Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion. We show that Phd2 (also known as Egln1) haplodeficient (Phd2(+/-)) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2(+/-) mice was due to an expansion of tissue-resident, M2-like macrophages and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a pro-arteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-κB pathway in Phd2(+/-) macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders.     

A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ～4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ～60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.     

Coherent coupling of a superconducting flux qubit to an electron spin ensemble in diamond

During the past decade, research into superconducting quantum bits (qubits) based on Josephson junctions has made rapid progress. Many foundational experiments have been performed, and superconducting qubits are now considered one of the most promising systems for quantum information processing. However, the experimentally reported coherence times are likely to be insufficient for future large-scale quantum computation. A natural solution to this problem is a dedicated engineered quantum memory based on atomic and molecular systems. The question of whether coherent quantum coupling is possible between such natural systems and a single macroscopic artificial atom has attracted considerable attention since the first demonstration of macroscopic quantum coherence in Josephson junction circuits. Here we report evidence of coherent strong coupling between a single macroscopic superconducting artificial atom (a flux qubit) and an ensemble of electron spins in the form of nitrogen-vacancy colour centres in diamond. Furthermore, we have observed coherent exchange of a single quantum of energy between a flux qubit and a macroscopic ensemble consisting of about 3?×?10(7) such colour centres. This provides a foundation for future quantum memories and hybrid devices coupling microwave and optical systems.     

Hydrogen bonding at the water surface revealed by isotopic dilution spectroscopy

The air-water interface is perhaps the most common liquid interface. It covers more than 70 per cent of the Earth's surface and strongly affects atmospheric, aerosol and environmental chemistry. The air-water interface has also attracted much interest as a model system that allows rigorous tests of theory, with one fundamental question being just how thin it is. Theoretical studies have suggested a surprisingly short 'healing length' of about 3??ngstr?ms (1?? = 0.1?nm), with the bulk-phase properties of water recovered within the top few monolayers. However, direct experimental evidence has been elusive owing to the difficulty of depth-profiling the liquid surface on the ?ngstr?m scale. Most physical, chemical and biological properties of water, such as viscosity, solvation, wetting and the hydrophobic effect, are determined by its hydrogen-bond network. This can be probed by observing the lineshape of the OH-stretch mode, the frequency shift of which is related to the hydrogen-bond strength. Here we report a combined experimental and theoretical study of the air-water interface using surface-selective heterodyne-detected vibrational sum frequency spectroscopy to focus on the 'free OD' transition found only in the topmost water layer. By using deuterated water and isotopic dilution to reveal the vibrational coupling mechanism, we find that the free OD stretch is affected only by intramolecular coupling to the stretching of the other OD group on the same molecule. The other OD stretch frequency indicates the strength of one of the first hydrogen bonds encountered at the surface; this is the donor hydrogen bond of the water molecule straddling the interface, which we find to be only slightly weaker than bulk-phase water hydrogen bonds. We infer from this observation a remarkably fast onset of bulk-phase behaviour on crossing from the air into the water phase.     

固体的电子结构和磁光性质

本书是一本关于固体化合物和多层材料的电子结构、光学、磁光学、X射线磁圆二向色性等的理论研究的新著作。     

The Pendulum Swings Again: A Mathematical Reassessment of Galileo's Experiments with Inclined Planes

 After over 300 years of scrutiny, the subject of Galileo continues to be pursued with unabating intensity. Dava Sobel's Galileo's Daughter points to the popular interest in the man and his legacy. The Catholic Church, understandably interested in dispelling the notion that its censure of Galileo centuries ago is proof positive that religious faith and science as well as ecclesiastical authority and free pursuit of scholarship are irreconcilable, continues to offer explanations. New books, articles and conferences probe both in breadth and in depth the magnetic field charged by Galileo, science, and the Church. Galileo's analysis of the physics of motion has also received considerable attention. In particular, a great deal has been written during the past thirty years about the structure and objectives of three experiments with inclined planes. Galileo had carried them out in Padua and recorded them in his working papers. The assessments of the three experiments differ widely in points of detail, but all regard them as sophisticated, ingenious, and remarkable. This article presents a new critical study of these experiments. Its conclusion is that one of the experiments is indeed a success, but that the other two fail and are abandoned because Galileo did not have a firm enough grip on the underlying physical principles and mathematical relationships.