Immunomodulating activity of exogenous ceruloplasmin in experimental tumor growth]

Immunomodulating properties of ceruloplasmin were determined in vivo on healthy mice line C57BL/6 and mice with Lewis carcinoma. It was established, that ceruloplasmin at the concentration of 1-40 mg/kg stimulated both T- and B--systems of immunity and prevented immunodepression activity of tumor growth.     

Efficacy and Mechanisms of Murine Norovirus Inhibition by Pulsed-Light Technology

Pulsed light is a nonthermal processing technology recognized by the FDA for killing microorganisms on food surfaces, with cumulative fluences up to 12 J cm⁻². In this study, we investigated its efficacy for inactivating murine norovirus 1 (MNV-1) as a human norovirus surrogate in phosphate-buffered saline, hard water, mineral water, turbid water, and sewage treatment effluent and on food contact surfaces, including high-density polyethylene, polyvinyl chloride, and stainless steel, free or in an alginate matrix. The pulsed-light device emitted a broadband spectrum (200 to 1,000 nm) at a fluence of 0.67 J cm⁻² per pulse, with 2% UV at 8 cm beneath the lamp. Reductions in viral infectivity exceeded 3 log₁₀ in less than 3 s (5 pulses; 3.45 J cm⁻²) in clear suspensions and on clean surfaces, even in the presence of alginate, and in 6 s (11 pulses; 7.60 J cm⁻²) on fouled surfaces except for stainless steel (2.6 log₁₀). The presence of protein or bentonite interfered with viral inactivation. Analysis of the morphology, the viral proteins, and the RNA integrity of treated MNV-1 allowed us to elucidate the mechanisms involved in the antiviral activity of pulsed light. Pulsed light appeared to disrupt MNV-1 structure and degrade viral protein and RNA. The results suggest that pulsed-light technology could provide an effective alternative means of inactivating noroviruses in wastewaters, in clear beverages, in drinking water, or on food-handling surfaces in the presence or absence of biofilms.     

Evolutionarily conserved proteins MnmE and GidA catalyze the formation of two methyluridine derivatives at tRNA wobble positions

The wobble uridine of certain bacterial and mitochondrial tRNAs is modified, at position 5, through an unknown reaction pathway that utilizes the evolutionarily conserved MnmE and GidA proteins. The resulting modification (a methyluridine derivative) plays a critical role in decoding NNG/A codons and reading frame maintenance during mRNA translation. The lack of this tRNA modification produces a pleiotropic phenotype in bacteria and has been associated with mitochondrial encephalomyopathies in humans. In this work, we use in vitro and in vivo approaches to characterize the enzymatic pathway controlled by the Escherichia coli MnmE•GidA complex. Surprisingly, this complex catalyzes two different GTP- and FAD-dependent reactions, which produce 5-aminomethyluridine and 5-carboxymethylamino-methyluridine using ammonium and glycine, respectively, as substrates. In both reactions, methylene-tetrahydrofolate is the most probable source to form the C5-methylene moiety, whereas NADH is dispensable in vitro unless FAD levels are limiting. Our results allow us to reformulate the bacterial MnmE•GidA dependent pathway and propose a novel mechanism for the modification reactions performed by the MnmE and GidA family proteins.     

Two Independent Functions of Collier/Early B Cell Factor in the Control of Drosophila Blood Cell Homeostasis

Blood cell production in the Drosophila hematopoietic organ, the lymph gland, is controlled by intrinsic factors and extrinsic signals. Initial analysis of Collier/Early B Cell Factor function in the lymph gland revealed the role of the Posterior Signaling Center (PSC) in mounting a dedicated cellular immune response to wasp parasitism. Further, premature blood cell differentiation when PSC specification or signaling was impaired, led to assigning the PSC a role equivalent to the vertebrate hematopoietic niche. We report here that Collier is expressed in a core population of lymph gland progenitors and cell autonomously maintains this population. The PSC contributes to lymph gland homeostasis by regulating blood cell differentiation, rather than by maintaining core progenitors. In addition to PSC signaling, switching off Collier expression in progenitors is required for efficient immune response to parasitism. Our data show that two independent sites of Collier/Early B Cell Factor expression, hematopoietic progenitors and the PSC, achieve control of hematopoiesis.     

BaySTDetect: detecting unusual temporal patterns in small area data via Bayesian model choice

Space-time modeling of small area data is often used in epidemiology for mapping chronic disease rates and by government statistical agencies for producing local estimates of, for example, unemployment or crime rates. Although there is typically a general temporal trend, which affects all areas similarly, abrupt changes may occur in a particular area, e.g. due to emergence of localized predictors/risk factor(s) or impact of a new policy. Detection of areas with "unusual" temporal patterns is therefore important as a screening tool for further investigations. In this paper, we propose BaySTDetect, a novel detection method for short-time series of small area data using Bayesian model choice between two competing space-time models. The first model is a multiplicative decomposition of the area effect and the temporal effect, assuming one common temporal pattern across the whole study region. The second model estimates the time trends independently for each area. For each area, the posterior probability of belonging to the common trend model is calculated, which is then used to classify the local time trend as unusual or not. Crucial to any detection method, we provide a Bayesian estimate of the false discovery rate (FDR). A comprehensive simulation study has demonstrated the consistent good performance of BaySTDetect in detecting various realistic departure patterns in addition to estimating well the FDR. The proposed method is applied retrospectively to mortality data on chronic obstructive pulmonary disease (COPD) in England and Wales between 1990 and 1997 (a) to test a hypothesis that a government policy increased the diagnosis of COPD and (b) to perform surveillance. While results showed no evidence supporting the hypothesis regarding the policy, an identified unusual district (Tower Hamlets in inner London) was later recognized to have higher than national rates of hospital readmission and mortality due to COPD by the National Health Service, which initiated various local enhanced services to tackle the problem. Our method would have led to an early detection of this local health issue.     

Concordance of leishmaniasis cutaneous tests in Tunisia

A cross sectional study aimed to evaluate the effect of antigenic preparation (Leishmania infantum versus Leishmania major) and dose of leishmania antigens (5 x 10(6) versus 2.5 x 10(6) parasites in the same volume) on the reproducibility of delayed type hypersensitivity leishmania skin test. Results showed that among 34 individuals involved from visceral leishmaniasis endemic area. 26 (76.5%) had a positif Leishmania infantum leishmania (L-L. infantum) test and 27 (79.4%) to Leishmania major leishmania (L-L. major). Mean size of cutaneous reaction was 5.94 +/- 2.86 mm for L-L. infantum and 5.41 +/- 3.23 mm for L-L. major, with a significant positive linear association (p < 10-3). Intra-class correlation coefficient was 0.80 (CI95% = [0.64-0.93]) and concordance Kappa (kappa) was 0.57 (CI95% = [0.40-0.74]). Among 153 individuals from zoonotic cutaneous leishmaniasis. 92.9% revealed a positive test for both types of leishmanin (L-L. major full dose versus L-L. major half dose). Mean size of cutaneous reaction was 12.61 +/- 4.65 mm for the reference test and 11.30 +/- 3.95 mm for diluted one, with a positive linear association (p < 10-3). Intra-class correlation coefficient was 0.78 (IC95% = [0.71-0.84]) and concordance Kappa (kappa) was 0.82 (IC95% = [0.73-0.91]). These results demonstrate a limited effect of leishmania antigenic variation and antigen dose on the reproducibility of delayed type hypersensitivity induced by the leishmanin test.     

Leishmania infantum species-specific kDNA probes: isolation and evaluation

The study refers to the isolation of specific DNA probes to the parasite species Leishmania (L) infantum according to different strategies using recombinant minicircles isolated from L. infantum kinetoplast DNAs. A first probe was identified following a classical procedure. One mini-circle selected for strong reactivity to L. infantum total DNA was used to identify specific subfragments to this species among which the 95bp fragment, 3B8HaeIII-2 was selected. For the obtention of the second probe, a strategy based on sequential screenings for specificity and sensitivity was applied. This allowed identification of a set of minicircles showing an increased specificity to L. infantum as compared to other species, and an increased sensitivity of reaction as compared to the other minicircles. Subclonings and screenings allowed a final selection of a 137bp-minicircle fragment: 3E9HaeIII-12. Reactivities of the 2 probes were assessed on a panel of total DNAs and promastigotes from 74 isolates pertaining to 9 species encountered in the Old World. Parasites isolated in Tunisia from different foci, different hosts after different transmission seasons were included. Hybridizations have shown the exquisite specificity of these probes to L. infantum in this country. Probe 3E9HaeIII-12 was found to be the more sensitive where down to 10 ng of total DNA and 10(3) promastigotes could be detected. From this study and as compared to data provided in the literature, the second procedure allowed at least 10-fold increase in sensitivity.     

Toxin-based in-vitro selection and its potential application to date palm for resistance to the bayoud Fusarium wilt

Date palm (Phoenix dactylifera L.) is qualified as a 'tree' of great ecological and socio-economical importance in desert oases. Unfortunately, it is being decimated, especially in Morocco and Algeria, by a fusariosis wilt called bayoud and caused by Fusarium oxysporum f. sp. albedinis (Fao). Controlling this disease requires the implementation of an integrated management program. Breeding for resistance is one of the most promising component strategies of this program. Few naturally resistant cultivars with a mediocre fruit quality (dates) are known. Conventional and non-conventional methods are under development and have to use the simplest and easiest methods to screen for resistant individuals. The use of pathogen toxins as selective agents at the tissue culture step might be a source of variability that can lead to the selection of individuals with suitable levels of resistance to the toxin and/or to the pathogen among the genetic material available. Foa produces toxins such as fusaric, succinic, 3-phenyl lactic acids and their derivatives, marasmins and peptidic toxins. These toxins can be used bulked or separately as selective agents. The aim of this contribution was to give a brief overview on toxins and their use as a mean to select resistant lines and to initiate a discussion about the potential use of this approach for the date palm-Foa pathosystem. This review does not pretend to be comprehensive or exhaustive and was prepared mainly to highlight the potential use of Foa toxins for selecting date palm individuals with a suitable resistance level to bayoud using toxin-based selective media.     

Tubers from potato lines expressing a tomato Kunitz protease inhibitor are substantially equivalent to parental and transgenic controls

Recombinant protease inhibitors represent useful tools for the development of insect‐resistant transgenic crops, but questions have been raised in recent years about the impact of these proteins on endogenous proteases and chemical composition of derived food products. In this study, we performed a detailed compositional analysis of tubers from potato lines expressing the broad‐spectrum inhibitor of Ser and Asp proteases, tomato cathepsin D inhibitor (SlCDI), to detect possible unintended effects on tuber composition. A compositional analysis of key nutrients and toxic chemicals was carried out with tubers of SlCDI‐expressing and control (comparator) lines, followed by a two‐dimensional gel electrophoresis (2‐DE) proteomic profiling of total and allergenic proteins to detect eventual effects at the proteome level. No significant differences were observed among control and SlCDI‐expressing lines for most chemicals assayed, in line with the very low abundance of SlCDI in tubers. Likewise, proteins detected after 2‐DE showed no quantitative variation among the lines, except for a few proteins in some control and test lines, independent of slcdi transgene expression. Components of the patatin storage protein complex and Kunitz protease inhibitors immunodetected after 2‐DE showed unaltered deposition patterns in SlCDI‐expressing lines, clearly suggesting a null impact of slcdi on the intrinsic allergenic potential of potato tubers. These data suggest, overall, a null impact of slcdi expression on tuber composition and substantial equivalence between comparator and SlCDI‐expressing tubers despite reported effects on leaf protein catabolism. They also illustrate the usefulness of proteomics as a tool to assess the authenticity of foods derived from novel‐generation transgenic plants.