The Crim1 gene is predicted to encode a transmembrane protein containing six von Willebrand-like cysteine-rich repeats (CRRs) similar to those in the BMPbinding antagonist Chordin (Chrd). In this study, we verify that CRIM1 is a glycosylated, Type I transmembrane protein and demonstrate that the extracellular CRR-containing domain can also be secreted, presumably via processing at the membrane. We have previously demonstrated Crim1 expression at sites consistent with an interaction with bone morphogenetic proteins (BMPs). Here we show that CRIM1 can interact with both BMP4 and BMP7 via the CRR-containing portion of the protein and in so doing acts as an antagonist in three ways. CRIM1 binding of BMP4 and -7 occurs when these proteins are co-expressed within the Golgi compartment of the cell and leads to (i) a reduction in the production and processing of preprotein to mature BMP, (ii) tethering of pre-BMP to the cell surface, and (iii) an effective reduction in the secretion of mature BMP. Functional antagonism was verified by examining the effect of coexpression of CRIM1 and BMP4 on metanephric explant culture. The presence of CRIM1 reduced the effective BMP4 concentration of the media, thereby acting as a BMP4 antagonist. Hence, CRIM1 modulates BMP activity by affecting its processing and delivery to the cell surface.The TGF␤ 1 superfamily of ligands have prominent roles in nearly all tissues during development. There are over 30 members of this superfamily, including the TGF␤ isoforms, bone morphogenetic proteins (BMPs), and the closely related growth and differentiation factors, activins, and nodals (reviewed in Ref. 1). BMPs, like all members of the TGF␤ superfamily, are synthesized as preproteins, which are subsequently cleaved by furin and related subtilisin-like convertases within the Golgi apparatus at a conserved multibasic amino acid motif (Arg-X-X-Arg) to yield a dimeric C-terminal mature domain (2). Once secreted BMPs bind and facilitate the formation of heteromeric complexes of type I and type II serine/threonine kinase receptors (1). These signal via phosphorylation of Smad proteins, which can translocate into the nucleus and effect gene regulation and expression (reviewed in Ref. 1). Although TGF␤-1, -2, and -3 are secreted as a member of a large inactive complex containing the latency-associated peptide and a latent TGF␤-binding protein, the BMPs are currently thought to be processed and secreted as active mature molecules and not complexed with a latent TGF␤-binding protein-like molecule. However, like the TGF␤s, BMPs do not seem to act over a range of more than one to two cells, suggesting that there is some mechanism of "tethering" (3). This limit in signaling range is in part influenced by the prodomain of BMPs (3). The prodomain of the BMPs also influences the efficiency of processing and the stability of the mature BMP (2, 4). During development, TGF␤ superfamily members, and in particular BMPs, specify cell types by forming precisely controlled concentration gradients. The amount of activ...

Sequencing distinguished relapsing fever from other borrelial species but not B. duttonii from B. recurrentis.

We have used nuclear (ribosomal ITS1) and mitochondrial (ND1) sequences to characterize human and pig isolates of Echinococcus granulosus collected by fine needle aspiration biopsy (FNAB) in Poland. The data indicate clearly that the Polish patients were not infected with the common sheep strain (G1 genotype) of E. granulosus, normally associated with human cystic hydatid infection. Instead, the hydatid parasite infecting the Polish patients shares very similar ND1 sequence with the previously characterized pig (G7) genotype but it also exhibits some clear differences. In particular, E. granulosus DNA from the Polish patients amplified a single ITS1 fragment in PCR and distinct ITS1-RFLP patterns were obtained after restriction digestion. The form of hydatid isolated from the Polish patients appears, therefore, to represent a distinct, previously undescribed genotype (designated G9) of E. granulosus.

No abstract

The genus Brucella includes a number of species that are major animal pathogens worldwide and significant causes of zoonotic infections of humans. Traditional methods of identifying Brucella to the species level can be time-consuming, can be subjective, and can pose a hazard to laboratory personnel in the absence of suitable biocontainment facilities. Using a robust phylogenetic framework, a number of single-nucleotide polymorphisms (SNPs) that define particular species within the genus were identified. These SNPs were used to develop a multiplex SNP detection assay, based on primer extension technology, that can rapidly and unambiguously identify an isolate as a member of one of the six classical Brucella species or as a member of the recently identified marine mammal group.Brucellosis is a major cause of disease in livestock worldwide, with substantial implications for animal welfare and economic output. Furthermore, as the most common zoonotic disease, it remains a significant public health concern (22). Although a few parts of the developed world have eradicated the disease by a combination of strict veterinary hygiene measures, monitoring programs, and improved food safety measures, it remains endemic in large areas. Human disease usually reflects occupational exposure or the consumption of unpasteurized dairy products and can lead to a chronic debilitating infection.The causative organisms of brucellosis are members of the genus Brucella. Traditionally, the group is divided into six species with distinct host specificities (1), although at the genetic level, members of the genus are highly conserved (14, 32). Reflecting this, DNA hybridization experiments led to the traditional view of Brucella taxonomy being challenged and the group being described as monospecific (28). Practical considerations meant that this classification system never found widespread support, and recently, moves were made to return to the classical species designations (20). Of the currently recognized species, B. abortus is predominantly associated with bovine brucellosis, B. melitensis is predominantly associated with small ruminant brucellosis, B. canis is predominantly associated with canine brucellosis, B. ovis is predominantly associated with ram epididymitis, and B. neotomae has been reported only in the desert wood rat. The remaining species, B. suis, has a broader host range, being predominantly associated with porcine brucellosis (biovars 1, 2, and 3) but also being found in hares (biovar 2), rangifers (biovar 4), and rodents (biovar 5). More recently, novel Brucella isolates were detected in a variety of marine mammal species (7,10,12,17,23). These isolates clearly form new Brucella groups, although they have yet to receive formal taxonomic recognition (13a, 20).Classically, Brucella isolates are divided into species (and biovars in the case of B. abortus, B. melitensis, and B. suis) by a biotyping procedure that assesses a range of cultural, phenotypic, and antigenic properties (1). While biotyping has long been the mainst...