Lipocalin 2 is protective against E. coli pneumonia

<p>Abstract</p> <p>Background</p> <p>Lipocalin 2 is a bacteriostatic protein that binds the siderophore enterobactin, an iron-chelating molecule produced by <it>Escherichia coli </it>(<it>E. coli</it>) that is required for bacterial growth. Infection of the lungs by <it>E. coli </it>is rare despite a frequent exposure to this commensal bacterium. Lipocalin 2 is an effector molecule of the innate immune system and could therefore play a role in hindering growth of <it>E. coli </it>in the lungs.</p> <p>Methods</p> <p>Lipocalin 2 knock-out and wild type mice were infected with two strains of <it>E. coli</it>. The lungs were removed 48 hours post-infection and examined for lipocalin 2 and MMP9 (a myeloid marker protein) by immunohistochemical staining and western blotting. Bacterial numbers were assessed in the lungs of the mice at 2 and 5 days after infection and mortality of the mice was monitored over a five-day period. The effect of administering ferrichrome (an iron source that cannot be bound by lipocalin 2) along with E.coli was also examined.</p> <p>Results</p> <p>Intratracheal installation of <it>E. coli </it>in mice resulted in strong induction of lipocalin 2 expression in bronchial epithelium and alveolar type II pneumocytes. Migration of myeloid cells to the site of infection also contributed to an increased lipocalin 2 level in the lungs. Significant higher bacterial numbers were observed in the lungs of lipocalin 2 knock-out mice on days 2 and 5 after infection with <it>E. coli </it>(p < 0.05). In addition, a higher number of <it>E. coli </it>was found in the spleen of surviving lipocalin 2 knock-out mice on day 5 post-infection than in the corresponding wild-type mice (p < 0.05). The protective effect against <it>E. coli </it>infection in wild type mice could be counteracted by the siderophore ferrichrome, indicating that the protective effect of lipocalin 2 depends on its ability to sequester iron.</p> <p>Conclusions</p> <p>Lipocalin 2 is important for protection of airways against infection by <it>E. coli</it>.</p

Current role of surgery in small cell lung carcinoma

Small cell lung carcinoma represents 15–20% of lung cancer. Is is characterized by rapid growth and early disseminated disease with poor outcome. For many years surgery was considered a contraindication in Small Cell Lung Cancer (SCLC) since radiotherapy and chemoradiotherapy were found to be more efficient in the management of these patients. Never the less some surgeons continue to be in favor of surgery as part of a combined modality treatment in patients with SCLC. The revaluation of the role of surgery in this group of patients is based on clinical data indicating a much better prognosis in selected patients with limited disease (T1-2, N0, M0), the high rate of local recurrence after chemoradiotherapy with surgery considered eventually more efficient in the local control of the disease and the fact that surgery is the most accurate tool to access the response to chemotherapy, identify carcinoids misdiagnosed as SCLC and treat the Non Small Cell Lung Cancer component of mixed tumors. Performing surgery for local disease SCLC requires a complete preoperative assessment to exclude the presence of nodal involvement. In stage I surgery must always be followed by adjuvant chemotherapy, while in stage II and III surgery must be planned only in the context of clinical trials and after a pathologic response to induction chemoradiotherapy has been confirmed. Prophylactic cranial irradiation should be used to reduce the incidence of brain metastasi

Flexural behaviour of hot-finished high strength steel square and rectangular hollow sections

High strength steels, considered in the context of the structural Eurocodes, as steels with a yield strength over 460 MPa, are gaining increasing attention from structural engineers and researchers owing to their potential to enable lighter and more economic structures. This paper focuses on the bending strength of hot-finished high strength steel (HSS) square and rectangular hollow sections; the results of detailed experimental and numerical studies are presented and structural design rules for HSS cross-sections are proposed. A total of 22 in-plane bending tests, in three-point bending and four-point bending configurations, on HSS sections in grades S460 and S690 were conducted. The experimental results were replicated by means of non-linear finite element modelling. Upon validation of the finite element models, parametric studies were performed to assess the structural response of HSS sections over a wider range of cross-section slenderness, cross-section aspect ratio and moment gradient. The experimental results combined with the obtained numerical results were used to assess the suitability of the current European (EN 1993-1-1 and EN 1993-1-12) cross-section classification limits for HSS structural components. The reliability of the proposed cross-section classification limits was verified by means of the EN 1990 - Annex D method.The Research Fund for Coal and Steel (RFCS) under grant agreement No. RFSR CT 2012-00028. V&M DEUTSCHLAND GMBH, Mr. Gordon Herbert, Mr. Fillip Kirazov and Mr. Isaak Vryzidi

Clinical characteristics and risk behavior as a function of HIV status among heroin users enrolled in methadone treatment in northern Taiwan

<p>Abstract</p> <p>Background</p> <p>Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV), which is endemic among Taiwanese heroin users. The present study was aimed at examining the clinical and behavioral characteristics of methadone patients in northern Taiwan according to their HIV status.</p> <p>Methods</p> <p>The study was conducted at four methadone clinics. Participants were patients who had undergone methadone treatment at the clinics and who voluntarily signed a consent form. Between August and November 2008, each participant completed a face-to-face interview that included questions on demographics, risk behavior, quality of life, and psychiatric symptoms. Data on HIV and hepatitis C virus (HCV) infections, methadone dosage, and morphine in the urine were retrieved from patient files on the clinical premises, with permission of the participants.</p> <p>Results</p> <p>Of 576 participants, 71 were HIV positive, and 514 had hepatitis C. There were significant differences between the HIV-positive and HIV-negative groups on source of treatment payment, HCV infection, urine test results, methadone dosage, and treatment duration. The results indicate that HIV-negative heroin users were more likely to have sexual intercourse and not use condoms during the 6 months prior to the study. A substantial percent of the sample reported anxiety (21.0%), depression (27.2%), memory loss (32.7%), attempted suicide (32.7%), and administration of psychiatric medications (16.1%). There were no significant differences between the HIV-positive and HIV-negative patients on psychiatric symptoms or quality of life.</p> <p>Conclusions</p> <p>HIV-positive IDUs were comorbid with HCV, indicating the need to refer both HIV- and HCV-infected individuals for treatment in methadone clinics. Currently, there is a gap between psychiatric/psychosocial services and patient symptoms, and more integrated medical services should be provided to heroin-using populations.</p

Social odors conveying dominance and reproductive information induce rapid physiological and neuromolecular changes in a cichlid fish

Background: Social plasticity is a pervasive feature of animal behavior. Animals adjust the expression of their social behavior to the daily changes in social life and to transitions between life-history stages, and this ability has an impact in their Darwinian fitness. This behavioral plasticity may be achieved either by rewiring or by biochemically switching nodes of the neural network underlying social behavior in response to perceived social information. Independent of the proximate mechanisms, at the neuromolecular level social plasticity relies on the regulation of gene expression, such that different neurogenomic states emerge in response to different social stimuli and the switches between states are orchestrated by signaling pathways that interface the social environment and the genotype. Here, we test this hypothesis by characterizing the changes in the brain profile of gene expression in response to social odors in the Mozambique Tilapia, Oreochromis mossambicus. This species has a rich repertoire of social behaviors during which both visual and chemical information are conveyed to conspecifics. Specifically, dominant males increase their urination frequency during agonist encounters and during courtship to convey chemical information reflecting their dominance status. Results: We recorded electro-olfactograms to test the extent to which the olfactory epithelium can discriminate between olfactory information from dominant and subordinate males as well as from pre- and post-spawning females. We then performed a genome-scale gene expression analysis of the olfactory bulb and the olfactory cortex homolog in order to identify the neuromolecular systems involved in processing these social stimuli. Conclusions: Our results show that different olfactory stimuli from conspecifics' have a major impact in the brain transcriptome, with different chemical social cues eliciting specific patterns of gene expression in the brain. These results confirm the role of rapid changes in gene expression in the brain as a genomic mechanism underlying behavioral plasticity and reinforce the idea of an extensive transcriptional plasticity of cichlid genomes, especially in response to rapid changes in their social environment.Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [EXCL/BIA-ANM/0549/2012, Pest-OE/MAR/UI0331/2011]; Dwight W. and Blanche Faye Reeder Centennial Fellowship in Systematic and Evolutionary Biology; Institute for Cellular and Molecular Biology Fellowship; FCTinfo:eu-repo/semantics/publishedVersio

Widening of Socioeconomic Inequalities in U.S. Death Rates, 1993–2001

Background: Socioeconomic inequalities in death rates from all causes combined widened from 1960 until 1990 in the U.S., largely because cardiovascular death rates decreased more slowly in lower than in higher socioeconomic groups. However, no studies have examined trends in inequalities using recent US national data. Methodology/Principal Findings: We calculated annual age-standardized death rates from 1993–2001 for 25–64 year old non-Hispanic whites and blacks by level of education for all causes and for the seven most common causes of death using death certificate information from 43 states and Washington, D.C. Regression analysis was used to estimate annual percent change. The inequalities in all cause death rates between Americans with less than high school education and college graduates increased rapidly from 1993 to 2001 due to both significant decreases in mortality from all causes, heart disease, cancer, stroke, and other conditions in the most educated and lack of change or increases among the least educated. For white women, the all cause death rate increased significantly by 3.2 percent per year in the least educated and by 0.7 percent per year in high school graduates. The rate ratio (RR) comparing the least versus most educated increased from 2.9 (95 % CI, 2.8–3.1) in 1993 to 4.4 (4.1–4.6) in 2001 among white men, from 2.1 (1.8–2.5) to 3.4 (2.9–3–9) in black men, and from 2.6 (2.4–2.7) to 3.8 (3.6–4.0) in white women. Conclusion: Socioeconomic inequalities in mortality are increasing rapidly due to continued progress by educated whit

Protein analysis and gene expression indicate differential vulnerability of Iberian fish species under a climate change scenario

Current knowledge on the biological responses of freshwater fish under projected scenarios of climate change remains limited. Here, we examine differences in the protein configuration of two endemic Iberian freshwater fish species, Squalius carolitertii and the critically endangered S. torgalensis that inhabit in the Atlantic-type northern and in the Mediterranean-type southwestern regions, respectively. We performed protein structure modeling of fourteen genes linked to protein folding, energy metabolism, circadian rhythms and immune responses. Structural differences in proteins between the two species were found for HSC70, FKBP52, HIF1α and GPB1. For S. torgalensis, besides structural differences, we found higher thermostability for two proteins (HSP90 and GBP1), which can be advantageous in a warmer environment. Additionally, we investigated how these species might respond to projected scenarios of 3° climate change warming, acidification (ΔpH = -0.4), and their combined effects. Significant changes in gene expression were observed in response to all treatments, particularly under the combined warming and acidification. While S. carolitertii presented changes in gene expression for multiple proteins related to folding (hsp90aa1, hsc70, fkbp4 and stip1), only one such gene was altered in S. torgalensis (stip1). However, S. torgalensis showed a greater capacity for energy production under both the acidification and combined scenarios by increasing cs gene expression and maintaining ldha gene expression in muscle. Overall, these findings suggest that S. torgalensis is better prepared to cope with projected climate change. Worryingly, under the simulated scenarios, disturbances to circadian rhythm and immune system genes (cry1aa, per1a and gbp1) raise concerns for the persistence of both species, highlighting the need to consider multi-stressor effects when evaluating climate change impacts upon fish. This work also highlights that assessments of the potential of endangered freshwater species to cope with environmental change are crucial to help decision-makers adopt future conservation strategies.info:eu-repo/semantics/publishedVersio

A Novel Role for IκBζ in the Regulation of IFNγ Production

IκBζ is a novel member of the IκB family of NFκB regulators, which modulates NFκB activity in the nucleus, rather than controlling its nuclear translocation. IκBζ is specifically induced by IL-1β and several TLR ligands and positively regulates NFκB-mediated transcription of genes such as IL-6 and NGAL as an NFκB binding co-factor. We recently reported that the IL-1 family cytokines, IL-1β and IL-18, strongly synergize with TNFα for IFNγ production in KG-1 cells, whereas the same cytokines alone have minimal effects on IFNγ production. Given the striking similarities between the IL-1R and IL-18R signaling pathways we hypothesized that a common signaling event or gene product downstream of these receptors is responsible for the observed synergy. We investigated IκBζ protein expression in KG-1 cells upon stimulation with IL-1β, IL-18 and TNFα. Our results demonstrated that IL-18, as well as IL-1β, induced moderate IκBζ expression in KG-1 cells. However, TNFα synergized with IL-1β and IL-18, whereas by itself it had a minimal effect on IκBζ expression. NFκB inhibition resulted in decreased IL-1β/IL-18/TNFα-stimulated IFNγ release. Moreover, silencing of IκBζ expression led to a specific decrease in IFNγ production. Overall, our data suggests that IκBζ positively regulates NFκB-mediated IFNγ production in KG-1 cells

Novel haemodynamic structures in the human glomerulus

To investigate human glomerular structure under conditions of physiological perfusion we have analysed fresh and perfusion fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, confocal, multiphoton and electron microscope imaging. Afferent and efferent arterioles (21.5±1.2µm and 15.9±1.2µm diameter), recognised from vascular origins, lead into previously undescribed wider regions (43.2±2.8 µm and 38.4±4.9 µm diameter) we have termed vascular chambers (VCs) embedded in the mesangium of the vascular pole. Afferent VC(AVC) volume was 1.6 fold greater than Efferent VC(EVC) volume. From the AVC long non-branching high capacity conduit vessels (n=7) (Con; 15.9±0.7µm diameter) led to the glomerular edge where branching was more frequent. Conduit vessels have fewer podocytes than filtration capillaries. VCs were confirmed in fixed and unfixed specimens with a layer of banded collagen identified in AVC walls by multiphoton and electron microscopy. Thirteen highly branched efferent first order vessels (E1;9.9±0.4µm diam.) converge on the EVC draining into the efferent arteriole (15.9±1.2µm diam.). Banded collagen was scarce around EVC. This previously undescribed branching topology does not conform to the branching of minimum energy expenditure (Murray’s law), suggesting even distribution of pressure/flow to the filtration capillaries is more important than maintaining the minimum work required for blood flow. We propose that AVCs act as plenum manifolds possibly aided by vortical flow in distributing and balancing blood flow/pressure to conduit vessels supplying glomerular lobules. These major adaptations to glomerular capillary structure could regulate haemodynamic pressure and flow in human glomerular capillaries