Michael C. Carroll

Bio: Michael C. Carroll is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Complement system & Complement receptor. The author has an hindex of 100, co-authored 399 publications receiving 34818 citations. Previous affiliations of Michael C. Carroll include Newcastle University & University College Dublin.

Schizophrenia risk from complex variation of complement component 4

Abstract: Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

The complement system in regulation of adaptive immunity.

Abstract: The serum complement system, which represents a chief component of innate immunity, not only participates in inflammation but also acts to enhance the adaptive immune response. Specific activation of complement via innate recognition proteins or secreted antibody releases cleavage products that interact with a wide range of cell surface receptors found on myeloid, lymphoid and stromal cells. This intricate interaction among complement activation products and cell surface receptors provides a basis for the regulation of both B and T cell responses. This review highlights fundamental events, explaining how complement links innate and adaptive immunity as well as describing more recent studies on how this large family of proteins functions locally in peripheral lymph nodes to enhance B and T cell responses.

The BABAR detector

Abstract: BABAR, the detector for the SLAC PEP-II asymmetric e+e- B Factory operating at the upsilon 4S resonance, was designed to allow comprehensive studies of CP-violation in B-meson decays. Charged particle tracks are measured in a multi-layer silicon vertex tracker surrounded by a cylindrical wire drift chamber. Electromagentic showers from electrons and photons are detected in an array of CsI crystals located just inside the solenoidal coil of a superconducting magnet. Muons and neutral hadrons are identified by arrays of resistive plate chambers inserted into gaps in the steel flux return of the magnet. Charged hadrons are identified by dE/dx measurements in the tracking detectors and in a ring-imaging Cherenkov detector surrounding the drift chamber. The trigger, data acquisition and data-monitoring systems, VME- and network-based, are controlled by custom-designed online software. Details of the layout and performance of the detector components and their associated electronics and software are presented.

A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo.

Abstract: The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease susceptibility and severity according to the position of the missing protein in the activation pathway, with the severest disease associated with C1q deficiency. Here we demonstrate, using novel in vivo models of apoptotic cell clearance during sterile peritonitis, a similar hierarchical role for classical pathway complement proteins in vivo in the clearance of apoptotic cells by macrophages. Our results constitute the first demonstration of an impairment in the phagocytosis of apoptotic cells by macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a major source of the autoantigens of SLE, and impairment of their removal by complement may explain the link between hereditary complement deficiency and the development of SLE.

Adhesion receptors of the immune system.

Abstract: The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR.

Abstract: Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.

Alternative activation of macrophages

Abstract: The classical pathway of interferon-gamma-dependent activation of macrophages by T helper 1 (T(H)1)-type responses is a well-established feature of cellular immunity to infection with intracellular pathogens, such as Mycobacterium tuberculosis and HIV. The concept of an alternative pathway of macrophage activation by the T(H)2-type cytokines interleukin-4 (IL-4) and IL-13 has gained credence in the past decade, to account for a distinctive macrophage phenotype that is consistent with a different role in humoral immunity and repair. In this review, I assess the evidence in favour of alternative macrophage activation in the light of macrophage heterogeneity, and define its limits and relevance to a range of immune and inflammatory conditions.

The CMS experiment at the CERN LHC

Abstract: The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1) (10(27)cm(-2)s(-1)). At the core of the CMS detector sits a high-magnetic-field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4 pi solid angle. Forward sampling calorimeters extend the pseudo-rapidity coverage to high values (vertical bar eta vertical bar <= 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t.