Explore the vast range of titles available.

This study reports the identification of adult stem cells in the human parasite Schistosoma mansoni (blood fluke); the cells proliferate and differentiate into derivatives of multiple germ layers, and their maintenance requires a fibroblast growth factor receptor orthologue. Blood fluke stem cells key to robustness Adult stem cells (or neoblasts) are found in free-living planarians and parasitic tapeworms and can support impressive feats of tissue regeneration. Phillip Newmark and colleagues now report the identification of adult stem cells in the human parasite Schistosoma mansoni . This trematode flatworm, also known as the blood fluke, infects millions of people worldwide. The schistosomal stem cells proliferate and differentiate into derivatives of multiple germ layers, and express a fibroblast growth factor receptor orthologue. Using RNA interference, the authors showed that this gene is required for the maintenance of the neoblast-like cells. These findings might help to elucidate the mechanisms that promote the parasite's longevity and so could be relevant for medical treatment. Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide 1 . The aetiological agents of this disease are trematode flatworms ( Schistosoma ) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades 2 , elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms 3 , 4 (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms 5 , little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni . These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources 6 , 7 and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.

\"This Companion offers students and scholars a comprehensive introduction to the development and the diversity of the American short story as a literary form from its origins in the eighteenth century to the present day. Rather than define what the short story is as a genre, or defend its importance in comparison with the novel, this Companion seeks to understand what the short story does -- how it moves through national space, how it is always related to other genres and media, and how its inherent mobility responds to the literary marketplace and resonates with key critical themes in contemporary literary studies. Essays offer authoritative introductions and reinterpretations of a literary form that has reemerged as a major force in the twenty-first century public sphere dominated by the internet\"-- Provided by publisher.

A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.

Schistosomes infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection, yet our understanding of sexual reproduction by schistosomes is limited because normal egg production is not sustained for more than a few days in vitro. Here, we describe culture conditions that support schistosome sexual development and sustained egg production in vitro. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs. Exploiting these new culture conditions, we explore the process of male-stimulated female maturation and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. We further report the characterization of a nuclear receptor (NR), which we call Vitellogenic Factor 1 (VF1), that is essential for female sexual development following pairing with a male worm. Taken together, these results provide a platform to study the fascinating sexual biology of these parasites on a molecular level, illuminating new strategies to control schistosome egg production.

There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms.

Plastic pollution is rapidly increasing worldwide, causing adverse impacts on the environment, wildlife and human health. One tempting solution to this crisis is upcycling plastics into products with engineered microorganisms; however, this remains challenging due to complexity in conversion. Here we present a synthetic microbial consortium that efficiently degrades polyethylene terephthalate hydrolysate and subsequently produces desired chemicals through division of labor. The consortium involves two Pseudomonas putida strains, specializing in terephthalic acid and ethylene glycol utilization respectively, to achieve complete substrate assimilation. Compared with its monoculture counterpart, the consortium exhibits reduced catabolic crosstalk and faster deconstruction, particularly when substrate concentrations are high or crude hydrolysate is used. It also outperforms monoculture when polyhydroxyalkanoates serves as a target product and confers flexible tuning through population modulation for cis-cis muconate synthesis. This work demonstrates engineered consortia as a promising, effective platform that may facilitate polymer upcycling and environmental sustainability. Plastic pollution is rapidly increasing worldwide, causing adverse impacts on the environment, wildlife and human health. Here the authors present a synthetic microbial consortium that efficiently degrades polyethylene terephthalate hydrolysate and upcycles it to desired chemicals through cellular division of labor.

Schistosomes are blood dwelling parasitic flatworms that can survive in the circulation of their human hosts for decades. These parasites possess a unique syncytial skin-like surface tissue known as the tegument that is thought to be uniquely adapted for survival in the blood by mediating evasion of host defenses. Previous studies have shown that cell bodies within the tegumental syncytium are turned over and perpetually replaced by new tegumental cells derived from a pool of somatic stem cells called neoblasts. Thus, neoblast-driven tegumental homeostasis has been suggested to be a key part of the parasite’s strategy for long-term survival in the blood. However, the comprehensive set of molecular programs that control the specification of tegumental cells are not defined. To better understand these programs, we characterized a homolog of a Krüppel-like factor 4 ( klf4 ) transcription factor that was identified in previous single-cell RNA sequencing (scRNAseq) studies to be expressed in a putative tegument related lineage (TRL) of Schistosoma mansoni. Here, using a combination of RNAi, coupled with scRNAseq and bulk RNAseq approaches, we show that klf4 is essential for the maintenance of an entire TRL. Loss of this klf4 + TRL resulted in loss of a subpopulation of molecularly unique tegument cells, without altering the total number of mature tegumental cells. Thus, klf4 is critical for regulating the balance between different cell populations within the tegumental progenitor pool and thereby influences tegumental production dynamics and the fine-tuning of the molecular identity of the mature tegument. Understanding the functions of distinct populations of cells within the tegumental syncytium is expected to provide insights into parasite defense mechanisms and new avenues for combatting the disease these worms cause.

Key Points Early synthetic biology designs, namely the genetic toggle switch and repressilator, showed that regulatory components can be characterized and assembled to bring about complex, electronics-inspired behaviours in living systems (for example, memory storage and timekeeping). Through the characterization and assembly of genetic parts and biological building blocks, many more devices have been constructed, including switches, memory elements, oscillators, pulse generators, digital logic gates, filters and communication modules. Advances in the field are now allowing expansion beyond small gene networks to the realm of larger biological programs, which hold promise for a wide range of applications, including biosensing, therapeutics and the production of biofuels, pharmaceuticals and biomaterials. Synthetic biosensing circuits consist of sensitive elements that bind analytes and transducer modules that mobilize cellular responses. Balancing these two modules involves engineering modularity and specificity into the various circuits. Biosensor sensitive elements include environment-responsive promoters (transcriptional), RNA aptamers (translational) and protein receptors (post-translational). Biosensor transducer modules include engineered gene networks (transcriptional), non-coding regulatory RNAs (translational) and protein signal-transduction circuits (post-translational). The contributions of synthetic biology to therapeutics include: engineered networks and organisms for disease-mechanism elucidation, drug-target identification, drug-discovery platforms, therapeutic treatment, therapeutic delivery, and drug production and access. In the microbial production of biofuels and pharmaceuticals, synthetic biology has supplemented traditional genetic and metabolic engineering efforts by aiding the construction of optimized biosynthetic pathways. Optimizing metabolic flux through biosynthetic pathways is traditionally accomplished by driving the expression of pathway enzymes with strong, inducible promoters. New synthetic approaches include the rapid diversification of various pathway components, the rational and model-guided assembly of pathway components, and hybrid solutions. Advances in the synthetic biology field are allowing an expansion beyond small gene networks towards larger biological programs that hold promise for a wide range of applications, including biosensing, therapeutics and the production of biofuels, pharmaceuticals and biomaterials. Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, 'green' means to fuel our cars and targeted therapies for attacking 'superbugs' and diseases, such as cancer. The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications.

Acinetobacter baumannii is a nosocomial Gram-negative pathogen that often displays multidrug resistance. Discovering new antibiotics against A. baumannii has proven challenging through conventional screening approaches. Fortunately, machine learning methods allow for the rapid exploration of chemical space, increasing the probability of discovering new antibacterial molecules. Here we screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. We trained a neural network with this growth inhibition dataset and performed in silico predictions for structurally new molecules with activity against A. baumannii . Through this approach, we discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii . Further investigations revealed that abaucin perturbs lipoprotein trafficking through a mechanism involving LolE. Moreover, abaucin could control an A. baumannii infection in a mouse wound model. This work highlights the utility of machine learning in antibiotic discovery and describes a promising lead with targeted activity against a challenging Gram-negative pathogen. Using a neural network trained on bacterial growth inhibition data, in silico prediction of molecules with activity against Acinetobacter baumannii led to the identification of the narrow-spectrum abaucin, which perturbs lipoprotein trafficking.