Over the past decade it has become clear that various aspects of host physiology, metabolism, and immunity are intimately associated with the microbiome and its interactions with the host. ...Specifically, the gut microbiome composition and function has been shown to play a critical role in the etiology of different intestinal and extra-intestinal diseases. While attempts to identify a common pattern of microbial dysbiosis linked with these diseases have failed, multiple studies show that bacterial communities in the gut are spatially organized and that disrupted spatial organization of the gut microbiome is often a common underlying feature of disease pathogenesis. As a result, focus over the last few years has shifted from analyzing the diversity of gut microbiome by sequencing of the entire microbial community, towards understanding the gut microbiome in spatial context. Defining the composition and spatial heterogeneity of the microbiome is critical to facilitate further understanding of the gut microbiome ecology. Development in single cell genomics approach has advanced our understanding of microbial community structure, however, limitations in approaches exist. Single cell genomics is a very powerful and rapidly growing field, primarily used to identify the genetic composition of microbes. A major challenge is to isolate single cells for genomic analyses. This review summarizes the different approaches to study microbial genomes at single-cell resolution. We will review new techniques for microbial single cell sequencing and summarize how these techniques can be applied broadly to answer many questions related to the microbiome composition and spatial heterogeneity. These methods can be used to fill the gaps in our understanding of microbial communities.
How circuits self-assemble starting from neuronal stem cells is a fundamental question in developmental neurobiology. Here, we addressed how neurons from different stem cell lineages wire with each ...other to form a specific circuit motif. In
larvae, we combined developmental genetics (twin-spot mosaic analysis with a repressible cell marker, multi-color flip out, permanent labeling) with circuit analysis (calcium imaging, connectomics, network science). For many lineages, neuronal progeny are organized into subunits called temporal cohorts. Temporal cohorts are subsets of neurons born within a tight time window that have shared circuit-level function. We find sharp transitions in patterns of input connectivity at temporal cohort boundaries. In addition, we identify a feed-forward circuit that encodes the onset of vibration stimuli. This feed-forward circuit is assembled by preferential connectivity between temporal cohorts from different lineages. Connectivity does not follow the often-cited early-to-early, late-to-late model. Instead, the circuit is formed by sequential addition of temporal cohorts from different lineages, with circuit output neurons born before circuit input neurons. Further, we generate new tools for the fly community. Our data raise the possibility that sequential addition of neurons (with outputs oldest and inputs youngest) could be one fundamental strategy for assembling feed-forward circuits.
...we found that the transcription levels of Maoa and 5-hydroxyindoleacetic acid (5-HIAA), a serotonin degradation product, increased in virally infected or poly (I: A Dutch study including 95 ...patients showed a significant reduction in symptoms with SSRIs; however, this was not a randomised controlled trial.9 A preprint detailing a multicentre retrospective study of 17 933 patients by the National COVID Cohort Collaborative (N3C) found a 26% reduction in the relative risk of PASC in patients who received an SSRI compared to unexposed controls.10 Extensive, double-blind, prospective studies are needed to establish whether SSRIs or other interventions targeting peripheral serotonin signalling could play a role in managing the long-term disease burden of COVID-19. Foundation, the W. W. Smith Charitable Trust, the , The Burroughs Wellcome Fund, and grants from the Abramson Cancer Center (P30-CA- 016420), the PennCHOP microbiome program, Penn Center for Nutritional Science and Medicine, Penn Coronavirus Center, Penn Institute for Immunology, Penn Center for Molecular Studies in Digestive and Liver Diseases (P30-DK- 050306), Penn Center for Precision Medicine, Penn Institute on Aging, The Colton Center, Penn Center of Excellence in Environmental Toxicology (P30-ES 013508), and the Borrelli Family Pilot Grant in Lynch Syndrome.
Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the ...differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.
...different times of the day feature distinct microbial community configurations and microbiota functions. ...in addition to the intrinsic circadian timing systems identified in cyanobacteria, the ...intestinal microbiota undergoes community-scale rhythmicity on the level of metagenome composition 14. ...microbiota diurnal rhythms have been recently suggested to exist in humans, to be disturbed upon clock disruption of the host, and consequently to drive metabolic aberrations 12. ...in addition to morbidity induced by pathogens, microbiome diurnal rhythmicity may also influence noninfectious disease pathogenesis, including common multifactorial diseases that have been linked to disruptions in the circadian clock 14.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • The gut encompasses thousands of small metabolites, collectively termed the metabolome. • The metabolome is contributed by diet, the host, and its microbiome. • Multiple gut metabolites ...are bioactive and signal to the host immune system. • Alterations in gut metabolite profile are associated with innate and adaptive immune aberrations.
Life on Earth is dictated by circadian changes in the environment, caused by the planet's rotation around its own axis. All forms of life have evolved clock systems to adapt their physiology to the ...daily variations in geophysical parameters. The intestinal microbiome serves as a signaling hub in the communication between the host and its environment. We recently discovered that the microbiota undergoes diurnal oscillations in composition and function, and that these oscillations are required for metabolic homeostasis of the host. Here, we highlight these findings from the perspectives of microbial system stability and meta-organismal metabolic health. We also discuss the contribution of nutrition and biotic interventions on diurnal processes of the microbiota and their potential involvement in diseases commonly associated with circadian disruption.
microRNAs of the miR‐290–295 family are selectively expressed at high levels in mouse embryonic stem cells (mESCs) and have established roles in regulating self‐renewal. However, the potential ...influence of these microRNAs on cell fate acquisition during differentiation has been overlooked. Here, we show that miR‐290–295 regulate the propensity of mESCs to acquire specific fates. We generated a new miR‐290–295‐null mESC model, which exhibits increased propensity to generate ectoderm, at the expense of endoderm and mesoderm lineages. We further found that in wild‐type cells, miR‐290–295 repress Pax6 and ectoderm differentiation; accordingly, Pax6 knockdown partially rescues the mESCs differentiation impairment that is caused by loss of miR‐290–295. Thus, in addition to regulating self‐renewal, the large reservoir of miR‐290–295 in undifferentiated mESCs fine‐tunes the expression of master transcriptional factors, such as Pax6, thereby regulating the equilibrium of fate acquisition by mESC descendants. Stem Cells 2013;31:2266–2272