Correction to: Sex and race differences of cerebrospinal fluid metabolites in healthy individuals

Metabolomics - Metabolomics applications to the aquaculture research are increasing steadily. The use of standardized proton nuclear magnetic resonance (1H NMR) spectroscopy can provide the...     

The evolving systemic and local biomarker milieu at different stages of disease progression in rat collagen-induced arthritis

Rats with collagen-induced arthritis (CIA) were necropsied on 14 occasions from 4 days after induction to 27 days after disease onset to evaluate the kinetics of local (joint protein extracts) and systemic (serum) levels of inflammatory and pro-erosive factors. Systemic increases in α1 acid glycoprotein and KC/GRO together with systemic and local enrichment of interleukin (IL)-1β, IL-6, CCL2, transforming growth factor (TGF)-β and elevated IL-1α and IL-18 in joint extracts preceded the onset of clinical disease. Systemic upregulation of IL-1β, IL-6, TGF-β CCL2, RANKL and prostaglandin E₂ (PGE₂) during acute and/or chronic CIA coincided with systemic leukocytosis and a CD4+ T-cell increase in blood and spleen. In contrast, progression of joint erosions during clinical CIA was associated with intra-articular increases in IL-1α/β, IL-6, IL-18, CCL2, KC/GRO and RANKL, and a dramatic decline in osteoprotegerin (OPG). These data indicate that systemic and local events in inflammatory arthritis can be discrete processes, driven by multiple cellular and humoral mediators with distinct temporospatial profiles.     

Landscape influences on climate‐related lake shrinkage at high latitudes

Climate‐related declines in lake area have been identified across circumpolar regions and have been characterized by substantial spatial heterogeneity. An improved understanding of the mechanisms underlying lake area trends is necessary to predict where change is most likely to occur and to identify implications for high latitude reservoirs of carbon. Here, using a population of ca. 2300 lakes with statistically significant increasing and decreasing lake area trends spanning longitudinal and latitudinal gradients of ca. 1000 km in Alaska, we present evidence for a mechanism of lake area decline that involves the loss of surface water to groundwater systems. We show that lakes with significant declines in lake area were more likely to be located: (1) in burned areas; (2) on coarser, well‐drained soils; and (3) farther from rivers compared to lakes that were increasing. These results indicate that postfire processes such as permafrost degradation, which also results from a warming climate, may promote lake drainage, particularly in coarse‐textured soils and farther from rivers where overland flooding is less likely and downslope flow paths and negative hydraulic gradients between surface water and groundwater systems are more common. Movement of surface water to groundwater systems may lead to a deepening of subsurface flow paths and longer hydraulic residence time which has been linked to increased soil respiration and CO₂ release to the atmosphere. By quantifying relationships between statewide coarse resolution maps of landscape characteristics and spatially heterogeneous responses of lakes to environmental change, we provide a means to identify at‐risk lakes and landscapes and plan for a changing climate.     

A preliminary assessment of the response of a native reptile assemblage to spot‐spraying invasive Bitou Bush with glyphosate herbicide

During recent work examining the effects of Bitou Bush (Chrysanthemoides monilifera ssp. rotundata) invasion on native reptile assemblages in coastal heathland vegetation in Eastern Australia, unplanned spot‐spraying of glyphosate occurred at some of our experimental sites invaded by Bitou Bush. We used this unexpected herbicide application as an opportunity to provide a preliminary assessment of the short‐term impacts on reptiles of glyphosate spot‐spraying of Bitou Bush. Using an M‐BARCI design, we compared reptile assemblages among uninvaded (reference) sites, invaded (control) sites and invaded and sprayed (impact) sites before and after spraying. We found no significant short‐term (7 – 10 months) differences in reptile abundance, species richness or assemblage composition among invaded, uninvaded and sprayed sites before and after glyphosate application. We cautiously interpret our results to generate a preliminary finding that spot‐spraying of Bitou Bush with glyphosate appears not to have a deleterious effect on reptile assemblages at seven and ten months following herbicide application. While we would not recommend basing management decisions on the outcomes of our study alone, we suggest that our findings can be used to assist in the development of strategic analyses of glyphosate impacts on native flora and fauna.     

Characterization of a New Chronic Lymphocytic Leukemia Cell Line for Mechanistic In Vitro and In Vivo Studies Relevant to Disease

Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient’s CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient’s normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease.     

Relationship between the Magnitude of Intraocular Pressure during an Episode of Acute Elevation and Retinal Damage Four Weeks later in Rats

Purpose

To determine relationship between the magnitude of intraocular pressure (IOP) during a fixed-duration episode of acute elevation and the loss of retinal function and structure 4 weeks later in rats.

Methods

Unilateral elevation of IOP (105 minutes) was achieved manometrically in adult Brown Norway rats (9 groups; n = 4 to 8 each, 10–100 mm Hg and sham control). Full-field ERGs were recorded simultaneously from treated and control eyes 4 weeks after IOP elevation. Scotopic ERG stimuli were white flashes (−6.04 to 2.72 log cd.s.m⁻²). Photopic ERGs were recorded (1.22 to 2.72 log cd.s.m⁻²) after 15 min of light adaptation (150 cd/m²). Relative amplitude (treated/control, %) of ERG components versus IOP was described with a cummulative normal function. Retinal ganglion cell (RGC) layer density was determined post mortem by histology.

Results

All ERG components failed to recover completely normal amplitudes by 4 weeks after the insult if IOP was 70 mmHg or greater during the episode. There was no ERG recovery at all if IOP was 100 mmHg. Outer retinal (photoreceptor) function demonstrated the least sensitivity to prior acute IOP elevation. ERG components reflecting inner retinal function were correlated with post mortem RGC layer density.

Conclusions

Retinal function recovers after IOP normalization, such that it requires a level of acute IOP elevation approximately 10 mmHg higher to cause a pattern of permanent dysfunction similar to that observed during the acute event. There is a ‘threshold’ for permanent retinal functional loss in the rat at an IOP between 60 and 70 mmHg if sustained for 105 minutes or more.     

Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite

CD8 T cells protect the host from disease caused by intracellular pathogens, such as the Toxoplasma gondii (T. gondii) protozoan parasite. Despite the complexity of the T. gondii proteome, CD8 T cell responses are restricted to only a small number of peptide epitopes derived from a limited set of antigenic precursors. This phenomenon is known as immunodominance and is key to effective vaccine design. However, the mechanisms that determine the immunogenicity and immunodominance hierarchy of parasite antigens are not well understood.Here, using genetically modified parasites, we show that parasite burden is controlled by the immunodominant GRA6-specific CD8 T cell response but not by responses to the subdominant GRA4- and ROP7-derived epitopes. Remarkably, optimal processing and immunodominance were determined by the location of the peptide epitope at the C-terminus of the GRA6 antigenic precursor. In contrast, immunodominance could not be explained by the peptide affinity for the MHC I molecule or the frequency of T cell precursors in the naive animals. Our results reveal the molecular requirements for optimal presentation of an intracellular parasite antigen and for eliciting protective CD8 T cells.