Frequency analysis of cytolytic T cell precursors (CTL-P) generated in vivo during lethal rabies infection of mice. I. Distinction of CTL-P with different interleukin 2 sensitivity

The aim of this study was to determine the number and state of activity of cytolytic T lymphocytes (CTL) and their precursors (CTL-P) present in vivo during the early stages of viral infection. The local response to lethal infection with rabies virus was used as a model system that is not accessible to analysis by secondary activation in vitro. The local response to alloantigen served as a control. Experimental protocols were established that allow frequency estimates of in vivo antigen-triggered CTL-P. Data allow a distinction between CTL-P activated in vivo by alloantigen and viral antigen with respect to their different capacity to utilize T cell growth factors (inter-leukins). In vivo alloantigen-primed CTL-P generate, in vitro, an active effector progeny in the presence of interleukins of xenogeneic origin, whereas the majority of virus-specific CTL-P, in spite of considerable expansion in vivo, fail to generate CTL in vitro unless antigen is added

Recent development and perspectives of machines for lattice QCD

I highlight recent progress in cluster computer technology and assess status and prospects of cluster computers for lattice QCD with respect to the development of QCDOC and apeNEXT. Taking the LatFor test case, I specify a 512-processor QCD-cluster better than 1$/Mflops.Comment: 14 pages, 17 figures, Lattice2003(plenary

Light emission from a scanning tunneling microscope: Fully retarded calculation

The light emission rate from a scanning tunneling microscope (STM) scanning a noble metal surface is calculated taking retardation effects into account. As in our previous, non-retarded theory [Johansson, Monreal, and Apell, Phys. Rev. B 42, 9210 (1990)], the STM tip is modeled by a sphere, and the dielectric properties of tip and sample are described by experimentally measured dielectric functions. The calculations are based on exact diffraction theory through the vector equivalent of the Kirchoff integral. The present results are qualitatively similar to those of the non-retarded calculations. The light emission spectra have pronounced resonance peaks due to the formation of a tip-induced plasmon mode localized to the cavity between the tip and the sample. At a quantitative level, the effects of retardation are rather small as long as the sample material is Au or Cu, and the tip consists of W or Ir. However, for Ag samples, in which the resistive losses are smaller, the inclusion of retardation effects in the calculation leads to larger changes: the resonance energy decreases by 0.2-0.3 eV, and the resonance broadens. These changes improve the agreement with experiment. For a Ag sample and an Ir tip, the quantum efficiency is $\approx$ 10$^{-4}$ emitted photons in the visible frequency range per tunneling electron. A study of the energy dissipation into the tip and sample shows that in total about 1 % of the electrons undergo inelastic processes while tunneling.Comment: 16 pages, 10 figures (1 ps, 9 tex, automatically included); To appear in Phys. Rev. B (15 October 1998

Fungal ecology: principles and mechanisms of colonization and competition by saprotrophic fungi

Decomposer fungi continually deplete the organic resources they inhabit, so successful colonization of new resources is a crucial part of their ecology. Colonization success can be split into (i) the ability to arrive at, gain entry into, and establish within a resource and (ii) the ability to persist within the resource until reproduction and dissemination. Fungi vary in their life history strategies, the three main drivers of which are stress (S-selected), disturbance (ruderal, or R-selected), and incidence of competitors (C-selected); however, fungi often have combinations of characteristics from different strategies. Arrival at a new resource may occur as spores or mycelium, with successful entry and establishment (primary resource capture) within the resource largely dependent on the enzymatic ability of the fungus. The communities that develop in a newly available resource depend on environmental conditions and, in particular, the levels of abiotic stress present (e.g., high temperature, low water availability). Community change occurs when these initial colonizers are replaced by species that are either more combative (secondary resource capture) or better able to tolerate conditions within the resource, either through changing abiotic conditions or due to modification of the resource by the initial colonizers. Competition for territory may involve highly specialized species-specific interactions such as mycoparasitism or may be more general; in both cases combat involves changes in morphology, metabolism, and reactive oxygen species production, and outcomes of these interactions can be altered under different environmental conditions. In summary, community development is not a simple ordered sequence, but a complex ever-changing mosaic

Perivascular cells for regenerative medicine

Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We and others recently described that MSC originate from two types of perivascular cells, namely pericytes and adventitial cells and contain the in situ counterpart of MSC in developing and adult human organs, which can be prospectively purified using well defined cell surface markers. Pericytes encircle endothelial cells of capillaries and microvessels and express the adhesion molecule CD146 and the PDGFRβ, but lack endothelial and haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is a pericyte marker exclusively associated with the arterial system. Besides its expression in smooth muscle cells, smooth muscle actin (αSMA) is also detected in subsets of pericytes. Adventitial cells surround the largest vessels and, opposite to pericytes, are not closely associated to endothelial cells. Adventitial cells express CD34 and lack αSMA and all endothelial and haematopoietic cell markers, as for pericytes. Altogether, pericytes and adventitial perivascular cells express in situ and in culture markers of MSC and display capacities to differentiate towards osteogenic, adipogenic and chondrogenic cell lineages. Importantly, adventitial cells can differentiate into pericyte-like cells under inductive conditions in vitro. Altogether, using purified perivascular cells instead of MSC may bring higher benefits to regenerative medicine, including the possibility, for the first time, to use these cells uncultured

Pathways and bioenergetics of anaerobic carbon monoxide fermentation

Carbon monoxide can act as a substrate for different modes of fermentative anaerobic metabolism. The trait of utilizing CO is spread among a diverse group of microorganisms, including members of bacteria as well as archaea. Over the last decade this metabolism has gained interest due to the potential of converting CO-rich gas, such as synthesis gas, into bio-based products. Three main types of fermentative CO metabolism can be distinguished: hydrogenogenesis, methanogenesis, and acetogenesis, generating hydrogen, methane and acetate, respectively. Here, we review the current knowledge on these three variants of microbial CO metabolism with an emphasis on the potential enzymatic routes and bio-energetics involved.The authors involved were financially supported by an ERC grant (project 323009) and the Gravitation grant (project 024.002.002) of the Netherlands Ministry of Education, Culture and Science and the Netherlands Science Foundation (NWO)

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries.

Globally, group B Streptococcus (GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation. This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations

STRAIN DIFFERENCES IN THE EXPRESSION OF THE EPA-1-RESTRICTING ELEMENT

Epa-1-specific cytotoxic T lymphocytes (CTL) lyse epidermal cells (EC) of different Epa-1 + H-2 k strains, such as AKR, CBA, C58, and RF, at different levels. We used an H-2K k -specific monoclonal antibody (mAb) to test the hypothesis that this phenomenon is due to differences in the H-2-restricting element. Initially, we established the specificity of this mAb for the Epa-1-restricting element by demonstrating its capacity to inhibit the lysis of CBA EC by Epa-1-specific CTL. We then used it as the probe in a cellular radioimmunoassay to quantify the expression of the restricting element by EC of different H-2 k strains. We found that C58 and RF EC bound significantly less of the mAb than did CBA EC. Although AKR also bound less of the mAb than did CBA EC, the difference was not statistically significant. To examine the generality of this phenomenon, we quantified the expression of K k antigens on spleen cells (SC) of the same four strains. We found that RF SC, but not AKR or C58 SC, bound significantly less of the K k mAb than did CBA SC. Thus, the differential CTL lysis of Epa-1 + EC of different strains probably reflects differences in expression of the H-2-restricting element rather than of the nominal antigen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75485/1/j.1744-313X.1987.tb00375.x.pd