ALBERT

Description: A reverse-genetics approach has been used to probe the mechanism underlying immune escape for influenza A virus-specific CD8+ T cells responding to the immunodominant DbNP366 epitope. Engineered viruses with a substitution at a critical residue (position 6, P6M) all evaded recognition by WT DbNP366-specific CD8+ T cells, but only the...

Description: An improved mesoscopic model is presented for simulating the drying of porous media. The aim of this model is to account for two scales simultaneously: the scale of the whole product and the scale of the heterogeneities of the porous medium. The innovation of this method is the utilization of a new mass-conservative scheme based on the Control-Volume Finite-Element (CV-FE) method that partitions the moisture content field over the individual sub-control volumes surrounding each node within the mesh. Although the new formulation has potential for application across a wide range of transport processes in heterogeneous porous media, the focus here is on applying the model to the drying of small sections of softwood consisting of several growth rings. The results conclude that, when compared to a previously published scheme, only the new mass-conservative formulation correctly captures the true moisture content evolution in the earlywood and latewood components of the growth rings during drying. A new mesoscopic model was proposed for simulating the drying of porous media. Applying the new model to cross-sections of a pinewood board, the distribution of water within each control volume is correctly captured, which provides a better representation of the true moisture content distribution during drying.

Description: ABSTRACT Growing evidence indicates that lake-dominated ecosystems at high latitudes are undergoing significant hydrological changes. Research examining these changes is complicated because both thermokarst and climatic processes likely influence lake dynamics. To examine the relative impacts these processes in permafrost landscapes we investigated the dynamics of lake area and number in Old Crow Flats (OCF) using historical air photos and satelite imagery. Between 1951 and 2007, the OCF experienced a decline of ~6000 ha in total lake area, but gained 232 lakes. Close to half (49%) of the difference in lake area was driven by the rapid and persistent drainage of 38 large lakes. These catastrophic drainages were associated with new or enlarged outlet channels, resulted in the formation of numerous residual ponds, and were likely driven by thermokarst processes. Our analysis shows that catastrophic lake drainages have become more than 5X more frequent in recent decades. These changes are likely related to the impacts of increased temperature and precipitation on thermokarst processes. 59 of the 170 intensively studied lakes showed either large bi-directional fluctuations or gradual cumulative declines. These changes affected a much smaller portion of the OCF and were likely driven by interactions between increased precipitation and temperature and individual catchment characteristics. To anticipate landscape-scale changes in these systems, and assess their impact on hydrology, wildlife habitat, and carbon storage, field research is required to better characterize the mechanisms responsible for changes.

Description: Analytical Chemistry DOI: 10.1021/ac3021888

Description: Journal of Medicinal Chemistry DOI: 10.1021/jm300685s

Description: Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected and unselected parasites was analyzed using a variant surface antigen-supplemented microarray chip. After selection, the most highly and consistently up-regulated genes were a subset of group A-like var genes (HB3var3, 3D7_PFD0020c, ITvar7, and ITvar19) that showed 11- to 〉100-fold increased transcription levels. These var genes encode P. falciparum erythrocyte membrane protein (PfEMP)1 variants with distinct N-terminal domain types (domain cassette 8 or domain cassette 13). Antibodies to HB3var3 and PFD0020c recognized the surface of live IEs and blocked binding to HBEC-5i, thereby confirming the adhesive function of these variants. The clinical in vivo relevance of the HBEC-selected parasites was supported by significantly higher surface recognition of HBEC-selected parasites compared with unselected parasites by antibodies from young African children suffering cerebral malaria (Mann–Whitney test, P = 0.029) but not by antibodies from controls with uncomplicated malaria (Mann–Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria.

Description: Recent studies using remote sensing analysis of lake-rich thermokarst landscapes have documented evidence of declining lake surface area in response to recent warming. However, images alone cannot identify whether these declines are due to increasing frequency of lake drainage events associated with accelerated thermokarst activity or to increasing evaporation in response to longer ice-free season duration. Here, we explore the potential of combining aerial photograph time series with paleolimnological analyses to track changes in hydrological conditions of a thermokarst lake in the Old Crow Flats (OCF), Canada, and to identify their causes. Images show water level in lake OCF 48 declined markedly sometime between 1972 and 2001. In a sediment core from OCF 48, complacent stratigraphic profiles of several physical, geochemical and biological parameters from 1874-1967 indicate hydro-limnological conditions were relatively stable. From 1967-1989, declines in organic matter content, organic carbon isotope values and pigment concentrations are interpreted to reflect an increase in supply of minerogenic sediment, and subsequent decline in aquatic productivity, caused by increased thermo-erosion of shoreline soils. Lake expansion was likely caused by increased summer rainfall, as recorded by increased cellulose-inferred lake-water oxygen isotope compositions. Stratigraphic trends defining the lake expansion phase terminated at 1989, which likely marks the year when the lake drained. Above-average precipitation during the previous year probably raised the lake-level and promoted further thermo-erosion of the shoreline soils that caused the lake to drain. These are meteorological conditions that have led to other recent lake-drainage events in the OCF. Thus, the decline in lake-level evident in the aerial photograph from 2001 is unlikely to have been caused by evaporation, but rather is a remnant of a drainage event that took place more than a decade earlier. After drainage, the lake began to refill, and most paleolimnological parameters approach levels that are similar to those during the stable phase. These findings indicate that combined use of aerial images and paleolimnological methods offers much promise for identifying the hydrological consequences of recent climatic variations on thermokarst lakes. Copyright © 2011 John Wiley & Sons, Ltd.

Description: Encoding sensory input requires the expression of postsynaptic ion channels to transform key features of afferent input to an appropriate pattern of spike output. Although Ca2+-activated K+ channels are known to control spike frequency in central neurons, Ca2+-activated K+ channels of intermediate conductance (KCa3.1) are believed to be restricted to peripheral neurons. We now report that cerebellar Purkinje cells express KCa3.1 channels, as evidenced through single-cell RT-PCR, immunocytochemistry, pharmacology, and single-channel recordings. Furthermore, KCa3.1 channels coimmunoprecipitate and interact with low voltage-activated Cav3.2 Ca2+ channels at the nanodomain level to support a previously undescribed transient voltage- and Ca2+-dependent current. As a result, subthreshold parallel fiber excitatory postsynaptic potentials (EPSPs) activate Cav3 Ca2+ influx to trigger a KCa3.1-mediated regulation of the EPSP and subsequent after-hyperpolarization. The Cav3-KCa3.1 complex provides powerful control over temporal summation of EPSPs, effectively suppressing low frequencies of parallel fiber input. KCa3.1 channels thus contribute to a high-pass filter that allows Purkinje cells to respond preferentially to high-frequency parallel fiber bursts characteristic of sensory input.

Description: The ratio of mass and magnetic flux determines the relative importance of magnetic and gravitational forces in the evolution of molecular clouds and their cores. Its measurement is thus central in discriminating between different theories of core formation and evolution. Here, we discuss the effect of chemical depletion on measurements of the mass-to-flux ratio using the same molecule (OH) both for Zeeman measurements of the magnetic field and the determination of the mass of the region. The uncertainties entering through the OH abundance in determining separately the magnetic field and the mass of a region have been recognized in the literature. It has been proposed however that, when comparing two regions of the same cloud, the abundance will in both cases be the same. We show that this assumption is invalid. We demonstrate that when comparing regions with different densities, the effect of OH depletion, in measuring changes of the mass-to-flux ratio between different parts of the same cloud can even reverse the direction of the underlying trends (for example, the mass-to-flux ratio may appear to decrease as we move to higher density regions). The systematic errors enter primarily through the inadequate estimation of the mass of the region.

Description: Despite the extensive geographical range of palaeolimnological studies designed to assess the extent of surface water acidification in the United Kingdom during the 1980s, little attention was paid to the status of surface waters in the North York Moors (NYM). In this paper, we present sediment core data from a moorland pool in the NYM that provide a record of air pollution contamination and surface water acidification. The 41-cm-long core was divided into three lithostratigraphic units. The lower two comprise peaty soils and peats, respectively, that date to between approximately 8080 and 6740 cal. BP. The uppermost unit comprises peaty lake muds dating from between approximately ad 1790 and the present day ( ad 2006). The lower two units contain pollen dominated by forest taxa, whereas the uppermost unit contains pollen indicative of open landscape conditions similar to those of the present. Heavy metal, spheroidal carbonaceous particle, mineral magnetics and stable isotope analysis of the upper sediments show clear evidence of contamination by air pollutants derived from fossil-fuel combustion over the last c . 150 years, and diatom analysis indicates that the naturally acidic pool became more acidic during the 20th century. We conclude that the exceptionally acidic surface waters of the pool at present (pH = c . 4.1) are the result of a long history of air pollution and not because of naturally acidic local conditions. We argue that the highly acidic surface waters elsewhere in the NYM are similarly acidified and that the lack of evidence of significant recovery from acidification, despite major reductions in the emissions of acidic gases that have taken place over the last c . 30 years, indicates the continuing influence of pollutant sulphur stored in catchment peats, a legacy of over 150 years of acid deposition.