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A contractile sheath and rigid tube assembly is a widespread apparatus used by bacteriophages, tailocins, and the bacterial type VI secretion system to penetrate cell membranes. In this mechanism, contraction of an external sheath powers the motion of an inner tube through the membrane. The structure, energetics, and mechanism of the machinery imply rigidity and straightness. The contractile tail ofAgrobacterium tumefaciensbacteriophage Milano is flexible and bent to varying degrees, which sets it apart from other contractile tail-like systems. Here, we report structures of the Milano tail including the sheath-tube complex, baseplate, and putative receptor-binding proteins. The flexible-to-rigid transformation of the Milano tail upon contraction can be explained by unique electrostatic properties of the tail tube and sheath. All components of the Milano tail, including sheath subunits, are crosslinked by disulfides, some of which must be reduced for contraction to occur. The putative receptor-binding complex of Milano contains a tailspike, a tail fiber, and at least two small proteins that form a garland around the distal ends of the tailspikes and tail fibers. Despite being flagellotropic, Milano lacks thread-like tail filaments that can wrap around the flagellum, and is thus likely to employ a different binding mechanism.

TheJ= 5.5 → 4.5 andJ= 5 → 4 transitions of PO and PN, respectively, have been imaged in the envelope of hypergiant star VY Canis Majoris (VY CMa) using the Atacama Large Millimeter/submillimeter Array with angular resolutions of 0.″2 and 1.″5 and data from the Submillimeter Telescope of the Arizona Radio Observatory. These maps are the first high-fidelity images of PO and PN in a circumstellar envelope. Both molecules are primarily present in a spherical, star-centered region with a radius ∼60R_*(0.″5), indicating formation by LTE chemistry and then condensation into grains. PN, however, shows additional, fan-shaped emission 2″ southwest of the star, coincident with dust features resolved by Hubble Space Telescope (HST), as well as four newly identified distinct structures 1″–2″ toward the north, east, and west (Cloudlets I–IV), not visible in HST images. The “SW Fan” and the cloudlets are also prominent in theJ= 5.5 → 4.5 transition of NS. The correlation of PN with NS, SiO, and dust knots in the SW Fan suggests a formation in shocked gas enhanced with nitrogen. Excess nitrogen is predicted to favor PN synthesis over PO. Abundances for PN and PO in the spherical source aref∼ 4.4 × 10⁻⁸and 1.4 × 10⁻⁷, respectively, relative to H₂. Given a cosmic abundance of phosphorus, an unusually high fraction (∼35%) is contained in PO and PN. Alternatively, the stellar winds may be enriched in P (and N) by dredge-up from the interior of VY CMa.

Large gaps exist in our understanding of how bacteriophages, the most abundant biological entities on Earth, assemble and function. The structure of the “neck” region, where the DNA-filled capsid is connected to the host-recognizing tail remains poorly understood. We describe cryo-EM structures of the neck, the neck-capsid and neck-tail junctions, and capsid of theAgrobacteriumphage Milano. The Milano neck 1 protein connects the 12-fold symmetrical neck to a 5-fold vertex of the icosahedral capsid. Comparison of Milano neck 1 homologs leads to four proposed classes, likely evolved from the simplest one in siphophages to more complex ones in myo- and podophages. Milano neck is surrounded by the atypical collar, which covalently crosslinks the tail sheath to neck 1. The Milano capsid is decorated with three types of proteins, a minor capsid protein (mCP) and two linking proteins crosslinking the mCP to the major capsid protein. The extensive network of disulfide bonds within and between neck, collar, capsid and tail provides an exceptional structural stability to Milano.

Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current symptom criteria restrict the diagnosis to recurrent abdominal pain associated with altered bowel habits, but the majority of patients also report non-painful abdominal discomfort, associated psychiatric conditions (anxiety and depression), as well as other visceral and somatic pain-related symptoms. For decades, IBS was considered an intestinal motility disorder, and more recently a gut disorder. However, based on an extensive body of reported information about central, peripheral mechanisms and genetic factors involved in the pathophysiology of IBS symptoms, a comprehensive disease model of brain-gut-microbiome interactions has emerged, which can explain altered bowel habits, chronic abdominal pain, and psychiatric comorbidities. In this review, we will first describe novel insights into several key components of brain-gut microbiome interactions, starting with reported alterations in the gut connectome and enteric nervous system, and a list of distinct functional and structural brain signatures, and comparing them to the proposed brain alterations in anxiety disorders. We will then point out the emerging correlations between the brain networks with the genomic, gastrointestinal, immune, and gut microbiome-related parameters. We will incorporate this new information into a systems-based disease model of IBS. Finally, we will discuss the implications of such a model for the improved understanding of the disorder and the development of more effective treatment approaches in the future.

We introduce and study a class of optimization problems we call replenishment problems with fixed turnover times: a very natural model that has received little attention in the literature. Clients with capacity for storing a certain commodity are located at various places; at each client the commodity depletes within a certain time, the turnover time, which is constant but can vary between locations. Clients should never run empty. The natural feature that makes this problem interesting is that we may schedule a replenishment (well) before a client becomes empty, but then the next replenishment will be due earlier also. This added workload needs to be balanced against the cost of routing vehicles to do the replenishments. In this paper, we focus on the aspect of minimizing routing costs. However, the framework of recurring tasks, in which the next job of a task must be done within a fixed amount of time after the previous one is much more general and gives an adequate model for many practical situations. Note that our problem has an infinite time horizon. However, it can be fully characterized by a compact input, containing only the location of each client and a turnover time. This makes determining its computational complexity highly challenging and indeed it remains essentially unresolved. We study the problem for two objectives:min–avg  minimizes the average tour cost andmin–max  minimizes the maximum tour cost over all days. Formin–max  we derive a logarithmic factor approximation for the problem on general metrics and a 6-approximation for the problem on trees, for which we have a proof of NP-hardness. Formin–avg  we present a logarithmic factor approximation on general metrics, a 2-approximation for trees, and a pseudopolynomial time algorithm for the line. Many intriguing problems remain open.

Irritable bowel syndrome (IBS) is a common disorder of brain-gut interactions characterized by chronic abdominal pain, altered bowel movements, often accompanied by somatic and psychiatric comorbidities. We aimed to test the hypothesis that a baseline phenotype composed of multi-modal neuroimaging and clinical features predicts clinical improvement on the IBS Symptom Severity Scale (IBS-SSS) at 3 and 12 months without any targeted intervention. Female participants (N = 60) were identified as “improvers” (50-point decrease on IBS-SSS from baseline) or “non-improvers.” Data integration analysis using latent components (DIABLO) was applied to a training and test dataset to determine whether a limited number of sets of multiple correlated baseline’omics data types, including brain morphometry, anatomical connectivity, resting-state functional connectivity, and clinical features could accurately predict improver status. The derived predictive models predicted improvement status at 3-months and 12-months with 91% and 83% accuracy, respectively. Across both time points, non-improvers were classified as having greater correlated morphometry, anatomical connectivity and resting-state functional connectivity characteristics within salience and sensorimotor networks associated with greater pain unpleasantness, but lower default mode network integrity and connectivity. This suggests that non-improvers have a greater engagement of attentional systems to perseverate on painful visceral stimuli, predicting IBS exacerbation. The ability of baseline multimodal brain-clinical signatures to predict symptom trajectories may have implications in guiding integrative treatment in the age of precision medicine, such as treatments targeted at changing attentional systems such as mindfulness or cognitive behavioral therapy.