The glyoxylate cycle is required for fungal virulence.

Candida albicans, a normal component of the mammalian gastrointestinal flora, is responsible for most fungal infections in immunosuppressed patients. Candida is normally phagocytosed by macrophages and neutrophils, which secrete cytokines and induce hyphal development in this fungus. Neutropenic patients, deficient in these immune cells, are particularly susceptible to systemic candidiasis. Here we use genome-wide expression profiles of the related yeast Saccharomyces cerevisiae to obtain a signature of the events that take place in the fungus on ingestion by a mammalian macrophage. Live S. cerevisiae cells isolated from the phagolysosome are induced for genes of the glyoxylate cycle, a metabolic pathway that permits the use of two-carbon compounds as carbon sources. In C. albicans, phagocytosis also upregulates the principal enzymes of the glyoxylate cycle, isocitrate lyase (ICL1) and malate synthase (MLS1). Candida albicans mutants lacking ICL1 are markedly less virulent in mice than the wild type. These findings in fungi, in conjunction with reports that isocitrate lyase is both upregulated and required for the virulence of Mycobacterium tuberculosis, demonstrate the wide-ranging significance of the glyoxylate cycle in microbial pathogenesis.     

Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells

Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens. It is unclear how virus particles are cleared from afferent lymph and presented to cognate B cells to induce antibody responses. Here we identify a population of CD11b+CD169+MHCII+ macrophages on the floor of the subcapsular sinus (SCS) and in the medulla of lymph nodes that capture viral particles within minutes after subcutaneous injection. Macrophages in the SCS translocated surface-bound viral particles across the SCS floor and presented them to migrating B cells in the underlying follicles. Selective depletion of these macrophages compromised local viral retention, exacerbated viraemia of the host, and impaired local B-cell activation. These findings indicate that CD169+ macrophages have a dual physiological function. They act as innate 'flypaper' by preventing the systemic spread of lymph-borne pathogens and as critical gatekeepers at the lymph-tissue interface that facilitate the recognition of particulate antigens by B cells and initiate humoral immune responses.     

Climbing the Jaynes-Cummings ladder and observing its nonlinearity in a cavity QED system

The field of cavity quantum electrodynamics (QED), traditionally studied in atomic systems, has gained new momentum by recent reports of quantum optical experiments with solid-state semiconducting and superconducting systems. In cavity QED, the observation of the vacuum Rabi mode splitting is used to investigate the nature of matter-light interaction at a quantum-mechanical level. However, this effect can, at least in principle, be explained classically as the normal mode splitting of two coupled linear oscillators. It has been suggested that an observation of the scaling of the resonant atom-photon coupling strength in the Jaynes-Cummings energy ladder with the square root of photon number n is sufficient to prove that the system is quantum mechanical in nature. Here we report a direct spectroscopic observation of this characteristic quantum nonlinearity. Measuring the photonic degree of freedom of the coupled system, our measurements provide unambiguous spectroscopic evidence for the quantum nature of the resonant atom-field interaction in cavity QED. We explore atom-photon superposition states involving up to two photons, using a spectroscopic pump and probe technique. The experiments have been performed in a circuit QED set-up, in which very strong coupling is realized by the large dipole coupling strength and the long coherence time of a superconducting qubit embedded in a high-quality on-chip microwave cavity. Circuit QED systems also provide a natural quantum interface between flying qubits (photons) and stationary qubits for applications in quantum information processing and communication.     

Correlations between T-cell specificity and the structure of the antigen receptor

The derived amino-acid sequences of the heterodimeric antigen receptors expressed by a series of murine T-cell clones are presented. A comparison of the receptor sequences indicates that several mechanisms for generating receptor diversity can influence T-cell specificity, including junctional diversity, combinatorial joining, and combinatorial chain associations.     

Structured spheres generated by an in-fibre fluid instability

From drug delivery to chemical and biological catalysis and cosmetics, the need for efficient fabrication pathways for particles over a wide range of sizes, from a variety of materials, and in many different structures has been well established. Here we harness the inherent scalability of fibre production and an in-fibre Plateau-Rayleigh capillary instability for the fabrication of uniformly sized, structured spherical particles spanning an exceptionally wide range of sizes: from 2?mm down to 20?nm. Thermal processing of a multimaterial fibre controllably induces the instability, resulting in a well-ordered, oriented emulsion in three dimensions. The fibre core and cladding correspond to the dispersed and continuous phases, respectively, and are both frozen in situ on cooling, after which the particles are released when needed. By arranging a variety of structures and materials in a macroscopic scaled-up model of the fibre, we produce composite, structured, spherical particles, such as core-shell particles, two-compartment 'Janus' particles, and multi-sectioned 'beach ball' particles. Moreover, producing fibres with a high density of cores allows for an unprecedented level of parallelization. In principle, 10(8) 50-nm cores may be embedded in metres-long, 1-mm-diameter fibre, which can be induced to break up simultaneously throughout its length, into uniformly sized, structured spheres.