Composite lymphoma of concurrent T zone lymphoma and large cell B cell lymphoma in a dog.

BackgroundEvolution of indolent to aggressive lymphoma has been described in dogs but is difficult to distinguish from the de novo development of a second, clonally distinct lymphoma. Differentiation of these scenarios can be aided by next generation sequencing (NGS)-based assessment of clonality of lymphocyte antigen receptor genes.Case presentationAn 8-year-old male intact Mastiff presented with generalized lymphadenomegaly was diagnosed with nodal T zone lymphoma (TZL) based on cytology, histopathology, immunohistochemistry and flow cytometry. Thirteen months later, the dog re-presented with progressive lymphadenomegaly, and based on cytology and flow cytometry, a large B cell lymphoma (LBCL) was diagnosed. Sequencing-based clonality testing confirmed the de novo development of a LBCL and the persistence of a TZL.ConclusionsThe occurrence of two distinct lymphoid neoplasms should be considered if patient features and tumor cytomorphology or immunophenotype differ among sequential samples. Sequencing-based clonality testing may provide conclusive evidence of two concurrent and distinct clonal lymphocyte populations, termed most appropriately "composite lymphoma"

Stolpersteine und Erfolgsfaktoren: Kooperationen im Rahmen der EU-Bildungsprogramme

Die europaweite Zusammenarbeit zwischen Institutionen der Erwachsenenbildung ist inzwischen selbstverständlich: Lehrende und Entwickler pädagogischer Programme, Leitungspersonal und Bildungsforscher werden mobil im Rahmen von Austauschprogrammen, Partnerschaften, Projekten und Netzwerken, um berufliche Erfahrungen auszutauschen, am aktuellen Stand der fachlichen Debatte teilzuhaben oder gemeinsam innovative Konzepte und Bildungsprodukte zu entwickeln. Einen entscheidenden Beitrag zu diesem Kooperationsboom leisten die Förderprogramme der Europäischen Union. Der Autor dieses Artikels beschäftigt sich seit Jahren in verschiedenen Funktionen mit europäischer Kooperation von Bildungseinrichtungen: als Berater, externer Experte der Europäischen Kommission, Evaluator, Koordinator und Partner zahlreicher Kooperationsprojekte. Vor dem Hintergrund dieser Praxis stellt er die europäische Zusammenarbeit zwischen Bildungseinrichtungen als komplexe Herausforderung dar.Looking at consultancy for European project work, the article reveals the common obstacles and success factors for cooperative ventures between adult education institutions as part of EU funding programmes. The author recommends paying particular attention to all the parties' interests to ensure there is joint ownership

Expressed sequence tags from Madagascar periwinkle (Catharanthus roseus)

AbstractThe Madagascar periwinkle (Catharanthus roseus) is well known to produce the chemotherapeutic anticancer agents, vinblastine and vincristine. In spite of its importance, no expressed sequence tag (EST) analysis of this plant has been reported. Two cDNA libraries were generated from RNA isolated from the base part of young leaves and from root tips to select 9824 random clones for unidirectional sequencing, to yield 3327 related sequences and 1696 singletons by cluster analysis. Putative functions of 3663 clones were assigned, from 5023 non-redundant ESTs to establish a resource for transcriptome analysis and gene discovery in this medicinal plant

Sequence variant analysis of RNA sequences in severe equine asthma

Background Severe equine asthma is a chronic inflammatory disease of the lung in horses similar to low-Th2 late-onset asthma in humans. This study aimed to determine the utility of RNA-Seq to call gene sequence variants, and to identify sequence variants of potential relevance to the pathogenesis of asthma. Methods RNA-Seq data were generated from endobronchial biopsies collected from six asthmatic and seven non-asthmatic horses before and after challenge (26 samples total). Sequences were aligned to the equine genome with Spliced Transcripts Alignment to Reference software. Read preparation for sequence variant calling was performed with Picard tools and Genome Analysis Toolkit (GATK). Sequence variants were called and filtered using GATK and Ensembl Variant Effect Predictor (VEP) tools, and two RNA-Seq predicted sequence variants were investigated with both PCR and Sanger sequencing. Supplementary analysis of novel sequence variant selection with VEP was based on a score of <0.01 predicted with Sorting Intolerant from Tolerant software, missense nature, location within the protein coding sequence and presence in all asthmatic individuals. For select variants, effect on protein function was assessed with Polymorphism Phenotyping 2 and screening for non-acceptable polymorphism 2 software. Sequences were aligned and 3D protein structures predicted with Geneious software. Difference in allele frequency between the groups was assessed using a Pearson’s Chi-squared test with Yates’ continuity correction, and difference in genotype frequency was calculated using the Fisher’s exact test for count data. Results RNA-Seq variant calling and filtering correctly identified substitution variants in PACRG and RTTN. Sanger sequencing confirmed that the PACRG substitution was appropriately identified in all 26 samples while the RTTN substitution was identified correctly in 24 of 26 samples. These variants of uncertain significance had substitutions that were predicted to result in loss of function and to be non-neutral. Amino acid substitutions projected no change of hydrophobicity and isoelectric point in PACRG, and a change in both for RTTN. For PACRG, no difference in allele frequency between the two groups was detected but a higher proportion of asthmatic horses had the altered RTTN allele compared to non-asthmatic animals. Discussion RNA-Seq was sensitive and specific for calling gene sequence variants in this disease model. Even moderate coverage (<10–20 counts per million) yielded correct identification in 92% of samples, suggesting RNA-Seq may be suitable to detect sequence variants in low coverage samples. The impact of amino acid alterations in PACRG and RTTN proteins, and possible association of the sequence variants with asthma, is of uncertain significance, but their role in ciliary function may be of future interest

X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe Malaria

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A− form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. METHODS AND FINDINGS: We conducted large case-control studies of the A− form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. CONCLUSIONS: The A− form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is present among heterozygous females. Although these conclusions are consistent with data from at least one previous study, they have not heretofore been realized to our knowledge, and they therefore give fresh perspectives on malaria protection by G6PD deficiency as an X-linked trait

Allomonal effect of breath contributes to differential attractiveness of humans to the African malaria vector Anopheles gambiae

BACKGROUND: Removal of exhaled air from total body emanations or artificially standardising carbon dioxide (CO(2)) outputs has previously been shown to eliminate differential attractiveness of humans to certain blackfly (Simuliidae) and mosquito (Culicidae) species. Whether or not breath contributes to between-person differences in relative attractiveness to the highly anthropophilic malaria vector Anopheles gambiae sensu stricto remains unknown and was the focus of the present study. METHODS: The contribution to and possible interaction of breath (BR) and body odours (BO) in the attraction of An. gambiae s.s. to humans was investigated by conducting dual choice tests using a recently developed olfactometer. Either one or two human subjects were used as bait. The single person experiments compared the attractiveness of a person's BR versus that person's BO or a control (empty tent with no odour). His BO and total emanations (TE = BR+BO) were also compared with a control. The two-person experiments compared the relative attractiveness of their TE, BO or BR, and the TE of each person against the BO of the other. RESULTS: Experiments with one human subject (P(1)) as bait found that his BO and TE collected more mosquitoes than the control (P = 0.005 and P < 0.001, respectively), as did his BO and the control versus his BR (P < 0.001 and P = 0.034, respectively). The TE of P(1 )attracted more mosquitoes than that of another person designated P(8 )(P < 0.021), whereas the BR of P(8 )attracted more mosquitoes than the BR of P(1 )(P = 0.001). The attractiveness of the BO of P(1 )versus the BO of P(8 )did not differ (P = 0.346). The BO from either individual was consistently more attractive than the TE from the other (P < 0.001). CONCLUSIONS: We demonstrated for the first time that human breath, although known to contain semiochemicals that elicit behavioural and/or electrophysiological responses (CO(2), ammonia, fatty acids) in An. gambiae also contains one or more constituents with allomonal (~repellent) properties, which inhibit attraction and may serve as an important contributor to between-person differences in the relative attractiveness of humans to this important malaria vector

Decline of placental malaria in southern Ghana after the implementation of intermittent preventive treatment in pregnancy

<p>Abstract</p> <p>Background</p> <p>Intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) has been adopted as policy by many countries in sub-Saharan Africa. However, data on the post-implementation effectiveness of this measure are scarce.</p> <p>Methods</p> <p>Clinical and parasitological parameters were assessed among women delivering at a district hospital in rural southern Ghana in the year 2000 when pyrimethamine chemoprophylaxis was recommended (<it>n </it>= 839) and in 2006 (<it>n </it>= 226), approximately one year after the implementation of IPTp-SP. Examinations were performed in an identical manner in 2000 and 2006 including the detection of placental <it>Plasmodium falciparum </it>infection by microscopy, histidine-rich protein 2, and PCR.</p> <p>Results</p> <p>In 2006, 77% of the women reported to have taken IPTp-SP at least once (26%, twice; 24%, thrice). In 2006 as compared to 2000, placental <it>P. falciparum </it>infection was reduced by 43–57% (<it>P </it>< 0.0001) and maternal anaemia by 33% (<it>P </it>= 0.0009), and median birth weight was 130 g higher (<it>P </it>= 0.02). In 2006, likewise, women who had taken ≥ 1 dose of IPTp-SP revealed less infection and anaemia and their children tended to have higher birth weights as compared to women who had not used IPTp-SP. However, placental <it>P. falciparum </it>infection was still observed in 11% (microscopy) to 26% (PCR) of those women who had taken three doses of IPTp-SP.</p> <p>Conclusion</p> <p>In southern Ghana, placental malaria and maternal anaemia have declined substantially and birth weight has increased after the implementation of IPTp-SP. Likely, these effects can further be increased by improving IPTp-SP coverage and adherence. However, the remnant prevalence of infection in women having taken three doses of IPTp-SP suggests that additional antimalarial measures are needed to prevent malaria in pregnancy in this region.</p

High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia

BACKGROUND: In Ethiopia, malaria is caused by both Plasmodium falciparum and Plasmodium vivax. Drug resistance of P. falciparum to sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) is frequent and intense in some areas. METHODS: In 100 patients with uncomplicated malaria from Dilla, southern Ethiopia, P. falciparum dhfr and dhps mutations as well as P. vivax dhfr polymorphisms associated with resistance to SP and P. falciparum pfcrt and pfmdr1 mutations conferring CQ resistance were assessed. RESULTS: P. falciparum and P. vivax were observed in 69% and 31% of the patients, respectively. Pfdhfr triple mutations and pfdhfr/pfdhps quintuple mutations occurred in 87% and 86% of P. falciparum isolates, respectively. Pfcrt T76 was seen in all and pfmdr1 Y86 in 81% of P. falciparum. The P. vivax dhfr core mutations N117 and R58 were present in 94% and 74%, respectively. CONCLUSION: These data point to an extraordinarily high frequency of drug-resistance mutations in both P. falciparum and P. vivax in southern Ethiopia, and strongly support that both SP and CQ are inadequate drugs for this region

L´Art du Networking. Réseaux européens pour l´education

Bienzle H, Gelabert E, Jütte W, Kolyva K, Meyer N, Tilkin G. L´Art du Networking. Réseaux européens pour l´education. Wien: die Berater - Unternehmensberatungs GmbH; 2007

Kunst des Netzwerkens. Europäische Netzwerke im Bildungsbereich

Bienzle H, Gelabert E, Jütte W, Kolyva K, Meyer N, Tilkin G. Kunst des Netzwerkens. Europäische Netzwerke im Bildungsbereich. Wien: die Berater - Unternehmensberatungs GmbH; 2007