Rescue of myeloid lineage-committed preprogenitor cells from cytomegalovirus-infected bone marrow stroma

The effect of murine cytomegalovirus on myelopoiesis was studied in long-term bone marrow culture to find an in vitro correlate for the lethal virus interference with bone marrow reconstitution (W. Mutter, M. J. Reddehase, F. W. Busch, H.-J. Bühring, and U. H. Koszinowski, J. Exp. Med. 167:1645-1658, 1988). The in vitro generation of granulocyte-monocyte progenitors (CFU-GM) discontinued after infection of the stromal cell layer, whereas the proliferation and differentiation of CFU-GM to granulocyte-monocyte colonies remained unaffected. A protocol was established to probe the functional integrity of earlier hematopoietic cells. Pre-CFU-GM (the progenitors of the CFU-GM) could be recovered from an infected bone marrow donor culture by transfer onto an inductive recipient stromal cell layer. Thus, at least in vitro, infection of bone marrow stroma appears to be the only cause of the defect in myelopoiesis

The effect of cyanoacrylate fuming on subsequent protein stain enhancement of fingermarks in blood

This study investigates the effect of cyanoacrylate (CA) fuming, at atmospheric and vacuum conditions, on subsequent protein stain (acid violet 17) enhancement of fingermarks in blood. Fingermark depletions in blood were deposited on three nonporous surfaces (e.g., plastic bag) and aged for a set period of time (up to 28 days) before enhancement with the water-ethanol-acetic acid and methanol formulations of acid violet 17 (AV17). All trials were carried out in duplicate. One depletion was pre-treated with CA fuming followed by the enhancement technique and the other depletion was treated with only the enhancement technique (control).As expected, atmospheric CA fuming hindered the subsequent enhancement of blood with the AV17 water-ethanol-acetic acid formulation but not the methanol formulation. The same observations were also recorded under vacuum CA fuming conditions. Preliminary work with vacuum metal deposition did not hinder subsequent AV17 protein stain enhancement with either formulation

In vivo application of recombinant interleukin 2 in the immunotherapy of established cytomegalovirus infection

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that in vivo application of recombinant human IL-2 (rhIL-2) can enhance the antiviral effect of a limited number of CD8+T lymphocytes, not only in prophylaxis, but also in therapy, when virus has already colonized host tissues. The observed net effect of IL-2 was consistent with the assumption of daily effector population doublings. The prospects for IL-2-supported immunotherapy of established CMV infection depend upon the tissues involved in disease. It appears that the prospects for controlling established CMV adrenalitis are less promising than for a therapy of interstitial CMV pneumonia

Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that CMV infection interferes with the earliest detectable step in hemopoiesis, the generation of the stem cell CFU-S-I, and thereby prevents the autoreconstitution of bone marrow after sublethal irradiation. The antihemopoietic effect could not be ascribed to a direct infection of stem cells. The failure in hemopoiesis was prevented by adoptive transfer of antiviral CD8+ T lymphocytes and could be overcome by syngeneic bone marrow transplantation. CD8+ T lymphocytes and bone marrow cells both mediated survival, although only CD8+ T lymphocytes were able to limit virus multiplication in host tissues. We concluded that not the cytopathic effect of virus replication in host tissues, but the failure in hemopoiesis, is the primary cause of death in murine CMV disease

Femtosecond resolution timing jitter correction on a TW scale Ti:sapphire laser system for FEL pump-probe experiments

Intense ultrashort pulse lasers are used for fs resolution pumpprobe experiments more and more at large scale facilities, such as free electron lasers (FEL). Measurement of the arrival time of the laser pulses and stabilization to the machine or other sub-systems on the target, is crucial for high time-resolution measurements. In this work we report on a single shot, spectrally resolved, non-collinear cross-correlator with sub-fs resolution. With a feedback applied we keep the output of the TW class Ti:sapphire amplifier chain in time with the seed oscillator to ~3 fs RMS level for several hours. This is well below the typical pulse duration used at FELs and supports fs resolution pump-probe experiments. Short term jitter and long term timing drift measurements are presented. Applicability to other wavelengths and integration into the timing infrastructure of the FEL are also covered to show the full potential of the device

Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes

We have established a murine model system for exploring the ability of a CD4 subset-deficient host to cope with cytomegalovirus infection, and reported three findings. First, an antiviral response of the CD8 subset of T lymphocytes could be not only initiated but also maintained for a long period of time despite a continued absence of the CD4 subset, whereas the production of antiviral antibody proved strictly dependent upon help provided by the CD4 subset. Second, no function in the defense against infection could be ascribed as yet to CD4-CD8- T lymphocytes, which were seen to accumulate to a new subset as a result of depletion of the CD4 subset. This newly arising subset did not substitute for CD4+ T lymphocytes in providing help to B lymphocytes, and was also not effective in controlling the spread of virus in host tissues. As long as a function of these cells in the generation and maintenance of a CD8 subset-mediated response is not disproved, caution is indicated with concern to an autonomy of the CD8 subset. Third, even though with delay, the CD8+ effector cells raised in the CD4 subset- deficient host were able of clear vital tissues from productive infection and to restrict asymptomatic, persistent infection to acinar glandular epithelial cells in salivary gland tissue

CD4-helper-independent antiviral function of CD8-positive memory T lymphocytes derived from latently infected donors

The ability of memory T lymphocytes derived from latently infected mice to control murine cytomegalovirus disease in the immunocompromised host was studied by adoptive transfer experiments. At a stage of pathogenesis when virus had already colonized target tissues, a therapeutic antiviral function could be ascribed to the CD8+ subset. This in vivo function was not restricted to sites in which intravenously infused lymphocytes usually are trapped or home in, such as the lungs or the spleen, respectively, but was also evident in the adrenal glands, a site to which antiviral effector cells have to specifically migrate. Specific infiltration of adrenal gland cortical tissue by donor-derived CD8+ memory T lymphocytes was demonstrated. CD4+ memory T lymphocytes had no antiviral effect by themselves and also were not required for the function of the CD8+ effector cells in this short-term immunotherapy model. These findings should help settle the debate about which subset of T lymphocytes comprises the effector cells that can directly control cytomegalovirus infection in the murine model system

Crustal thickness and Moho character of the fast-spreading East Pacific Rise from 9°42′N to 9°57′N from poststack-migrated 3-D MCS data

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 15 (2014): 634–657, doi:10.1002/2013GC005069.We computed crustal thickness (5740 ± 270 m) and mapped Moho reflection character using 3-D seismic data covering 658 km2 of the fast-spreading East Pacific Rise (EPR) from 9°42′N to 9°57′N. Moho reflections are imaged within ∼87% of the study area. Average crustal thickness varies little between large sections of the study area suggesting regionally uniform crustal production in the last ∼180 Ka. However, individual crustal thickness measurements differ by as much as 1.75 km indicating that the mantle melt delivery has not been uniform. Third-order, but not fourth-order ridge discontinuities are associated with changes in the Moho reflection character and/or near-axis crustal thickness. This suggests that the third-order segmentation is governed by melt distribution processes within the uppermost mantle while the fourth-order ridge segmentation arises from midcrustal to upper-crustal processes. In this light, we assign fourth-order ridge discontinuity status to the debated ridge segment boundary at ∼9°45′N and third-order status at ∼9°51.5′N to the ridge segment boundary previously interpreted as a fourth-order discontinuity. Our seismic results also suggest that the mechanism of lower-crustal accretion varies along the investigated section of the EPR but that the volume of melt delivered to the crust is mostly uniform. More efficient mantle melt extraction is inferred within the southern half of our survey area with greater proportion of the lower crust accreted from the axial magma lens than that for the northern half. This south-to-north variation in the crustal accretion style may be caused by interaction between the melt sources for the ridge and the Lamont seamounts.This research was supported by the National Science Foundation grants OCE0327872 to J. C. M., S. M. C., OCE327885 to J. P. C., OCE0624401 to M. R. N., and NSERC Discovery, CRC and CFI grants to M. R. N.2014-09-1

Distribution of melt along the East Pacific Rise from 9°30′ to 10°N from an amplitude variation with angle of incidence (AVA) technique

Author Posting. © The Author(s), 2015. This article is posted here by permission of The Royal Astronomical Society for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 203 (2015): 1-21, doi:10.1093/gji/ggv251.We examine along-axis variations in melt content of the axial magma lens (AML) beneath the fast-spreading East Pacific Rise (EPR) using an amplitude variation with angle of incidence (AVA) crossplotting method applied to multichannel seismic data acquired in 2008. The AVA crossplotting method, which has been developed for and, so far, applied for hydrocarbon prospection in sediments, is for the first time applied to a hardrock environment. We focus our analysis on 2-D data collected along the EPR axis from 9°29.8′N to 9°58.4′N, a region which encompasses the sites of two well-documented submarine volcanic eruptions (1991–1992 and 2005–2006). AVA crossplotting is performed for a ∼53 km length of the EPR spanning nine individual AML segments (ranging in length from ∼3.2 to 8.5 km) previously identified from the geometry of the AML and disruptions in continuity. Our detailed analyses conducted at 62.5 m interval show that within most of the analysed segments melt content varies at spatial scales much smaller (a few hundred of metres) than the length of the fine-scale AML segments, suggesting high heterogeneity in melt concentration. At the time of our survey, about 2 yr after the eruption, our results indicate that the three AML segments that directly underlie the 2005–2006 lava flow are on average mostly molten. However, detailed analysis at finer-scale intervals for these three segments reveals AML pockets (from >62.5 to 812.5 m long) with a low melt fraction. The longest such mushy section is centred beneath the main eruption site at ∼9°50.4′N, possibly reflecting a region of primary melt drainage during the 2005–2006 event. The complex geometry of fluid flow pathways within the crust above the AML and the different response times of fluid flow and venting to eruption and magma reservoir replenishment may contribute to the poor spatial correlation between incidence of hydrothermal vents and presence of highly molten AML. The presented results are an important step forward in our ability to resolve small-scale characteristics of the AML and recommend the AVA crossplotting as a tool for examining mid-ocean ridge magma-systems elsewhere.This research was supported by NSF awards OCE0327872 to J.C.M. and S.M.C., OCE-0327885 to J.P.C., and OCE0624401 to M.R.N