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Scavenger endothelial cells alleviate tissue damage by engulfing toxic molecules derived from hemolysis

Hemolysis induces tissue damage by releasing cellular contents into the plasma. It is widely accepted that hemolysis-derived toxic molecules are cleared by macrophages or metabolized in hepatocytes. In zebrafish, we found that scavenger endothelial cells (SECs), a specialized endothelium with remarkable endocytosis capability, engulf both macromolecular hemoglobin (Hb) and small molecular unconjugated bilirubin (UCB), two primary toxic byproducts of hemolysis. These engulfment processes are mediated by the scavenger receptor Stab2. To demonstrate the protective function of SECs during hemolysis, we employed a zebrafish model of erythropoietic porphyria, characterized by excessive protoporphyrin IX (PPIX) accumulation due to ferrochelatase mutation, leading to light-sensitive hemolysis and larva death. We found that SECs facilitate the clearance of excess PPIX via Stab2, thereby mitigating PPIX-induced larval mortality. In addition, mouse SECs possess a conserved capability of scavenging Hb/UCB/PPIX. In conclusion, our study identifies SECs as a detoxification system during physiological and pathological hemolysis, shedding light on their protective role against hemolysis-induced damage.

Genome-wide SNP discovery and phylogeography of sandlances (Ammodytes japonicus and Ammodytes heian) in the Northwest pacific by MIG-Seq with evolutionary implications

Retraction for Hiramatsu et al., DAT (deacylating autotransporter toxin) from <i>Bordetella parapertussis</i> demyristoylates Gα _i GTPases and contributes to cough

Functionalization of magnetic nanoparticles with 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid as an efficient adsorbent for the Gefitinib removal from water

Multi-robot hierarchical safe reinforcement learning autonomous decision-making strategy based on uniformly ultimate boundedness constraints

Maple samaras recover autorotation following raindrop collisions

Samaras are known for their elegant and robust autorotation, a resilience that persists in the adverse conditions imposed by high-speed raindrops. Like flying insects, samaras descending from tall trees are likely to be struck by raindrops in an intense storm. In this study, we detail the collision dynamics for impact regions across the samara body and the drop-shedding mechanisms that samaras exhibit to return to autorotation. Impacts across the samara body can pitch the samara up to 60 degrees and, in some cases, induce spanwise roll. Raindrops may shatter or remain intact upon impact, pushing the undamaged samara downward before autorotation is recovered. Drops that strike near the wingtip elicit the greatest recovery distance, while impacts onto the nutlet mass are the least disruptive to the samara and most likely to cause the drop to induce fragmentation. Faster drops allow for quicker drop shedding and a subsequent rapid return to autorotation in less than 50 ms. Our results indicate that samaras are robust to raindrop impacts and consistently recover autorotation, resulting in a minor reduction in dispersal distance. To recover, the entire drop is shed from the spinning samara over a time closely tied to the shedding mode and ensuing drop rejection forces.

A reappraisal of cell cycle phase enrichment in synchronized estrogen receptor-positive cell models derived from breast adenocarcinomas

Bacterial species with different nanocolony morphologies have distinct flow-dependent colonization behaviors

Fluid flows are dominant features of many bacterial environments, and flow can often impact bacterial behaviors in unexpected ways. For example, the most common type of cardiovascular infection is heart valve colonization by gram-positive bacteria like Staphylococcus aureus and Enterococcus faecalis (endocarditis). This behavior is counterintuitive because heart valves experience high shear rates that would naively be expected to reduce colonization. To determine whether these bacteria preferentially colonize higher shear rate environments, we developed a microfluidic system to quantify the effect of flow conditions on the colonization of S. aureus and E. faecalis . We find that the preferential colonization in high flow of both species is not specific to heart valves and can be found in simple configurations lacking any host factors. This behavior enables bacteria that are outcompeted in low flow to dominate in high flow. Surprisingly, experimental and computational studies reveal that the two species achieve this behavior via distinct mechanisms. S. aureus grows in cell clusters and produces a dispersal signal whose transport is affected by shear rate. Meanwhile, E. faecalis grows in linear chains whose mechanical properties result in less dispersal in the presence of higher shear force. In addition to establishing two divergent mechanisms by which these bacteria each preferentially colonize high-flow environments, our findings highlight the importance of understanding bacterial behaviors at the level of collective interactions among cells. These results suggest that distinct multicellular nanocolony morphologies have previously unappreciated costs and benefits in different environments, like those introduced by fluid flow.

The influence of cyclothymic and hyperthymic affective temperaments on glycemic control in patients with type 2 diabetes

Abstract Affective temperaments are inherited parts of personality determining mood and activity, affecting the management of somatic conditions. We aimed to investigate the association between affective temperaments, depressive symptoms, and self-care (physical activity, smoking, alcohol consumption), and their effect on glycemic control, among patients with type 2 diabetes (T2DM) in general practice, in a cross-sectional study enrolling 338 consecutive patients from six primary care practices in Hungary. A self-administered questionnaire (history, anthropometric, socioeconomic, laboratory parameters), the Beck Depression Inventory (BDI), the Hamilton Anxiety Scale, and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire were used. Cyclothymic affective temperament determined HbA1c levels in regression analysis (p = 0.002), and the BDI score (p = 0.048). In causal mediation analyses, cyclothymic affective temperament was directly associated with higher HbA1c (p = 0.008). Hyperthymic affective temperament was indirectly associated with lower HbA1c, mediated by BDI (p = 0.034). Depressive, anxious, and irritable affective temperaments, and lifestyle factors were not associated with HbA1c neither in regression nor in mediation analysis as direct or mediating factors. Among primary care patients with T2DM, cyclothymic temperament correlates with worse glycemic control, independently of depressive symptoms. Hyperthymic temperament reduces depressive symptoms, thereby improving glycemic control. Identifying affective temperaments may improve diabetes care.

Wholesale flat subduction of the Indian slab and northward mantle convective flow: Plateau growth and driving force of the India–Asia collision

The tectonic evolution of the Tibetan Plateau has been influenced by continental collision and postcollisional convergence of Indian and Eurasian plates, both of which have undoubtedly imposed their imprints on the lithosphere and upper-mantle structures beneath the collision zone. However, the mode by which the Indian Plate has subducted beneath Tibet, and its driving forces, have been highly uncertain. Here, we present seismic evidence from a full-waveform tomographic model that reveals flat subduction of the Indian Plate beneath nearly the entire plateau at ∼ 300 km depth, implying that the slab may have transitioned to positive/neutral buoyancy and is no longer capable of supporting steep-angle deep subduction. The horizontal distance over which the flat slab slides northward increases from west (where it collides with the Tarim lithospheric keel) to east (where it has resided approximately north of the Songpan-Ganzi Fold Belt beyond the Qiangtang Block). The Asian lithosphere is subducting beneath northeastern Tibet without colliding with the Indian slab. The low-velocity zone, with a thickness of 50 to 110 km, sandwiched between the Tibetan crust and Indian slab, is positively correlated with the high-elevation, low-relief topography of Tibet, suggesting partial melting of the uppermost mantle that has facilitated the growth and flatness of the plateau by adding buoyant material to its base. We propose that deep mantle convective currents, traced to the Réunion plume and imaged as large-scale low-velocity anomalies from the upper mantle under the Indian Plate downward toward the uppermost lower mantle under the Baikal-Mongolia Plateau, are the primary force driving the ongoing India–Asia postcollisional convergence.

Impact of internet use on pro-environmental behaviour mediated by environmental concern

Seesaw protein: Design of a protein that adopts interconvertible alternative functional conformations and its dynamics

According to classical Anfinsen’s dogma, a protein folds into a single unique conformation with minimal Gibbs energy under physiological conditions. However, certain proteins may fold into two or more conformations from single amino acid sequences. Here, we designed a protein that adopts interconvertible alternative functional conformations, termed “seesaw” protein (SSP). An SSP was engineered by fusing GFP lacking the C-terminal β-strand and dihydrofolate reductase (DHFR) lacking the N-terminal β-strand with an overlapping linker, which can be competitively incorporated into either the GFP or the DHFR moiety. In vivo and biochemical analyses, including atomic force microscopy (AFM) imaging, demonstrated that the SSP adopts two alternative conformations, which can be biased by point mutations and ligand binding. The drastic conformational change upon the ligand binding was directly visualized by high-speed AFM. Furthermore, the balance of the seesaw can be reversibly changed depending on buffer conditions. In summary, our design strategy for SSP provides a unique direction for creating artificial proteins with on–off behaviors.

Experimental investigation on flexural fatigue performance of recycled aggregate concrete hybrid with basalt-polyacrylonitrile fiber

Photostationary state assumption seriously underestimates NO _x emissions near large point sources at 10 to 60 m pixel resolution

A novel blockchain-based clustering model for linked open data storage and retrieval

Identification of FSH-regulated and estrous stage–specific transcriptional networks in mouse ovaries

Follicle-stimulating hormone (FSH) acts by binding to FSHRs expressed on ovarian granulosa cells and produces estradiol. FSH is essential for female fertility because mice lacking FSH ( Fshb KO ) are anestrous and infertile. Although several in vitro cell culture and ex vivo approaches combined with pharmacological hormone treatment were used to identify FSH-regulated genes, how FSH orchestrates ovarian gene networks in vivo has not been investigated. Whether FSH-regulated genes display estrous stage–specific expression changes has also not been studied. Here, we functionally rescued Fshb null mice with a gonadotrope-targeted HFSHB transgene and performed RNA-Seq analysis on ovarian RNAs obtained from FSH-intact ( WT ), FSH-deficient ( Fshb KO ), and FSH-rescue ( HFSHB + rescue) mice. By comparing WT vs. Fshb KO and Fshb KO vs. HFSHB + rescue ovarian gene expression datasets, we identified FSH-responsive genes in vivo. Cross interrogation of these datasets further allowed us to identify several transcription factors (TFs) and RNA-binding proteins specific to FSH-regulated genes. In an independent set of experiments, we performed RNA-Seq analysis on ovarian RNAs from mice in diestrous (DE), proestrous (PE), and estrous (E) and identified estrous stage–specific ovarian gene expression patterns. Interestingly, many of the FSH-regulated TFs themselves were estrous-stage specifically expressed. We found that ESR2 and GATA6, two known FSH-responsive TFs, and their target genes are reciprocally regulated with distinct patterns of expression in estrous stages. Together, our in vivo models and RNA-Seq analyses identify FSH-regulated ovarian genes in specific estrous stages that are under transcriptional and posttranscriptional control.

Sex Chromosomes and Sex Hormones: Dissecting the Forces That Differentiate Female and Male Hearts

The heart is a highly sex-biased organ, as sex shapes innumerable aspects of heart health and disease. Sex chromosomes and sex hormones —testosterone, progesterone, and estrogen— establish and perpetuate the division between male and female myocardium. Of these differentiating factors, the insulating effects of estrogen have been rigorously interrogated and reviewed, whereas the influence of sex chromosomes, testosterone, and progesterone remains in dispute or ill-defined. Here, we synthesize growing evidence that sex chromosomes and sex hormones substantially bias heart form, function, and dysfunction in a context-dependent fashion. The discrete protective functions ascribed to each of the 3 estrogen receptors are also enumerated. Subsequently, we overview obstacles that have historically discouraged the inclusion of female subjects in basic science such as the impact of the female estrus cycle and reproductive senescence on data reliability and reproducibility. Furthermore, we weigh the utility of several common strategies to intercept and rescue sex-specific protection. Last, we warn of common compounds in animal chow and cell culture that interfere with estrogen signaling. In sum, we survey the controversies and challenges that stem from sex-inclusive cardiovascular research, comparing the possible causes of cardiac sex bias, elucidating sex chromosome or hormone-dependent processes in the heart, describing common lapses that imperil female and male cell and animal work, and illuminating facets of the female heart yet unexplored or still uncertain.

Massive Dirac magnons in the three-dimensional honeycomb magnetic oxide $$\hbox {FeTiO}_3$$

In the shadow of antibiotics

Addressing Cardiovascular Health Inequities in Indigenous Women: Insights from Australia and Global Perspectives