Scaled consensus for second-order multi-agent systems subject to communication noise with stochastic approximation-type protocols.

This work is dedicated to the leaderless/leader-following stochastic scaled consensus issue of second-order stochastic multi-agent systems (SMASs) in a noisy environment. Scaled consensus represents that the ratios among agents asymptotically tend to designated constants rather than the common convergence value. To lessen the influence of communication noise, some stochastic approximation protocols with time-varying gain are designed for our underlying system, where the time-varying gain remove the restriction of nonnegative value. Compared with the existing consensus results with communication noise, the major challenge is that the introduction of time-varying gain results in the inapplicability of Lyapunov-based technique. To cope with it, a state decomposition method is utilized, and a series of sufficient necessary conditions are set up for interacting agents with constant velocity and zero velocity if the topology includes a spanning tree. Furthermore, it is conducted that the consensus and bipartite consensus can be seen as two special cases of our work. Finally, the validity of our results is demonstrated by a simulation example.

DNA polymerase ε harmonizes topological states and R-loops formation to maintain genome integrity in Arabidopsis.

Genome topology is tied to R-loop formation and genome stability. However, the regulatory mechanism remains to be elucidated. By establishing a system to sense the connections between R-loops and genome topology states, we show that inhibiting DNA topoisomerase 1 (TOP1i) triggers the global increase of R-loops (called topoR-loops) and DNA damages, which are exacerbated in the DNA damage repair-compromised mutant atm. A suppressor screen identifies a mutation in POL2A, the catalytic subunit of DNA polymerase ε, rescuing the TOP1i-induced topoR-loop accumulation and genome instability in atm. Importantly we find that a highly conserved junction domain between the exonuclease and polymerase domains in POL2A is required for modulating topoR-loops near DNA replication origins and facilitating faithful DNA replication. Our results suggest that DNA replication acts in concert with genome topological states to fine-tune R-loops and thereby maintain genome integrity, revealing a likely conserved regulatory mechanism of TOP1i resistance in chemotherapy for ATM-deficient cancers.

Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression.

KRAS is the most commonly mutated oncogene in human cancer, and mutant KRAS is responsible for over 90% of pancreatic ductal adenocarcinoma (PDAC), the most lethal cancer. Here, we show that RNA polymerase II-associated factor 1 complex (PAF1C) is specifically required for survival of PDAC but not normal adult pancreatic cells. We show that PAF1C maintains cancer cell genomic stability by restraining overaccumulation of enhancer RNAs (eRNAs) and promoter upstream transcripts (PROMPTs) driven by mutant Kras. Loss of PAF1C leads to cancer-specific lengthening and accumulation of pervasive transcripts on chromatin and concomitant aberrant R-loop formation and DNA damage, which, in turn, trigger cell death. We go on to demonstrate that the global transcriptional hyperactivation driven by Kras signaling during tumorigenesis underlies the specific demand for PAF1C by cancer cells. Our work provides insights into how enhancer transcription hyperactivation causes general transcription factor addiction during tumorigenesis.

Hair shaft miniaturization causes stem cell depletion through mechanosensory signals mediated by a Piezo1-calcium-TNF-α axis.

In aging, androgenic alopecia, and genetic hypotrichosis disorders, hair shaft miniaturization is often associated with hair follicle stem cell (HFSC) loss. However, the mechanism causing this stem cell depletion in vivo remains elusive. Here we show that hair shaft loss or a reduction in diameter shrinks the physical niche size, which results in mechanical compression of HFSCs and their apoptotic loss. Mechanistically, cell compression activates the mechanosensitive channel Piezo1, which triggers calcium influx. This confers tumor necrosis factor alpha (TNF-α) sensitivity in a hair-cycle-dependent manner in otherwise resistant HFSCs and induces ectopic apoptosis. Persistent hair shaft miniaturization during aging and genetic hypotrichosis disorders causes long-term HFSC loss by inducing continuous ectopic apoptosis through Piezo1. Our results identify an unconventional role of the inert hair shaft structure as a functional niche component governing HFSC survival and reveal a mechanosensory axis that regulates physical-niche-atrophy-induced stem cell depletion in vivo.

Anatomically distinct fibroblast subsets determine skin autoimmune patterns.

The skin serves as a physical barrier and an immunological interface that protects the body from the external environment1-3. Aberrant activation of immune cells can induce common skin autoimmune diseases such as vitiligo, which are often characterized by bilateral symmetric lesions in certain anatomic regions of the body4-6. Understanding what orchestrates the activities of cutaneous immune cells at an organ level is necessary for the treatment of autoimmune diseases. Here we identify subsets of dermal fibroblasts that are responsible for driving patterned autoimmune activity, by using a robust mouse model of vitiligo that is based on the activation of endogenous auto-reactive CD8+ T cells that target epidermal melanocytes. Using a combination of single-cell analysis of skin samples from patients with vitiligo, cell-type-specific genetic knockouts and engraftment experiments, we find that among multiple interferon-γ (IFNγ)-responsive cell types in vitiligo-affected skin, dermal fibroblasts are uniquely required to recruit and activate CD8+ cytotoxic T cells through secreted chemokines. Anatomically distinct human dermal fibroblasts exhibit intrinsic differences in the expression of chemokines in response to IFNγ. In mouse models of vitiligo, regional IFNγ-resistant fibroblasts determine the autoimmune pattern of depigmentation in the skin. Our study identifies anatomically distinct fibroblasts with permissive or repressive IFNγ responses as the key determinant of body-level patterns of lesions in vitiligo, and highlights mesenchymal subpopulations as therapeutic targets for treating autoimmune diseases.

Crosstalk Analysis and Performance Evaluation for Torus-Based Optical Networks-on-Chip Using WDM.

Insertion loss and crosstalk noise will influence network performance severely, especially in optical networks-on-chip (ONoCs) when wavelength division multiplexing (WDM) technology is employed. In this paper, an insertion loss and crosstalk analysis model for WDM-based torus ONoCs is proposed to evaluate the network performance. To demonstrate the feasibility of the proposed methods, numerical simulations of the WDM-based torus ONoCs with optimized crossbar and crux optical routers are presented, and the worst-case link and network scalability are also revealed. The numerical simulation results demonstrate that the scale of the WDM-based torus ONoCs with the crux optical router can reach 6 × 5 or 5 × 6 before the noise power exceeds the signal power, and the network scale is 5 × 4 in the worst case when the optimized crossbar router is employed. Additionally, the simulated results of OptiSystem reveal that WDM-based torus ONoCs have better signal transmission quality when using the crux optical router, which is consistent with previous numerical simulations. Furthermore, compared with the single-wavelength network, WDM-based ONoCs have a great performance improvement in end-to-end (ETE) delay and throughput according to the simulated results of OPNET. The proposed network analysis method provides a reliable theoretical basis and technical support for the design and performance optimization of ONoCs.

Serum Cholesterol-Lowering Activity of ß-Sitosterol Laurate Is Attributed to the Reduction of Both Cholesterol Absorption and Bile Acids Reabsorption in Hamsters.

The research was performed to delineate how ß-sitosterol laurate (ß-SLE) consumption influenced serum and hepatic lipids. The results showed that 220 mg/5 mL oil/kg body weight of ß-SLE robustly reduced serum total triglyceride and cholesterol levels and the epididymal adipocyte size, and efficiently protected hepatic polyunsaturated fatty acids against lipid peroxidation through superoxide dismutase and glutathione transferase activity enhancement and malondialdehyde level reduction. Based on the changes of fecal cholesterol contents, fecal and hepatic bile acid (BAs) levels, and related protein expression, it was concluded that the mechanisms for lowering serum cholesterol by ß-SLE involved (i) the enhanced excretion of fecal cholesterol via down-regulation of intestinal Niemann-Pick C1-like 1 protein; (ii) the increased conversion from cholesterol to primary BAs via up-regulation of cholesterol-7α-hydroxylase and sterol 27-hydroxylase, which was induced by the reduced BAs reabsorption through up-regulating ileal apical sodium-dependent bile acid transporter and ileal bile acid-binding protein.

The complete chloroplast genome of Papaver setigerum and comparative analyses in Papaveraceae.

Papaver setigerum is an annual herb that is closely related to the opium poppy, P. somniferum. Genetic resources for P. setigerum are scarce. In the present study, we assembled the complete chloroplast (cp) genome of P. setigerum based on genome skimming data, and we conducted comparative cp genome analyses to study the evolutionary pattern in Papaveraceae. The cp genome of P. setigerum is 152,862 bp in length with a typical quadripartite structure. Comparative analyses revealed no gene rearrangement in the Papaveraceae family, although differences were evident in genome size, gene losses, as well as inverted repeats (IR) region expansion and contraction. The rps15 gene has been lost from the genomes of Meconopsis racemosa, Coreanomecon hylomeconoides, P. orientale, P. somniferum, and P. setigerum, and the ycf15 gene is found only in C. hylomeconoides. Moreover, 13 cpDNA markers, including psbA-trnH, rps16-trnQ, trnS-trnG, trnC-petN, trnE-trnT, trnL-trnF, trnF-ndhJ, petA-psbJ, ndhF-rpl32, rpl32-trnL, ccsA-ndhD, ndhE-ndhG, and rps15-ycf1, were identified with relatively high levels of variation within Papaver, which will be useful for species identification in this genus. Among those markers, psbA-trnH is the best one to distinguish P. somniferum and P. setigerum.

Consumption of Interesterified Medium- and Long-Chain Triacylglycerols Improves Lipid Metabolism and Reduces Inflammation in High-Fat Diet-Induced Obese Rats.

Medium- and long-chain triacylglycerols (MLCTs) were synthesized from rapeseed oil (RO), one kind of commonly used edible long-chain triacylglycerols (TGs), and then delivered to high-fat diet (HFD)-induced obese rats. Compared with RO, MLCT consumption exhibited more potent effects on reducing body and tissue weight gains, plasma TG, and total cholesterol (TC) levels and on improving hepatic TG, TC, fatty acid synthase, acetyl-CoA carboxylase, and lipoprteinlipase contents. Meanwhile, lower amounts of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1, and endotoxin in plasma, lower levels of interleukin-6 and TNF-α, and higher levels of interleukin-10 in both livers and white adipose tissues were detected in MLCT-fed rats. MLCT intake also remarkably suppressed the size of adipocytes and the number of macrophages. In conclusion, our study suggested that the interesterified MLCT was more efficacious in improving the lipid metabolism and inflammation in HFD-induced obese rats than RO.

Plastome Evolution in Saxifragaceae and Multiple Plastid Capture Events Involving Heuchera and Tiarella.

Saxifragaceae, a family of over 600 species and approximately 30 genera of herbaceous perennials, is well-known for intergeneric hybridization. Of the main lineages in this family, the Heuchera group represents a valuable model for the analysis of plastid capture and its impact on phylogeny reconstruction. In this study, we investigated plastome evolution across the family, reconstructed the phylogeny of the Heuchera group and examined putative plastid capture between Heuchera and Tiarella. Seven species (11 individuals) representing Tiarella, as well as Mitella and Heuchera, were selected for genome skimming. We assembled the plastomes, and then compared these to six others published for Saxifragaceae; the plastomes were found to be highly similar in overall size, structure, gene order and content. Moreover, ycf15 was lost due to pseudogenization and rpl2 lost its only intron for all the analyzed plastomes. Comparative plastome analysis revealed that size variations of the plastomes are purely ascribed to the length differences of LSC, SSC, and IRs regions. Using nuclear ITS + ETS and the complete plastome, we fully resolved the species relationships of Tiarella, finding that the genus is monophyletic and the Asian species is most closely related to the western North American species. However, the position of the Heuchera species was highly incongruent between nuclear and plastid data. Comparisons of nuclear and plastid phylogenies revealed that multiple plastid capture events have occurred between Heuchera and Tiarella, through putative ancient hybridization. Moreover, we developed numerous molecular markers for Tiarella (e.g., plastid hotspot and polymorphic nuclear SSRs), which will be useful for future studies on the population genetics and phylogeography of this disjunct genus.

Complete chloroplast genome sequence and phylogenetic analysis of Erysimum cheiranthoides.

Erysimum cheiranthoides is commonly known as treacle-mustard or wormseed wallflower with value for reducing high temperature and inducing diuresis. Here, we characterized the complete chloroplast (cp) genome of E. cheiranthoides using genome skimming sequencing. The circular complete cp genome is 154,611 bp in length, containing a large single-copy (LSC) region of 83,809 bp, two copies of IR (26,475 bp each) regions, and a small single-copy (SSC) region of 17,852 bp. It comprises 113 unique genes, including 79 different protein-coding genes, 30 tRNA genes, and 4 rRNA genes with 19 duplicated genes in the IR regions. Phylogenetic analysis suggests that E. cheiranthoides is sister to Olimarabidopsis pumila with full support value in Brassicaceae.

Complete plastome sequence of Osmanthus armatus and phylogenetic implications in Oleaceae.

Osmanthus armatus (Oleaceae) is mainly distributed in the southwest of China and also planted in arboretums as an ornamental plant. In the present study, the plastome of O. armatus was reconstructed using genome skimming sequencing, and the phylogeny analysis was inferred based on whole plastome data. The plastome of O. armatus is 155,259 bp in length, comprising two copies of inverted regions (IR, 25,680 bp) separated by the large single copy (LSC, 86,534 bp) and small single copy (SSC, 17,365 bp) regions. The genome encodes 114 unique genes, including 80 different protein-coding genes, 30 tRNA genes, and four rRNA genes, with 20 duplicated genes in the IR regions. Phylogenetic analysis suggests that the representative species from Osmanthus is monophyletic, and O. armatus is sister to O. fragrans within this genus.