Hantavirus infection in rodents and haemorrhagic fever with renal syndrome in Shaanxi province, China, 1984-2012.

The transmission of haemorrhagic fever with renal syndrome (HFRS) is deeply influenced by the reservoir and hantavirus prevalence rate. In this study, a surveillance on human HFRS cases, relative rodent abundance, and hantavirus infection prevalence was conducted in Shaanxi province, China, during 1984-2012. A generalized linear model with Poisson-distributed residuals and a log link was used to quantify the relationship between reservoir, virus and HFRS cases. The result indicated that there was a significant association of HFRS incidence with relative rodent density and the prevalence rate. This research provides evidence that the changes of infection prevalence in the reservoir could lead directly to the emergence of a new epidemic. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

Molecular cloning, characterization and expression analysis of a Doublesex gene from Daphnia carinata (Crustacea: Cladocera) during different reproductive stages.

To better understand the reproductive transformation mechanism of Daphnia carinata, a Doublesex (Dsx) gene was cloned based on rapid amplification of cDNA ends (RACE), and was designated DapcaDsx2. Next, we compared similarities and assumed homology based on deduced amino acid sequences. It showed 97.52, 87.94, and 85.11% identity to orthologous genes in D. magna, D. pulex, and D. galeata respectively. Phylogenetic analysis revealed that DapcaDsx2 clustered in the same class, and was evolutionarily more distant to sequences from other species. qRT-PCR showed that DapcaDsx2 was most abundantly expressed during sexual reproduction (P < 0.05). Using digoxigenin-labeled RNA probes, we studied DapcaDsx2 expression in parthenogenetic and sexual females by whole-mount in situ hybridization. The results revealed that DapcaDsx2 was mainly expressed in the second antennae and several sites of the ventral carapace, whereas higher expression levels were found in sexual than in parthenogenetic females. This suggests that the DapcaDsx2 gene is involved in switching modes of reproduction and in sexual differentiation.

ERBIN deficiency links STAT3 and TGF-ß pathway defects with atopy in humans.

Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these congenital disorders have been associated with either increased TGF-ß activity or impaired STAT3 activation, suggesting that these pathways might intersect and that their disruption may contribute to atopy. In this study, we show that STAT3 negatively regulates TGF-ß signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation and SMAD2/3 binding protein. Individuals with dominant-negative STAT3 mutations (STAT3mut ) or a loss-of-function mutation in ERBB2IP (ERBB2IPmut ) have evidence of deregulated TGF-ß signaling with increased regulatory T cells and total FOXP3 expression. These naturally occurring mutations, recapitulated in vitro, impair STAT3-ERBIN-SMAD2/3 complex formation and fail to constrain nuclear pSMAD2/3 in response to TGF-ß. In turn, cell-intrinsic deregulation of TGF-ß signaling is associated with increased functional IL-4Rα expression on naive lymphocytes and can induce expression and activation of the IL-4/IL-4Rα/GATA3 axis in vitro. These findings link increased TGF-ß pathway activation in ERBB2IPmut and STAT3mut patient lymphocytes with increased T helper type 2 cytokine expression and elevated IgE.

Costs and incentives in a behavioral health carve-out.

A carve-out of mental health and substance abuse services initiated in 1993 by the Group Insurance Commission (GIC) of the Commonwealth of Massachusetts resulted in changes in the costs of those services. Those changes were related to incentives in the contract between the GIC and its managed behavioral health vendor. Total and plan costs were reduced by 30-40 percent after adjusting for trends. Incentives to produce savings of this magnitude not only were a consequence of the payer/vendor contract but, we speculate, derive from the growth potential facing companies in the managed behavioral health care market.

Behavioral health expenditures and state organizational structure.

The authors present a study on expenditures by state mental health, substance abuse, and developmental disability agencies in the United States for the period between 1981 and 1993. The relationship between agency spending and organizational structure of state bureaucracy was examined. Results indicate that organizational structure is a determinant of agency spending. The more independent an agency, the higher its spending; conversely, the more independent its competitor, the lower the agency's spending. The number of levels between an agency and the governor's office was not significant in explaining agency expenditures.

Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia.

The gene that encodes nuclear factor kappaB (NF-kappaB) essential modulator (or NEMO, also known as IKKgamma) is required for activation of the transcription factor NF-kappaB. We describe mutations in the putative zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-kappaB alpha (IkappaB-alpha) and account for the following observations: B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells (APCs) are unable to synthesize the NF-kappaB-regulated cytokines interleukin 12 (IL-12) or tumor necrosis factor alpha (TNF-alpha) when stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40-mediated NF-kappaB activation for B cell immunoglobulin class-switching.