Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.     

Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III

The T-cell tropic retrovirus of macaque monkeys STLV-III has morphologic, growth, and antigenic properties indicating that it is related to HTLV-III/LAV, the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Four of six rhesus monkeys died within 160 days of STLV-III inoculation with a wasting syndrome, opportunistic infections, a primary retroviral encephalitis, and immunologic abnormalities including a decrease in T4+ peripheral blood lymphocytes. These data show that an immunodeficiency syndrome can be produced experimentally in a nonhuman primate by an agent from the HTLV-III/LAV group of retroviruses. The STLV-III-macaque system will thus provide a useful model for the study of antiviral agents and vaccine development for human AIDS.     

Beef authentication and retrospective dietary verification using stable isotope ratio analysis of bovine muscle and tail hair

Stable isotope ratio analysis (SIRA) was used as an analytical tool to verify the preslaughter diet of beef cattle. Muscle and tail hair samples were collected from animals fed either pasture (P), a barley-based concentrate (C), silage followed by pasture (SiP), or silage followed by pasture with concentrate (SiPC) for 1 year (n = 25 animals per treatment). The (13)C/(12)C, (15)N/(14)N, (2)H/(1)H, and (34)S/(32)S isotope ratios in muscle clearly reflected those of the diets consumed by the animals. By applying a stepwise canonical discriminant analysis, a good discrimination of bovine meat according to dietary regimen was obtained. On the basis of the classification success rate, the (13)C/(12)C and (34)S/(32)S ratios in muscle were the best indicators for authentication of beef from animals consuming the different diets. Analysis of (13)C/(12)C and (15)N/(14)N in tail hair sections provided an archival record of changes to the diet of the cattle for periods of over 1 year preslaughter.     

A spatially explicit height�Cdiameter model for Scots pine in Estonia

This contribution presents an approach to model individual tree height?Cdiameter relationships for Scots pine (Pinus sylvestris) in multi-size and mixed-species stands in Estonia using the Estonian Permanent Forest Research Plot Network. The dataset includes 22,347 trees. The main focus of the study was to use an approach that is spatially explicit allowing for high accuracy prediction from a minimum set of predictor variables that can be easily derived. Consequently, the height?Cdiameter relationship is modeled as a function of only the stand quadratic mean diameter (dg) and the plot geographical coordinates. A specific generalized additive model gam is employed that allows for the integration of a varying coefficient term and 2-dimensional surface estimators representing a spatial trend and a spatially varying coefficient term. The high flexibility of the model is needed due to the very few predictor variables that subsume a variety of potential influential factors. Subsequently, a linear mixed model is used that quantifies the random variation between plots and between measurement occasions within plots, respectively. Hence, our model is based on the theory of structured additive regression models (Fahrmeir et al. 2007) and separates a structured (correlated) spatial effect from an unstructured (uncorrelated) spatial effect. Additionally, the linear mixed model allows for calibration of the model using height measurements as pre-information. Model bias is small, despite the somewhat irregular distribution of experimental areas within the country. The overall model shows some similarity with earlier applications in Finland. However, there are important differences involving the model form, the predictors and the method of parameter estimation.     

Serum chemistry comparisons between captive and free-ranging giraffes (Giraffa camelopardalis)

Serum chemistry analyses were compared between captive and free-ranging giraffes (Giraffa camelopardalis) in an attempt to better understand some of the medical issues seen with captive giraffes. Illnesses, including peracute mortality, energy malnutrition, pancreatic disease, urolithiasis, hoof disease, and severe intestinal parasitism, may be related to zoo nutrition and management issues. Serum samples were collected from 20 captive giraffes at 10 United States institutions. Thirteen of the captive animal samples were collected from animals trained for blood collection; seven were banked samples obtained from a previous serum collection. These samples were compared with serum samples collected from 24 free-ranging giraffes in South Africa. Differences between captive and free-ranging giraffes, males and females, and adults and subadults were analyzed by using a 2 x 2 x 2 factorial and Fisher's least significant difference for mean separation; when necessary variables were ranked and analyzed via analysis of variance. Potassium and bilirubin concentrations and alanine aminotransferase (ALT) activities were different between captive and free-ranging giraffes, but all fell within normal bovid reference ranges. The average glucose concentration was significantly elevated in free-ranging giraffes (161 mg/dl) compared with captive giraffes (113 mg/dl). All giraffes in this study had glucose concentrations higher than bovine (42-75 mg/ dl) and caprine (48-76 mg/dl) reference ranges. Differences were also seen in lipase, chloride, and magnesium though these findings are likely not clinically significant. There were no differences detected between sexes. Adults had higher concentrations of potassium, total protein, globulins, and chloride and higher gamma glutamyltransferase activities, whereas subadults had higher concentrations of phosphorus. Within the captive group, nonimmobilized animals had higher concentrations of total protein and globulins. Captive giraffe diets need further investigation to determine if the differences seen in this study, especially glucose and bilirubin concentrations and ALT activities, may result in some health problems often seen in captive giraffes.     

Screening of soil bacteria for plasmids carrying antibiotic resistance

Summary To evaluate the role of plasmids in soil communities antibiotic-resistant bacteria have been isolated from soil. Among them, 419 l-aminopeptidase positive strains (Gram-negative) and 28 l-aminopeptidase negative strains (Gram-positive) were screened for the presence of plasmids. None of the Gram-negative organisms contained plasmids. Among the Gram-positive bacteria plasmid-harboring strains were detected.     

Genetic diversity in sweetpotato [Ipomoea batatas (L.) Lam.] in relationship to geographic sources as assessed with RAPD markers

Available evidence shows that sweetpotato originated from either Central or South American lowlands with subsequent dispersal to North America, Europe, Africa, Asia and the pacific islands. A total of 71 polymorphic RAPD molecular markers were used to assess the genetic relationships amongst 74 sweetpotato varieties originating from a total of 23 sweetpotato producing countries within six geographical regions, namely, South America, Central America/Caribbean, United States of America (USA), East Africa, Asia and Oceania. An Analysis of Molecular Variance (AMOVA) indicated that 93.4% of the total variance was due to the differences between genotypes within regions. The difference between regions was significant (P < 0.001) but only contributed 6.6% to the variance. Genetic distance (PhiST) calculated with AMOVA and multidimensional scaling (MDS) revealed that the South American and the Central American/Caribbean genotypes formed two separate clusters. East African varieties, which have unique characteristics from other traditional varieties, were distinct from other traditional varieties from South America and Oceania. These results support the reported hypothesis of the origin and dispersal of the sweetpotato and indicate that the primary centre of diversity probably has two distinct genepools. It is proposed that the dispersal of the sweetpotato from its origin may have mainly involved varieties from Central America/Caribbean as opposed to varieties from South America. There is an indication that new genepools may be evolving in Africa and Asia due to hybridisation and adaptation to the local environments.     

Longitudinal trends in pH and aluminum chemistry of the Coxing Kill,Ulster County,New York

The purpose of this work was to characterize the Al chemistry along the longitudinal pH gradient of the Coxing Kill and thereby provide a basis for an in depth study of aluminum chemistry and transport as a function of pH. Water samples were collected along the pH gradient and analyzed for monomeric Al species, strong acid anions, base cations, ammonium, dissolved organic C and dissolved silica. Inorganic monomeric Al, organic momonmeric Al and dissolved organic C decreased in concentration as the stream's drainage area and pH increased. The ratio of organic to inorganic monomeric Al and the concentration of all other species increased with increasing pH. An abrupt change in stream chemistry occurred in conjunction with the gradual changes expected for a low order stream draining an acid sensitive watershed impacted by acid deposition. This abrupt change partially resulted from geological characteristics of the watershed.     

Factors affecting the collection and fitting of nuclear magnetic cross-relaxation spectroscopy data with application to waxy corn starch

An examination of the methods for nuclear magnetic cross-relaxation spectroscopy (CRS) data collection and analysis was conducted using water and an aqueous waxy corn starch suspension to better perform and interpret the results obtained using CRS. The CRS data collection properties evaluated were the time to achieve steady state saturation, the direct saturation of liquid protons, generation of transverse magnetization, and dependence of the offset frequency and radio frequency (RF) field strength of longitudinal relaxation in the presence of RF saturation. Effects were evaluated for variations of input values of RF saturation field strength, apparent cross-relaxation rate, and solid longitudinal relaxation rate on the results for solid content and solid internal mobility from fitting NMR data to modified theoretical expressions. Discrepancies between fitted and stoichiometric values for the solid to liquid proton ratio were investigated. The fitting procedure used a Gaussian line shape for RF saturation of the solid-like spin system and a Lorentzian line shape for RF saturation of the liquid-spin system. Conditions under which acceptable results can be obtained with limited data sets are discussed.