Data from large‐scale debris‐flow experiments are combined with modeling of particle‐size segregation to explain the formation of lateral levees enriched in coarse grains. The experimental flows ...consisted of 10 m3 of water‐saturated sand and gravel, which traveled ∼80 m down a steeply inclined flume before forming an elongated leveed deposit 10 m long on a nearly horizontal runout surface. We measured the surface velocity field and observed the sequence of deposition by seeding tracers onto the flow surface and tracking them in video footage. Levees formed by progressive downslope accretion approximately 3.5 m behind the flow front, which advanced steadily at ∼2 m s−1 during most of the runout. Segregation was measured by placing ∼600 coarse tracer pebbles on the bed, which, when entrained into the flow, segregated upwards at ∼6–7.5 cm s−1. When excavated from the deposit these were distributed in a horseshoe‐shaped pattern that became increasingly elevated closer to the deposit termination. Although there was clear evidence for inverse grading during the flow, transect sampling revealed that the resulting leveed deposit was strongly graded laterally, with only weak vertical grading. We construct an empirical, three‐dimensional velocity field resembling the experimental observations, and use this with a particle‐size segregation model to predict the segregation and transport of material through the flow. We infer that coarse material segregates to the flow surface and is transported to the flow front by shear. Within the flow head, coarse material is overridden, then recirculates in spiral trajectories due to size‐segregation, before being advected to the flow edges and deposited to form coarse‐particle‐enriched levees.
Key Points
Coarse particle levees form in debris flows by progressive streamwise accretion
Coarse grains are transported to the flow front, then laterally into the levees
Grain size segregation profoundly affects flow dynamics and deposit structure
The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse ...striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed ten differentiated, distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSNs) that have specific markers and that overexpress genes linked to cognitive disorders and addiction. We also describe continuous cellular identities, which increase heterogeneity within discrete cell types. Finally, we identified cell type-specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns. Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states.
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•Transcriptomes of 1,208 single striatal cells•Description of previously unknown medium spiny neuron subtypes•Discrete cell types that exist in a continuous spectrum of transcriptional states•Neurons that have the largest transcriptome and more complex splicing patterns
The striatum, the gateway to basal ganglia circuitry, is critical for motor functions. However, its cell types are incompletely characterized. Gokce et al. reveal the diversity of striatal cells using scRNA-seq. They also describe continuous expression gradients within all MSN subtypes and astrocytes that may be fundamental to transcriptional diversity.
Particle-size segregation commonly occurs in both wet and dry granular free-surface flows through the combined processes of kinetic sieving and squeeze expulsion. As the granular material is sheared ...downslope, the particle matrix dilates slightly and small grains tend to percolate down through the gaps, because they are more likely than the large grains to fit into the available space. Larger particles are then levered upwards in order to maintain an almost uniform solids volume fraction through the depth. Recent experimental observations suggest that a single small particle can percolate downwards through a matrix of large particles faster than a large particle can be levered upwards through a matrix of fines. In this paper, this effect is modelled by using a flux function that is asymmetric about its maximum point, differing from the symmetric quadratic form used in recent models of particle-size segregation. For illustration, a cubic flux function is examined in this paper, which can be either a convex or a non-convex function of the small-particle concentration. The method of characteristics is used to derive exact steady-state solutions for non-diffuse segregation in two dimensions, with an inflow concentration that is (i) homogeneous and (ii) normally graded, with small particles above the large. As well as generating shocks and expansion fans, the new asymmetric flux function generates semi-shocks, which have characteristics intersecting with the shock just from one side. In the absence of diffusive remixing, these can significantly enhance the distance over which complete segregation occurs.
The aim of this meta‐analysis was to quantify the effects of high‐intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or ...continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference SMD = −0.49, confidence intervals CIs −0.87 to −0.12, P = 0.009; CT: SMD = −0.35, −0.68 to −0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (−0.36 to −0.03, P = 0.021) and body weight decreased by 1.3 kg (−1.9 to −0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (−0.92 mmol L⁻¹, −1.22 to −0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta‐analysis are required to confirm these results.
The cumulative activity of all of the body's cells, with their myriad interactions, life histories, and environmental experiences, gives rise to a condition that is distinctly human and specific to ...each individual. It is an enduring goal to catalog our human cell types, to understand how they develop, how they vary between individuals, and how they fail in disease. Single-cell genomics has revolutionized this endeavor because sequencing-based methods provide a means to quantitatively annotate cell states on the basis of high-information content and high-throughput measurements. Together with advances in stem cell biology and gene editing, we are in the midst of a fascinating journey to understand the cellular phenotypes that compose human bodies and how the human genome is used to build and maintain each cell. Here, we will review recent advances into how single-cell genomics is being used to develop personalized phenotyping strategies that cross subcellular, cellular, and tissue scales to link our genome to our cumulative cellular phenotypes.
Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. ...Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.
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•A strong correlation between epithelial adhesion and Th17 induction by SFB and EHEC•Twenty Th17-inducing strains isolated from human feces show epithelial-adhesive property•Bacterial adhesion elicits a Th17-inducing gene-expression program in epithelium
The adhesion of specific members of the gut microbiome to intestinal epithelial cells is found to be essential for the induction of Th17 cells, thus highlighting location as an additional layer of regulation for the adaptive immune system.
Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. However, the molecular understanding of ...blastema formation had previously been hampered by the inability to identify and isolate blastema precursor cells in the adult tissue. We have used a combination of Cre-loxP reporter lineage tracking and single-cell messenger RNA sequencing (scRNA-seq) to molecularly track mature connective tissue (CT) cell heterogeneity and its transition to a limb blastema state. We have uncovered a multiphasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that recapitulates an embryonic limb bud-like phenotype including multipotency within the CT lineage. Together, our data illuminate molecular and cellular reprogramming during complex organ regeneration in a vertebrate.
Ectopic expression of defined transcription factors can force direct cell-fate conversion from one lineage to another in the absence of cell division. Several transcription factor cocktails have ...enabled successful reprogramming of various somatic cell types into induced neurons (iNs) of distinct neurotransmitter phenotype. However, the nature of the intermediate states that drive the reprogramming trajectory toward distinct iN types is largely unknown. Here we show that successful direct reprogramming of adult human brain pericytes into functional iNs by Ascl1 and Sox2 encompasses transient activation of a neural stem cell-like gene expression program that precedes bifurcation into distinct neuronal lineages. During this transient state, key signaling components relevant for neural induction and neural stem cell maintenance are regulated by and functionally contribute to iN reprogramming and maturation. Thus, Ascl1- and Sox2-mediated reprogramming into a broad spectrum of iN types involves the unfolding of a developmental program via neural stem cell-like intermediates.
To understand human development and disease, as well as to regenerate damaged tissues, scientists are working to engineer certain cell types in vitro and to create 3D microenvironments in which cells ...behave physiologically. Single-cell genomics (SCG) technologies are being applied to primary human organs and to engineered cells and tissues to generate atlases of cell diversity in these systems at unparalleled resolution. Moving beyond atlases, SCG methods are powerful tools for gaining insight into the engineering and disease process. Here we discuss how scientists can use single-cell sequencing to optimize human cell and tissue engineering by measuring precision, detecting inefficiencies, and assessing accuracy. We also provide a perspective on how emerging SCG methods can be used to reverse-engineer human cells and tissues and unravel disease mechanisms.
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