Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy. Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis, galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1 was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived antibody responses.     

Trace elements in rock salt and their bioavailability estimated from solubility in acid

In this study, 18 partly commercially available samples of rock salt from Austria, Germany, Pakistan, Poland, Switzerland, and Ukraine were investigated with respect to their content of trace elements using instrumental neutron activation analysis. Elements detected were Al, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Eu, Fe, Hf, La, Mn, Na, Rb, Sb, Sc, Sm, Sr, Ta, Tb, Th, and Zn, some of them only in individual cases. An estimation of the bioavailability of these trace elements was performed by dissolving an equivalent of the sodium chloride samples in diluted hydrochloric acid (simulating stomach acid), filtering off the insoluble components, and analyzing the evaporated filtrate. It could be shown that in most cases bioactive trace elements like Fe can be found in rock salt in the form of almost insoluble compounds and are therefore not significantly bioavailable, whereas thorium, for example, was partly bioavailable in two cases. A significant contribution to the recommended daily intake of metal trace elements by using rock salt for nutrition can be excluded.     

Head width–body mass equation: facilitating worker termite biomass estimates

1. Termites are one of the most important invertebrate ecosystem engineers in tropical regions, which may be quantified using termite biomass data. However, biomass data are particularly difficult to collect as they rely on termites being weighed in the field, which may neither be possible nor convenient. Local scale linear regression models, based on termite head widths (mm) and body masses (mg), have been used in the past to estimate termite biomass using head width and abundance data. However, these models represent very limited numbers of termite taxa from single sites. In the present study, I provide one of the most representative linear regression models available based on 90 samples from three different countries (Peru, Kenya, and Malaysia). 2. Although the linear regression model under‐ or overestimated body weights of taxa with characteristic features (e.g. large heads of Odontotermes workers or elongated abdomens of Kalotermitidae) it provides a robust method for estimating termite biomass at the community level. Additionally, while there are limitations related to the general model, which may be solved by focusing on taxa specific data and the use of higher accuracy equipment, it is the first model to facilitate termite biomass estimates using the head with and abundance data only. 3. This study encourages the use of termite biomass data to gain a better understanding of termites in ecosystem processes and calls for comparative data to be gathered for the purpose of creating models that may be representative of the variability among termite taxa.     

Body size but not colony size increases with altitude in the holarctic ant,Leptothorax acervorum

1. Bergmann's rule states that organisms inhabiting colder environments show an increase in body size or mass in comparison to their conspecifics living in warmer climates. Although originally proposed for homoeothermic vertebrates, this rule was later extended to ectotherms. In social insects, only a few studies have tested this rule and the results were ambiguous. Here, ‘body size’ can be considered at two different levels (the size of the individual workers or the size of the colony). 2. In this study, data from 53 nests collected along altitudinal gradients in the Alps were used to test the hypotheses that the worker body size and colony size of the ant Leptothorax acervorum increase with increasing altitude and therefore follow Bergmann's rule. 3. The results show that the body size of workers but not the colony size increases with altitude. Whether this pattern is driven by starvation resistance or other mechanisms remains to be investigated.     

Gross intestinal morphometry and allometry in primates

Although it is generally assumed that among mammals and within mammal groups, those species that rely on diets consisting of greater amounts of plant fiber have larger gastrointestinal tracts (GIT), statistical evidence for this simple claim is largely lacking. We compiled a dataset on the length of the small intestine, caecum, and colon in 42 strepsirrhine, platyrrhine, and catarrhine primate species, using specimens with known body mass (BM). We tested the scaling of intestine length with BM, and whether dietary proxies (percentage of leaves and a diet quality index) were significant covariates in these scaling relationships, using two sets of models: one that did not account for the phylogenetic structure of the data, and one that did. Intestine length mainly scaled geometrically at exponents that included 0.33 in the confidence interval; Strepsirrhini exhibited particularly long caeca, while those of Catarrhini were comparatively short. Diet proxies were only significant for the colon and the total large intestine (but not for the small intestine or the caecum), and only in conventional statistics (but not when accounting for phylogeny), indicating the pattern occurred across but not within clades. Compared to terrestrial Carnivora, primates have similar small intestine lengths, but longer large intestines. The data on intestine lengths presented here corroborate recent results on GIT complexity, suggesting that diet, as currently described, does not exhaustively explain GIT anatomy within primate clades.     

From the Schnauzenorgan to the back: Morphological comparison of mormyromast electroreceptor organs at different skin regions of Gnathonemus petersii

The nocturnally active weakly electric fish Gnathonemus petersii is known to employ active electrolocation for the detection of objects and for orientation in its environment. The fish emits pulse‐type electric signals with an electric organ and perceives these signals with more than 3,000 epidermal electroreceptor organs, the mormyromasts, which are distributed over the animal's skin surface. In this study, we measured the metric dimensions of the mormyromasts from different body regions to find structural and functional specialization of the various body parts. We focused on the two foveal regions of G. petersii, which are located at the elongated and movable chin (the Schnauzenorgan; SO) and at the nasal region (NR), the skin region between the mouth and the nares. These two foveal regions were compared to the dorsal part (back) of the fish, which contains typical nonfoveal mormyromasts. While the gross anatomy of the mormyromasts from all skin regions is similar, the metric dimensions of the main substructures differed. The mormyromasts at the SO are the smallest and contain the smallest receptor cells. In addition, the number of receptor cells per organ is lowest at the SO. In contrast, at the back the biggest receptor organs with the highest amount of receptor cells per organ occur. The mormyromasts at the NR are in several respects intermediate between those from the back and the SO. However, mormyromasts at the NR are longer than those at all other skin regions, the canal leading from the receptor pore to the inner chambers were the longest and the overlaying epidermal layers are the thickest. These results show that mormyromasts and the epidermis they are embedded in at both foveal regions differ specifically from those found on the rest of the body. The morphological specializations lead to functional specialization of the two foveae. J. Morphol., 2012. © 2012 Wiley Periodicals, Inc.     

A Mathematical Framework for Combining Decisions of Multiple Experts toward Accurate and Remote Diagnosis of Malaria Using Tele-Microscopy

We propose a methodology for digitally fusing diagnostic decisions made by multiple medical experts in order to improve accuracy of diagnosis. Toward this goal, we report an experimental study involving nine experts, where each one was given more than 8,000 digital microscopic images of individual human red blood cells and asked to identify malaria infected cells. The results of this experiment reveal that even highly trained medical experts are not always self-consistent in their diagnostic decisions and that there exists a fair level of disagreement among experts, even for binary decisions (i.e., infected vs. uninfected). To tackle this general medical diagnosis problem, we propose a probabilistic algorithm to fuse the decisions made by trained medical experts to robustly achieve higher levels of accuracy when compared to individual experts making such decisions. By modelling the decisions of experts as a three component mixture model and solving for the underlying parameters using the Expectation Maximisation algorithm, we demonstrate the efficacy of our approach which significantly improves the overall diagnostic accuracy of malaria infected cells. Additionally, we present a mathematical framework for performing ‘slide-level’ diagnosis by using individual ‘cell-level’ diagnosis data, shedding more light on the statistical rules that should govern the routine practice in examination of e.g., thin blood smear samples. This framework could be generalized for various other tele-pathology needs, and can be used by trained experts within an efficient tele-medicine platform.     

Production of the lepidoptera-specific crystal protein by a local isolate of Bacillus thuringiensis

Summary A local isolate of Bacillus thuringiensis (B.t.81) produced crystal protein which was identified as a cry I gene of Class I. The synthesis and assembly of crystal complements were investigated at intervals throughout the growth cycle. Incubation temperature had a marked effect on toxin synthesis; production being the highest at 25°C and the lowest at 42°C. The mutants of B. t. 81, unable to synthesize crystal protein complements, have also been described.