A distinct role for B1b lymphocytes in T cell-independent immunity

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell memory, which requires the formation of germinal centers and T cells, the development of B1b cell-mediated long-lasting antibody responses occurs independent of T cell help. T cell-independent (TI) antigens are important virulence factors expressed by a number of bacterial pathogens, including those associated with biological threats. TI antigens cannot be processed and presented to T cells and therefore are known to possess restricted T cell-dependent (TD) immunogenicity. Nevertheless, specific recognition of TI antigens by B1b cells and the highly protective antibody responses mounted by them clearly indicate a crucial role for this subset of B cells. Understanding the mechanisms of long-term immunity conferred by B1b cells may lead to improved vaccine efficacy for a variety of TI antigens

Devensian Late-glacial environmental change in the Gordano Valley, North Somerset, England: A rare archive for southwest Britain

The Late-glacial and Holocene environmental history of the Gordano Valley, North Somerset, UK has been reconstructed using pollen, sediment particle size and mineralogical analyses and radiocarbon dating. A Devensian sediment ridge across the valley confined the waters of a small lake, within which the initial sedimentation was minerogenic. Radiocarbon dating of overlying organic-rich deposits suggests that this began late in the Dimlington Stadial c. 18,000-15,000 Cal. BP. Petrographic analyses indicate the minerogenic sediments were partly wind-blown in origin. Climatic amelioration during the Windermere Interstadial c. 15,000 Cal. BP encouraged a shift from minerogenic to biogenic sedimentation. A brief return to minerogenic sedimentation between c. 10,400 and c. 9,520 Cal. BP was followed by uninterrupted fen peat accumulation throughout the Holocene. The later minerogenic horizon appears to represent the Loch Lomond Stadial. Few stratigraphic sequences preserving the complete Devensian Late-glacial-Holocene transition exist in southwest Britain, making the sedimentary archive of the Gordano Valley valuable regionally for reconstructing Late-glacial climate change. © 2007 Springer Science+Business Media B.V

mTOR intersects antibody-inducing signals from TACI in marginal zone B cells

Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB. Disruption of TACI-mTOR interaction by rapamycin, truncation of the MyD88-binding domain of TACI, or B-cell-conditional mTOR deficiency interrupts TACI signaling via NF-κB and cooperation with TLRs, thereby hampering IgG production to T-cell-independent antigens but not B-cell survival. Thus, mTOR drives innate-like antibody responses by linking proximal TACI signaling events with distal immunometabolic transcription programs.T.T. was supported by the Academy of Finland (285725), Finnish Cultural Foundation, Orion-Farmos Research Foundation and Emil Aaltonen Foundation. K.J.K. is supported by a NIGMS Fellowship (F32GM115208). This work was supported by NIH grants U54DK105566, R01MH101820 and R01GM104371 to D.G.M. The Genotype-Tissue Expression (GTEx) project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171) and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute; this grant also provided funding to D.G.M. and T.T. Biorepository operations were funded through an SAIC-F subcontract to the Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by supplements to University of Miami grants DA006227 and DA033684 and to contract N01MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 and MH101814), the University of Chicago (MH090951, MH090937, MH101820 and MH101825), the University of North Carolina, Chapel Hill (MH090936 and MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St. Louis (MH101810) and the University of Pennsylvania (MH101822)

Nanowear of polymers

The use of viscoelastic materials, such as polymers, constantly increases in the field of nanotechnology. These materials are softer than metallic and inorganic ones, and, because of that, they are easier to deform and wear off. The wear mechanisms occurring for viscoelastic materials are rather complex, and, generally, present more complications for a direct investigation with respect to metals or ceramics materials. With the advent of Scanning Probe Microscopy (SPM), well characterized forces can be applied to a surface with a nanometer-scale spatial resolution. In particular Atomic ForceMicroscopy (AFM), working at high contact forces, can significantly modify many surfaces. Polymers are soft enough to be modified by hard AFM tips, such as those of silicon, silicon nitride or diamond. For these reasons, the AFM is today the main tool employed to investigate wear occurrence on polymer surfaces. The wear of a polymer surface caused by an AFM tip in a regime of single asperity contact is an articulate process that depends on conditions such as, namely, the applied forces, the tip shape, size and the relative velocity. Since the influence of all these parameters is in close connection with the sample properties, one can expect a dependence of the wearing process on the mechanical properties of the sample surfaces. These properties can vary significantly from the bulk properties, if cross linking is made or, on contrary, residual solvents are present in the specimens. This chapter is divided in three sections following a general introduction. Specifically, the first section deals with wear induced by means of AFM tips to study the mechanical properties of films at the nanoscale; the second one regards the exploitation of wear for the creation of nanolithographic patterns; the last one is finally dedicated to an applicative field such as the characterization ofwear of polymers for biomedical applications at the meso- and nanoscales