Modulation of human macrophage responses to mycobacterium tuberculosis by silver nanoparticles of different size and surface modification

Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications

Transvaginal Endoscopic Appendectomy

Since Kalloo and colleagues first reported the feasibility and safety of a peroral transgastric approach in the porcine model in 2004, various groups have reported more complex natural orifice transluminal endoscopic surgery (NOTES) procedures, such as the cholecystectomy, splenectomy and liver biopsy, in the porcine model. Natural orifice access to the abdominal cavity, such as transgastric, transvesical, transcolonic, and transvaginal, has been described. Although a novel, minimally invasive approach to the abdominal cavity is a peroral endoscopic transgastric approach, there are still some challenging issues, such as the risk of infection and leakage, and the method of gastric closure. Hybrid-NOTES is an ideal first step in humans. Human hybrid transvaginal access has been used for years by many surgeons for diagnostic and therapeutic purposes. Here, we report a transvaginal flexible endoscopic appendectomy, with a 5-mm umbilical port using ultrasonic scissors in a 74-year-old woman with acute appendicitis

Enrichment and characterization of ammonia-oxidizing archaea from the open ocean : phylogeny, physiology and stable isotope fractionation

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 5 (2011): 1796–1808, doi:10.1038/ismej.2011.58.Archaeal genes for ammonia oxidation are widespread in the marine environment, but direct physiological evidence for ammonia oxidation by marine archaea is limited. We report the enrichment and characterization of three strains of pelagic ammonia-oxidizing archaea (AOA) from the north Pacific Ocean that have been maintained in laboratory culture for over three years. Phylogenetic analyses indicate the three strains belong to a previously identified clade of water column-associated AOA and possess 16S rRNA genes and ammonia monooxygenase subunit a (amoA) genes highly similar (98-99% identity) to those recovered in DNA and cDNA clone libraries from the open ocean. The strains grow in natural seawater-based liquid medium while stoichiometrically converting ammonium (NH4 +) to nitrite (NO2 -). Ammonia oxidation by the enrichments is only partially inhibited by allylthiourea at concentrations known to inhibit cultivated ammonia-oxidizing bacteria. The three strains were used to determine the nitrogen stable isotope effect (15εNH3) during archaeal ammonia oxidation, an important parameter for interpreting stable isotope ratios in the environment. Archaeal 15εNH3 ranged from 13- 41‰, within the range of that previously reported for ammonia-oxidizing bacteria. Despite low amino acid identity between the archaeal and bacterial Amo proteins, their functional diversity as captured by 15εNH3 is similar.This work was supported by a Woods Hole Oceanographic Institution (WHOI) Postdoctoral Scholar fellowship to AES and the WHOI Ocean Life Institute

'You can take a horse to water but you can't make it drink': Exploring children's engagement and resistance in family therapy

The final publication is available at Springer via http://dx.doi.org/10.1007/s10591-012-9220-8Children’s engagement and disengagement, adherence and non-adherence, compliance and non-compliance in healthcare have important implications for services. In family therapy mere attendance to the appointments is no guarantee of engaging in the treatment process and as children are not the main initiators of attendance engaging them through the process can be a complex activity for professionals. Through a conversation analysis of naturally occurring family therapy sessions we explore the main discursive strategies that children employ in this context to passively and actively disengage from the therapeutic process and investigate how the therapists manage and attend to this. We note that children competently remove themselves from therapy through passive resistance, active disengagement, and by expressing their autonomy. Analysis reveals that siblings of the constructed ‘problem’ child are given greater liberty in involvement. We conclude by demonstrating how therapists manage the delicate endeavour of including all family members in the process and how engagement and re-engagement are essential for meeting goals and discuss broader implications for healthcare and other settings where children may disengage

Microbial regulation of the soil carbon cycle: evidence from gene-enzyme relationships.

A lack of empirical evidence for the microbial regulation of ecosystem processes, including carbon (C) degradation, hinders our ability to develop a framework to directly incorporate the genetic composition of microbial communities in the enzyme-driven Earth system models. Herein we evaluated the linkage between microbial functional genes and extracellular enzyme activity in soil samples collected across three geographical regions of Australia. We found a strong relationship between different functional genes and their corresponding enzyme activities. This relationship was maintained after considering microbial community structure, total C and soil pH using structural equation modelling. Results showed that the variations in the activity of enzymes involved in C degradation were predicted by the functional gene abundance of the soil microbial community (R2>0.90 in all cases). Our findings provide a strong framework for improved predictions on soil C dynamics that could be achieved by adopting a gene-centric approach incorporating the abundance of functional genes into process models

The Mechanism of Enhanced Insulin Amyloid Fibril Formation by NaCl Is Better Explained by a Conformational Change Model

The high propensity of insulin to fibrillate causes severe biomedical and biotechnological complications. Insulin fibrillation studies attain significant importance considering the prevalence of diabetes and the requirement of functional insulin in each dose. Although studied since the early years of the 20th century, elucidation of the mechanism of insulin fibrillation has not been understood completely. We have previously, through several studies, shown that insulin hexamer dissociates into monomer that undergoes partial unfolding before converting into mature fibrils. In this study we have established that NaCl enhances insulin fibrillation mainly due to subtle structural changes and is not a mere salt effect. We have carried out studies both in the presence and absence of urea and Gdn.HCl and compared the relationship between conformation of insulin induced by urea and Gdn.HCl with respect to NaCl at both pH 7.4 (hexamer) and pH 2 (monomer). Fibril formation was followed with a Thioflavin T assay and structural changes were monitored by circular dichroism and size-exclusion chromatography. The results show salt-insulin interactions are difficult to classify as commonly accepted Debye-Hückel or Hofmeister series interactions but instead a strong correlation between the association states and conformational states of insulin and their propensity to fibrillate is evident

Principles of Hand Fracture Management

The hand is essential in humans for physical manipulation of their surrounding environment. Allowing the ability to grasp, and differentiated from other animals by an opposing thumb, the main functions include both fine and gross motor skills as well as being a key tool for sensing and understanding the immediate surroundings of their owner