Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Expression analysis of immune-related genes in CD34(+) progenitor-derived dendritic cells after exposure to the chemical contact allergen DNCB.

We studied the changes in gene expression after exposure of human dendritic cells (DCs) to the model allergen dinitrochlorobenzene (DNCB). DCs were derived from CD34(+) progenitor cells of three different donors and exposed to 10 microM DNCB or solvent for several time intervals (3, 6 and 12h). cDNA microarrays were used to assess the transcriptional activity of 11,000 human genes. Compared to control gene expression, changes larger than +/-two-fold were observed for 241 genes after exposure to DNCB. Of these genes, 137 were up-regulated and 104 down-regulated. Twenty of these genes encode proteins that are related to the immune response (cytokines, chemokines, their receptors, cytokine/chemokines-related genes, transcription and signal transduction genes) and are discussed in more detail. Our data indicate that exposure to DNCB does not induce a typical maturation pattern in DCs.

Development of the labial gland of the ponerine ant Pachycondyla obscuricornis (Hymenoptera, Formicidae) during the pupal stage.

The labial gland of adult workers of the ant Pachycondyla obscuricornis is made up of many acini, each consisting of one central cell surrounded by approximately 10 parietal cells. Both cell types are associated with a system of ramified canaliculi that remove the secretion towards a ductule outside the acinus. These ductules, each associated with one acinus, fuse together and form a ramified system of ducts, ending in two paired ducts. These paired ducts widen to form a reservoir and anteriorly join into a common unpaired duct, which ends at the base of the labium. During development in the pupal stage, epithelial acini are formed first, consisting of a monolayered epithelium lining a central lumen. In these acini, one cell grows out to become the central cell, while the others will re-arrange around it to form the parietal cells. At the end of the pupal stage, the canaliculi are formed inside the acini by the central and parietal cells that secrete a lipidic substance and a cuticle. This gland type, which also occurs in some other Hymenoptera, is structurally different from the epithelial glands and the glands consisting of bicellular units, that have been traditionally distinguished until now.

Symbiosis-specific expression of Rhizobium etli casA encoding a secreted calmodulin-related protein.

Symbiosis between Rhizobium and its leguminous host requires elaborate communication between the partners throughout the interaction process. A calmodulin-like protein, termed calsymin, was identified in Rhizobium etli; a calmodulin-related protein in a Gram-negative bacterium had not been described previously. Calsymin possesses three repeated homologous domains. Each domain contains two predicted EF-hand Ca(2+)-binding motifs. Ca(2+)-binding activity of calsymin was demonstrated on purified protein. R. etli efficiently secretes calsymin without N-terminal cleavage of the protein. The gene encoding calsymin, casA, is exclusively expressed during colonization and infection of R. etli with the host. Expression of casA is controlled by a repressor protein, termed CasR, belonging to the TetR family of regulatory proteins. Mutation of the casA gene affects the development of bacteroids during symbiosis and symbiotic nitrogen fixation.

The importance of the spermathecal duct in bumblebees.

The elongated spermathecal duct of bumblebees has been studied in hibernating queens, queens shortly after hibernation, mature egg-laying queens and uninseminated queens captured during summer, and workers. Only rather small size differences are found when comparing spermathecae of queens and workers. Clear differences between bumblebee queens and workers are found when comparing the histochemistry of the spermathecal ducts. Adult queens, regardless of age and reproductive status have spermathecal ducts that contain PAS positive material, whereas workers do not. It is suggested that the polysaccharides in the spermathecal ducts of queens are necessary as a source of energy for the rapid activation of spermatozoa passing through the duct prior to oocyte fertilization. An ultrastructural investigation revealed the presence of high glycogen content in the cells lining the duct of queens. Assuming that sperm cells are kept in a rather inactive state in the reservoir, the carbohydrate (glycogen) probably serves as an energy source for the sperm. The comparatively increased spermathecal duct length of bumblebees may increase the retention time of sperm inside the lumen.

Task-related variation of postpharyngeal and cuticular hydrocarbon compositions in the ant Myrmicaria eumenoides.

In the ant Myrmicaria eumenoides we investigated postpharyngeal and cuticular hydrocarbons. At eclosion the glands contained almost no hydrocarbons and there were no lipid inclusions in the glandular epithelium. During the first 3 weeks of adult life the amount of hydrocarbons in the gland increased until day 5, and then remained constant while the lipid content in the epithelium increased steadily. Intracolonial hydrocarbon compositions were not uniform. Compositions of post-pharyngeal and cuticular hydrocarbons in individual ants varied simultaneously, but in different manner depending on the tasks of the ant (brood-tenders, foragers, scouts). Variations on the cuticle were greater than in the gland, but they were strongly correlated. Independent of ants' age and task, cuticular hydrocarbon compositions were dominated by alkenes and alkadienes. Task-specific differences in cuticular compositions were mainly in the amount of alkenes (high in foragers) and alkadienes (high in brood-tenders). Variation of hydrocarbons was low in ants up to 10 weeks old. Thereafter, ants fell into two groups: (1) ants that did not change their hydrocarbons and remained in the nest, and (2) ants that changed their hydrocarbon compositions and became foragers. These results contribute to an ongoing discussion of the dynamic relationship between post-pharyngeal and cuticular hydrocarbons.

Chemistry of metapleural gland secretions of three attine ants,Atta sexdens rubropilosa, Atta cephalotes, andAcromyrmex octospinosus (Hymenoptera: Formicidae).

The chemical composition of the secretions of the metapleural glands of workers and soldiers of twoAtta species,Atta sexdens rubropilosa andA. cephalotes, and workers ofAcromyrmex octospinosus, has been studied. As indicated by infrared spectrometry and confirmed by the ninhydrin test, the secretions contain chiefly proteins. Of the volatile acidic portion, which is present as ionized salts, phenylacetic acid is the major component in workers and soldiers ofA. s. rubropilosa andA. cephalotes. BothAtta species also contain 3-hydroxydecanoic acid and its homolog as minor components together with indoleacetic acid. While there are qualitative similarities in the acidic composition in the secretions ofA. s. rubropilosa andA. cephalotes, they differ quantitatively. The secretion ofAcromyrmex octospinosus contains 3-hydroxydecanoic and indoleacetic acids, but lacks phenylacetic acid. The bactericidal and fungicidal actions of the three major substances have been confirmed.

Volatile secretions of old world army antAenictus rotundatus and chemotaxonomic implications of army ant dufour gland chemistry.

The Dufour glands ofAenictus rotundatus contain a complex mixture of terpenoids with geranylgeraniol comprising over 50% of the secretion. Some novel compounds have been tentatively identified as higher homologs of 1,3,3-trimethyl-2,7-dioxabicyclo[2,2,1]heptane based on GC-MS data. The Dufour gland secretion ofA. rotundatus is more similar in composition to the secretions of members of the subfamily Ecitoninae than to its closer relatives from the tribe Dorylini, a result that further complicates studies on the phylogeny of army ants. The mandibular glands ofA. rotundatus contain a mixture of 4-methyl-3-heptanone and limonene in trace amounts, and the well-developed postpygidial glands contain methyl anthranilate only.

Variation with caste of the mandibular gland secretion in the leaf-cutting antAtta sexdens rubropilosa.

InAtta sexdens rubropilosa, a strongly polyethic and polymorphic species of myrmicine ant, the contents of the mandibular gland vary with caste. Small workers of head width 0.5-1.8 mm, those generally engaged in duties inside the nest, contain chiefly 4-methyl-3-heptanone. Larger workers, those chiefly engaged in foraging, and the soldier caste contain a mixture dominated by neral and geranial, with very little of the ketone of the smaller workers. The soldiers have massive glands containing milligram amounts of neral and geranial. Virgin and mated females contain essentially only 4-methyl-3-heptanone, the amount increasing after mating, while virgin males have 4-methyl-3-heptanone and 4-methyl-3-heptanol in approximately equal proportions. Mated males have less secretion and lose the 4-methyl-3-heptanol.