Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient's environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema.

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia.

Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P<0.01) and less likely to receive aggressive treatment (P=0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P=0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.

Nestling detectability affects parental feeding preferences in a cavity-nesting bird

In many avian species, nestlings have evolved striking plumage, behaviours and mouth colours to obtain a greater share of parental investment. Studies revealing parental feeding preferences for nestlings with red gapes have proposed that red mouth colour in songbirds can act as a signal of nestling need or condition. Alternative hypotheses suggest that bright nestling mouths in cavity-nesting birds evolved to increase nestling detectability by the parents. We tested whether nestling mouth colour affects parental feeding preferences in great tits, Pants major L. In broods of six young, we experimentally painted mouth gapes and flanges either red or yellow and tested the effect of mouth colour on nestlings' mass gain under two lighting conditions. In nests with high luminosity, there was no significant effect of mouth colour on mass gain. In nests with low luminosity, nestlings with red gapes and flanges gained less mass than nestlings with red gapes and yellow flanges or both yellow gapes and flanges. Our results suggest that, in nests with low luminosity, red mouths decreased nestling detectability to the feeding parents and support the hypothesis that poor luminosity in nesting cavities can select for pale mouths. Overall, our results do not support the hypothesis that red mouth colour signals nestling need or condition to parent great tits.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Fusion telomérique de deux chromosomes X par leurs bras courts chez une patiente présentant un syndrome de Turner atypique. [Telomeric fusion of the short arms of both X chromosomes in a patient presenting an atypical Turner syndrome.]

A case of atypical Turner's syndrome with unusual karyotype is reported. The chromosome complements of the patient, studied with different banding techniques, is 45,XO/46,X,dic(X)(Xqter leads to p22::p22 leads to qter). In the literature 8 similar cases have been reported. Short stature and amenorrhea are the most constant findings. The mechanisms by which the observed chromosomal "rearrangement" can be produced are briefly discussed.

Disease in the dark: molecular characterization of Polychromophilus murinus in temperate zone bats revealed a worldwide distribution of this malaria-like disease.

For a better understanding of the complex coevolutionary processes between hosts and parasites, accurate identification of the actors involved in the interaction is of fundamental importance. Blood parasites of the Order Haemosporidia, responsible for malaria, have become the focus of a broad range of studies in evolutionary biology. Interestingly, molecular-based studies on avian malaria have revealed much higher species diversity than previously inferred with morphology. Meanwhile, studies on bat haemosporidian have been largely neglected. In Europe, only one genus (Polychromophilus) and two species have been morphologically described. To evaluate the presence of potential cryptic species and parasite prevalence, we undertook a molecular characterization of Polychromophilus in temperate zone bats. We used a nested-PCR approach on the cytochrome b mitochondrial gene to detect the presence of parasites in 237 bats belonging to four different species and in the dipteran bat fly Nycteribia kolenatii, previously described as being the vector of Polychromophilus. Polychromophilus murinus was found in the four bat species and in the insect vector with prevalence ranging from 4% for Myotis myotis to 51% for M. daubentoni. By sequencing 682 bp, we then investigated the phylogenetic relationships of Polychromophilus to other published malarial lineages. Seven haplotypes were found, all very closely related, suggesting the presence of a single species in our samples. These haplotypes formed a well-defined clade together with Haemosporidia of tropical bats, revealing a worldwide distribution of this parasite mostly neglected by malarial studies since the 1980s.

Hearing loss in Adult Women with Turner Syndrome

L'objectiu d'aquest estudi és definir els patrons d’hipoacúsia en dones amb Síndrome de Turner i els possibles factors que poden afavorir el desenvolupament d’hipoacúsia neurosensorial en dones adultes amb Síndrome de Turner. Es va trobar que més de la meitat de les dones amb Sindrome de Turner presenten hipoacúsia a l’audiometria, confirmat pels potencials evocats auditius de tronc; la hipoacúsia neurosensorial és el tipus de pèrdua d'audició més freqüent entre dones de mitjana edat amb síndrome de Turner i l'edat, el cariotip i la història prèvia d'otitis mitja recurrent són possibles factors de risc per l’aparició d’hipoacúsia en aquestes pacients.

Using a Bayesian method to assign individuals to karyotypic taxa in shrew hybrid zones.

Individuals sampled in hybrid zones are usually analysed according to their sampling locality, morphology, behaviour or karyotype. But the increasing availability of genetic information more and more favours its use for individual sorting purposes and numerous assignment methods based on the genetic composition of individuals have been developed. The shrews of the Sorex araneus group offer good opportunities to test the genetic assignment on individuals identified by their karyotype. Here we explored the potential and efficiency of a Bayesian assignment method combined or not with a reference dataset to study admixture and individual assignment in the difficult context of two hybrid zones between karyotypic species of the Sorex araneus group. As a whole, we assigned more than 80% of the individuals to their respective karyotypic categories (i.e. 'pure' species or hybrids). This assignment level is comparable to what was obtained for the same species away from hybrid zones. Additionally, we showed that the assignment result for several individuals was strongly affected by the inclusion or not of a reference dataset. This highlights the importance of such comparisons when analysing hybrid zones. Finally, differences between the admixture levels detected in both hybrid zones support the hypothesis of an impact of chromosomal rearrangements on gene flow.

Origins and functional evolution of Y chromosomes across mammals.

Y chromosomes underlie sex determination in mammals, but their repeat-rich nature has hampered sequencing and associated evolutionary studies. Here we trace Y evolution across 15 representative mammals on the basis of high-throughput genome and transcriptome sequencing. We uncover three independent sex chromosome originations in mammals and birds (the outgroup). The original placental and marsupial (therian) Y, containing the sex-determining gene SRY, emerged in the therian ancestor approximately 180 million years ago, in parallel with the first of five monotreme Y chromosomes, carrying the probable sex-determining gene AMH. The avian W chromosome arose approximately 140 million years ago in the bird ancestor. The small Y/W gene repertoires, enriched in regulatory functions, were rapidly defined following stratification (recombination arrest) and erosion events and have remained considerably stable. Despite expression decreases in therians, Y/W genes show notable conservation of proto-sex chromosome expression patterns, although various Y genes evolved testis-specificities through differential regulatory decay. Thus, although some genes evolved novel functions through spatial/temporal expression shifts, most Y genes probably endured, at least initially, because of dosage constraints.

Cytogenetic and molecular relationships between Zarudny's rock shrew (Crocidura zarudnyi; Mammalia : Soricomorpha) and Eurasian taxa

We karyotyped and sequenced 1,140 base pairs of the mitochondrial DNA cytochrome b of a specimen of Zarudny's rock shrew (Crocidura zarudnyi) from Baluchestan, southeastern Iran, to clarify its cytogenetic and molecular relationships with other Eurasian species of Crocidura. According to the karyotype (2N = 40, FN = 50), Zarudny's rock shrew belongs to the group of the lesser white-toothed shrew (C. suaveolens), which is different from other known crocidurine karyotypes, considering the combination of the diploid and fundamental number of chromosomes. Molecular results revealed that C. zarudnyi is included in a monophyletic clade with the C. suaveolens group, where it is a sister taxon to the others (mean Kimura 2-parameter distance = 9.7%).

Regulation of foreign gene in fowlpox virus by a vaccinia virus promoter.

A vaccinia virus promoter was evaluated for regulation of a foreign gene in fowlpox virus by a transient expression assay. Fowlpox virus-infected quail cells, transfected with plasmid DNA containing chloramphenicol acetyltransferase (CAT) gene ligated to a vaccinia virus promoter, expressed CAT activity. No CAT activity was detected either in uninfected cells or fowlpox virus-infected cells. These results indicated that a heterologous vaccinia virus promoter can regulate expression of a foreign gene in fowlpox virus.

Technology transfer of an oil-in-water vaccine-adjuvant for strengthening pandemic influenza preparedness in Indonesia.

With the current enzootic circulation of highly pathogenic avian influenza viruses, the ability to increase global pandemic influenza vaccine production capacity is of paramount importance. This has been highlighted by, and is one of the main pillars of, the WHO Global Action Plan for Influenza Vaccines (GAP). Such capacity expansion is especially relevant in developing countries. The Vaccine Formulation Laboratory at University of Lausanne is engaged in the technology transfer of an antigen-sparing oil-in-water adjuvant in order to empower developing countries vaccine manufacturers to increase pandemic influenza vaccine capacity. In a one-year project funded by United States Department of Health and Human Services, the Vaccine Formulation Laboratory transferred the process know-how and associated equipment for the pilot-scale manufacturing of an oil-in-water adjuvant to Bio Farma, Indonesia's state-owned vaccine manufacturer, for subsequent formulation with H5N1 pandemic influenza vaccines. This paper describes the experience acquired and lessons learnt from this technology transfer project.

Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated.

The role of territory choice mate choice and arrival date on breeding success in the Savi's warbler (Locustella luscinioides)

We investigated how territory quality, settlement date and morphometry affected several components of yearly breeding success of a Swiss population of Savi's Warblers Locustella luscinioides. Territories occupied by males differed from unoccupied sites of similar size and location by having higher and denser reeds, a more extensive straw litter, and a thicker cover of dead sedge leaves. Territories with these characteristics were the ones first chosen by males upon spring arrival. These males, however, did not differ in morphometry from those that arrived later. Availability of suitable nesting sites; rather than food availability, appears to be an important choice criterion for territories. Early arriving males had higher breeding success than late males because of a higher mating success and more successful clutches. The positive correlation between male breeding success and territory quality was thus mediated through their common dependence on occupancy date. Female breeding success decreased with the date of first-clutch laying, mainly because late-nesting females fledged fewer broods. Breeding success in either sex did not correlate with morphometry. Our results provide clear support for territory choice by males, but not for mate or territory choice by females, and show the crucial role played by individual settlement date on many aspects of the breeding cycle of both sexes. We propose a lottery model of mate choice. arriving females obtain the best available territories even without choosing mates or territories; since males occupy territories sequentially and in order of decreasing quality, the few unpaired males available at any moment also occupy the best available territories.

Phylogenetic structures of the Holarctic Sorex araneus group and its relationships with S-samniticus, as inferred from mtDNA sequences

The shrews of the Sorex araneus group, characterized by the sexual chromosome complex XY1, Y2 have been intensively studied by morphological, karyotypical, and biochemical analyses. Nevertheless, the phylogenetic relationships among the species belonging to the araneus complex are still under debate, as different approaches gave often contradictory results. In this paper, partial nucleotide sequences of the mitochondrial DNA cytochrome b gene (1011 bp) were determined for 6 species of the araneus group from Eurasia and North America. We also included in the data set the sequences of Sorex samniticus, whose relationships with the araneus group remain controversial. Three other species representing two major karyological groups were also examined. Both parsimony and distance trees strongly support the monophyly of the araneus group. Sorex sumniticus is significantly more closely related to the araneus complex than to the other species included in the analysis. Based on the branching pattern within the araneus group, an attempt has been made to reconstruct the colonization history of the Holarctic region.