Andes hantavirus (ANDV) causes hantavirus cardiopulmonary syndrome in Chile and is the only hantavirus for which person-to-person transmission has been proven. We describe an outbreak of 5 human cases of ANDV infection in which symptoms developed in 2 household contacts and 2 health care workers after exposure to the index case-patient. Results of an epidemiologic investigation and sequence analysis of the virus isolates support person-to-person transmission of ANDV for the 4 secondary case-patients, including nosocomial transmission for the 2 health care workers. Health care personnel who have direct contact with ANDV case-patients or their body fluids should take precautions to prevent transmission of the virus. In addition, because the incubation period of ANDV after environmental exposure is longer than that for person-to-person exposure, all persons exposed to a confirmed ANDV case-patient or with possible environmental exposure to the virus should be monitored for 42 days for clinical symptoms.

Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography.

In diabetic nephropathy, connective tissue growth factor (CTGF) is upregulated and bone morphogenetic protein 7 (BMP-7) is downregulated. CTGF is known to inhibit BMP-4, but similar cross-talk between BMP-7 and CTGF has not been studied. In this study, it was hypothesized that CTGF acts as an inhibitor of BMP-7 signaling activity in diabetic nephropathy. Compared with diabetic wild-type CTGF^+/+ mice, diabetic CTGF^+/− mice had approximately 50% lower CTGF mRNA and protein, less severe albuminuria, no thickening of the glomerular basement membrane, and preserved matrix metalloproteinase (MMP) activity. Although the amount of BMP-7 mRNA was similar in the kidneys of diabetic CTGF^+/+ and CTGF^+/− mice, phosphorylation of the BMP signal transduction protein Smad1/5 and expression of the BMP target gene Id1 were lower in diabetic CTGF^+/+ mice. Moreover, renal Id1 mRNA expression correlated with albuminuria (R = −0.86) and MMP activity (R = 0.76). In normoglycemic mice, intraperitoneal injection of CTGF led to a decrease of pSmad1/5 in the renal cortex. In cultured renal glomerular and tubulointerstitial cells, CTGF diminished BMP-7 signaling activity, evidenced by lower levels of pSmad1/5, Id1 mRNA, and BMP-responsive element–luciferase activity. Co-immunoprecipitation, solid-phase binding assay, and surface plasmon resonance analysis showed that CTGF binds BMP-7 with high affinity (Kd approximately 14 nM). In conclusion, upregulation of CTGF inhibits BMP-7 signal transduction in the diabetic kidney and contributes to altered gene transcription, reduced MMP activity, glomerular basement membrane thickening, and albuminuria, all of which are hallmarks of diabetic nephropathy.

Fibrotic disorders are the end point of many chronic diseases in different tissues, where an accumulation of the extracellular matrix occurs, mainly because of the action of the connective tissue growth factor (CTGF/CCN2). Little is known about how this growth factor activity is regulated. We found that decorin null myoblasts are more sensitive to CTGF than wild type myoblasts, as evaluated by the accumulation of fibronectin or collagen III. Decorin added exogenously negatively regulated CTGF pro-fibrotic activity and the induction of actin stress fibers. Using co-immunoprecipitation and in vitro interaction assays, decorin and CTGF were shown to interact in a saturable manner with a K(d) of 4.4 nM. This interaction requires the core protein of decorin. Experiments using the deletion mutant decorin indicated that the leucine-rich repeats (LRR) 10-12 are important for the interaction with CTGF and the negative regulation of the cytokine activity, moreover, a peptide derived from the LRR12 was able to inhibit CTGF-decorin complex formation and CTGF activity. Finally, we showed that CTGF specifically induced the synthesis of decorin, suggesting a mechanism of autoregulation. These results suggest that decorin interacts with CTGF and regulates its biological activity.