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  • Pena Ewing posted an update 3 days, 11 hours ago

    Microorganisms produce and excrete a versatile array of metabolites with different physico-chemical properties and biological activities. Fluzoparib PARP inhibitor However, the ability of microorganisms to release volatile compounds has only attracted research attention in the past decade. Recent research has revealed that microbial volatiles are chemically very diverse and have important roles in distant interactions and communication. Microbial volatiles can diffuse fast in both gas and water phases, and thus can mediate swift chemical interactions. As well as constitutively emitted volatiles, microorganisms can emit induced volatiles that are triggered by biological interactions or environmental cues. In this Review, we highlight recent discoveries concerning microbial volatile compounds and their roles in intra-kingdom microbial interactions and inter-kingdom interactions with plants and insects. Furthermore, we indicate the potential biotechnological applications of microbial volatiles and discuss challenges and perspectives in this emerging research field.Direct electrical stimulation can modulate the activity of brain networks for the treatment of several neurological and neuropsychiatric disorders and for restoring lost function. However, precise neuromodulation in an individual requires the accurate modelling and prediction of the effects of stimulation on the activity of their large-scale brain networks. Here, we report the development of dynamic input-output models that predict multiregional dynamics of brain networks in response to temporally varying patterns of ongoing microstimulation. In experiments with two awake rhesus macaques, we show that the activities of brain networks are modulated by changes in both stimulation amplitude and frequency, that they exhibit damping and oscillatory response dynamics, and that variabilities in prediction accuracy and in estimated response strength across brain regions can be explained by an at-rest functional connectivity measure computed without stimulation. Input-output models of brain dynamics may enable precise neuromodulation for the treatment of disease and facilitate the investigation of the functional organization of large-scale brain networks.Amputation destroys sensory end organs and does not provide an anatomical interface for cutaneous neuroprosthetic feedback. Here, we report the design and a biomechanical and electrophysiological evaluation of the cutaneous mechanoneural interface consisting of an afferent neural system that comprises a muscle actuator coupled to a natively pedicled skin flap in a cuff-like architecture. Muscle is actuated through electrical stimulation to induce strains or oscillatory vibrations on the skin flap that are proportional to a desired contact duration or contact pressure. In rat hindlimbs, the mechanoneural interface elicited native dermal mechanotransducers to generate at least four levels of graded contact and eight distinct vibratory afferents that were not significantly different from analogous mechanical stimulation of intact skin. The application of different patterns of electrical stimulation independently engaged slowly adapting and rapidly adapting mechanotransducers, and recreated an array of cutaneous sensations. The cutaneous mechanoneural interface can be integrated with current prosthetic technologies for tactile feedback.Intrauterine growth restriction (IUGR) is a common complication of pregnancy and increases the risk of the offspring developing type 2 diabetes mellitus (T2DM) later in life. Alterations in the immune system are implicated in the pathogenesis of IUGR-induced T2DM. The development of the fetal immune system is a delicate balance as it must remain tolerant of maternal antigens whilst also preparing for the post-birth environment. In addition, the fetal immune system is susceptible to an altered intrauterine milieu caused by maternal and placental inflammatory mediators or secondary to nutrient and oxygen deprivation. Pancreatic-resident macrophages populate the pancreas during fetal development, and their phenotype is dynamic through the neonatal period. Furthermore, macrophages in the islets are instrumental in islet development as they influence β-cell proliferation and islet neogenesis. In addition, cytokines, derived from β-cells and macrophages, are important to islet homeostasis in the fetus and adult and, when perturbed, can cause islet dysfunction. Several activated immune pathways have been identified in the islets of people who experienced IUGR, with alternations in the levels of IL-1β and IL-4 as well as changes in TGFβ signalling. Leptin levels are also altered. Immunomodulation has shown therapeutic benefit in T2DM and might be particularly useful in IUGR-induced T2DM.Single-cell multi-omics are powerful means to study cell-to-cell heterogeneity. Here, we present a single-tube, bisulfite-free method for the simultaneous, genome-wide analysis of DNA methylation and genetic variants in single cells epigenomics and genomics of single cells analyzed by restriction (epi-gSCAR). By applying this method, we obtained DNA methylation measurements of up to 506,063 CpGs and up to 1,244,188 single-nucleotide variants from single acute myeloid leukemia-derived cells. We demonstrate that epi-gSCAR generates accurate and reproducible measurements of DNA methylation and allows to differentiate between cell lines based on the DNA methylation and genetic profiles.Cells achieve highly efficient and accurate communication through cellular projections such as neurites and filopodia, yet there is a lack of genetically encoded tools that can selectively manipulate their composition and dynamics. Here, we present a versatile optogenetic toolbox of artificial multi-headed myosin motors that can move bidirectionally within long cellular extensions and allow for the selective transport of GFP-tagged cargo with light. Utilizing these engineered motors, we could transport bulky transmembrane receptors and organelles as well as actin remodellers to control the dynamics of both filopodia and neurites. Using an optimized in vivo imaging scheme, we further demonstrate that, upon limb amputation in axolotls, a complex array of filopodial extensions is formed. We selectively modulated these filopodial extensions and showed that they re-establish a Sonic Hedgehog signalling gradient during regeneration. Considering the ubiquitous existence of actin-based extensions, this toolbox shows the potential to manipulate cellular communication with unprecedented accuracy.

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