365 research outputs found
Hydrology, Water Chemistry and Ecological Relations in the Raised Mound of Cowles Bog
The Cowles Bog National Natural Landmark and the wetlands between the dunes near the south shore of Lake Michigan, in Indiana, contain plant species that are typical of circum-neutral fens. The distribution of eight, rather sharply delineated, vegetation types correlates most strongly with water level variations resulting from the presence of a 4.1-ha convex peat mound. A network of shallow ground-water wells installed in the wetland has identified an upwelling of water under artesian pressure at sites underlying the mound. The well-buffered water, containing high concentrations of inorganic solutes, is derived from an aquifer that is recharged on an upland moraine and is confined beneath a clay till sheet. A breach in this clay layer beneath the mound allows water to flow upward and radially outward as the hydraulic head is dissipated in the overlying marl and peat. The marl and organic lake sediments in the wetland were formed during the Nipissing level of ancestral Lake Michigan (4000-6000 years ago) when the wetland basin was probably a small bay of the lake. The peat mound developed when the lake level fell from the Algoma through to modern times. This increased the difference in hydraulic head and increased spring flows, which in turn induced peat formation
Interactions Between Ground Water and Wetlands, Southern Shore of Lake Michigan, USA
Wetlands between, and within, dune-beach complexes along the south shore of Lake Michigan are strongly affected by ground water. The hydrogeology of the glacial drift aquifer system in a 26 km2 area was investigated to determine the effects of ground water on the hydrology and hydrochemistry of Cowles Bog and its adjacent wetlands. The investigation showed that ground water from intermediate- and regional-scale flow systems discharges to Cowles Bog from confined aquifers that underlie the wetland. These flow systems are recharged in moraines south of the dune- beach complexes. Water from the confined aquifers discharges into the surficial aquifer mainly by upward leakage through a buried till sheet that serves as the confining layer. However, the till sheet is breached below a raised peat mound in Cowles Bog, allowing direct upward discharge from the confined aquifer into the surficial sand, marl, and peat. The shallow ground and wetland water in the area influenced by this leakage is a calcium magnesium bicarbonate type, with low tritium concentrations consistent with mixing of older ground water and more recent precipitation. Ground water and wetland water from surrounding areas are less mineralized and have higher tritium concentrations characteristic of precipitation in the late 1970s. The results of this study suggest that wetlands in complex hydrogeologic settings may be influenced by multiple ground-water flow systems that are affected by geomorphic features, stratigraphic discontinuities, and changes in sediment types. Discharge and recharge zones may both occur in the same wetland. Multidisciplinary studies incorporating hydrological, hydrochemical, geophysical, and sedimentological data are necessary to identify such complexities in wetland hydrology
Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms
AbstractHuman Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP
Blocking TLR7- and TLR9-mediated IFN-Ξ± Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection
Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-Ξ± that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-Ξ±, albeit at low levels. pDC mediate a marked but transient IFN-Ξ± response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-Ξ± response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-Ξ± production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-Ξ± production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-Ξ± production may not reduce HIV-associated immunopathology. Β© 2013 Kader et al
The genome of the green anole lizard and a comparative analysis with birds and mammals
The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments1. Among amniotes, genome sequences are available for mammals2 and birds3β5, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes3. Also, A. carolinensis mobile elements are very young and diverse β more so than in any other sequenced amniote genome. This lizard genomeβs GC content is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds6. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations
Vaccine delivery with microneedle skin patches in nonhuman primates
Transcutaneous drug delivery from planar skin patches is effective for small-molecule drugs and skin-permeable vaccine adjuvants. However, to achieve efficient delivery of vaccines and other macromolecular therapeutics into the skin, penetration of the stratum corneum is needed. Topically applied skin patches with micron-scale projections ('microneedles') pierce the upper layers of the skin and enable vaccines that are coated on or encapsulated within the microneedles to be dispersed into the skin. Although millimeter-scale syringes have shown promise for vaccine delivery in humans and technologies, such as the Dermaroller (Dermaroller, WolfenbΓΌttel, Germany), exist for creating microscale punctures in the skin for delivery of solutions of therapeutics, solid microprojection microneedles coated with dry vaccine formulations offer a number of valuable features for vaccination, including reduced risk of blood-borne pathogen transmission or needle-stick injury, the potential for vaccine administration by minimally trained personnel or even self administration and the use of solid-state vaccine formulations that may reduce or eliminate cold-chain requirements in vaccine distribution. Recent studies in mice have demonstrated the ability of microneedles to effectively deliver vaccines to the skin, eliciting protective immunity to influenza, hepatitis C and West Nile virus.Ragon Institute of MGH, MIT and HarvardMassachusetts Institute of TechnologyHarvard UniversityNational Institutes of Health (U.S.) (AI095109)National Institutes of Health (U.S.) (AI096040)National Institutes of Health (U.S.) (AI095985)National Institutes of Health (U.S.) (AI078526)National Institutes of Health (U.S.) (AI060354)United States. Dept. of Defense (Contract W911NF-07-D-0004
Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever
Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF
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