Personal resilience as a strategy for surviving and thriving in the face of workplace adversity: a literature review.
This paper is a report of a literature review to explore the concept of personal resilience as a strategy for responding to workplace adversity and to identify strategies to enhance personal resilience in nurses. Workplace adversity in nursing is associated with excessive workloads, lack of autonomy, bullying and violence and organizational issues such as restructuring, and has been associated with problems retaining nurses in the workforce. However, despite these difficulties many nurses choose to remain in nursing, and survive and even thrive despite a climate of workplace adversity. The literature CINAHL, EBSCO, Medline and Pubmed databases were searched from 1996 to 2006 using the keywords 'resilience', 'resilience in nursing', and 'workplace adversity' together with 'nursing'. Papers in English were included. Resilience is the ability of an individual to positively adjust to adversity, and can be applied to building personal strengths in nurses through strategies such as: building positive and nurturing professional relationships; maintaining positivity; developing emotional insight; achieving life balance and spirituality; and, becoming more reflective. Our findings suggest that nurses can actively participate in the development and strengthening of their own personal resilience to reduce their vulnerability to workplace adversity and thus improve the overall healthcare setting. We recommend that resilience-building be incorporated into nursing education and that professional support should be encouraged through mentorship programmes outside nurses' immediate working environments.


A coiled coil switch mediates cold sensing by the thermosensory protein DesK.
The thermosensor histidine kinase DesK from Bacillus subtilis senses changes in membrane fluidity initiating an adaptive response. Structural changes in DesK have been implicated in transmembrane signaling, but direct evidence is still lacking. On the basis of structure-guided mutagenesis, we now propose a mechanism of DesK-mediated signal sensing and transduction. The data indicate that stabilization/destabilization of a 2-helix coiled coil, which connects the transmembrane sensory domain of DesK to its cytosolic catalytic region, is crucial to control its signaling state. Computational modeling and simulations reveal couplings between protein, water and membrane mechanics. We propose that membrane thickening is the main driving force for signal sensing and that it acts by inducing helix stretching and rotation prompting an asymmetric kinase-competent state. Overall, the known structural changes of the sensor kinase, as well as further dynamic rearrangements that we now predict, consistently link structure determinants to activity modulation.


Medical management of the 'failing' Kasai portoenterostomy.
The only effective treatment for 'failing' Kasai portoenterostomy is liver transplantation (LT). However, to maximise a patient's chances to achieve the proclaimed >95% survival with sequential surgical management, medical follow-up and treatment must be planned carefully. This includes routine fat-soluble vitamin supplementation with choleretics, aggressive nutritional support, regular ultrasonography, optimal general paediatric care, and psychological support for the family once complications arise. Careful timing of LT is of critical importance, although recent trends include earlier consideration of LT in children with biliary atresia. This management can only be offered through centralised, specialised national services. Due to its ramifications in paediatric surgery, dietetics, metabolic, social, adolescent and transplantation medicine, paediatric hepatology is a fine example of patient care that is genuinely multidisciplinary.


Exogenous attention facilitates location transfer of perceptual learning.
Perceptual skills can be improved through practice on a perceptual task, even in adulthood. Visual perceptual learning is known to be mostly specific to the trained retinal location, which is considered as evidence of neural plasticity in retinotopic early visual cortex. Recent findings demonstrate that transfer of learning to untrained locations can occur under some specific training procedures. Here, we evaluated whether exogenous attention facilitates transfer of perceptual learning to untrained locations, both adjacent to the trained locations (Experiment 1) and distant from them (Experiment 2). The results reveal that attention facilitates transfer of perceptual learning to untrained locations in both experiments, and that this transfer occurs both within and across visual hemifields. These findings show that training with exogenous attention is a powerful regime that is able to overcome the major limitation of location specificity.


An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp.
Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens Fusarium verticillioides and Fusarium oxysporum f. sp. pisi. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many Fusarium species, including F. verticillioides, inhibited the production of DAPG by Pseudomonas spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of F. verticillioides by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed F. verticillioides due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of Fusarium spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism.


Robotic surgery in the pediatric airway: application and safety.
To assess the application and safety of transoral robotic surgery in the pediatric airway. An institutional review board-approved study. Experimental laryngeal surgery was performed on 4 pediatric cadaver larynxes as controls. Application of robotic equipment for laryngeal surgery was attempted on 5 patients. Tertiary care pediatric medical center. Five patients with laryngeal cleft and 4 pediatric cadaver larynxes. (1) The da Vinci Surgical Robot (Intuitive Surgical Inc, Sunnyvale, Calif) was used on 4 cadaver larynxes and assessed for the dexterity, precision, and depth perception that it allowed the surgeon during laryngeal surgery. Procedures were documented with still and video photography. (2) The da Vinci Surgical Robot was used through a transoral approach to attempt repair of a laryngeal cleft in 5 pediatric patients who were under spontaneously breathing general anesthesia. (1) Use of the surgical robot on cadaver larynxes provided great dexterity and precision, delicate tissue handling, good 3-dimensional depth perception, and relatively easy endolaryngeal suturing. (2) The surgical robot could not be used for repair of laryngeal cleft on 3 patients owing to limited transoral access. However, 1 patient with a type 1 laryngeal cleft and 1 patient with a type 2 laryngeal cleft underwent transoral robotic repair with great success. Surgical robots provide the ability to manipulate instruments at their distal end with great precision, increased freedom of movement, and excellent 3-dimensional depth perception. The size of the equipment can be a limiting factor with regard to the application and success of the transoral approach to airway surgery. We believe that further advances in device technology and a new generation of robotic equipment will facilitate the incorporation of surgical robotics in the advancement of minimally invasive endoscopic airway surgery.


Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study.
Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs. The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up <4 weeks after starting DAAs. A total of 3,917 out of 4,234 consecutive patients were included, with a mean follow-up of 536.2 ± 197.6 days. Overall, HCC was diagnosed in 55 patients. During the first year, HCC incidence was 0.46% (95% CI 0.12-1.17) in F3, 1.49% (1.03-2.08) in CTP-A and 3.61% (1.86-6.31) in CTP-B cirrhotics; in the second year, HCC incidences were 0%, 0.2%, and 0.69%, respectively. By multivariate analysis, HCC was significantly associated with an aspartate aminotransferase to platelet ratio ≥2.5 (hazard ratio [HR] 2.03; 95% CI 1.14-3.61; p = 0.016) and hepatitis B virus infection (HR 3.99; 1.24-12.91; p = 0.021). Failure to achieve a sustained virological response was strongly associated with development of HCC (HR 9.09; 5.2-16.1; p = 0.0001). A total of 29% of patients with HCC had an aggressive tumor, often seen in the early phase of treatment. These data, obtained in a large, prospective, population-based study, indicate that in patients with advanced hepatitis C receiving DAAs, the risk of "de novo" hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors. Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure.


Reduced X-linked rare polymorphism in males in comparison to females of Drosophila melanogaster.
Natural selection is assumed to act more strongly on X-linked loci than on autosomal loci because the fitness effect of a recessive mutation on the X chromosome is fully expressed in hemizygous males. Therefore, selection is expected to fix or remove recessive mutations on the X chromosome more efficiently than those on autosomes. However, the assumption that hemizygosity of the X chromosome selectively accelerates changes in allele frequency has not been confirmed directly. To examine this assumption, we investigated current natural selection on X-linked chemoreceptor genes in a natural population of Drosophila melanogaster by comparing nucleotide diversity, linkage disequilibrium (LD), and departure from the neutrality in 4 chemoreceptor genes on 100 X chromosomes each from female and male flies. The general pattern of nucleotide diversity and LD for the genes investigated was similar in females and males. In contrast, males harbored significantly fewer rare polymorphisms defined as singletons and doubletons. When all the gene sequences were concatenated, Tajima's D showed a significant departure from the neutrality in both females and males, whereas Fu and Li's F* value revealed departure only in males. These results suggest that some rare polymorphisms on the X chromosome from females are recessively deleterious and are removed by stronger purifying selection when transferred to hemizygous males.


Ocean acidification at high latitudes: potential effects on functioning of the Antarctic bivalve Laternula elliptica.
Ocean acidification is a well recognised threat to marine ecosystems. High latitude regions are predicted to be particularly affected due to cold waters and naturally low carbonate saturation levels. This is of concern for organisms utilising calcium carbonate (CaCO(3)) to generate shells or skeletons. Studies of potential effects of future levels of pCO(2) on high latitude calcifiers are at present limited, and there is little understanding of their potential to acclimate to these changes. We describe a laboratory experiment to compare physiological and metabolic responses of a key benthic bivalve, Laternula elliptica, at pCO(2) levels of their natural environment (430 µatm, pH 7.99; based on field measurements) with those predicted for 2100 (735 µatm, pH 7.78) and glacial levels (187 µatm, pH 8.32). Adult L. elliptica basal metabolism (oxygen consumption rates) and heat shock protein HSP70 gene expression levels increased in response both to lowering and elevation of pH. Expression of chitin synthase (CHS), a key enzyme involved in synthesis of bivalve shells, was significantly up-regulated in individuals at pH 7.78, indicating L. elliptica were working harder to calcify in seawater undersaturated in aragonite (Ω(Ar) = 0.71), the CaCO(3) polymorph of which their shells are comprised. The different response variables were influenced by pH in differing ways, highlighting the importance of assessing a variety of factors to determine the likely impact of pH change. In combination, the results indicate a negative effect of ocean acidification on whole-organism functioning of L. elliptica over relatively short terms (weeks-months) that may be energetically difficult to maintain over longer time periods. Importantly, however, the observed changes in L. elliptica CHS gene expression provides evidence for biological control over the shell formation process, which may enable some degree of adaptation or acclimation to future ocean acidification scenarios.


[Profiles of agencies serving the homeless or those at risk of homelessness in the region of Montreal].
This article presents a study of organizations serving people who are homeless or at risk of becoming homeless (PHRH) in Montreal, as well as the determinants of their inter-organizational relationships. The study shows that greater inter-organizational collaboration is needed, particularly within the network of health and social services (NHSS), to deal with the concomitant problems faced by PHRH. Among determinants that have an impact on the extent of inter-organizational relationships are the number of services offered, the appreciation of the relationships between organizations within the NHSS, and the ratio of Anglophones among the homeless and of individuals with gambling problems.


Sparse Binary Relation Representations for Genome Graph Annotation.
High-throughput DNA sequencing data are accumulating in public repositories, and efficient approaches for storing and indexing such data are in high demand. In recent research, several graph data structures have been proposed to represent large sets of sequencing data and to allow for efficient querying of sequences. In particular, the concept of labeled de Bruijn graphs has been explored by several groups. Although there has been good progress toward representing the sequence graph in small space, methods for storing a set of labels on top of such graphs are still not sufficiently explored. It is also currently not clear how characteristics of the input data, such as the sparsity and correlations of labels, can help to inform the choice of method to compress the graph labeling. In this study, we present a new compression approach, Multi-binary relation wavelet tree (BRWT), which is adaptive to different kinds of input data. We show an up to 29% improvement in compression performance over the basic BRWT method, and up to a 68% improvement over the current state-of-the-art for de Bruijn graph label compression. To put our results into perspective, we present a systematic analysis of five different state-of-the-art annotation compression schemes, evaluate key metrics on both artificial and real-world data, and discuss how different data characteristics influence the compression performance. We show that the improvements of our new method can be robustly reproduced for different representative real-world data sets.


Integrated polarimeters based on anisotropic photodetectors.
Anisotropic detectors (AD's) can be designed by coating a photosensitive surface (e.g., Si) with a birefringent thin film whose principal axes are in the plane of the film. An integrated polarimeter (IP) is described that uses four linear photodetectors, of which three are AD's. The light beam, whose Stokes parameters (SP's) are to be measured, is relayed from one detector to the next by near-normal-incidence partial specular reflection while remaining in one plane. By a suitable choice of surface properties and orientations of the AD's, the four output electrical signals of the four detectors determine completely and unambiguously all four SP's. This IP with AD's (IPAD) has all the advantages of the previously described four-detector polarimeter [Opt. Lett. 10, 309 (1985)]. In addition, the IPAD offers a compact design with small-area detectors.


Informing theoretical development of salutogenic, asset-based health improvement to reduce syndemics among gay, bisexual and other men who have sex with men: Empirical evidence from secondary analysis of multi-national, online cross-sectional surveys.
Globally, gay, bisexual and other men who have sex with men (GBMSM) experience an increased burden of poor sexual, mental and physical health. Syndemics theory provides a framework to understand comorbidities and health among marginalised populations. Syndemics theory attempts to account for the social, environmental, and other structural contexts that are driving and/or sustaining simultaneous multiple negative health outcomes, but has been widely critiqued. In this paper, we conceptualise a new framework to counter syndemics by assessing the key theoretical mechanisms by which pathogenic social context variables relate to ill-health. Subsequently, we examine how salutogenic, assets-based approaches to health improvement could function among GBMSM across diverse national contexts. Comparative quantitative secondary analysis of data on syndemics and community assets are presented from two international, online, cross-sectional surveys of GBMSM (SMMASH2 in Scotland, Wales, Northern Ireland and the Republic of Ireland and Sex Now in Canada). Negative sexual, mental and physical health outcomes were clustered as hypothesised, providing evidence of the syndemic. We found that syndemic ill-health was associated with social isolation and the experience of stigma and discrimination, but this varied across national contexts. Moreover, while some of our measures of community assets appeared to have a protective effect on syndemic ill-health, others did not. These results present an important step forward in our understanding of syndemic ill-health and provide new insights into how to intervene to reduce it. They point to a theoretical mechanism through which salutogenic approaches to health improvement could function and provide new strategies for working with communities to understand the proposed processes of change that are required. To move forward, we suggest conceptualising syndemics within a complex adaptive systems model, which enables consideration of the development, sustainment and resilience to syndemics both within individuals and at the population-level.


S1 sensitive sites in adenovirus DNA.
S1 nuclease has been used as a probe for regions of DNA secondary structure in supercoiled recombinant plasmids containing adenovirus (Ad) DNA sequences. In the sequences examined two S1 sensitive sites were identified in the left-terminal 16.5% of Ad 12 DNA, one of which aligned approximately with an inverted repeat region in the DNA sequence. In addition an S1 sensitive site was dictated by a potential cruciform structure in the region of the Ad 2 major late promoter. In contrast to the expected cleavage site at the loop of the cruciform, cleavage occurred at the base of the stem in the region of the TATA box. All three S1 sensitive sites identified were more sensitive to S1 than the endogenous sites in the parent plasmids.


Syntactic mixing across generations in an environment of community-wide bilingualism.
A quantitative analysis of a trans-generational, conversational corpus of Chintang (Tibeto-Burman) speakers with community-wide bilingualism in Nepali (Indo-European) reveals that children show more code-switching into Nepali than older speakers. This confirms earlier proposals in the literature that code-switching in bilingual children decreases when they gain proficiency in their dominant language, especially in vocabulary. Contradicting expectations from other studies, our corpus data also reveal that for adults, multi-word insertions of Nepali into Chintang are just as likely to undergo full syntactic integration as single-word insertions. Speakers of younger generations show less syntactic integration. We propose that this reflects a change between generations, from strongly asymmetrical, Chintang-dominated bilingualism in older generations to more balanced bilingualism where Chintang and Nepali operate as clearly separate systems in younger generations. This change is likely to have been triggered by the increase of Nepali presence over the past few decades.


Unraveling the local structure and luminescence evolution in Nd3+-doped LiYF4: a new theoretical approach.
Neodymium ion (Nd3+)-doped yttrium lithium fluoride (LiYF4, YLF) laser crystals have shown significant prospects as excellent laser materials in many kinds of solid-state laser systems. However, the origins of the detailed information of their local structure and luminescence evolution are still poorly understood. Herein, we use an unbiased CALYPSO structure searching technique and density functional theory to study the local structure of Nd3+-doped YLF. Our results reveal a new stable phase with the P4[combining macron] (No. 81) space group for Nd3+-doped YLF, indicating that the host Y3+ ion site was naturally occupied by the Nd3+ ion impurity. On the basis of our newly developed WEPMD method, we adopt a specific type of orthogonal correlation crystal field to obtain a new set of crystal-field parameters as well as 182 complete Stark energy levels. Many absorption and emission lines for Nd3+-doped YLF are calculated and discussed based on Judd-Ofelt theory, and our results indicate that some of the observed absorption and emission lines are perfectly reproduced by our theoretical calculations. Additionally, we predict several promising transition lines in the visible and near-infrared spectral regions, including the electronic dipole emission lines 4F5/2 → 4I9/2 at 808 nm and 2H9/2 → 4I9/2 at 799 nm, as well as the magnetic dipole emission lines 4F3/2(27) → 4I11/2(6) at 1047 nm and 4F3/2(27) → 4I11/2(8) at 1052 nm. These transition channels indicate that Nd3+-doped YLF laser crystals have greatly promising laser actions for serving as a solid-state laser material.


3,3'-diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells.
HER2/neu positive breast tumors are difficult to treat. About 25 to 30% of invasive breast tumors overexpress the HER2/neu oncogene. These tumors are aggressive and become resistant to chemotherapeutic drugs. 3'3'-diindolylmethane (DIM), the active metabolite of indole-3-carbinol, a naturally occurring compound found in cruciferous vegetables, has been found to have anti-cancer properties in both humans and animals. DIM has been shown to induce cell cycle arrest and apoptosis in animal breast cancer models. Because HER2/neu overexpression confers resistance to paclitaxel, and DIM has anti-tumor effects, we hypothesized that DIM will enhance the cytotoxic effects of paclitaxel, a common taxane drug, on human Her2/neu breast cancer cells by potentiating its effect on cell cycle and stimulating apoptosis. The MDA-MB-435eB1 human Her2/neu breast cancer cells were treated with varying concentrations of DIM and paclitaxel. The cells were analyzed at different time points (24, 48, and 72 h). Proliferation was measured by a commercial cell proliferation assay (Promega Procheck Assay). Cell-cycle analysis and apoptosis were determined by flow cytometry. Western blot analysis was performed on to determine the effect of DIM and/or paclitaxel on the proteins involved in apoptosis, and epidermal growth factor-induced activation of HER2/neu and ERK1/2 signaling proteins. Both DIM and paclitaxel exhibited time and concentration dependent inhibition of cell proliferation. TUNEL assay indicated that the combination also increased the number of apoptotic cells more than either agent alone. The presence of cleaved poly (ADP-Ribose) polymerase (PARP) significantly increased in the combination treatment, whereas Bcl-2 is decreased. DIM alone decreased the activation of the Her2/neu receptor; the combination decreased the activation of ERK1/ERK2. DIM in combination with paclitaxel synergistically inhibits growth of Her2/neu human breast cancer cells through G2M phase cell-cycle arrest and induction of apoptosis/necrosis. The Her2/neu receptor and its downstream signaling protein ERK1/2 appear to be involved in DIM's affect on cell growth and differentiation, whereas apoptosis appears to be mediated through the mitochondrial pathway (Bcl-2/PARP). It appears DIM, a naturally occurring, nontoxic compound, may be a beneficial addition to a traditional (taxane-based) chemotherapy regimen.


Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study.
Knowledge of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization is important to prevent nosocomial spread but also to start prompt adequate antibiotic therapy in patients with suspicion of infection. However, few studies have examined the incidence and risk factors for CR-KP bloodstream infection (BSI) among rectal carriers. To identify risk factors for CR-KP BSI among carriers, we performed a multicentre prospective matched case-control study of all adult CR-KP rectal carriers hospitalized in five tertiary teaching hospitals in Italy over a 2-year period. Carriers who developed CR-KP BSI were compared with those who did not develop subsequent BSI. Overall, 143 CR-KP BSIs were compared with 572 controls without a documented infection during their hospitalization. Multivariate analysis revealed that admission to the Intensive Care Unit (ICU) (OR, 1.65; 95% CI, 1.05-2.59; p 0.03), abdominal invasive procedure (OR, 1.87; 95% CI, 1.16-3.04; p 0.01), chemotherapy/radiation therapy (OR, 3.07; 95% CI, 1.78-5.29; p <0.0001), and number of additional colonization sites (OR, 3.37 per site; 95% CI, 2.56-4.43; p <0.0001) were independent risk factors for CR-KP BSI development among CR-KP rectal carriers. A CR-KP BSI risk score ranging from 0 to 28 was developed based on these four independent variables. At a cut-off of ≥2 the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 42%, 29% and 93%, respectively. Colonization at multiple sites with CR-KP was the strongest predictor of BSI development in our large cohort of CR-KP rectal carriers.


Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers.
Pancreatic cancer (PC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote its earlier diagnosis and hence also avoid its development. Considering the known involvement in pancreatic disease of exon 11 of the bile salt-dependent lipase (BSDL) gene that encodes variable number of tandem repeat (VNTR) sequences, we hypothesized upon the existence of a genetic link between predisposition to PC and mutations in VNTR loci. To test this, BSDL VNTR were amplified by touchdown-PCR performed on genomic DNA extracted from cancer tissue or blood samples from a French patient cohort and amplicons were Sanger sequenced. A robust method using probes for droplet digital (dd)-PCR was designed to discriminate the C/C major from C/T or T/T minor genotypes. We report that the c.1719C > T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC versus 27.30% in the control group). The odds ratio of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that a germline T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. We propose that the detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of patients in whom an association with other potential risk factors of pancreatic cancer may be present.


CpxR/OmpR interplay regulates curli gene expression in response to osmolarity in Escherichia coli.
Curli fibers could be described as a virulence factor able to confer adherence properties to both abiotic and eukaryotic surfaces. The ability to adapt rapidly to changing environmental conditions through signal transduction pathways is crucial for the growth and pathogenicity of bacteria. OmpR was shown to activate csgD expression, resulting in curli production. The CpxR regulator was shown to negatively affect curli gene expression when binding to its recognition site that overlaps the csgD OmpR-binding site. This study was undertaken to clarify how the interplay between the two regulatory proteins, OmpR and CpxR, can affect the transcription of the curli gene in response to variation of the medium osmolarity. Band-shift assays with purified CpxR proteins indicate that CpxR binds to the csgD promoter region at multiple sites that are ideally positioned to explain the csg repression activity of CpxR. To understand the physiological meaning of this in vitro molecular phenomenon, we analyzed the effects of an osmolarity shift on the two-component pathway CpxA/CpxR. We establish here that the Cpx pathway is activated at both transcriptional and posttranscriptional levels in response to a high osmolarity medium and that CpxR represses csgD expression in high-salt-content medium, resulting in low curli production. However, csgD repression in response to high sucrose content is not mediated by CpxR but by the global regulatory protein H-NS. Therefore, multiple systems (EnvZ/OmpR, Cpx, Rcs, and H-NS) appear to be involved in sensing environmental osmolarity, leading to sophisticated regulation of the curli genes.


Chromium released from leather - II: the importance of environmental parameters.
Approximately 1-3% of the adult population in Europe are allergic to chromium (Cr). A new restriction in Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) based on the ISO 17075 standard has recently been adopted in the EU to limit Cr(VI) in consumer and occupational leather products to < 3 mg/kg. To investigate the influence of storage conditions [relative humidity, temperature, ultraviolet (UV) irradiation, and duration] on Cr release, and to assess several parameters relevant for occupational exposure (repeated exposure, wear, alkaline solutions, and sequential wet and dry exposures). A leather of relevance for work gloves was investigated for its release of Cr(III) and Cr(VI) under these different experimental conditions. Relative humidity (water content in leather) during storage prior to Cr extraction was the single most important parameter. Cr(VI) levels could vary from non-detectable to levels significantly exceeding the restriction limit, depending on the relative humidity. Leather contact with alkaline solution and UV irradiation during storage could increase the Cr(VI) levels in subsequent extractions. The amount of Cr(VI) in leather is not an intrinsic property, but is influenced by environmental conditions of relevance for occupations and skin exposure.


Structure of the Munc18c/Syntaxin4 N-peptide complex defines universal features of the N-peptide binding mode of Sec1/Munc18 proteins.
Sec1/Munc18 proteins (SM proteins) bind to soluble NSF attachment protein receptors (SNAREs) and play an essential role in membrane fusion. Divergent modes of regulation have been proposed for different SM proteins indicating that they can either promote or inhibit SNARE assembly. This is in part because of discrete modes of binding that have been described for various SM/SNARE complexes. One mode suggests that SM proteins bind only to Syntaxins (Stx) preventing SNARE assembly, whereas in another they facilitate SNARE assembly and bind to SNARE complexes. The mammalian cell surface SM protein Munc18c binds to an N-peptide in Stx4, and this is compatible with its interaction with SNARE complexes. Here we describe the crystal structure of Munc18c in complex with the Stx4 N-peptide. This structure shows remarkable similarity with a yeast complex indicating that the mode of binding, which can accommodate SNARE complexes, is highly conserved throughout evolution. Modeling reveals the presence of the N-peptide binding mode in most but not all yeast and mammalian SM/Stx pairs, suggesting that it has coevolved to fulfill a specific regulatory function. It is unlikely that the N-peptide interaction alone accounts for the specificity in SM/SNARE binding, implicating other contact surfaces in this function. Together with other data, our results support a sequential two-state model for SM/SNARE binding involving an initial interaction via the Stx N-peptide, which somehow facilitates a second, more comprehensive interaction comprising other contact surfaces in both proteins.


Focal shifts in focused nonuniformly polarized beams.
We present a simple formula to evaluate the relative focal shift in a circular-aperture lens system illuminated by a nonuniformly polarized (NUP) light wave. Specifically, it is shown that the relative focal shift is determined by the effective Fresnel number. The effective Fresnel number is equal to the product of the Fresnel number of the lens aperture and the parameter sigma, which describes the uniformity of the polarization distribution of the NUP beam across the lens aperture. Some examples are given to illustrate the use of this approach. The influence of the polarization distribution of the incident NUP light wave on the polarization distribution in the axial points of the focused field is also presented.


Incorporating personalized gene sequence variants, molecular genetics knowledge, and health knowledge into an EHR prototype based on the Continuity of Care Record standard.
The current volume and complexity of genetic tests, and the molecular genetics knowledge and health knowledge related to interpretation of the results of those tests, are rapidly outstripping the ability of individual clinicians to recall, understand and convey to their patients information relevant to their care. The tailoring of molecular genetics knowledge and health knowledge in clinical settings is important both for the provision of personalized medicine and to reduce clinician information overload. In this paper we describe the incorporation, customization and demonstration of molecular genetic data (mainly sequence variants), molecular genetics knowledge and health knowledge into a standards-based electronic health record (EHR) prototype developed specifically for this study. We extended the CCR (Continuity of Care Record), an existing EHR standard for representing clinical data, to include molecular genetic data. An EHR prototype was built based on the extended CCR and designed to display relevant molecular genetics knowledge and health knowledge from an existing knowledge base for cystic fibrosis (OntoKBCF). We reconstructed test records from published case reports and represented them in the CCR schema. We then used the EHR to dynamically filter molecular genetics knowledge and health knowledge from OntoKBCF using molecular genetic data and clinical data from the test cases. The molecular genetic data were successfully incorporated in the CCR by creating a category of laboratory results called "Molecular Genetics" and specifying a particular class of test ("Gene Mutation Test") in this category. Unlike other laboratory tests reported in the CCR, results of tests in this class required additional attributes ("Molecular Structure" and "Molecular Position") to support interpretation by clinicians. These results, along with clinical data (age, sex, ethnicity, diagnostic procedures, and therapies) were used by the EHR to filter and present molecular genetics knowledge and health knowledge from OntoKBCF. This research shows a feasible model for delivering patient sequence variants and presenting tailored molecular genetics knowledge and health knowledge via a standards-based EHR system prototype. EHR standards can be extended to include the necessary patient data (as we have demonstrated in the case of the CCR), while knowledge can be obtained from external knowledge bases that are created and maintained independently from the EHR. This approach can form the basis for a personalized medicine framework, a more comprehensive standards-based EHR system and a potential platform for advancing translational research by both disseminating results and providing opportunities for new insights into phenotype-genotype relationships.


Acute overactive endocannabinoid signaling induces glucose intolerance, hepatic steatosis, and novel cannabinoid receptor 1 responsive genes.
Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP), perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG) and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251) and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control), IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2), which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50%) the majority (303 of 533) of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and identify novel cannabinoid responsive genes.


The effect of hair color on the incorporation of codeine into human hair.
The influence of melanin on the binding of xenobiotics in hair will impact the interpretation of drug concentrations determined by hair testing. The purpose of this study was to determine if codeine, as a model compound of abused drugs, would be incorporated into black, brown, blond, or red hair as a function of melanin concentration. Such data would assist in the interpretation of codeine concentrations in hair and help elucidate the potential influence of hair color on incorporation of drugs. Male and female Caucasians with black (n = 6), brown (n = 12), blond (n = 8), or red hair (n = 6) and non-Caucasians with black hair (n = 12) aged 21-40 years were enrolled in the study. Each subject was administered oral codeine phosphate syrup in a dosage of 30 mg three times a day for five days. Twenty-four hours after the end of the treatment period, a 30-mg codeine dose was administered and the subject's plasma area under the concentration time curve (AUC) for codeine was determined. Codeine and melanin were measured in the first 3 cm of hair closest to the vertex region of the scalp prior to and 1, 4, 5, 6, and 7 weeks after dosing. The quantitative and qualitative melanin profiles were determined for each subject's hair to provide an objective measure of hair color. The plasma concentrations of codeine were measured to eliminate differences in the bioavailability and clearance of codeine as factors that might account for the differences in codeine hair concentrations. The subjects were asked not to cut their hair in the vertex region of the scalp or to use any form of chemical treatment on their hair, but otherwise normal hygienic measures were permitted. The mean (+/- SE) hair codeine concentrations 5 weeks after dosing were 1429 (+/- 249) pg/mg in black hair; 208 (+/- 17) pg/mg in brown hair; 99 (+/- 10) pg/mg in blond hair; and 69 (+/- 11) in red hair pg/mg. In black hair, codeine concentrations were 2564 (+/- 170) pg/mg for Asians and 865 (+/- 162) pg/mg for Caucasians. Similar concentration relationships were observed at weeks 4, 6, and 7. A strong relationship between the hair concentrations of codeine and melanin (R(2) = 0.73) was observed. Normalization of the codeine concentration with the melanin concentration reduced the hair color differences observed. These data demonstrate that the interpretation and reporting of hair test results for codeine are influenced by hair color. After this dosing protocol, the proposed federal guideline cutoff of 200 pg/mg of codeine would result in 100% of subjects with black hair and 50% of subjects with brown hair being reported as positive, and subjects with blond or red hair would be reported as negative. The incorporation of these drugs into hair should be studied carefully in humans to ensure the appropriate interpretation of drug concentrations.


[Sleep quality of patients in End Stage Renal Disease before and after starting chronic hemodialysis treatment: a longitudinal study].
Introduction: Sleep disorders are very common in patients with chronic kidney disease, with a prevalence of poor sleep quality of around 40%. Objectives: The purpose of the study is to compare the sleep quality of ESRD patients before hemodialysis (Pre-HD), three months (Post-HD 1) and six months after the start of treatment (Post-HD 2) through the use of the Pittsburgh Sleep Quality Index (PSQI). Methods: Patients in ESRD were recruited from the U.O.C. of Nephrology and Dialysis of the Maggiore Hospital in Modica and biographical and anamnestic data were collected. The PSQI was administered in-person at the Pre-HD stage and by telephone re-test at the three- and six-month follow-up. Results: A total of 71 patients (males=62%, age 68 ± 16) were included. At Pre-HD assessment 93% reported poor sleep quality, the percentage increased to 98% during Post-HD 1 and it partially improved during Post-HD 2 with a prevalence of 95%. Analysis of variance (ANOVA) by repeated measures showed a difference in sleep quality between the three time points. Conclusions: Sleep quality undergoes important changes during the transition from conservative to hemodialysis patient, highlighting a critical period related to the first three months of treatment. More attention to this phase may improve the patient's quality of life and reduce the associated risk of mortality.


Work-aged stroke survivors' psychosocial challenges narrated during and after participating in a dialogue-based psychosocial intervention: a feasibility study.
Studies point to the lack of psychosocial support and rehabilitation services that are adjusted to the work-aged stroke survivors' specific needs in order to promote psychosocial well-being. The aim of the study was to illuminate the psychosocial challenges work-aged participants (i.e. aged 18-67 years) thematised during and after participating a dialogue-based psychosocial intervention during the first year following a stroke. The study was a feasibility study guided by the UK Medical Research Council Framework for developing and evaluating complex interventions. Qualitative data from in-depth interviews with fourteen stroke-survivors aged 33-66 years, researcher field notes and log notes written during the intervention were analysed applying a hermeneutic-phenomenological approach. The stroke and its consequences had a substantial impact on family and work life. Their experiences were summarised in the two themes The threat of becoming marginalised in family life and The threat of becoming marginalised in work life. Life as a work-aged stroke survivor was experienced as challenging and created a threat of becoming marginalised in family and work life. The study highlights the need to understand the specific psychosocial challenges and needs facing work-aged stroke survivors' in order to promote their psychosocial well-being. More research is needed concerning specific life-span challenges amongst work-aged stroke survivors in order to further develop appropriate interventions that helps address this issue.


The adjuvant effect of Corynebacterium parvum: T-cell dependence of macrophage activation.
Splenic and peritoneal macrophages from mice treated with Corynebacterium parvum enhanced the antibody response in vitro of normal nonadherent spleen cells to SRBC, but not to DNP-POL. This enhancement was dependent on the dose and time of administration of C. parvum and could be abrogated by pretreatment with carrageenan. Macrophages from T-cell-depleted mice failed to enhance the response, but this ability was restored if the mice had been reconstituted with purified T lymphocytes. Macrophages that are activated by C. parvum are a resident nondividing population. It is postulated that activated macrophages, capable of enhancing antibody responses to T-cell-dependent antigens, arise through a cell-mediated reaction to C. parvum.


Real and imaginary rotary motion processing: functional parcellation of the human parietal lobe revealed by fMRI.
Functional magnetic resonance imaging was performed in 16 healthy subjects while they undertook orientation discrimination tasks of real rotating and mentally rotating alphanumeric characters. Perception of rotating and stationary abstract characters was also performed. Mental rotation and the perception of alphanumeric characters undergoing real rotation activated equivalent cortical areas, in keeping with the analogue hypothesis of mental rotation. In addition, areas along the dorsal stream, including the V5/middle temporal complex and the intraparietal sulcus (IPS), were activated during both the real and imaginary rotary conditions. Within the parietal lobe there were areas of convergence (i.e., recruited by all three motion conditions) and areas of divergence (i.e., selectively activated by a particular condition). Tasks requiring canonical-mirror orientation discrimination revealed involvement of neural substrates localized to the ventrolateral bank of the IPS. Tasks in which this judgment was not performed and during which the subject viewed rotary motion of abstract stimuli recruited activity in the medial bank of the IPS. These results indicate subspecialization of the human posterior parietal lobe according to function.


Dynamic Regulation of Auxin Response during Rice Development Revealed by Newly Established Hormone Biosensor Markers.
The hormone auxin is critical for many plant developmental processes. Unlike the model eudicot plant Arabidopsis (Arabidopsis thaliana), auxin distribution and signaling in rice tissues has not been systematically investigated due to the absence of suitable auxin response reporters. In this study we observed the conservation of auxin signaling components between Arabidopsis and model monocot crop rice (Oryza sativa), and generated complementary types of auxin biosensor constructs, one derived from the Aux/IAA-based biosensor DII-VENUS but constitutively driven by maize ubiquitin-1 promoter, and the other termed DR5-VENUS in which a synthetic auxin-responsive promoter (DR5rev ) was used to drive expression of the yellow fluorescent protein (YFP). Using the obtained transgenic lines, we observed that during the vegetative development, accumulation of DR5-VENUS signal was at young and mature leaves, tiller buds and stem base. Notably, abundant DR5-VENUS signals were observed in the cytoplasm of cortex cells surrounding lateral root primordia (LRP) in rice. In addition, auxin maxima and dynamic re-localization were seen at the initiation sites of inflorescence and spikelet primordia including branch meristems (BMs), female and male organs. The comparison of these observations among Arabidopsis, rice and maize suggests the unique role of auxin in regulating rice lateral root emergence and reproduction. Moreover, protein localization of auxin transporters PIN1 homologs and GFP tagged OsAUX1 overlapped with DR5-VENUS during spikelet development, helping validate these auxin response reporters are reliable markers in rice. This work firstly reveals the direct correspondence between auxin distribution and rice reproductive and root development at tissue and cellular level, and provides high-resolution auxin tools to probe fundamental developmental processes in rice and to establish links between auxin, development and agronomical traits like yield or root architecture.


Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease.
The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.


Methodological issues in measuring the impact of interventions against female genital cutting.
With increasing efforts being made to introduce systematic interventions for encouraging abandonment of female genital cutting (FGC) comes the need to better understand how such interventions work and what effects they have. Many interventions are based on theoretical models of behaviour change and so studies to evaluate them should develop indicators appropriate to the type of behaviour change anticipated. Systematic evaluations need also to use some form of quasi-experimental design to be able to attribute change to the intervention and not to any 'natural' change in FGC behaviour or other activities that may be concurrent. A sustained change in the prevalence of FGC is the ultimate indicator and there are several ways this can be measured, although with many limitations given the intimate nature of the practice. Moreover, appropriate sample sizes must be calculated and used to be able to draw valid conclusions. Many of those implementing FGC interventions are not familiar with such basic research principles and so there is an urgent need to ensure that projects are well designed so that valid conclusions concerning their effectiveness can be drawn.


Genome-wide tissue-specific occupancy of the Hox protein Ultrabithorax and Hox cofactor Homothorax in Drosophila.
The Hox genes are responsible for generating morphological diversity along the anterior-posterior axis during animal development. The Drosophila Hox gene Ultrabithorax (Ubx), for example, is required for specifying the identity of the third thoracic (T3) segment of the adult, which includes the dorsal haltere, an appendage required for flight, and the ventral T3 leg. Ubx mutants show homeotic transformations of the T3 leg towards the identity of the T2 leg and the haltere towards the wing. All Hox genes, including Ubx, encode homeodomain containing transcription factors, raising the question of what target genes Ubx regulates to generate these adult structures. To address this question, we carried out whole genome ChIP-chip studies to identify all of the Ubx bound regions in the haltere and T3 leg imaginal discs, which are the precursors to these adult structures. In addition, we used ChIP-chip to identify the sites bound by the Hox cofactor, Homothorax (Hth). In contrast to previous ChIP-chip studies carried out in Drosophila embryos, these binding studies reveal that there is a remarkable amount of tissue- and transcription factor-specific binding. Analyses of the putative target genes bound and regulated by these factors suggest that Ubx regulates many downstream transcription factors and developmental pathways in the haltere and T3 leg. Finally, we discovered additional DNA sequence motifs that in some cases are specific for individual data sets, arguing that Ubx and/or Hth work together with many regionally expressed transcription factors to execute their functions. Together, these data provide the first whole-genome analysis of the binding sites and target genes regulated by Ubx to specify the morphologies of the adult T3 segment of the fly.


Static and dynamic electronic characterization of organic monolayers grafted on a silicon surface.
Organic layers chemically grafted on silicon offer excellent interfaces that may open up the way for new organic-inorganic hybrid nanoelectronic devices. However, technological achievements rely on the precise electronic characterization of such organic layers. We have prepared ordered grafted organic monolayers (GOMs) on Si(111), sometimes termed self-assembled monolayers (SAMs), by a hydrosilylation reaction with either a 7-carbon or an 11-carbon alkyl chain, with further modification to obtain amine-terminated surfaces. X-ray photoelectron spectroscopy (XPS) is used to determine the band bending (∼ 0.3 eV), and ultraviolet photoelectron spectroscopy (UPS) to measure the work function (∼ 3.4 eV) and the HOMO edge. Scanning tunneling microscopy (STM) confirms that the GOM surface is clean and smooth. Finally, conductive AFM is used to measure electron transport through the monolayer and to identify transition between the tunneling and the field emission regimes. These organic monolayers offer a promising alternative to silicon dioxide thin films for fabricating metal-insulator-semiconductor (MIS) junctions. We show that gold nanoparticles can be covalently attached to mimic metallic nano-electrodes and that the electrical quality of the GOMs is completely preserved in the process.


Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor.
T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and T-cell activation-induced DNA methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an evolutionarily conserved CpG (CpG -41), CCR5 cis-regions manifest lower vs. higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naïve T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and in vitro induced T-cell activation is associated with demethylation of these cis-regions. CCR5 haplotypes associated with increased vs. decreased gene/surface expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell activation-associated demethylation. Methylation status of CCR5 intron 2 explains a larger proportion of the variation in CCR5 levels than genotype or T-cell activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at CpG -41 that is (i) specific to southern Africa, (ii) abrogates binding of the transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for overrepresentation in persons with reduced susceptibility to HIV and disease progression. Genotypes lacking the CCR5-Δ32 mutation but with hypermethylated cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-Δ32. In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite restoration of CD4+ counts (≥800 cells per mm(3)) with antiretroviral therapy. Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant of T-cell CCR5 levels, and possibly HIV-related outcomes.


Yeast two-hybrid interactions between Arabidopsis lyrata S Receptor Kinase and the ARC1 E3 ligase.
Here we describe protein-protein interactions between signaling components in the conserved self-incompatibility pathway from Brassica spp. and Arabidopsis lyrata. Previously, we had demonstrated that ARC1 is necessary in A. lyrata for the rejection of self-pollen by the self-incompatibility pathway. The results described here demonstrate that A. lyrata ARC1 interacts with A. lyrata S Receptor Kinase (SRK1) in the yeast 2-hybrid system. A. lyrata ARC1 also interacted with B. napus SRK910 illustrating that interactions in this pathway are conserved across species. Finally, we discuss how the more widely occurring interactions between SRK and ARC1-related family members may be modulated in vivo by expression and subcellular localization patterns resulting in a particular response.


MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clusters.
A variable proportion of patients with generalized myasthenia gravis (MG) have autoantibodies to muscle specific tyrosine kinase (MuSK). During development agrin, released from the motor nerve, interacts with low density lipoprotein receptor-related protein-4 (LRP4), which then binds to MuSK; MuSK interaction with the intracellular protein Dok7 results in clustering of the acetylcholine receptors (AChRs) on the postsynaptic membrane. In mature muscle, MuSK helps maintain the high density of AChRs at the neuromuscular junction. MuSK antibodies are mainly IgG4 subclass, which does not activate complement and can be monovalent, thus it is not clear how the antibodies cause disruption of AChR numbers or function to cause MG. We hypothesised that MuSK antibodies either reduce surface MuSK expression and/or inhibit the interaction with LRP4. We prepared MuSK IgG, monovalent Fab fragments, IgG1-3 and IgG4 fractions from MuSK-MG plasmas. We asked whether the antibodies caused endocytosis of MuSK in MuSK-transfected cells or if they inhibited binding of LRP4 to MuSK in co-immunoprecipitation experiments. In parallel, we investigated their ability to reduce AChR clusters in C2C12 myotubes induced by a) agrin, reflecting neuromuscular development, and b) by Dok7- overexpression, producing AChR clusters that more closely resemble the adult neuromuscular synapse. Total IgG, IgG4 or IgG1-3 MuSK antibodies were not endocytosed unless cross-linked by divalent anti-human IgG. MuSK IgG, Fab fragments and IgG4 inhibited the binding of LRP4 to MuSK and reduced agrin-induced AChR clustering in C2C12 cells. By contrast, IgG1-3 antibodies did not inhibit LRP4-MuSK binding but, surprisingly, did inhibit agrin-induced clustering. Moreover, both IgG4 and IgG1-3 preparations dispersed agrin-independent AChR clusters in Dok7-overexpressing C2C12 cells. Thus interference by IgG4 antibodies of the LRP4-MuSK interaction will be one pathogenic mechanism of MuSK antibodies, but IgG1-3 MuSK antibodies will also contribute to the reduced AChR density and neuromuscular dysfunction in myasthenia patients with MuSK antibodies.


Purification and characterization of adenovirus core protein VII: a histone-like protein that is critical for adenovirus core formation.
Adenovirus protein VII is a highly cationic core protein that forms a nucleosome-like structure in the adenovirus core by condensing DNA in combination with protein V and mu. It has been proposed that protein VII could condense DNA in a manner analogous to mammalian histones. Due to the lack of an expression and purification protocol, the interactions between protein VII and DNA are poorly understood. In this study we describe methods for the purification of biologically active recombinant protein VII using an E. coli expression system. We expressed a cleavable fusion of protein VII with thioredoxin and established methods for purification of this fusion protein in denatured form. We describe an efficient method for resolving the cleavage products to obtain pure protein VII using hydroxyapatite column chromatography. Mass spectroscopy data confirmed its mass and purity to be 19.4 kDa and >98 %, respectively. Purified recombinant protein VII spontaneously condensed dsDNA to form particles, as shown by dye exclusion assay, electrophoretic mobility shift assay and nuclease protection assay. Additionally, an in vitro bioluminescence assay revealed that protein VII can be used to enhance the transfection of mammalian cells with lipofectamine/DNA complexes. The availability of recombinant protein VII will facilitate future studies of the structure of the adenovirus core. Improved understanding of the structure and function of protein VII will be valuable in elucidating the mechanism of adenoviral DNA condensation, defining the morphology of the adenovirus core and establishing the mechanism by which adenoviral DNA enters the nucleus.


Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses.
Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV) is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1) and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1) roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity differences. These findings support a set-point control mechanism rather than immaturity for explaining not only neonatal susceptibility but also resilience to infection. In summary, our findings show that neonatal HCMV infection leads to a highly plastic and functional robust programming of dendritic cells in vivo and in vitro. In comparison with adults, a minimal number of subtle quantitative and temporal differences may contribute to variability in host susceptibility and resilience, in a context dependent manner.


Finger Twitches are More Frequent in REM Sleep Than in Non-REM Sleep.
Abnormal rapid eye movement (REM) sleep is often symptomatic of chronic disorders, however polysomnography, the gold standard method to measure REM sleep, is expensive and often impractical. Attempts to develop cost-effective ambulatory systems to measure REM sleep have had limited success. As elevated twitching is often observed during REM sleep in some distal muscles, the aim of this study was to assess the potential for a finger-mounted device to measure finger twitches, and thereby differentiate periods of REM and non-REM (NREM) sleep. One night of sleep data was collected by polysomnography from each of 18 (3f, 15m) healthy adults aged 23.2 ± 3.3 (mean ± SD) years. Finger movement was detected using a piezo-electric limb sensor taped to the index finger of each participant. Finger twitch densities were calculated for each stage of sleep. Finger twitch density was greater in REM than in NREM sleep (p < 0.001). Each sleep stage had a unique finger twitch density, except for REM and stage N1 sleep which were similar. Finger twitch density was greater in late REM than in early REM sleep (p = 0.005), and there was a time-state interaction: the difference between finger twitch densities in REM and NREM sleep was greater in late sleep than in early sleep (p = 0.007). Finger twitching is more frequent in REM sleep than in NREM sleep and becomes more distinguishable as sleep progresses. Finger twitches appear to be too infrequent to make definitive 30-second epoch determinations of sleep stage. However, an algorithm informed by measures of finger twitch density has the potential to detect periods of REM sleep and provide estimates of total REM sleep time and percentage.


Robustostrongylus aferensis gen. nov. et sp. nov. (Nematoda: Trichostrongyloidea) in kob (Kobus kob) and hartebeest (Alcelaphus buselaphus jacksoni) (Artiodactyla) from sub-Saharan Africa, with further ruminations on the Ostertagiinae.
Abomasal nematodes (Ostertagiinae: Trichostrongyloidea), representing a previously unrecognized genus and species, were discovered in kob (Kobus kob) and kongoni (hartebeest) (Alcelaphus buselaphus jacksoni) from Uganda during surveys of ungulate parasites in the 1960s. Robustostrongylus aferensis gen. nov. et sp. nov. is characterized by a ventriculus-like, bilobed valve at the junction of the esophagus and intestine, a synlophe with unusually robust ridges, cervical papillae and excretory pore situated posterior to the mid-length of the esophagus, a unique body form and large diameter in males and females, a relatively anterior position for the vulva, and strongly convoluted and spiraled ovarian tracks in females. Bursal structure is 2-1-2, with subequal Rays 2/3, strongly reduced and robust Rays 8, and relatively narrow Rays 9/10 contained within a reduced, laterally inflated dorsal lobe. Spicules are filamentous and tripartite; the gubernaculum is cryptic, alate, and heart-shaped in the anterior. Robustostrongylus aferensis, with narrow filamentous spicules that trifurcate distally near 80%, paired arcuate "0" papillae that terminate in bulbous expansions, and a reduced dorsal lobe and ray most closely resembles species of Longistrongylus. A suite of unique characters, consistent in males and females, however, unequivocally distinguishes specimens of R. aferensis from all ostertagiines with either a 2-1-2 or 2-2-1 bursal pattern. Among 15 genera of the Ostertagiinae in the global fauna, 5 are entirely limited in distribution to Africa, including Africanastrongylus, Hamulonema, Longistrongylus, Pseudomarshallagia, and Robustostrongylus gen. nov.; species among 5 additional genera, including Cervicaprastrongylus, Hyostrongylus, Marshallagia, Ostertagia, and Teladorsagia, also occur in Africa, but they are represented as mosaics, with diversity centered in Eurasia or the Holarctic.


Reactions of 11-vertex rhodathiaboranes with HCl: synthesis and reactivity of new Cl-ligated clusters.
Reactions of [8,8,8-(H)(PPh(3))(2)-9-(Py)-nido-8,7-RhSB(9)H(9)] (1), [1,1-(PPh(3))(2)-3-(Py)-closo-1,2-RhSB(9)H(8)] (2), and [1,1-(CO)(PPh(3))-3-(Py)-closo-1,2-RhSB(9)H(8)] (4), where Py = Pyridine, with HCl to give the Cl-ligated clusters, [8,8-(Cl)(PPh(3))-9-(Py)-nido-8,7-RhSB(9)H(9)] (3) and [8,8,8-(Cl)(CO)(PPh(3))-9-(Py)-nido-8,7-RhSB(9)H(8)] (5), have recently demonstrated the remarkable nido-to-closo redox flexibility and bifunctional character of this class of 11-vertex rhodathiaboranes. To get a sense of the scope of this chemistry, we report here the reactions of PR(3)-ligated analogues, [8,8,8-(H)(PR(3))(2)-9-(Py)-nido-8,7-RhSB(9)H(9)], where PR(3) = PMePh(2) (6), or PPh(3) and PMe(3) (7); and [1,1-(PR(3))(2)-3-(Py)-closo-1,2-RhSB(9)H(8)], where PR(3) = PPh(3) and PMe(3) (8), PMe(3) (9) or PMe(2)Ph (10), with HCl to give Cl-ligated clusters. The results demonstrate that in contrast to the PPh(3)-ligated compounds, 1, 2, and 3, the reactions with 6-10 are less selective, giving rise to the formation of mixtures that contain monophosphine species, [8,8-(Cl)(PR(3))-9-(Py)-nido-8,7-RhSB(9)H(9)], where PR(3) = PMe(3) (11), PMe(2)Ph (12), or PMePh(2) (15), and bis-ligated derivatives, [8,8,8-(Cl)(PR(3))(2)-9-(Py)-nido-8,7-RhSB(9)H(9)], where PR(3) = PMe(3) (13) or PMe(2)Ph (14). The {RhCl(PR(3))}-containing compounds, 3, 11, 12, and 15, are formally unsaturated 12 skeletal electron pair (sep) clusters with nido-structures. Density functional theory (DFT) calculations demonstrate that the nido-structure is more stable than the predicted closo-isomers. In addition, studies have been carried out that involve the reactivity of 3 with Lewis bases. Thus, it is reported that 3 interacts with MeCN in solution, and it reacts with CO and pyridine to give the corresponding Rh-L adducts, [8,8,8-(Cl)(L)(PPh(3))-9-(Py)-nido-8,7-RhSB(9)H(9)], where L = CO (5) or Py (20). On the other hand, the treatment of 3 and 5 with Proton Sponge (PS) promotes the abstraction of HCl, as [PSH]Cl, from the nido-clusters, and the regeneration of the parent closo-species, completing two new stoichiometric cycles that are driven by Brønsted acid/base chemistry.


Performance of the American Urological Association Symptom Index with and without an additional urge incontinence item.
To examine the value of adding an urge incontinence question to the American Urological Association Symptom Index (AUASI) among men in the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) trial. The CAMUS study was a randomized trial of Saw palmetto fruit extract versus placebo among men aged ≥45 years with an AUASI score of ≥8 and ≤24. The baseline measurements included the AUASI, a question about urge incontinence (UI), the International Prostate Symptom Score quality of life question, and the Benign Prostatic Hyperplasia Impact Index. We correlated the items and scales and examined whether adding the UI question resulted in better prediction of disease-specific health status. The mean age of the 369 men in the CAMUS trial was 61 years, and mean baseline AUASI score was 14.6. UI was reported infrequently; about 82% of the respondents answered the question "not at all" or "<1 time in 5." UI correlated significantly with all other AUASI items, except for weak stream; the strongest correlation was to urgency (R=0.51, P<.0001). The correlation between the AUASI score and the AUASI+UI score was 0.98 (P<.0001). In a logistic regression analysis predicting the International Prostate Symptom Score quality of life score, adding UI to the AUASI slightly increased the discriminating ability (c statistic increased from 0.77 to 0.78, P<.0001). Similarly, in a linear regression analysis predicting the Benign Prostatic Hyperplasia Impact Index score, adding UI to the AUASI slightly increased the predictive ability (R2 statistic increased from 0.22 to 0.26, P<.0001). According to our analysis in the CAMUS trial population, the value of adding a UI question to the AUASI in terms of predicting bother seemed small at best.


A comparative analysis of retrieval features used in the TREC 2006 Genomics Track passage retrieval task.
Identify the set of features that best explained the variation in the performance measure of TREC 2006 Genomics information extraction task, Mean Average Passage Precision (MAPP). A multivariate regression model was built using a backward-elimination approach as a function of certain generalized features that were common to all the algorithms used by TREC 2006 Genomics track participants. Our regression analysis found that the following four factors were collectively associated with variation in MAPP: (1) Normalization of keywords in the query (2) Use of Entrez gene thesaurus for synonymous terms look-up (3) Unit of text retrieved using respective IR algorithms and (4) The way a passage was defined. These reasonably likely hypotheses, generated by an exploratory data analysis, are informative in understanding results of the TREC 2006 Genomics passage extraction task. This approach has general value for analyzing the results of similar common challenge tasks.


Mesozoic fossils (>145 Mya) suggest the antiquity of the subgenera of Daphnia and their coevolution with chaoborid predators.
The timescale of the origins of Daphnia O. F. Mueller (Crustacea: Cladocera) remains controversial. The origin of the two main subgenera has been associated with the breakup of the supercontinent Pangaea. This vicariance hypothesis is supported by reciprocal monophyly, present day associations with the former Gondwanaland and Laurasia regions, and mitochondrial DNA divergence estimates. However, previous multilocus nuclear DNA sequence divergence estimates at < 10 Million years are inconsistent with the breakup of Pangaea. We examined new and existing cladoceran fossils from a Mesozoic Mongolian site, in hopes of gaining insights into the timescale of the evolution of Daphnia. We describe new fossils of ephippia from the Khotont site in Mongolia associated with the Jurassic-Cretaceous boundary (about 145 MYA) that are morphologically similar to several modern genera of the family Daphniidae, including the two major subgenera of Daphnia, i.e., Daphnia s. str. and Ctenodaphnia. The daphniid fossils co-occurred with fossils of the predaceous phantom midge (Chaoboridae). Our findings indicate that the main subgenera of Daphnia are likely much older than previously known from fossils (at least 100 MY older) or from nuclear DNA estimates of divergence. The results showing co-occurrence of the main subgenera far from the presumed Laurasia/Gondwanaland dispersal barrier shortly after formation suggests that vicariance from the breakup of Pangaea is an unlikely explanation for the origin of the main subgenera. The fossil impressions also reveal that the coevolution of a dipteran predator (Chaoboridae) with the subgenus Daphnia is much older than previously known -- since the Mesozoic.


Plasmid Classification in an Era of Whole-Genome Sequencing: Application in Studies of Antibiotic Resistance Epidemiology.
Plasmids are extra-chromosomal genetic elements ubiquitous in bacteria, and commonly transmissible between host cells. Their genomes include variable repertoires of 'accessory genes,' such as antibiotic resistance genes, as well as 'backbone' loci which are largely conserved within plasmid families, and often involved in key plasmid-specific functions (e.g., replication, stable inheritance, mobility). Classifying plasmids into different types according to their phylogenetic relatedness provides insight into the epidemiology of plasmid-mediated antibiotic resistance. Current typing schemes exploit backbone loci associated with replication (replicon typing), or plasmid mobility (MOB typing). Conventional PCR-based methods for plasmid typing remain widely used. With the emergence of whole-genome sequencing (WGS), large datasets can be analyzed using in silico plasmid typing methods. However, short reads from popular high-throughput sequencers can be challenging to assemble, so complete plasmid sequences may not be accurately reconstructed. Therefore, localizing resistance genes to specific plasmids may be difficult, limiting epidemiological insight. Long-read sequencing will become increasingly popular as costs decline, especially when resolving accurate plasmid structures is the primary goal. This review discusses the application of plasmid classification in WGS-based studies of antibiotic resistance epidemiology; novel in silico plasmid analysis tools are highlighted. Due to the diverse and plastic nature of plasmid genomes, current typing schemes do not classify all plasmids, and identifying conserved, phylogenetically concordant genes for subtyping and phylogenetics is challenging. Analyzing plasmids as nodes in a network that represents gene-sharing relationships between plasmids provides a complementary way to assess plasmid diversity, and allows inferences about horizontal gene transfer to be made.


Development of gene therapy for neurological disorders.
Given improvements in viral vector design, production and efficiency of transduction in the central nervous system (CNS), as well as increased knowledge of neuropathological mechanisms in neurological disorders, success in treating a CNS disorder with gene transfer seems inevitable. Several different vector systems have been studied extensively and the adeno-associated viral vector system has been utilized in most early stage clinical trials in neurological disorders. Other vector systems, such as lentivirus, adenovirus, and herpes simplex virus are also viable vector platforms that should fill significant clinical niches based on their specific characteristics. In addition to the choice of the appropriate vector, the proper choice of transgene for the appropriate strategy to treat a neurological disorder is also critical. The example of glial cell line-derived neurotrophic factor ligands to treat Parkinson's disease is used to illustrate the importance of the interface between interpretation of pre-clinical data and consideration of the natural history of the disorder. This interface dictates the proper design of clinical trials that are capable of testing whether the treatment is actually successful.


11R-P53 and GM-CSF Expressing Oncolytic Adenovirus Target Cancer Stem Cells with Enhanced Synergistic Activity.
Targeting cancer stem cells with oncolytic virus (OV) holds great potential for thorough elimination of cancer cells. Based on our previous studies, we here established 11R-P53 and mGM-CSF carrying oncolytic adenovirus (OAV) SG655-mGMP and investigated its therapeutic effect on hepatocellular carcinoma stem cells Hep3B-C and teratoma stem cells ECCG5. Firstly, the augmenting effect of 11R in our construct was tested and confirmed by examining the expression of EGFP with Fluorescence and FCM assays after transfecting Hep3B-C and ECCG5 cells with OVA SG7605-EGFP and SG7605-11R-EGFP. Secondly, the expressions of 11R-P53 and GM-CSF in Hep3B-C and ECCG5 cells after transfection with OAV SG655-mGMP were detected by Western blot and Elisa assays, respectively. Thirdly, the enhanced growth inhibitory and augmented apoptosis inducing effects of OAV SG655-mGMP on Hep3B-C and ECCG5 cells were tested with FCM assays by comparing with the control, wild type 5 adenovirus, 11R-P53 carrying OVA in vitro. Lastly, the in vivo therapeutic effect of OAV SG655-mGMP toward ECCG5 cell-formed xenografts was studied by measuring tumor volumes post different treatments with PBS, OAV SG655-11R-P53, OAV SG655-mGM-CSF and OAV SG655-mGMP. Treatment with OAV SG655-mGMP induced significant xenograft growth inhibition, inflammation factor AIF1 expression and immune cells infiltration. Therefore, our OAV SG655-mGMP provides a novel platform to arm OVs to target cancer stem cells.


Health care in Brazil.
Brazil has great geopolitical importance because of its size, environmental resources, and potential economic power. The organisation of its health care system reflects the schisms within Brazilian society. High technology private care is available to the rich and inadequate public care to the poor. Limited financial resources have been overconcentrated on health care in the hospital sector and health professionals are generally inappropriately trained to meet the needs of the community. However, recent changes in the organisation of health care are taking power away from federal government to state and local authorities. This should help the process of reform, but many vested interests remain to be overcome. A link programme between Britain and Brazil focusing on primary care has resulted in exchange of ideas and staff between the two countries. If primary care in Brazil can be improved it could help to narrow the health divide between rich and poor.


Depression and anxiety during pregnancy and six months postpartum: a follow-up study.
To investigate the relationship between antenatal and postpartum depression and anxiety and to explore associated maternal characteristics. From a population-based sample of 1,555 women attending two obstetric clinics in Sweden, all women with an antenatal psychiatric diagnosis (n = 220) and a random selection of healthy women (n = 500) were contacted for a second assessment three to six months postpartum. The Primary Care Evaluation of Mental Disorders was used for evaluation on both occasions. Fewer cases of depressive and/or anxiety disorders were prevalent postpartum compared with the second trimester screening. Depression and/or anxiety were prevalent in 16.5% of postpartal women versus 29.2% of pregnant women. There was a significant shift from a majority of subthreshold diagnoses during pregnancy to full Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnoses during the postpartum period. A history of previous psychiatric disorder, living single, and obesity were significantly associated with a new-onset postpartum psychiatric disorder. The absence of a previous psychiatric disorder was significantly associated with a postpartum recovery of depression or anxiety. Depression and anxiety appear to be less common postpartum than during pregnancy.


Multiple Anesthetic Exposure in Infant Monkeys Alters Emotional Reactivity to an Acute Stressor.
Retrospective studies in humans have shown a higher prevalence of learning disabilities in children that received multiple exposures to general anesthesia before the age of 4 yr. Animal studies, primarily in rodents, have found that postnatal anesthetic exposure causes neurotoxicity and neurocognitive deficits in adulthood. The authors addressed the question of whether repeated postnatal anesthetic exposure was sufficient to cause long-term behavioral changes in a highly translationally relevant rhesus monkey model, allowing study of these variables against a background of protracted nervous system and behavioral development. Rhesus monkeys of both sexes underwent either three 4-h exposures to sevoflurane anesthesia (anesthesia group n = 10) or brief maternal separations (control group n = 10) on postnatal day 6 to 10 that were repeated 14 and 28 days later. Monkeys remained with their mothers in large social groups at all times except for overnight observation after each anesthetic/control procedure. At 6 months of age, each monkey was tested on the human intruder paradigm, a common test for emotional reactivity in nonhuman primates. The frequency of anxiety-related behaviors was significantly higher in monkeys that were exposed to anesthesia as neonates as compared with controls: anesthesia 11.04 ± 1.68, controls 4.79 ± 0.77, mean ± SEM across all stimulus conditions. Increased emotional behavior in monkeys after anesthesia exposure in infancy may reflect long-term adverse effects of anesthesia.


To worry or not to worry: breast cancer genetic counseling communication with low-income Latina immigrants.
The purpose of this pilot study was to describe communication practices during hereditary breast cancer genetic counseling (GC) with low-income immigrant Latina patients in a public hospital setting. We utilized qualitative ethnographic methods, including direct observation of GC appointments with Latina patients at a public hospital offering free GC and BRCA testing and in-depth qualitative interviews with patients after they had received their BRCA genetic test results. Twenty-five patients participated; 20 were observed during genetic counseling appointments, and ten participated in interviews after BRCA testing with six participating in both observations and an interview. Analyses of qualitative data from observation field notes and interviews identified both strengths and limitations of current communication practices within the following themes: (1) family health history communication, (2) education regarding genes and genetics and patient information needs, (3) the purpose of the genetic test, (4) genetic test results and cancer risk, (5) building rapport and providing support, and (6) medical interpretation for monolingual Spanish speakers. As access to cancer GC expands in the public safety net settings and for the diverse populations they serve, it is critical to ensure effective communication in order for patients, whether or not they have a BRCA mutation, to understand the nature of their cancer risk and recommended methods of screening and prevention. Intervention strategies that address both structural constraints and patient-provider communication are needed to improve GC communication with immigrant Latinas, especially monolingual Spanish speakers.


Legible cities: focus-dependent multi-resolution visualization of urban relationships.
Numerous systems have been developed to display large collections of data for urban contexts; however, most have focused on layering of single dimensions of data and manual calculations to understand relationships within the urban environment. Furthermore, these systems often limit the userâs perspectives on the data, thereby diminishing the userâs spatial understanding of the viewing region. In this paper, we introduce a highly interactive urban visualization tool that provides intuitive understanding of the urban data. Our system utilizes an aggregation method that combines buildings and city blocks into legible clusters, thus providing continuous levels of abstraction while preserving the userâs mental model of the city. In conjunction with a 3D view of the urban model, a separate but integrated information visualization view displays multiple disparate dimensions of the urban data, allowing the user to understand the urban environment both spatially and cognitively in one glance. For our evaluation, expert users from various backgrounds viewed a real city model with census data and confirmed that our system allowed them to gain more intuitive and deeper understanding of the urban model from different perspectives and levels of abstraction than existing commercial urban visualization systems.


Comparative efficacy of uncontrolled and controlled intermittent preventive treatment during pregnancy (IPTp) with combined use of LLTNs in high resistance area to sulfadoxine-pyrimethamine in Côte d'Ivoire.
In recent years, intermittent preventive treatment for pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) has become policy in much of sub-Saharan Africa. But resistance to SP has been spreading across sub-Saharan Africa and thus the effectiveness of IPTp-SP has been questioned. The present study therefore sought to assess the incidence of placental malaria, low birth weight, and anemia of two IPTp-SP approaches (directly observed treatment scheme versus no directly observed treatment) in Anonkoua-Kouté and Samo, Côte d'Ivoire where the reported prevalence of dfr single mutant 108 was 62% and 52.2%, respectively. The study was a longitudinal design involving pregnant women and was conducted in Anonkoua-Kouté, a suburban area, and Samo, a rural area, from January 2008 through March 2009. Women of a pregnancy less than 28 weeks duration were randomized to receive SP (1.5 g/0.075 g SP) in a single intake twice and were followed up monthly until delivery. Doses were administered under supervision in the controlled IPTp group, while SP was given free to women in the uncontrolled IPTp group with a recommendation to take it at home. The primary end point was the proportion of low birth weight infants (body weight < 2500 g) and the secondary end point was the rate of severe anemia and placental malaria detected at delivery. A total of 420 pregnant women were enrolled (212 and 208, respectively, in the controlled and uncontrolled groups). Delivery outcome was available for 378 women. In the modified intention-to-treat analysis, low birth weight infants were born from 15.5% of women of the uncontrolled IPTp group and from 11.9% of women in the controlled IPTp group (P = 0.31). The per-protocol population analysis showed consistent results. The proportion of women with placental malaria infection, moderate anemia (hemoglobin < 11 g/dL), and severe anemia (hemoglobin < 8 g/dL) at delivery were similar between the two groups (P > 0.05). The study showed that the two approaches were equivalent, suggesting that unsupervised IPTp-SP free of charge should be used in areas where implementation of the directly observed treatment scheme suffers from many constraints.


Characterisation of functional domains within the mouse erythropoietin 3' enhancer conveying oxygen-regulated responses in different cell lines.
We have analysed sequences within the mouse erythropoietin enhancer which are required for oxygen regulated operation in the erythropoietin producing cell line, HepG2, and in two non-erythropoietin producing cell lines; the lung fibroblastoid cell line a23, and mouse erythroleukaemia (MEL) cells. At least three critical sites were demonstrated within a 96 nucleotide sequence. Oxygen regulated operation was dependent on sites within the first 26 nucleotides. Sequences lying 3' to this region modulated enhancer function but did not themselves convey oxygen regulated operation. In HepG2 cells these 3' sequences co-operated to permit operation of the inducible element at a distance from a promoter, but in MEL cells 3' sequences repressed activity of the inducible element. Though operation of this 3' sequence differed according to the cell type, oxygen regulated operation was dependent on the same two critical sites in the 5' region in both erythropoietin producing and non-erythropoietin producing cells. These findings support the existence of a widespread oxygen sensing system in mammalian cells which is similar to that operating in specific cells to regulate erythropoietin production, and they indicate that the system activates factors with similar DNA sequence specificity in different cells.


Class IIa bacteriocins: diversity and new developments.
Class IIa bacteriocins are heat-stable, unmodified peptides with a conserved amino acids sequence YGNGV on their N-terminal domains, and have received much attention due to their generally recognized as safe (GRAS) status, their high biological activity, and their excellent heat stability. They are promising and attractive agents that could function as biopreservatives in the food industry. This review summarizes the new developments in the area of class IIa bacteriocins and aims to provide uptodate information that can be used in designing future research.


Measurement of clinical wear of two packable composites after 6 months in service.
Original large-particle composites exhibited poor wear characteristics. With the packable composites, there has been a reintroduction of large particles. The clinical wear characteristics of such packable composites are relatively unknown. The purpose of this study was to compare wear between two types of packable composites: Alert (Jeneric Pentron) and Surefil (Dentsply Caulk). Each material was compared with and without a surface sealant. Fifty-two subjects were included. Subjects had to have two to four eligible teeth, be 21 years of age, in good health and in need of moderate to large class 2 restorations on molars, and/or a two-surface class 1 on molars. Wear was assessed, using the Moffa-Lugassy (ML) scale, by evaluating stone models made from polyvinyl siloxane (PVS) impressions taken at baseline and 6 months. Rating was done by four calibrated examiners using a forced consensus model. The use of a surface sealant with Alert significantly reduced the median wear rate at 6 months compared with that of the SureFil restorations.


Biomass and neutral lipid production in geothermal microalgal consortia.
Recently, technologies have been developed that offer the possibility of using algal biomass as feedstocks to energy producing systems - in addition to oil-derived fuels (Bird et al., 2011, 2012). Growing native mixed microalgal consortia for biomass in association with geothermal resources has the potential to mitigate negative impacts of seasonally low temperatures on biomass production systems as well as mitigate some of the challenges associated with growing unialgal strains. We assessed community composition, growth rates, biomass, and neutral lipid production of microalgal consortia obtained from geothermal hot springs in the Great Basin/Nevada area that were cultured under different thermal and light conditions. Biomass production rates ranged from 39.0 to 344.1 mg C L(-1) day(-1). The neutral lipid production in these consortia with and without shifts to lower temperatures and additions of bicarbonate (both environmental parameters that have been shown to enhance neutral lipid production) ranged from 0 to 38.74 mg free fatty acids (FFA) and triacylglycerols (TAG) L(-1 )day(-1); the upper value was approximately 6% of the biomass produced. The higher lipid values were most likely due to the presence of Achnanthidium sp. Palmitic and stearic acids were the dominant free fatty acids. The S/U ratio (the saturated to unsaturated FA ratio) decreased for cultures shifted from their original temperature to 15°C. Biomass production was within the upper limits of those reported for individual strains, and production of neutral lipids was increased with secondary treatment. All results demonstrate a potential of culturing and manipulating resultant microalgal consortia for biomass-based energy production and perhaps even for biofuels.