Deaths. A stricken cruise ship. Quarantines. Hastily arranged WHO press briefings. Scientists interviewed on radio and television about what is known—and, more importantly, not known—about disease transmission. WHO has assessed the public health risk as low. But for the families of the three passengers on the MV Hondius who died, together with those with either confirmed or suspected hantavirus infection, the news of an outbreak of a mysterious virus will be frightening.
Peru is expanding access to surgery and care for patients with cleft conditions in remote areas through intensive capacity-building led by local volunteers. Jacqui Thornton reports.
As part of a series on medicine in unusual settings, Talha Burki takes a look at medical practice in UK prisons.
“In Viet Nam, health challenges are rarely abstract”, says Thu-Anh Nguyen, Director of the University of Sydney Vietnam Institute (SVI) and Professor in Global Health at the University of Sydney, Australia. “They are visible in overcrowded clinics, in families navigating long treatment journeys, and in communities where preventable diseases persist. Building health research in this context is not simply about generating evidence. It is about creating the conditions under which evidence can be trusted, used, and sustained.”
For decades, the thymus has been regarded as a vestigial organ of childhood, essential for T-cell education early in life, but thought to lose relevance as it involutes into fatty tissue after adolescence. This dogma was challenged a few years ago when a study showed that removal of the thymus during thoracic surgery was linked to poor outcomes. More recent work, enabled by artificial intelligence (AI), brings new insights about the potential role of the thymus across the lifespan.
The use of artificial intelligence (AI) and generative AI in medicine provokes important questions about the nature of clinical work performed by human practitioners as well as the limitations and benefits of this technology. In the light of the possibilities and pitfalls of AI in clinical work, there is a need to re-examine the basic nature of the therapeutic value of human interaction in clinical medicine and to discuss some pervasive misconceptions (in practice if not in theory) about the nature of the societally embedded human mind.
Virologist and expert in influenza surveillance, pandemic preparedness, and infectious disease response. Born on July 21, 1948, in Emmetsburg, IA, USA, she died from glioblastoma on April 24, 2026, in Atlanta, GA, aged 77 years.
We read with interest Marcello Ienca and colleagues’ Review on the increasing erosion of trust in health institutions.1 We also believe that restoring emotional engagement and resonance are essential, but were surprised that the authors did not suggest youth advocacy as a scalable strategy and co-production mechanism (WHO framework) for rebuilding trust, which encompasses most aspects of their proposed solutions.2
Marcello Ienca and colleagues1 in their Review identify a trust paradox in which rigorous institutions lose credibility while unaccountable voices gain it. We argue that large language model (LLM)-based chatbots represent a qualitatively distinct escalation of this paradox, extending beyond the social media dynamics described.
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, although invaluable for global health metrics, presents concerning estimates of life expectancy at birth for Monaco.1 Monaco is a microstate typically synonymous with world-leading levels of life expectancy at birth, with official sources, such as statistics from the Monaco Government and UN reports, consistently placing Monaco's life expectancy among the highest globally.2,3 The most recent estimate from the Monegasque Demography Observatory for 2022–24 places life expectancy at birth at 87·0 years;3 however, GBD estimates are substantially lower, at 80·4 years in 2023.