Notes

Salinomycin sparks prostate cancer mobile or portable apoptosis by causing oxidative and endoplasmic reticulum stress by means of controlling Nrf2 signaling.
Erbium-doped fiber amplifiers revolutionized long-haul optical communications and laser technology. Erbium ions could provide a basis for efficient optical amplification in photonic integrated circuits but their use remains impractical as a result of insufficient output power. We demonstrate a photonic integrated circuit-based erbium amplifier reaching 145 milliwatts of output power and more than 30 decibels of small-signal gain-on par with commercial fiber amplifiers and surpassing state-of-the-art III-V heterogeneously integrated semiconductor amplifiers. We apply ion implantation to ultralow-loss silicon nitride (Si3N4) photonic integrated circuits, which are able to increase the soliton microcomb output power by 100 times, achieving power requirements for low-noise photonic microwave generation and wavelength-division multiplexing optical communications. see more Endowing Si3N4 photonic integrated circuits with gain enables the miniaturization of various fiber-based devices such as high-pulse-energy femtosecond mode-locked lasers.Researchers showcase a 3D-printed millirobot made out of multifunctional metamaterials.A platform to enable precise modifications of insulin could improve drug functionality.A miniature amplifier with high power is realized with an ion-doped waveguide.Scientists strive to unravel what is driving disabling symptoms.Use of D NA markers in research that are used in law enforcement risks undermining public trust and participation.Effective tissue repair after myocardial infarction entails a vigorous angiogenic response, guided by incompletely defined immune cell-endothelial cell interactions. We identify the monocyte- and macrophage-derived cytokine METRNL (meteorin-like) as a driver of postinfarction angiogenesis and high-affinity ligand for the stem cell factor receptor KIT (KIT receptor tyrosine kinase). METRNL mediated angiogenic effects in cultured human endothelial cells through KIT-dependent signaling pathways. In a mouse model of myocardial infarction, METRNL promoted infarct repair by selectively expanding the KIT-expressing endothelial cell population in the infarct border zone. Metrnl-deficient mice failed to mount this KIT-dependent angiogenic response and developed severe postinfarction heart failure. Our data establish METRNL as a KIT receptor ligand in the context of ischemic tissue repair.The elongation of eukaryotic selenoproteins relies on a poorly understood process of interpreting in-frame UGA stop codons as selenocysteine (Sec). We used cryo-electron microscopy to visualize Sec UGA recoding in mammals. A complex between the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and 40S ribosomal subunit enables Sec-specific elongation factor eEFSec to deliver Sec. eEFSec and SBP2 do not interact directly but rather deploy their carboxyl-terminal domains to engage with the opposite ends of the SECIS. By using its Lys-rich and carboxyl-terminal segments, the ribosomal protein eS31 simultaneously interacts with Sec-specific transfer RNA (tRNASec) and SBP2, which further stabilizes the assembly. eEFSec is indiscriminate toward l-serine and facilitates its misincorporation at Sec UGA codons. Our results support a fundamentally distinct mechanism of Sec UGA recoding in eukaryotes from that in bacteria.Increased government scrutiny of cross-border university research relationships, tightened export controls on technologies, and strengthened national regimes regulating technology-related foreign direct investment are now priorities for most democracies. These policy changes are motivated by the common goal of shoring up economic and national security. But the approaches are neither uniform nor harmonized, even among the relatively homogeneous G7 nations, undermining cross-border research and development (R&D) collaboration. When the leaders of G7 meet in late June in Schloss Elmau, Germany, they should make it a priority to coordinate controls on knowledge flows and technology. They need to act together to demonstrate how democracies can counter illicit activities for acquiring technologies.Inexpensive "liquid mirrors" could be used in giant telescopes on the Moon.Concern grows that virus will get footholds in species outside Africa.Increasing potential for fast, cheap genomes may break open biology's bottleneck and broaden clinical uses.The anthropogenic share of marine oil discharge is much larger than previously thought.A new biography juxtaposes the physicist's life story with the search for the Higgs boson.Ocean oil slicks can be attributed to natural seepages or to anthropogenic discharges. To date, the global picture of their distribution and relative natural and anthropogenic contributions remains unclear. Here, by analyzing 563,705 Sentinel-1 images from 2014-2019, we provide the first global map of oil slicks and a detailed inventory of static-and-persistent sources (natural seeps, platforms, and pipelines). About 90% of oil slicks were within 160 kilometers of shorelines, with 21 high-density slick belts coinciding well with shipping routes. Quantified by slick area, the proportion of anthropogenic discharges was an order of magnitude greater than natural seepages (94 versus 6%), in contrast to the previous estimate quantified by volume during 1990-1999 (54 versus 46%). Our findings reveal that the present-day anthropogenic contribution to marine oil pollution may have been substantially underestimated.In eukaryotes, RNA polymerase (Pol) II transcribes chromatin and must move past nucleosomes, often resulting in nucleosome displacement. How Pol II unwraps the DNA from nucleosomes to allow transcription and how DNA rewraps to retain nucleosomes has been unclear. Here, we report the 3.0-angstrom cryo-electron microscopy structure of a mammalian Pol II-DSIF-SPT6-PAF1c-TFIIS-nucleosome complex stalled 54 base pairs within the nucleosome. The structure provides a mechanistic basis for nucleosome retention during transcription elongation where upstream DNA emerging from the Pol II cleft has rewrapped the proximal side of the nucleosome. The structure uncovers a direct role for Pol II and transcription elongation factors in nucleosome retention and explains how nucleosomes are retained to prevent the disruption of chromatin structure across actively transcribed genes.Advances in additive manufacturing techniques have enabled the creation of stimuli-responsive materials with designed three-dimensional (3D) architectures. Unlike biological systems in which functions such as sensing, actuation, and control are closely integrated, few architected materials have comparable system complexity. We report a design and manufacturing route to create a class of robotic metamaterials capable of motion with multiple degrees of freedom, amplification of strain in a prescribed direction in response to an electric field (and vice versa), and thus, programmed motions with self-sensing and feedback control. These robotic metamaterials consist of networks of piezoelectric, conductive, and structural elements interwoven into a designed 3D lattice. The resulting architected materials function as proprioceptive microrobots that actively sense and move.Record-shattering events spur climate attribution advances.Can the international conservation agreement protect these bears?Graves in Kyrgyzstan hold early victims of plague that swept medieval Europe.In Arabia, the first half of the sixth century CE was marked by the demise of Himyar, the dominant power in Arabia until 525 CE. Important social and political changes followed, which promoted the disintegration of the major Arabian polities. Here, we present hydroclimate records from around Southern Arabia, including a new high-resolution stalagmite record from northern Oman. These records clearly indicate unprecedented droughts during the sixth century CE, with the most severe aridity persisting between ~500 and 530 CE. We suggest that such droughts undermined the resilience of Himyar and thereby contributed to the societal changes from which Islam emerged.Ten years ago, physicists found what they predicted. Little new has followed.Ultracold atoms confined to periodic potentials have proven to be a powerful tool for quantum simulation of complex many-body systems. We confine fermions to one dimension to realize the Tomonaga-Luttinger liquid model, which describes the highly collective nature of their low-energy excitations. We use Bragg spectroscopy to directly excite either the spin or charge waves for various strengths of repulsive interaction. We observe that the velocity of the spin and charge excitations shift in opposite directions with increasing interaction, a hallmark of spin-charge separation. The excitation spectra are in quantitative agreement with the exact solution of the Yang-Gaudin model and the Tomonaga-Luttinger liquid theory. Furthermore, we identify effects of nonlinear corrections to this theory that arise from band curvature and back-scattering.The centrosome provides an intracellular anchor for the cytoskeleton, regulating cell division, cell migration, and cilia formation. We used spatial proteomics to elucidate protein interaction networks at the centrosome of human induced pluripotent stem cell-derived neural stem cells (NSCs) and neurons. Centrosome-associated proteins were largely cell type-specific, with protein hubs involved in RNA dynamics. Analysis of neurodevelopmental disease cohorts identified a significant overrepresentation of NSC centrosome proteins with variants in patients with periventricular heterotopia (PH). Expressing the PH-associated mutant pre-mRNA-processing factor 6 (PRPF6) reproduced the periventricular misplacement in the developing mouse brain, highlighting missplicing of transcripts of a microtubule-associated kinase with centrosomal location as essential for the phenotype. Collectively, cell type-specific centrosome interactomes explain how genetic variants in ubiquitous proteins may convey brain-specific phenotypes.The cytokine meteorin-like (METRNL) improves cardiac function after heart attack in mice.The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes. We engineered penicillin G acylases to distinguish among free amino moieties of insulin (two at amino termini and an internal lysine) and manipulate cleavable phenylacetamide groups in a programmable manner to form protected insulin derivatives. This enables selective and specific chemical ligation to synthesize homogeneous bioconjugates, improving yield and purity compared to the existing methods, and generally opens avenues in the functionalization of native proteins to access biological probes or drugs.
Chagas disease is a potentially life-threatening neglected disease of poverty that is endemic in continental Latin America. Caused by Trypanosoma cruzi (T. cruzi), it is one of six parasitic diseases in the United States targeted by the Centers for Disease Control as a public health problem in need of action. An estimated 300,000 people are infected with T. cruzi in the United States (US). Although its morbidity, mortality and economic burden are high, awareness of Chagas disease is lacking among many healthcare providers in the US. The purpose of this analysis is to determine if the number of diagnostic tests performed at a community health center serving an at-risk population for Chagas disease increased after information sessions. A secondary aim was to determine if there was a difference by provider type, i.e., nurse practitioner vs. physician, or by specialty in the number of patients screened.

We conducted a retrospective data analysis of the number of Chagas serology tests performed at a community health center before and after information sessions for clinicians.
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