Cross-tissue single-cell transcriptomics reveals organizing principles of fibroblasts in health and disease

Fibroblasts are non-hematopoietic structural cells that define the architecture of organs, support the homeostasis of tissue-resident cells and play key roles in fibrosis, cancer, autoimmunity and wound healing. Recent studies have described fibroblast heterogeneity within individual tissues. However, the field lacks a definition of fibroblasts at single-cell resolution across tissues in healthy and diseased organs. Here, we integrated single-cell RNA transcriptomic data from ~150,000 fibroblast cells derived from 16 steady- and 11 perturbed-state mouse organs into fibroblast atlases. These data revealed two universal fibroblast cell subtypes, marked by expression of Pi16 or Col15a1, in all tissues; it also revealed discrete subsets of five specialized fibroblast subtypes in steady-state tissues and three activated fibroblast subtypes in perturbed or diseased tissues. These subsets were transcriptionally shaped by microenvironmental context rather than tissue-type alone. Inference of fibroblast lineage structure from the murine steady-state and perturbed-state fibroblast atlases suggested that specialized and activated subtypes are developmentally related to universal tissue-resident fibroblasts. Analysis of human samples revealed that fibroblast subtypes found in mice are conserved between species, including universal fibroblasts and activated phenotypes associated with pathogenicity in human cancer, fibrosis, arthritis and inflammation. In sum, a cross-species and pan-tissue approach to transcriptomics at single-cell resolution enabled us to define the organizing principles of the fibroblast lineage in health and disease.

Global pleiotropic effects in adaptively evolved Escherichia coli lacking CRP reveal molecular mechanisms that define growth physiology

Evolution entails the orchestration of cellular resources together with mutations to achieve fitter phenotypes. Here, we determined the system-wide pleiotropic effects that redress the significant perturbations caused by the deletion of global transcriptional regulator CRP in Escherichia coli when evolved in the presence of glucose. We elucidated that absence of CRP results in alterations in key metabolic pathways instrumental for the precise functioning of protein biosynthesis machinery that subsequently corroborated with intracellular metabolite profiles. Apart from acquiring mutations in the promoter of glucose transporter ptsG, the evolved populations recovered the metabolic pathways to their pre-perturbed state with amelioration of protein biosynthesis machinery coupled with fine-tuned proteome re-allocation that enabled growth recovery. However, ineffective utilization of carbon towards biomass as perceived from ATP maintenance flux and costly amino acid accumulations poses a limitation. Overall, we comprehensively illustrate the genetic and metabolic adjustments underlying adaptive evolvability, fundamental for understanding the growth physiology.

Interpretation of grace system data for solving geodynamic monitoring tasks

The study is devoted to the analysis of the features of the change in the EWH (Equivalent Water Height) parameter over the geoid by satellite measurements of the GRACE space system in various regions of the World Ocean. A GRACE satellite data archive has been created. The perturbed state of the geomedium is interpreted using digital maps of the spatial distribution of the EWH parameter based on the histogram approach and correlation analysis.

Reduction approach to second order perturbed state-dependent sweeping process

In this paper, we present a new approach to solving second order nonconvex perturbed sweeping process in finite dimensional setting. It consists in a reduction of the problem to a first order one without use of the standard methods of fixed point theory. The perturbation, that is the external force applied on the system is not necessary with bounded values.

Quantum Complexity and Chaos in Young Black Holes

We argue that the problem of calculating retention time scales in young black holes is a problem of relative state complexity. In particular, we suggest that Alice’s ability to estimate the time scale for a perturbed black hole to release the extra n qubits comes down to her decoding the Hilbert space of the Hawking radiation. We then demonstrate the decoding task Alice faces is very difficult, and in order to calculate the relative state complexity she would either need to act with an exponentially complex unitary operator or apply an extremely fine-tuned future precursor operator to the perturbed state in S U ( 2 K ) .

Effect of Gravity Modulation on Single Component Convection in a Couple Stress Fluid with Maxwell-Cattaneo Law

The outset of convection in a thin layer of couple stress fluid is analyzed using the linear stability analysis when the fluid is heated from below. In order to assimilate the inertial effects Maxwell-Cattaneo law is used in lieu of the classical Fourier's heat conduction law. The normal mode analysis is used to arrive at the eigenvalues of the perturbed state and a regular perturbation method to find the analytical solutions. The effect of Cattaneo number, couple stress parameter and Prandtl number is discussed and it is concluded that gravity modulation can delay or advance the onset of convection.

Analysis of the efficiency of earthquake prediction based on the anomalous behavior of ionospheric parameters on the eve of earthquakes in the Kamchatka region

A method is presented for short-term prediction of strong earthquakes, in which the precursors are considered the excess of current values of foF2 critical frequency of the ionospheric F2 layer over the median values in periods of perturbed state of the magnetosphere, the appearance of ionospheric disturbances: K-layer, Es-spread F-spread, the stratification of the F2 layer, Es is the r type. As predicted earthquakes were considered earthquakes with magnitudes M ≥ 5:0. Assessment of the effectiveness of the forecast was carried out in the spring and autumn periods for 2013–2017 according to the methods of A. A. Gusev and G. M. Molchan. It is shown that the method under consideration has the best prognostic efficiency for seismic events with M ≥ 6:5 magnitude.