Defects in acute responses to TLR4 in Btk-deficient mice result in impaired dendritic cell-induced IFN-γ production by natural killer cells.

This study defines a critical role for Btk in regulating TLR4-induced crosstalk between antigen presenting cells (APCs) and natural killer (NK) cells. Reduced levels of IL-12, IL-18 and IFN-γ were observed in Btk-deficient mice and ex vivo generated macrophages and dendritic cells (DCs) following acute LPS administration, whilst enhanced IL-10 production was observed. In addition, upregulation of activation markers and antigen presentation molecules on APCs was also impaired in the absence of Btk. APCs, by virtue of their ability to produce IL-12 and IL-18, are strong inducers of NK-derived IFN-γ. Co-culture experiments demonstrate that Btk-deficient DCs were unable to drive wild-type or Btk-deficient NK cells to induce IFN-γ production, whereas these responses could be restored by exogenous administration of IL-12 and IL-18. Thus Btk is a critical regulator of APC-induced NK cell activation by virtue of its ability to regulate IL-12 and IL-18 production in response to acute LPS administration.

Calcium-phosphorus interactions at a nano-structured silicate surface.

Nano-structured calcium silicate (NCS), a highly porous material synthesized by controlled precipitation from geothermal fluids or sodium silicate solution, was developed as filler for use in paper manufacture. NCS has been shown to chemisorb orthophosphate from an aqueous solution probably obeying a Freundlich isotherm with high selectivity compared to other common environmental anions. Microanalysis of the products of chemisorption indicated there was significant change from the porous and nano-structured morphology of pristine NCS to fibrous and crystalline morphologies and non-porous detritus. X-ray diffraction analysis of the crystalline products showed it to be brushite, CaHPO42H2O, while the largely X-ray amorphous component was a mixture of calcium phosphates. A two-step mechanism was proposed for the chemisorption of phosphate from an aqueous solution by NCS. The first step, which was highly dependent on pH, was thought to be desorption of hydroxide ions from the NCS surface. This was kinetically favoured at lower initial pH, where the predominant form of phosphate present was H2PO(-)4, and led to decreased phosphorus uptake with increasing pH. The second step was thought to be a continuing chemisorption process after stabilization of the pH-value. The formation of brushite as the primary chemisorption product was found to be consistent with the proposed mechanism.

In situ synthesis of polysulfides covalently bonded to silica.

Silanol groups, triple bond SiOH, on the surface of silica were esterified with unsaturated alcohols and long-chain alcohols bearing thiol groups. The modified silicas obtained were used as substrates for a vulcanization-analogous reaction with sulfur catalyzed by zinc dimethyldithiocarbamate. Surface-esterified thiols could be smoothly converted to bridged polysulfides bonded to the silica surface, whereas the use of surface-esterified unsaturated alcohols led to removal of the surface-esterified alcohol from the silica surface. The materials were characterized by solid-state NMR and thermal and microanalytical analysis. The linking of surface-esterified alkenols and thiols by sulfide bridges was investigated by a numerical model for a flat surface. This showed that for a typical density of 3-4 micromol/m(2) surface groups, a statistical maximum of 70-75% of groups could be linked by S(n) bridges (n=2-4).

Comparison of HIV/AIDS rates between U.S.-born Blacks and African-born Blacks in Utah, 2000 - 2009.

The Utah Department of Health currently groups African-born blacks with U.S.-born blacks when reporting HIV/AIDS surveillance data. Studies suggest that categorizing HIV/AIDS cases in this manner may mask important epidemiological trends, and the distinct differences between these two populations warrant disaggregating data prior to reporting. The purpose of this study was to characterize the HIV/AIDS positive populations in U.S. and African-born blacks in Utah and evaluate the need for disaggregating the two groups. A total of 1,111 cases were identified through the statewide electronic HIV/AIDS Reporting System from 2000 - 2009. Data were analyzed for prevalence of HIV diagnosis for African-born blacks, U.S.-born blacks, and U.S.-born whites. Secondary analysis included HIV diagnosis by age, sex, African region of nativity, transmission risk factors, and differences in late diagnosis of HIV infection. U.S.-born whites accounted for 914 (82.3%) cases, and had the lowest annual prevalence (4/100,000). Conversely, African-born and U.S.- born blacks had the highest prevalence, 162/100,000 and 24/100,000 respectively. African-born blacks made up 0.25% of the total population, but accounted for 7.9% of all HIV/AIDS cases. African-born black males were more likely to report "no reported risk" for HIV transmission than U.S.-born black males. Of African-born blacks, 55.7% reported East-African nativity. These results demonstrate the importance of stratifying the black/African American racial category by African-born and U.S.-born blacks when collecting and reporting HIV/AIDS state surveillance data even in a low-incidence state,which will better inform prevention and linkage-to-care efforts in Utah.

Complete versus anterior two-thirds corpus callosotomy in children: analysis of outcome.

OBJECT: The goal of this study was to evaluate the efficacy of anterior versus complete sectioning of the corpus callosum in children suffering from medically refractory epilepsy. The authors report seizure outcome in patients who underwent anterior two-thirds or complete corpus callosotomy (CC) during the period 1995-2008 at St. Louis Children's Hospital. METHODS: The medical records of 27 children and adolescents with a minimum follow-up of 6 months were retrospectively evaluated with respect to seizure status, anticonvulsant outcomes, and subjective results. Preoperatively, patients suffered from a variety of seizure types that occurred daily, weekly, or episodically. The male/female ratio was 19:8, and patients ranged in age between 3 and 19 years (mean 9.93 years). Seizure outcome, parental assessment of daily function, and changes in the number of prescribed antiepileptic drugs were all assessed. RESULTS: Fifteen patients underwent an initial anterior two-thirds CC, and 12 underwent a complete CC. Of the 15 patients who underwent an anterior CC, 7 went on to receive a posterior CC. Seizure control was superior in children undergoing a complete CC (91%, Class I-III) versus an anterior two-thirds CC (75%, Class I-III). Seizure types most affected by CC included atonic, myoclonic, and absence. The number of postoperative antiepileptic drugs did not significantly change following CC in either the anterior only or complete groups. One patient experienced a transient disconnection syndrome that resolved within 4 weeks, and 4 patients experienced mild hemiparesis and speech delays that resolved with therapy. Three patients experienced surgical complications requiring a second operation. The overall daily function and attentiveness of the patients improved. CONCLUSIONS: A complete CC should be considered as the initial procedure in lower-functioning children afflicted by absence, atonic, or myoclonic seizures. Severely affected higher-functioning children may also benefit from a complete CC, without clinically significant disconnection syndromes. A completion posterior CC may benefit patients in whom a prior anterior CC has failed.

Trends in global protected area governance, 1992-2002.

Governance refers to the interactions among structures, processes, and traditions that determine direction, how power is exercised, and how the views of citizens or stakeholders are incorporated into decision-making. Governance is now recognized as a critical aspect of effective conservation and is a prominent part of the Convention on Biological Diversity's work program on protected areas. This study reports on a global survey to assess changes in governance of protected area systems between 1992 and 2002 based on responses from 41 countries. Results indicate that substantial changes have taken place with overall trends towards increased participation of more stakeholders, greater use of formal accountability mechanisms, and a wider range of participatory techniques. Many of these changes are supported by legislative and policy requirements and 75% of respondents reported changes in legislation over the past decade. Protected areas are becoming more influenced by global forces. A majority of respondents reported increased involvement of the private sector. Funding is coming from a broader range of sources, with a smaller proportion of income coming from government sources in 2002. Absolute funding amounts have increased, but almost two-thirds report that budgets fall short of requirements. Almost 90% of respondents felt that protected area governance had improved over the last decade; 67% felt that this had also led to improved management effectiveness. Respondents felt that secure funding, capacity building, and increased community involvement were the main governance needs for the future.

Insulin induces SOCS-6 expression and its binding to the p85 monomer of phosphoinositide 3-kinase, resulting in improvement in glucose metabolism.

The suppressors of cytokine signaling (SOCS) family is thought to act largely as a negative regulator of signaling by cytokines and some growth factors. Surprisingly, the SOCS-6 transgenics had no significant defects in the cytokine signaling and hematopoietic system but displayed significant improvements in glucose metabolism. Insulin stimulation of Akt/protein kinase B was also potentiated. Biochemical analysis showed that, after insulin stimulation, SOCS-6 interacted with the monomeric p85 subunit of class-Ia phosphoinositide (PI) 3-kinase but not with p85/p110 dimers. Furthermore, SOCS-6 expression is transiently increased by serum and insulin in normal fibroblasts. However, both the mRNA and protein of SOCS-6 were rapidly degraded after induction by insulin. The degradation of the SOCS-6 protein was partially inhibited by a proteasome inhibitor, suggesting a proteasome-mediated degradation mechanism. In contrast, SOCS-6-associated p85 was not degraded and could be recruited to the newly synthesized SOCS-6 molecules in the presence of insulin, suggesting that SOCS-6 expression and its interaction with p85, but not the degradation, is regulated by insulin. The phenotype of SOCS-6 transgenic mice bears a striking resemblance to p85 knock-out mouse models in which glucose metabolism stimulated by insulin is significantly improved despite reduced activation of PI 3-kinase. This suggests that monomeric p85 might play a physiologically important role in attenuating signaling through PI 3-kinase-dependent pathways in unstimulated cells. Therefore, our results indicate that SOCS-6 may provide a dynamically regulated mechanism by which insulin can transiently overcome the negative effects that p85 monomers have on signaling via PI 3-kinase-dependent signaling pathways.