Fundamentals of host immune response against Brucella abortus: what the mouse model has revealed about control of infection

The studies reviewed here evaluated the role cellular immune system components play in control of brucellosis by conducting comparative studies with brucella-resistant C57BL/10 or C57BL/6 mice and susceptible BALB/c mice. We have shown by both in vitro and in vivo studies that activation of macrophages with interferon-gamma (IFN-γ) is an important factor for control of infection with B. abortus in the mouse model and that the mechanism of anti-brucella activity largely involved reactive oxygen intermediates. Differences in control of the organism by resistant and susceptible mice was not related to inherent differences in the ability of their macrophages to control infection either with or without IFN-γ activation nor was it attributable to NK cells since we found no role for them in control of brucellosis in either mouse strain. However, relative resistance to brucellosis did correlate with increased production of IFN-γ by CD4 T cells during the first weeks after infection while IL-10 contributed to susceptibility in BALB/c mice. Moreover, by 3 weeks post-infection splenocytes from the susceptible BALB/c mice failed to produce IFN-γ and relied on TNF- as well as CD8 T cells to control infection until the end of the plateau phase around 6 weeks post-infection when IFN-γ production resumed and clearance began. In contrast, IFN-γ was crucial for control throughout the infection in the more resistant C57BL/6 mice and the mice died in its absence by 6 weeks post-infection compared to 12 weeks for the more susceptible mice that relied on additional mechanisms of control. In contrast to the IFN-γ knock-out mice, both β2 microglobulin knock-out C57BL/6 mice, which do not express conventional MHC class I molecules and thus cannot present antigen to CD8 T cells, or perforin knock-out C57BL/6 mice, which have no T cell cytotoxic activity, controlled and cleared the infection as well as normal C57BL/6 mice. The hiatus of IFN-γ production in BALB/c mice correlated with very high levels of total IL-12 and it was postulated that the lack of IFN-γ was a consequence of p40 homodimer blocking activity. However, reduction of p40 IL-12 in vivo through administration of indomethacin reduced the infection without a concomitant measurable increase in IFN-γ. Current studies are aimed at elucidating the mechanism of the IFN-γ hiatus.     

Identification of infrared absorption spectral characteristics of synovial fluid of horses with osteochondrosis of the tarsocrural joint

OBJECTIVE: To determine the feasibility of the use of Fourier-transform infrared (FTIR) spectroscopy within the midinfrared range to differentiate synovial fluid samples of joints with osteochondrosis from those of control samples. ANIMALS: 33 horses with osteochondrosis of the tarsocrural joint and 31 horses free of tarsocrural joint disease. PROCEDURES: FTIR spectroscopy of synovial fluid was used. Sixty-four synovial fluid samples from the tarsocrural joint were collected. Of these, 33 samples were from horses with radiographic evidence of osteochondrosis of the tarsocrural joint and 31 from control joints. Disease-associated features within infrared spectra of synovial fluid were statistically selected for spectral classification, and the variables identified were used in a classification model. Linear discriminant analysis and leave-one-out cross-validation were used to develop a classifier to identify joints with osteochondrosis. RESULTS: 12 significant subregions were identified that met the selection criteria. The stepwise discriminant procedure resulted in the final selection of 6 optimal regions that most contributed to the discriminatory power of the classification algorithm. Infrared spectra derived from synovial fluid of joints with osteochondrosis were differentiated from the control samples with accuracy of 77% (81% specificity and 73% sensitivity). CONCLUSIONS AND CLINICAL RELEVANCE: The disease-associated characteristics of infrared spectra of synovial fluid from joints with osteochondrosis may be exploited via appropriate feature selection and classification algorithms to differentiate joints with osteochondrosis from those of control joints. Further study with larger sample size including age-, breed-, and sex-matched control horses would further validate the clinical value of infrared spectroscopy for the diagnosis of osteochondrosis in horses.     

Soil organic matter and related physical properties in a Mediterranean wheat-based rotation trial

Under semi-arid Mediterranean conditions, limited moisture is the main constraint to rainfed cropping with wheat (Triticum aestivum), barley (Hordeum vulgare), and food and forage legumes. With increasing land-use pressure, moisture-conserving fallowing is being replaced by continuous cropping, which is considered an unsustainable practice. Thus, a long-term trial with durum wheat (T. turgidum var. durum) was established in 1983 at Tel Hadya, Aleppo, Syria (mean annual rainfall 330 mm) to assess alternative rotation options to fallow and continuous cropping. Nitrogen (N) and grazing/residue management were secondary factors. Soil aggregation, infiltration, hydraulic conductivity, and total soil organic matter and component fractions (fulvic and humic acids and polysaccharides) were determined at the end of 12 years. Some rotations, e.g., medic (Medicago sativa) and vetch (Vicia faba), significantly increased soil organic matter (12.5–13.8 g kg⁻¹ versus 10.9–11 g kg⁻¹ for continuous wheat and wheat/fallow). All measurements, or indices, indicated parallel trends with increasing organic matter, e.g., coefficients of macro-structure, micro-aggregation, and water-stable aggregates, and decreasing dispersion. Similarly, legume rotations had higher infiltration rates (16.2–21.8 cm h⁻¹ versus 13.9–14.4 cm h⁻¹ with continuous wheat and wheat/fallow) and hydraulic conductivity rates (8.7–12.4 cm h⁻¹ versus 6.2–7.4 cm h⁻¹ with continuous wheat and wheat/fallow). We conclude that cereal/legume rotations, in addition to being biologically and economically attractive, also enhance soil quality and thus promote soil use sustainability in fragile semi-arid areas as in the Mediterranean zone.     

Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state

Tolerant self-antigen-specific CD8 T cells fail to proliferate in response to antigen, thereby preventing autoimmune disease. By using an in vivo mouse model, we show that tolerant T cells proliferate and become functional under lymphopenic conditions, even in a tolerogenic environment. However, T cell rescue is only transient, with tolerance reimposed upon lymphorepletion even in the absence of tolerogen (self-antigen), challenging the prevailing paradigm that continuous antigen exposure is critical to maintain tolerance. Genome-wide messenger RNA and microRNA profiling revealed that tolerant T cells have a tolerance-specific gene profile that can be temporarily overridden under lymphopenic conditions but is inevitably reimposed, which suggests epigenetic regulation. These insights into the regulatory mechanisms that maintain or break self-tolerance may lead to new strategies for the treatment of cancer and autoimmunity.     

Potential errors in measurement of nonuniform sap flow using heat dissipation probes

The empirical calibration of Granier-type heat dissipation sap flow probes that relate temperature difference (DeltaT) to sap velocity (v) was reevaluated in stems of three tropical tree species. The original calibration was confirmed when the entire heated probe was in contact with conducting xylem, but mean v was underestimated when part of the probe was in contact with nonconducting xylem or bark. Analysis of the effects of nonuniform sap velocity profiles on heat dissipation estimates showed that errors increased as v and the proportion of the probe in nonconducting wood increased. If half of a 20-mm probe is in sapwood with a v of 0.15 mm s(-1) and the other half is in nonconducting wood, then mean v for the whole probe can be underestimated by as much as 50%. A correction was developed that can be used if the proportion of the probe in nonconducting wood is known. Even with the entire heated probe in contact with conducting xylem, v would be underestimated when radial velocity gradients are present. In this case, the error would be smaller except when velocity gradients are very steep, as can occur in species with ring-porous wood anatomy. Errors occur because the relationship between DeltaT and v is nonlinear. Mean DeltaT along the probe is therefore not a measure of mean v, and users of heat dissipation probes should not assume that v is integrated along the length of the probe. The same type of error can occur when DeltaT is averaged through time while v is changing, but the error is small unless there are sudden, step changes between zero and high sap velocity. It is recommended that relatively short probes (20 mm or less) be used and that probes longer than the depth of conducting sapwood be avoided. Multiple probes inserted to a range of depths should be used in situations where steep gradients in v are expected. If these conditions are met, heat dissipation probes remain useful and widely applicable for measuring sap flow in woody stems.     

Bovine spongiform encephalopathy: aspects of the clinical picture and analyses of possible changes 1986-1990.

A standard questionnaire was used to record the presence of specific clinical signs reported for histopathologically confirmed cases of bovine spongiform encephalopathy observed before June 30, 1990, and the frequencies of these signs were analysed. The signs most frequently recorded were apprehension, hyperaesthesia and ataxia, and there were variations in the frequency with which some signs were recorded in animals observed at different times during the epidemic. These variations were considered to be the result of differences between observers and differences in the duration of the illness, rather than a change in the clinical picture, which could possibly have occurred with a change in the nature of the agent to which the cattle had been exposed, or to a change in their response to the agent.     

Decline and extirpation of an endangered Panamanian stream frog population (Craugastor punctariolus) due to an outbreak of chytridiomycosis

We conducted a mark-recapture study of three subpopulations of Craugastor punctariolus at a mid-elevation site in central Panama between 1999 and 2005. The study spans a period over which the pathogenic fungus Batrachochytrium dendrobatidis (Bd) was absent from the site, invaded the site and decimated all amphibian populations, and now persists. We quantified natural demographic parameters prior to and during an event of mass mortality due to chytridiomycosis caused by Bd. Prior to the event of mass mortality, all three subpopulations of C. punctariolus were large (19-68 animals/200 m), showed a stable age-size distribution, and had high survival. All age-size classes of this species co-occurred on boulder clumps along streams, and adults showed high site fidelity and were likely territorial. Following detection of Bd at this site in late September 2004, four dead C. punctariolus were found infected with Bd and all three subpopulations completely disappeared from this site within 2 months. The association of all age-size classes with microhabitats appropriate for survival and growth of Bd likely contributed to the rapid and severe degree of decline of this species at this site. These data provide insight into the patterns and mechanisms of decline within a species due to Bd.     

Resource-use,body condition and parasite load metrics indicate contrasting health of stocked and native game fishes in Canadian prairie lakes

This study evaluated the status of native and stocked fish species in 13 prairie lakes in central Canada over eight years (2007–14) using three metrics: resource-use (benthic versus pelagic carbon via stable isotopes); body condition (relative weight index W_r); and parasite load (cestode gut enumerations). Analyses included game and non-game fishes, like naturally occurring northern pike, Esox lucius L., and yellow perch, Perca flavescens Mitchill, but focused on stocked walleye, Sander vitreus (Mitchill) because it supports a robust recreational fishery. Walleye and northern pike were significantly more reliant on benthic carbon than yellow perch or forage fishes (p < 0.05), but this reliance was not associated with any measured environmental variables for any species. In lakes with game fishes, forage fishes exhibited higher reliance on benthic energy, possibly due to predator avoidance strategy, particularly yellow perch. Walleye body condition index was consistently lower (<95–105) than values exhibited by the other two game fishes (81–139), and parasites were only common in walleye and associated with lake-water salinity (r² = 0.93, p < 0.05) and sex (p < 0.05). Based on the results, the most desirable game fish, walleye, appears less resilient to environmental variability than northern pike and yellow perch, making this species more susceptible to impacts of future climate change.