Colloquiam: Documents published in 2017

A Bright Future for Sustainable Development: Ushered in by Innovation

Scipedia content — Thu, 06 Apr 2017 15:22:07 +0200

The Future of Nuclear Energy Relies on Integrated Reactor Development Processes

Scipedia content — Thu, 06 Apr 2017 15:22:03 +0200

The Beginnings of Wisdom: Challenges in Engineering Education

Scipedia content — Thu, 06 Apr 2017 15:21:59 +0200

The Traveling Wave Reactor: Design and Development

Scipedia content — Thu, 06 Apr 2017 15:21:52 +0200

The traveling wave reactor (TWR) is a once-through reactor that uses in situ breeding to greatly reduce the need for enrichment and reprocessing. Breeding converts incoming subcritical reload fuel into new critical fuel, allowing a breed-burn wave to propagate. The concept works on the basis that breed-burn waves and the fuel move relative to one another. Thus either the fuel or the waves may move relative to the stationary observer. The most practical embodiments of the TWR involve moving the fuel while keeping the nuclear reactions in one place−sometimes referred to as the standing wave reactor (SWR). TWRs can operate with uranium reload fuels including totally depleted uranium, natural uranium, and low-enriched fuel (e.g., 5.5% 235 U and below), which ordinarily would not be critical in a fast spectrum. Spent light water reactor (LWR) fuel may also serve as TWR reload fuel. In each of these cases, very efficient fuel usage and significant reduction of waste volumes are achieved without the need for reprocessing. The ultimate advantages of the TWR are realized when the reload fuel is depleted uranium, where after the startup period, no enrichment facilities are needed to sustain the first reactor and a chain of successor reactors. TerraPowers conceptual and engineering design and associated technology development activities have been underway since late 2006, with over 50 institutions working in a highly coordinated effort to place the first unit in operation by 2026. This paper summarizes the TWR technology: its development program, its progress, and an analysis of its social and economic benefits.

A New Look at Building Facades as Infrastructure

Scipedia content — Thu, 06 Apr 2017 15:21:43 +0200

Like the hard surfaces of streets and sidewalks in an urban environment, the vertical and horizontal surface area on the outside of urban buildings contributes to the constant heating of large cities around the world. However, little is done to design this surface to benefit the public sphere. Instead, the facade of a building performs either as a component that focuses only on the quality of comfort for interior occupants, while ignoring effects on the exterior of the building, or as an identifiable aesthetic for the buildings owners. This essay proposes the rethinking of the building facade as a steward of outdoor pedestrian welfare, and the conception of public health as an added function of the building envelope−a concept that may fall into the jurisdiction of public works. If the huge total surface area of a citys buildings is thought of as part of the citys infrastructure, then its public contribution may not only make outdoor areas comfortable, clean, and enjoyable, but also help to alleviate the bigger problem of rising temperatures in cities.

The Greatest Global Grand Challenge: Preparing Our Next Generations to Solve the Challenges of Tomorrow: International First and the National Academies Partnership

Scipedia content — Thu, 06 Apr 2017 15:21:38 +0200

Application of Biomaterials in Cardiac Repair and Regeneration

Scipedia content — Thu, 06 Apr 2017 15:21:34 +0200

Cardiovascular disease is a leading cause of death throughout the world. The demand for new therapeutic interventions is increasing. Although pharmacological and surgical interventions dramatically improve the quality of life of cardiovascular disease patients, cheaper and less invasive approaches are always preferable. Biomaterials, both natural and synthetic, exhibit great potential in cardiac repair and regeneration, either as a carrier for drug delivery or as an extracellular matrix substitute scaffold. In this review, we discuss the current treatment options for several cardiovascular diseases, as well as types of biomaterials that have been investigated as potential therapeutic interventions for said diseases. We especially highlight investigations into the possible use of conductive polymers for correcting ischemic heart disease-induced conduction abnormalities, and the generation of biological pacemakers to improve the conduction pathway in heart block.

Tumor Molecular Imaging with Nanoparticles

Scipedia content — Thu, 06 Apr 2017 15:21:28 +0200

Molecular imaging (MI) can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging imaging techniques. Over the past decade, the utilization of nanotechnology in MI has exhibited many significant advantages and provided new opportunities for the imaging of living subjects. It is expected that multimodality nanoparticles (NPs) can lead to precise assessment of tumor biology and the tumor microenvironment. This review addresses topics related to engineered NPs and summarizes the recent applications of these nanoconstructs in cancer optical imaging, ultrasound, photoacoustic imaging, magnetic resonance imaging (MRI), and radionuclide imaging. Key challenges involved in the translation of NPs to the clinic are discussed.

Good Morning Engineers: A Wake up Call

Scipedia content — Thu, 06 Apr 2017 15:21:23 +0200

Marine Renewable Energy Seascape

Scipedia content — Thu, 06 Apr 2017 15:21:16 +0200

Energy production based on fossil fuel reserves is largely responsible for carbon emissions, and hence global warming. The planet needs concerted action to reduce fossil fuel usage and to implement carbon mitigation measures. Ocean energy has huge potential, but there are major interdisciplinary problems to be overcome regarding technology, cost reduction, investment, environmental impact, governance, and so forth. This article briefly reviews ocean energy production from offshore wind, tidal stream, ocean current, tidal range, wave, thermal, salinity gradients, and biomass sources. Future areas of research and development are outlined that could make exploitation of the marine renewable energy (MRE) seascape a viable proposition, these areas include energy storage, advanced materials, robotics, and informatics. The article concludes with a sustainability perspective on the MRE seascape encompassing ethics, legislation, the regulatory environment, governance and consenting, economic, social, and environmental constraints. A new generation of engineers is needed with the ingenuity and spirit of adventure to meet the global challenge posed by MRE.

Tackling Global Grand Challenges in Our Cities

Scipedia content — Thu, 06 Apr 2017 15:21:06 +0200

The Status of the US High-Temperature Gas Reactors

Scipedia content — Thu, 06 Apr 2017 15:20:59 +0200

In 2005, the US passed the Energy Policy Act of 2005 mandating the construction and operation of a high-temperature gas reactor (HTGR) by 2021. This law was passed after a multiyear study by national experts on what future nuclear technologies should be developed. As a result of the Act, the US Congress chose to develop the so-called Next-Generation Nuclear Plant, which was to be an HTGR designed to produce process heat for hydrogen production. Despite high hopes and expectations, the current status is that high temperature reactors have been relegated to completing research programs on advanced fuels, graphite and materials with no plans to build a demonstration plant as required by the US Congress in 2005. There are many reasons behind this diminution of HTGR development, including but not limited to insufficient government funding requirements for research, unrealistically high temperature requirements for the reactor, the delay in the need for a “hydrogen” economy, competition from light water small modular light water reactors, little utility interest in new technologies, very low natural gas prices in the US, and a challenging licensing process in the US for non-water reactors.

The Lead Fast Reactor: An Opportunity for the Future?

Scipedia content — Thu, 06 Apr 2017 13:00:46 +0200

Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 ) in Cancer

Scipedia content — Thu, 06 Apr 2017 12:11:57 +0200

Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16INK4a protein, has a causal link with several different types of cancers. The p16INK4a protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK) 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis. In these cases, the restoration of genetic and epigenetic reactivation of CDKN2A is a practical approach for the prevention and therapy of cancer. This review highlights the genetic status of CDKN2A as a prognostic and predictive biomarker in various cancers.

Leaving History Behind: CD4/CD8 Ratio as a Diagnostic Tool in Sarcoidosis

Scipedia content — Thu, 06 Apr 2017 12:11:53 +0200

Gap Junctions Contribute to Ictal/Interictal Genesis in Human Hypothalamic Hamartomas

Scipedia content — Thu, 06 Apr 2017 12:11:47 +0200

Human hypothalamic hamartoma (HH) is a rare subcortical lesion associated with treatment-resistant epilepsy. Cellular mechanisms responsible for epileptogenesis are unknown. We hypothesized that neuronal gap junctions contribute to epileptogenesis through synchronous activity within the neuron networks in HH tissue. We studied surgically resected HH tissue with Western-blot analysis, immunohistochemistry, electron microscopy, biocytin microinjection of recorded HH neurons, and microelectrode patch clamp recordings with and without pharmacological blockade of gap junctions. Normal human hypothalamus tissue was used as a control. Western blots showed increased expression of both connexin-36 (Cx36) and connexin-43 (Cx43) in HH tissue compared with normal human mammillary body tissue. Immunohistochemistry demonstrated that Cx36 and Cx43 are expressed in HH tissue, but Cx36 was mainly expressed within neuron clusters while Cx43 was mainly expressed outside of neuron clusters. Gap-junction profiles were observed between small HH neurons with electron microscopy. Biocytin injection into single recorded small HH neurons showed labeling of adjacent neurons, which was not observed in the presence of a neuronal gap-junction blocker, mefloquine. Microelectrode field recordings from freshly resected HH slices demonstrated spontaneous ictal/interictal-like discharges in most slices. Bath-application of gap-junction blockers significantly reduced ictal/interictal-like discharges in a concentration-dependent manner, while not affecting the action-potential firing of small gamma-aminobutyric acid (GABA) neurons observed with whole-cell patch-clamp recordings from the same patients HH tissue. These results suggest that neuronal gap junctions between small GABAergic HH neurons participate in the genesis of epileptic-like discharges. Blockade of gap junctions may be a new therapeutic strategy for controlling seizure activity in HH patients.

Corrigendum to “Syk and ye shall find” [EBioMedicine 2 (11) (2015) 190-1591]

Scipedia content — Thu, 06 Apr 2017 12:11:41 +0200

Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations

Scipedia content — Thu, 06 Apr 2017 12:11:36 +0200

Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution.

The Effect of Latency Reversal Agents on Primary CD8 + T Cells: Implications for Shock and Kill Strategies for Human Immunodeficiency Virus Eradication

Scipedia content — Thu, 06 Apr 2017 12:11:27 +0200

Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4 + T cells (shock) followed by immune mediated clearance of the reactivated cells (kill), have been proposed as a method of eliminating latently infected CD4 + T cells. The combination of the histone deacetylase (HDAC) inhibitor romidepsin and protein kinase C (PKC) agonist bryostatin-1 is very effective at reversing latency in vitro. However, we found that primary HIV-1 specific CD8 + T cells were not able to eliminate autologous resting CD4 + T cells that had been reactivated with these drugs. We tested the hypothesis that the drugs affected primary CD8 + T cell function and found that both agents had inhibitory effects on the suppressive capacity of HIV-specific CD8 + T cells from patients who control viral replication without antiretroviral therapy (elite suppressors/controllers). The inhibitory effect was additive and multi-factorial in nature. These inhibitory effects were not seen with prostratin, another PKC agonist, either alone or in combination with JQ1, a bromodomain-containing protein 4 inhibitor. Our results suggest that because of their adverse effects on primary CD8 + T cells, some LRAs may cause immune-suppression and therefore should be used with caution in shock and kill strategies.

LEDGIN-mediated Inhibition of Integrase–LEDGF/p75 Interaction Reduces Reactivation of Residual Latent HIV

Scipedia content — Thu, 06 Apr 2017 12:11:17 +0200

Persistence of latent, replication-competent Human Immunodeficiency Virus type 1 (HIV-1) provirus is the main impediment towards a cure for HIV/AIDS (Acquired Immune Deficiency Syndrome). Therefore, different therapeutic strategies to eliminate the viral reservoirs are currently being explored. We here propose a novel strategy to reduce the replicating HIV reservoir during primary HIV infection by means of drug-induced retargeting of HIV integration. A novel class of integration inhibitors, referred to as LEDGINs, inhibit the interaction between HIV integrase and the LEDGF/p75 host cofactor, the main determinant of lentiviral integration site selection. We show for the first time that LEDGF/p75 depletion hampers HIV-1 reactivation in cell culture. Next we demonstrate that LEDGINs relocate and retarget HIV integration resulting in a HIV reservoir that is refractory to reactivation by different latency-reversing agents. Taken together, these results support the potential of integrase inhibitors that modulate integration site targeting to reduce the likeliness of viral rebound.

Oral Anticoagulants and Renal Impairment: The Convoluting Dilemma

Scipedia content — Thu, 06 Apr 2017 12:11:10 +0200

What Lies Beneath: Antibody Dependent Natural Killer Cell Activation by Antibodies to Internal Influenza Virus Proteins

Scipedia content — Thu, 06 Apr 2017 12:11:02 +0200

The conserved internal influenza proteins nucleoprotein (NP) and matrix 1 (M1) are well characterised for T cell immunity, but whether they also elicit functional antibodies capable of activating natural killer (NK) cells has not been explored. We studied NP and M1-specific ADCC activity using biochemical, NK cell activation and killing assays with plasma from healthy and influenza-infected subjects. Healthy adults had antibodies to M1 and NP capable of binding dimeric FcγRIIIa and activating NK cells. Natural symptomatic and experimental influenza infections resulted in a rise in antibody dependent NK cell activation post-infection to the hemagglutinin of the infecting strain, but changes in NK cell activation to M1 and NP were variable. Although antibody dependent killing of target cells infected with vaccinia viruses expressing internal influenza proteins was not detected, opsonising antibodies to NP and M1 likely contribute to an antiviral microenvironment by stimulating innate immune cells to secrete cytokines early in infection. We conclude that effector cell activating antibodies to conserved internal influenza proteins are common in healthy and influenza-infected adults. Given the significance of such antibodies in animal models of heterologous influenza infection, the definition of their importance and mechanism of action in human immunity to influenza is essential.

Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1 -deficient Mice

Scipedia content — Thu, 06 Apr 2017 12:10:54 +0200

Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis. This system is referred to as the gut-brain axis. Here we show that both brush cells and type II taste cells are eliminated in the gastrointestinal tract of transcription factor Skn-1 knockout (KO) mice. Despite unaltered food intake, Skn-1 KO mice have reduced body weight with lower body fat due to increased energy expenditure. In this model, 24-h urinary excretion of catecholamines was significantly elevated, accompanied by increased fatty acid β-oxidation and fuel dissipation in skeletal muscle and impaired insulin secretion driven by glucose. These results suggest the existence of brain-mediated energy homeostatic pathways originating from brush cells and type II taste cells in the gastrointestinal tract and ending in peripheral tissues, including the adrenal glands. The discovery of food-derived factors that regulate these cells may open new avenues the treatment of obesity and diabetes. Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis along the gut-brain axis. We propose the concept that taste-receiving cells in the oral cavity and/or food-borne chemicals-receiving brush cells in the gut are involved in regulation of the body weight and adiposity via the brain. The discovery of food-derived factors that regulate these cells may open new avenues for the treatment of obesity and diabetes.

Low Circulating Amino Acids and Protein Quality: An Interesting Piece in the Puzzle of Early Childhood Stunting

Scipedia content — Thu, 06 Apr 2017 12:10:48 +0200

A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics

Scipedia content — Thu, 06 Apr 2017 12:10:38 +0200

Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened > 320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human) and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests.

A Nexus Consisting of Beta-Catenin and Stat3 Attenuates BRAF Inhibitor Efficacy and Mediates Acquired Resistance to Vemurafenib

Scipedia content — Thu, 06 Apr 2017 12:10:02 +0200

Acquired resistance to second generation BRAF inhibitors (BRAFis), like vemurafenib is limiting the benefits of long term targeted therapy for patients with malignant melanomas that harbor BRAF V600 mutations. Since many resistance mechanisms have been described, most of them causing a hyperactivation of the MAPK- or PI3K/AKT signaling pathways, one potential strategy to overcome BRAFi resistance in melanoma cells would be to target important common signaling nodes. Known factors that cause secondary resistance include the overexpression of receptor tyrosine kinases (RTKs), alternative splicing of BRAF or the occurrence of novel mutations in MEK1 or NRAS. In this study we show that β-catenin is stabilized and translocated to the nucleus in approximately half of the melanomas that were analyzed and which developed secondary resistance towards BRAFi. We further demonstrate that β-catenin is involved in the mediation of resistance towards vemurafenib in vitro and in vivo . Unexpectedly, β-catenin acts mainly independent of the TCF/LEF dependent canonical Wnt-signaling pathway in resistance development, which partly explains previous contradictory results about the role of β-catenin in melanoma progression and therapy resistance. We further demonstrate that β-catenin interacts with Stat3 after chronic vemurafenib treatment and both together cooperate in the acquisition and maintenance of resistance towards BRAFi.

Diagnostic Performance of Bronchoalveolar Lavage Fluid CD4/CD8 Ratio for Sarcoidosis: A Meta-analysis

Scipedia content — Thu, 06 Apr 2017 12:09:50 +0200

The usefulness of bronchoalveolar lavage fluid (BALF) CD4/CD8 ratio for diagnosing sarcoidosis has been reported in many studies with variable results. Therefore, we performed a meta-analysis to estimate the overall diagnostic accuracy of BALF CD4/CD8 ratio based on the bulk of published evidence. Studies published prior to June 2015 and indexed in PubMed, OVID, Web of Science, Scopus and other databases were evaluated for inclusion. Data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled from included studies. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deekss funnel plot was used to detect publication bias. Sixteen publications with 1885 subjects met our inclusion criteria and were included in this meta-analysis. Summary estimates of the diagnostic performance of the BALF CD4/CD8 ratio were as follows: sensitivity, 0.70 (95%CI 0.64–0.75), specificity, 0.83 (95%CI 0.78–0.86), PLR, 4.04 (95%CI 3.13–5.20), NLR, 0.36 (95%CI 0.30–0.44), and DOR, 11.17 (95%CI 7.31–17.07). The area under the SROC curve was 0.84 (95%CI 0.81–0.87). There was no evidence of publication bias. Measuring the BALF CD4/CD8 ratio may assist in the diagnosis of sarcoidosis when interpreted in parallel with other diagnostic factors.

Deciphering “B-others”: Novel fusion genes driving B-cell acute lymphoblastic leukemia

Scipedia content — Thu, 06 Apr 2017 12:09:46 +0200

Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals

Scipedia content — Thu, 06 Apr 2017 12:09:37 +0200

While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host.

Ethnicity matters: A Systematic Review and Meta-Analysis of the Non-Linear Relationship Between Alcohol Consumption and Prevalence and Incidence of Hepatic Steatosis

Scipedia content — Thu, 06 Apr 2017 12:09:21 +0200

Fatty liver (hepatic steatosis) is one of the most common diseases globally, with increasing prevalence. The role of alcohol consumption in the development of hepatic steatosis has not been systematically examined. We searched Medline, Embase, and ProQuest Dissertations & Theses Global for original data on the relationship between alcohol consumption and hepatic steatosis measured by non-invasive imagery, excluding studies conducted in participants

One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study

Scipedia content — Thu, 06 Apr 2017 12:09:14 +0200

Immune activation in HIV-1-infected individuals is reduced under antiretroviral therapies, but persists, resulting in various morbidities. To better characterize this phenomenon, using a panel of 68 soluble and cell surface markers, we measured the level of activation in circulating CD4+ and CD8+ T cells, B cells, monocytes, NK cells, polynuclear and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45 years of age. As compared with age- and sex-matched uninfected individuals, we observed a persistence of activation in all the cell subpopulations analyzed, together with marks of inflammation and fibrinolysis. Two independent hierarchical clustering analyses allowed us to identify five clusters of markers that varied concurrently, and five patient groups, each with the same activation profile. The five groups of patients could be characterized by a marker of CD4+ T cell, CD8+ T cell, NK cell, monocyte activation or of inflammation, respectively. One of these profiles was strongly associated with marks of metabolic syndrome, particularly with hyperinsulinemia (OR 12.17 [95% CI 1.79–82.86], p = 0.011). In conclusion, our study unveils biomarkers linked to metabolic syndrome that could be tested as predictive markers, and opens the way to new therapeutic approaches tailored to each patient group.

Chronic Kidney Disease, Time in Therapeutic Range and Adverse Clinical Outcomes in Anticoagulated Patients with Non-valvular Atrial Fibrillation: Observations from the SPORTIF Trials

Scipedia content — Thu, 06 Apr 2017 12:09:06 +0200

Chronic kidney disease (CKD) is highly prevalent in atrial fibrillation (AF) patients and associated with an increased risk of adverse outcomes. Our objectives were to study clinical features associated with CKD in AF patients and the impact of CKD on anticoagulation control, as reflected by time in therapeutic range (TTR). We also determined the impact of CKD and TTR in predicting adverse outcomes. We analysed pooled datasets from SPORTIF III and V trials, including 3646 patients assigned to warfarin with data on renal function. CKD (creatinine clearance 70%, whilst diabetes mellitus, aspirin use and CKD were inversely associated with TTR > 70%. On Cox regression analysis, CKD was an independent predictor for stroke (p = 0.006) and death (p 70% was independently associated with a lower risk of stroke (p = 0.024), death (p = 0.001) and major bleeding (p = 0.001). CKD is highly prevalent amongst AF patients and a risk factor for stroke and death. Adjusting for CKD, good quality anticoagulation control (TTR > 70%) was an independent predictor for lower risks of stroke, death and major bleeding.

Liver Flukes and the Microbiota in Cancer

Scipedia content — Thu, 06 Apr 2017 12:09:01 +0200

Identification of Immune Activation Profiles That May Predict Morbidity During Antiretroviral Therapy Treated HIV Infection

Scipedia content — Thu, 06 Apr 2017 12:08:58 +0200

Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability

Scipedia content — Thu, 06 Apr 2017 12:08:50 +0200

Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl LewisX (SLeX ), O -GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.

Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival

Scipedia content — Thu, 06 Apr 2017 12:08:04 +0200

SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of deregulations exists: an unexpected SCRIB exon usage pattern appears to mark a more malignant tumor phenotype and significantly correlates with survival. Conserved exons encoding the leucine-rich repeats tend to be overexpressed while others are underused. Mechanistic studies revealed that the underused exons encode part of the protein necessary for interaction with Vimentin and Numa1, a protein which is required for proper positioning of the mitotic spindle. Thus, the inclusion/exclusion of specific SCRIB exons is a mechanistic hallmark of breast cancer, which could potentially be exploited to develop more efficient diagnostics and therapies.

Will LEDGIN molecules be able to play a role in a cure for HIV infection?

Scipedia content — Thu, 06 Apr 2017 12:07:58 +0200

Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor

Scipedia content — Thu, 06 Apr 2017 12:07:48 +0200

Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb ), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment.

Alcohol and Steatosis: The Japanese Paradox

Scipedia content — Thu, 06 Apr 2017 12:07:32 +0200

Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation

Scipedia content — Thu, 06 Apr 2017 12:07:25 +0200

Mesenchymal stem cell (MSC)-derived exosomes have diverse functions in regulating wound healing and inflammation, however, the molecular mechanism of human umbilical cord MSC (hUCMSC)-derived exosomes in regulating burn-induced inflammation is not well understood. We found that burn injury significantly increased the inflammatory reaction of rats or macrophages exposed to lipopolysaccharide (LPS), increased tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) levels and decreased IL-10 levels. hUCMSC-exosome administration successfully reversed this reaction. Further studies showed that miR-181c in the exosomes played a pivotal role in regulating inflammation. Compared to control hUCMSC-exosomes, hUCMSC-exosomes overexpressing miR-181c more effectively suppressed the TLR4 signaling pathway and alleviated inflammation in burned rats. Administration of miR-181c-expressing hUCMSC-exosomes or TLR4 knockdown significantly reduced LPS-induced TLR4 expression by macrophages and the inflammatory reaction. In summary, miR-181c expression in hUCMSC-exosomes reduces burn-induced inflammation by downregulating the TLR4 signaling pathway.

Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

Scipedia content — Thu, 06 Apr 2017 12:07:15 +0200

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4 -IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

Humoral Immune Pressure Selects for HIV-1 CXC-chemokine Receptor 4-using Variants

Scipedia content — Thu, 06 Apr 2017 12:06:53 +0200

Although both C-C chemokine receptor 5 (CCR5)- and CXC chemokine receptor 4 (CXCR4)-using HIV-1 strains cause AIDS, the emergence of CXCR4-utilizing variants is associated with an accelerated decline in CD4 + T cells. It remains uncertain if CXCR4-using viruses hasten disease or if these variants only emerge after profound immunological damage. We show that exclusively CXCR4- as compared to cocirculating CCR5-utilizing variants are less sensitive to neutralization by both contemporaneous autologous plasma and plasma pools from individuals that harbor only CCR5-using HIV-1. The CXCR4-utilizing variants, however, do not have a global antigenic change because they remain equivalently susceptible to antibodies that do not target coreceptor binding domains. Studies with envelope V3 loop directed antibodies and chimeric envelopes suggest that the neutralization susceptibility differences are potentially influenced by the V3 loop. In vitro passage of a neutralization sensitive CCR5-using virus in the presence of autologous plasma and activated CD4 + T cells led to the emergence of a CXCR4-utilizing virus in 1 of 3 cases. These results suggest that in some but not necessarily all HIV-1 infected individuals humoral immune pressure against the autologous virus selects for CXCR4-using variants, which potentially accelerates disease progression. Our observations have implications for using antibodies for HIV-1 immune therapy.

The Power of an Idea: The International Impacts of the Grand Challenges for Engineering

Scipedia content — Thu, 06 Apr 2017 12:06:47 +0200

Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers

Scipedia content — Thu, 06 Apr 2017 12:06:36 +0200

Transcription factors have traditionally been viewed with skepticism as viable drug targets, but they offer the potential for completely novel mechanisms of action that could more effectively address the stem cell like properties, such as self-renewal and chemo-resistance, that lead to the failure of traditional chemotherapy approaches. Core binding factor is a heterodimeric transcription factor comprised of one of 3 RUNX proteins (RUNX1-3) and a CBFβ binding partner. CBFβ enhances DNA binding of RUNX subunits by relieving auto-inhibition. Both RUNX1 and CBFβ are frequently mutated in human leukemia. More recently, RUNX proteins have been shown to be key players in epithelial cancers, suggesting the targeting of this pathway could have broad utility. In order to test this, we developed small molecules which bind to CBFβ and inhibit its binding to RUNX. Treatment with these inhibitors reduces binding of RUNX1 to target genes, alters the expression of RUNX1 target genes, and impacts cell survival and differentiation. These inhibitors show efficacy against leukemia cells as well as basal-like (triple-negative) breast cancer cells. These inhibitors provide effective tools to probe the utility of targeting RUNX transcription factor function in other cancers.

The right and wrong of DOKing the nuclear receptor

Scipedia content — Thu, 06 Apr 2017 12:06:23 +0200

“Universal Flu Vaccine”: Can NK Cell-mediated ADCC Tip the Scales?

Scipedia content — Thu, 06 Apr 2017 12:06:20 +0200

Multifunctional Fanconi proteins, inflammation and the Fanconi phenotype

Scipedia content — Thu, 06 Apr 2017 12:06:17 +0200

Gap Junctions and Epileptogenesis: No Laughing Matter

Scipedia content — Thu, 06 Apr 2017 12:06:13 +0200

Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer

Scipedia content — Thu, 06 Apr 2017 12:06:05 +0200

Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive. PPARγ-agonist increased expression of endogenous DOK1 and interaction with PPARγ. Forward translation of this cell-based signaling model predicted compartmentalization of DOK1 in patients. In a large series of CRC patients, loss of DOK1 protein was associated with poor prognosis at early tumor stages (*p = 0.001, n = 1492). In tumors with cytoplasmic expression of DOK1, survival was improved, whereas nuclear localization of DOK1 correlated with poor outcome, indicating that compartmentalization of DOK1 is critical for CRC progression. Thus, DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARγ-agonist, may constitute a potential target for future cancer treatments.

Huntingtons Disease: The Most Curable Incurable Brain Disorder?

Scipedia content — Thu, 06 Apr 2017 12:05:57 +0200

The Eyes Have it! Protective Role of Prolactin in the Retina

Scipedia content — Thu, 06 Apr 2017 12:05:53 +0200

Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma

Scipedia content — Thu, 06 Apr 2017 12:05:46 +0200

Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini ) associated (OVa, n = 28) and non-O. viverrini associated (non-OVa, n = 32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae ). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer.

Upregulated LINE-1 Activity in the Fanconi Anemia Cancer Susceptibility Syndrome Leads to Spontaneous Pro-inflammatory Cytokine Production

Scipedia content — Thu, 06 Apr 2017 12:05:35 +0200

Fanconi Anemia (FA) is a genetic disorder characterized by elevated cancer susceptibility and pro-inflammatory cytokine production. Using SLX4FANCP deficiency as a working model, we questioned the trigger for chronic inflammation in FA. We found that absence of SLX4 caused cytoplasmic DNA accumulation, including sequences deriving from active Long INterspersed Element-1 (LINE-1), triggering the cGAS-STING pathway to elicit interferon (IFN) expression. In agreement, absence of SLX4 leads to upregulated LINE-1 retrotransposition. Importantly, similar results were obtained with the FANCD2 upstream activator of SLX4. Furthermore, treatment of FA cells with the Tenofovir reverse transcriptase inhibitor (RTi), that prevents endogenous retrotransposition, decreased both accumulation of cytoplasmic DNA and pro-inflammatory signaling. Collectively, our data suggest a contribution of endogenous RT activities to the generation of immunogenic cytoplasmic nucleic acids responsible for inflammation in FA. The additional observation that RTi decreased pro-inflammatory cytokine production induced by DNA replication stress-inducing drugs further demonstrates the contribution of endogenous RTs to sustaining chronic inflammation. Altogether, our data open perspectives in the prevention of adverse effects of chronic inflammation in tumorigenesis.

Cognitive Enhancement in Infants Associated with Increased Maternal Fruit Intake During Pregnancy: Results from a Birth Cohort Study with Validation in an Animal Model

Scipedia content — Thu, 06 Apr 2017 12:05:23 +0200

In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton sub-cohort subjects, 688 (85%) had 1-year cognitive outcome data. We found that each maternal daily serving of fruit (sum of fruit plus 100% fruit juice) consumed during pregnancy was associated with a 2.38 point increase in 1-year cognitive development (95% CI 0.39, 4.37, p

Non-specific Effects of Vaccines and Stunting: Timing May Be Essential

Scipedia content — Thu, 06 Apr 2017 12:05:15 +0200

Bacillus Calmette-Guérin (BCG) vaccination possesses effects on health beyond its target disease, the so called “non-specific effects”. We evaluate these effects, as well as the effect of timing of BCG and other vaccinations, on stunting in Sub-Saharan African (SSA) children under five. We use a Big Data design, including cross-sectional data for 368, 450 children from 33 SSA countries. Logistic regression analysis is used with control factors at child, mother, household and context level. Overall, BCG vaccination did not affect stunting in SSA children (OR 1.00 [0.98–1.03]). Timing of BCG vaccination was of importance (βtime = 0.067 [0.061–0.073]): compared to unvaccinated children, BCG was associated with lower odds on stunting for children vaccinated early in life (OR 0.92 [0.89–0.94]) and higher odds for children vaccinated later in infancy (OR 1.64 [1.53–1.76]). Similar findings were done for diphtheria-tetanus-pertussis (DTP)1 and measles vaccination, and when hemoglobin concentration was used as outcome variable. We found a general time-dependent pattern of non-specific effects of vaccination, with positive associations for vaccinations given early in life and negative associations for vaccinations given later in infancy. If confirmed in further research, our findings may provide a new perspective on the non-specific effects of vaccination.

Nanobodies as Versatile Tools to Understand, Diagnose, Visualize and Treat Cancer

Scipedia content — Thu, 06 Apr 2017 12:05:08 +0200

Since their discovery, nanobodies have been used extensively in the fields of research, diagnostics and therapy. These antigen binding fragments, originating from Camelid heavy-chain antibodies, possess unusual hallmarks in terms of (small) size, stability, solubility and specificity, hence allowing cost-effective production and sometimes outperforming monoclonal antibodies. In this review, we evaluate the current status of nanobodies to study, diagnose, visualize or inhibit cancer-specific proteins and processes. Nanobodies are highly adaptable tools for cancer research as they enable specific modulation of targets, enzymatic and non-enzymatic proteins alike. Molecular imaging studies benefit from the rapid, homogeneous tumor accumulation of nanobodies and their fast blood clearance, permitting previously unattainable fast tumor visualization. Moreover, they are endowed with considerable therapeutic potential as inhibitors of receptor-ligand pairs and deliverers of drugs or drug-loaded nanoparticles towards tumors. More in vivo and clinical studies are however eagerly awaited to unleash their full potential.

Functional Rescue of Dopaminergic Neuron Loss in Parkinsons Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells

Scipedia content — Thu, 06 Apr 2017 12:04:57 +0200

Parkinsons disease is a common neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and for which no definitive cure is currently available. Cellular functions in mouse and human tissues can be restored after fusion of bone marrow (BM)-derived cells with a variety of somatic cells. Here, after transplantation of hematopoietic stem and progenitor cells (HSPCs) in the SNpc of two different mouse models of Parkinsons disease, we significantly ameliorated the dopaminergic neuron loss and function. We show fusion of transplanted HSPCs with neurons and with glial cells in the ventral midbrain of Parkinsons disease mice. Interestingly, the hybrids can undergo reprogramming in vivo and survived up to 4 weeks after transplantation, while acquiring features of mature astroglia. These newly generated astroglia produced Wnt1 and were essential for functional rescue of the dopaminergic neurons. Our data suggest that glial-derived hybrids produced upon fusion of transplanted HSPCs in the SNpc can rescue the Parkinsons disease phenotype via a niche-mediated effect, and can be exploited as an efficient cell-therapy approach.

Preconceptional exposure to oral contraceptive pills and the risk of wheeze, asthma and rhinitis in children

Scipedia content — Wed, 05 Apr 2017 15:05:13 +0200

The prevalence of maternal oral contraceptive pills (OCP) use and that of childhood asthma are high in western countries. The aim of this study is to examine the association of OCP use with childhood wheeze and allergic diseases in Japan. Relevant data were extracted from a hospital based birth cohort study named as Tokyo-Childrens Health, Illness and Development Study (T-CHILD) of which questionnaire conducted during pregnancy included maternal history and duration of OCP use. To identify wheeze and allergic diseases in the children, the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) was used. Logistic regression models were applied to estimate those association and adjustments were made for maternal history of allergy, maternal education level, maternal age at pregnancy, maternal BMI, maternal smoking during pregnancy, mode of delivery, gestational age at delivery, daycare attendance, number of previous live births, and gender of child. OCP use was associated with ever wheeze (adjusted odds ratio [aOR], 1.62, 95% confidence interval [CI], 1.10–2.40), current wheeze (aOR, 1.59, 95% CI, 1.01–2.50), ever asthma (aOR, 1.65, 95% CI, 1.02–2.65), and ever rhinitis (aOR, 1.90, 95% CI, 1.30–2.80). Compared with no prior OCP use, using OCP for more than three months statistically increased the odds of ever wheeze (P = 0.012), current wheeze (P = 0.035), and ever rhinitis (P = 0.002). Our findings suggest that maternal OCP use has a role in the development of wheeze, asthma and rhinitis in children. Extended use of OCP is likely to increase the risk of wheeze and rhinitis.

Development of a Japanese Culturally Modified Version of the Childhood Atopic Dermatitis Impact Scale (JCMV-CADIS)

Scipedia content — Wed, 05 Apr 2017 15:05:07 +0200

The Childhood Atopic Dermatitis Impact Scale (CADIS) was developed to measure the impact of AD on QoL in both affected children and their families. However, no scale of this kind exists in Japan. The aims of this study were to validate the Japanese Culturally Modified Version of the CADIS (JCMV-CADIS) and to describe the family impact of children with AD in a Japanese context. Participants included primary-caregivers for children with AD between 2 and 6 years of age. Interviews were conducted, and new items for the Japanese version were drafted. Reliability and validity were evaluated and compared with the original CADIS, and unique features of the Japanese version were analyzed. Exploratory factor analysis revealed the following factors: “Symptoms” and “Activity Limitations and Behavior” in the Child domain, and “Emotions Related to Social Factors, ” “Emotions Related to the Childs Condition, ” “Family and Social Function, ” “Complexity of Care, ” and “Approaches to Management of AD in Daily Life” in the Parent domain. The latter two factors were unique to the JCMV-CADIS and were not derived from the Original. “Emotion” was split into two independent factors. All factors showed good reliability (internal consistency and stability) and validity (concurrent validity and discriminant validity), except for the concurrent validity of “Approaches to Management of AD in Daily Life.” This factor seemed to reflect characteristics similar to the family-related function. The JCMV-CADIS is a QoL scale developed for Japanese children with AD and their families. Further evaluation of clinical applicability is needed.

Photodistributed telangiectasia following use of escitalopram

Scipedia content — Wed, 05 Apr 2017 15:05:02 +0200

Drug eruption due to entecavir: A case report and mini-review

Scipedia content — Wed, 05 Apr 2017 15:04:56 +0200

Increase in autoimmune pulmonary alveolar proteinosis after the 2011 Fukushima disaster

Scipedia content — Wed, 05 Apr 2017 15:04:52 +0200

A case of black garlic-induced pneumonia as an adverse reaction

Scipedia content — Wed, 05 Apr 2017 15:04:46 +0200

Development of a prediction model of severe reaction in boiled egg challenges

Scipedia content — Wed, 05 Apr 2017 15:04:38 +0200

We have proposed a new scoring system (Anaphylaxis SCoring Aichi: ASCA) for a quantitative evaluation of the anaphylactic reaction that is observed in an oral food challenge (OFC). Furthermore, the TS/Pro (Total Score of ASCA/cumulative protein dose) can be a marker to represent the overall severity of a food allergy. We aimed to develop a prediction model for a severe allergic reaction that is provoked in a boiled egg white challenge. We used two separate datasets to develop and validate the prediction model, respectively. The development dataset included 198 OFCs, that tested positive. The validation dataset prospectively included 140 consecutive OFCs, irrespective of the result. A ‘severe reaction’ was defined as a TS/Pro higher than 31 (the median score of the development dataset). A multivariate logistic regression analysis was performed to identify the factors associated with a severe reaction and develop the prediction model. The following four factors were independently associated with a severe reaction: ovomucoid specific IgE class (OM-sIgE: 0–6), aged 5 years or over, a complete avoidance of egg, and a total IgE

Right middle lobe atelectasis in children with asthma and prognostic factors

Scipedia content — Wed, 05 Apr 2017 15:04:31 +0200

Although right middle lobe (RML)-atelectasis of the lungs is a common complication of asthma, the relevant data is limited. The aim of this study is to define the characteristics of RML atelectasis in asthma during childhood. Children with asthma who had recently developed RML atelectasis were included, anti-inflammatory medications, clarithromycin, and inhaled salbutamol were prescribed, chest-physiotherapy (starting on the sixth day) was applied. Patients were reevaluated on the sixth, fourteenth, thirtieth, and ninetieth days, chest X-rays were taken if the atelectasis had not resolved at the time of the previous visit. Twenty-seven patients (6.8 (4.8–8.3) years, 48.1% male) with RML atelectasis were included. Symptoms started 15 (7–30) days before admission. The thickness of the atelectasis was 11.8 ± 5.8 mm, FEV1% was 75.9 ± 14.2 and Childhood Asthma Control Test scores were 11.8 ± 5.6 at the time of admission. The atelectasis had been resolved by the sixth (n = 3), fourteenth (n = 9), thirtieth (n = 10), and ninetieth days (n = 3). The treatment response of the patients whose atelectasis resolved in fourteen days was better on the sixth-day (atelectasis thickness: 4.7 ± 1.7 vs. 11.9 ± 7.3 mm, p = 0.021) compared to those whose atelectasis resolved later. Nearly half (54.5%) of the patients whose atelectasis had resolved by fourteen days were using controller medications at the time of admission. However, only two patients (13.3%) were on controller treatment in the latter group (p = 0.032). Regression analysis didn't reveal any prognostic factors for the early resolution of atelectasis. Early diagnosis and treatment of RML atelectasis prevents complications. Patients who had early resolution of atelectasis had already been on anti-inflammatory medications, and responded better to aggressive treatment within the first week.

Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics

Scipedia content — Wed, 05 Apr 2017 15:04:25 +0200

Inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines and iNOS activity in bronchial epithelial cells is a major determinant of fractional exhaled nitric oxide (FeNO) levels. The aim of this study was to investigate the association of iNOS promoter gene polymorphisms and FeNO levels in Japanese asthmatics before the introduction of asthma treatment. Asthmatics were recruited from Fukushima Medical University Hospital. Genotyping of the pentanucleotide repeat (CCTTT)n and seven previously detected single nucleotide polymorphisms (SNPs) in the iNOS promoter lesion was performed. The relationships between the genotypes and FeNO levels before the introduction of asthma treatment were compared. In 91 asthmatics, the number of microsatellite repeats ranged from 9 to 20 and showed a bimodal distribution. According to this distribution, asthmatics were divided into two groups: genotypes with at least one long allele with more than 14 repeats (L/s or L/L) and genotypes with both short alleles with 14 or fewer repeats (s/s). No significant differences were observed in each parameter between the two groups. The mean FeNO level before treatment was significantly higher in the L/s or L/L subjects than in the s/s subjects. After treatment, the lowest FeNO level did not differ between the two groups. Three SNPs detected in the Japanese subjects were not associated with FeNO levels. The number of CCTTT repeats in the iNOS promoter region was associated with FeNO levels in asthmatics before treatment, suggesting the importance of iNOS genotype in the clinical application of FeNO for asthmatics.

Accidental usage of an adrenaline auto-injector in Japanese children with a food allergy

Scipedia content — Wed, 05 Apr 2017 15:04:20 +0200

Eosinophil chemotaxis assay in nasal polyps by using a novel optical device EZ-TAXIScan: Role of CC-chemokine receptor 3

Scipedia content — Wed, 05 Apr 2017 15:04:13 +0200

The chemokine receptor, CC-chemokine receptor 3 (CCR3), and its major ligands, eotaxin, RANTES, and MCP-4, are involved in eosinophil chemotaxis. It is thought that CCR3 plays an important role in the recruitment and activation of eosinophils in nasal polyposis. We examined nasal polyp extract-induced eosinophil chemotaxis and the effect of a CCR3 antagonist using EZ-TAXIScan, a novel real-time chemotaxis assay device. Nasal polyps were obtained from chronic rhinosinusitis (CRS) patients during surgery. The polyps were homogenized and eotaxin levels in the extracts were measured. Eosinophils were purified from human peripheral blood by the CD16 negative selection method. Nasal polyp extract-induced eosinophil chemotaxis, with or without CCR3 antagonist, was assessed by EZ-TAXIScan. There was a significant positive correlation between the eosinophil counts in nasal polyp and eotaxin levels in the nasal polyp extracts. Using EZ-TAXIScan, eosinophil chemotactic responses were observed following stimulation with nasal polyp extracts. There was a significant positive correlation between the chemotactic index toward the nasal polyp extracts and their eotaxin levels. Nasal polyp extract-induced chemotaxis was completely inhibited by CCR3 antagonist but not by chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist which inhibited PGD2-induced eosinophil chemotaxis. The CCR3 pathway may play an important role in the pathogenesis of eosinophil recruitment in nasal polyps through selective eosinophil chemotaxis.

Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis

Scipedia content — Wed, 05 Apr 2017 15:04:05 +0200

Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. In the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.

Anaphylaxis caused by casein used in artificially marbled beef: A case report

Scipedia content — Wed, 05 Apr 2017 15:04:00 +0200

Cross-reactivity between major IgE core epitopes on Cry j 2 allergen of Japanese cedar pollen and relevant sequences on Cha o 2 allergen of Japanese cypress pollen

Scipedia content — Wed, 05 Apr 2017 15:03:52 +0200

Cry j 2 and Cha o 2 are major allergens in Japanese cedar (Cryptomeria japonica, CJ) and Japanese cypress (Chamaecyparis obtusa, CO) pollen, respectively. Here, we assessed the epitopes related to the cross-reactivity between Cry j 2 and Cha o 2 using in vitro analyses. Peptides were synthesized based on Cry j 2 sequential epitopes and relevant Cha o 2 amino acid sequences. Four representative monoclonal antibodies (mAbs) against Cry j 2 were used according to their epitope recognitions. Serum samples were collected from 31 patients with CJ pollinosis. To investigate cross-reactivity between Cry j 2 and Cha o 2, ELISA and inhibition ELISA were performed with mAbs and sera from patients with CJ pollinosis. Two of four mAbs had reactivity to both Cry j 2 and Cha o 2. Of these two mAbs, one mAb (T27) recognized the amino acid sequence 169KVVNGRTV176 on Cha o 2. This is related to the core epitope 169KWVNGREI176 on Cry j 2, which is an important IgE epitope. In addition, we found that these correlative sequences and purified allergens showed cross-reactivity between Cry j 2 and Cha o 2 in IgE of CJ patients. We demonstrated the importance of 169KVVNGRTV176 in Cha o 2 for cross-reactivity with the Cry j 2 epitope 169KWVNGREI176, which plays an important role in allergenicity in CJ pollinosis. Our results are useful for the development of safer and more efficient therapeutic strategies for the treatment of CJ and CO pollen allergies.

Filaggrin exists in human nose

Scipedia content — Wed, 05 Apr 2017 15:03:46 +0200

Persistently high exhaled nitric oxide and loss of lung function in controlled asthma

Scipedia content — Wed, 05 Apr 2017 15:03:39 +0200

It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. This was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated. A FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p

Reactive airways dysfunction syndrome after hydrofluoric acid inhalation

Scipedia content — Wed, 05 Apr 2017 15:03:34 +0200

IgE-binding epitopes of various fish parvalbumins exist in a stereoscopic conformation maintained by Ca binding

Scipedia content — Wed, 05 Apr 2017 15:03:28 +0200

In vivo imaging in autoimmune diseases in the central nervous system

Scipedia content — Wed, 05 Apr 2017 15:03:22 +0200

Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, intravital imaging can be used to observe and analyze cells directly in vivo. In this review, I will summarize recent imaging studies of autoreactive T cell infiltration into the central nervous system (CNS) and provide technical background. During their in vivo journey, autoreactive T cells interact with many different cells. At first, autoreactive T cells interact with endothelial cells in the airways of the lung or with splenocytes, where they acquire a migratory phenotype to infiltrate into the CNS. After arriving at the CNS, they interact with endothelial cells of the leptomeningeal vessels or the choroid plexus before passing through the blood–brain barrier. CNS-infiltrating T cells become activated by recognizing endogenous autoantigens presented by local antigen-presenting cells (APCs). This activation was visualized in vivo by using protein-based sensors. One such sensor detects changes in intracellular calcium concentration as an early marker of T cell activation. Another sensor detects translocation of Nuclear factor of activated T-cells (NFAT) from cytosol to nucleus as a definitive sign of T cell activation. Importantly, intravital imaging is not just used to visualize cellular behavior. Together with precise analysis, intravital imaging deepens our knowledge of cellular functions in living organs and also provides a platform for developing therapeutic treatments.

Gastroesophageal dysmotility is associated with the impairment of cough-specific quality of life in patients with cough variant asthma

Scipedia content — Wed, 05 Apr 2017 15:03:17 +0200

Gastroesophageal reflux disease (GERD) is known as a common comorbidity of asthma and chronic cough. The impact of GERD symptoms on cough-specific quality of life (QoL) in patients with asthmatic cough is poorly understood. The aim of this study is to determine the association of GERD symptoms with cough-specific quality of life in patients with cough variant asthma (CVA) using the Leicester Cough Questionnaire (LCQ). A total of 172 consecutive patients (121 females) with mean cough duration of 45.1 months (range 2–480 months) completed the Japanese version of the LCQ. The Frequency Scale for the Symptoms of Gastroesophageal reflux was administered to assess symptoms of acid-reflux and dysmotility. A range of clinical variables that may determine cough-specific QoL (LCQ) were estimated. The mean LCQ scores was 12.9 (SD 3.5), consistent with severe impairment in QoL. Female gender, symptoms of gastroesophageal dysmotility, sensitization to allergens (house dust and Japanese cedar pollen) and the number of sensitized allergens were associated with lower LCQ scores (i.e. impaired cough-specific QoL) in univariate regression analysis. Acid-reflux symptoms, airway hyperresponsiveness, fractional exhaled nitric oxide, and sensitization to molds were unrelated to the LCQ score. After adjustment for gender, symptoms of gastroesophageal dysmotility was the only significant determinant of impaired cough-specific QoL accounting for 23% of the variance. Cough-specific QoL is severely impaired in patients with CVA. Symptoms of gastroesophageal dysmotility are an independent predictor of cough-specific QoL of patients with CVA.

Development of in vivo imaging

Scipedia content — Wed, 05 Apr 2017 15:03:12 +0200

Intravital imaging technology reveals immune system dynamics in vivo

Scipedia content — Wed, 05 Apr 2017 15:03:08 +0200

Fluorescent ‘intravital’ imaging is a new research technique by which the interior of living tissues and organs (in living bodies, if possible) can be observed, revealing the kinetics of cell and molecular processes in real time. Recent technological innovations in optical equipment and fluorescence imaging techniques have enabled a variety of cellular phenomena in different tissues and organs to be characterized under completely native conditions. This shift from static to dynamic biology constitutes the beginning of a new era in biomedical sciences.

Maculopapular type drug eruption caused by pregabalin: A case and literature review

Scipedia content — Wed, 05 Apr 2017 15:03:03 +0200

Anaphylaxis caused by γ-cyclodextrin in sugammadex

Scipedia content — Wed, 05 Apr 2017 15:02:58 +0200

Novel insights into cutaneous immune systems revealed by in vivo imaging

Scipedia content — Wed, 05 Apr 2017 15:02:52 +0200

In vivo imaging is a novel experimental approach for biological research. Multiphoton microscopy (MPM), a type of fluorescence microscopy, is a new tool for in vivo imaging analysis. MPM allows observation of both tissue structures and cell behaviors or cell–cell interactions in living animals in real time. Skin is an ideal tissue for MPM analysis as it is directly accessible to the microscope. In the skin, immune cells cooperate to maintain skin homeostasis or to exert immune responses against foreign antigens. In vivo imaging by MPM analysis provides precise information on cell dynamics in the skin, and has significantly expanded our knowledge of the cutaneous immune system. In this review, we will discuss recent insights related to the mechanisms of allergic skin inflammation that have been revealed by MPM analysis.

Optimal step-down approach for pediatric asthma controlled by salmeterol/fluticasone: A randomized, controlled trial (OSCAR study)

Scipedia content — Wed, 05 Apr 2017 15:02:44 +0200

Several guidelines, including the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL), recommend salmeterol/fluticasone combination therapy (SFC) as step 3 to 4 treatment for moderate to severe asthma. However, the optimal step-down approach to SFC remains unclear. In the current study, we examined step-down approaches in asthmatic children whose symptoms had been stabilized by SFC 100/200 μg/day. This randomized, multicenter, open-label, parallel-group study was conducted over 12 weeks. For step-down therapy, subjects aged 5–15 years were randomly assigned to an SFC group (25/50 μg b.i.d.) or an FP group (100 μg b.i.d.), and treated for 12 weeks. Childhood Asthma Control Test (C-ACT) scores, lung function, and exhaled nitric oxide (FeNO) levels were monitored. Of 131 enrolled subjects, 128 completed the study and were included in the analysis. Decreases in % peak expiratory flow rate and % forced expiratory flow at 50% of vital capacity (V50) were observed in the FP group at each time point. There was a significant difference between the two groups for the change in %V50 from its previous value at each time point. There were no significant changes in FeNO levels (range 15–20 ppb) or C-ACT scores (∼26 points) within or between groups. A high level of asthma control was maintained with both approaches. The use of SFC step-down resulted in somewhat better respiratory function, with no worsening of airway inflammation. However, halving the dose of SFC and switching to FP alone are both optimal step-down approaches.

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

Scipedia content — Wed, 05 Apr 2017 15:02:36 +0200

Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management.

Visibilidad y enunciabilidad en la larga duración de la violencia política: La sombra azul de Sergio Schmucler 1

Scipedia content — Mon, 03 Apr 2017 16:00:33 +0200

Una historia de vida, eje fundamental de un film, es la discursividad que hemos indagado para percibir sentidos nuevos en la relación cine, memoria y violencia en la zona amplia de los discursos producidos sobre el terrorismo de estado en Argentina. La sombra azul, con guión y dirección de Sergio Schmucler, irrumpe para desbaratar conciencias. Nuestro trabajo, filiado en el Análisis del Discurso, se ha detenido en la indagación de tres dispositivos: las visibilidades, las enunciabilidades y las temporalidades, superpuestas, fragmentarias a veces, otras omnipresentes, deslizadas en la larga duración de una memoria social. Estos dispositivos, elaborados por Foucault para blandir discursividades exasperantes de órdenes impuestos, constituyen un camino privilegiado para llegar, a través de su desgranamiento, a una verdad intolerable forjada en este film. En La sombra azul la larga duración de la violencia de estado, la impunidad de los represores durante la democracia y, fundamentalmente, un sobreviviente —a la tortura, la prisión, el exilio, perteneciente a la fuerza policial de una de las provincias más castigadas por la dictadura— son cincelados, en la heteroglosia, en el diálogo y en el antagonismo, con otras voces. Este sobreviviente, devenido en re-viviente señala cómo un marco ético, capaz de valorar la tragedia humana, lo erige en un don para dotar de verdad, para esclarecer a una sociedad que, en muchos espacios, aún permanece en sombra. Este recorrido discursivo señala cómo, desde la indecibilidad original de un sujeto doliente, irrumpen visibilidades y enunciabilidades capaces de decir verdad y así proseguir con una memoria que nunca cesa.

El delirio frente a la razón en el Quijote

Scipedia content — Mon, 03 Apr 2017 16:00:28 +0200

El artículo gira en torno a la tensión contrapuntística que crea el delirio frente a la razón en el Quijote. Partimos de la idea (que compartimos con María Zambrano) de que el delirio es una forma de inteligencia diferente a la inteligencia racional, y que es también una de las diferentes perspectivas (de acuerdo con Leo Spitzer) que conforman el mundo. Es el espacio de la metáfora, de la invención, de la alucinación, es el mundo de don Quijote. Nuestro caballero andante intentará verter su mundo sobre la realidad racional y allí se generará el enfrentamiento entre el delirio y la razón, en términos contrapuntísticos, la disonancia que se resuelve en consonancia casi siempre cuando es derrotado el delirio, en ese momento se acaba el tiempo sin tiempo de la aventura, y don Quijote vuelve al tiempo cronológico y distingue la realidad racional, pero no podrá aceptarla, a menos que esté encantada. Este tema es analizado a la luz de diversas obras, entre ellas: La ambigüedad en el Quijote de Manuel Durán, “Don Quijote” de Foucault, Meditaciones del Quijote, de Ortega y Gasset, “Ambigüedad de la novela”, de Octavio Paz, “Perspectivismo lingüístico en El Quijote”, de Leo Spitzer, etc.

Polisistemas anárquicos. La traducción política en el marco del polisistema

Scipedia content — Mon, 03 Apr 2017 16:00:21 +0200

En este texto se reflexiona sobre la capacidad de la teoría del polisistema para analizar la traducción de textos políticos. Partiendo de las definiciones de cultura y centralidad esbozadas por Even Zohar, se concluye que existe una exclusión de lo político del objeto de estudio. La hipótesis es que, al incluir en su modelo a un sujeto traductor actuante en las luchas materiales del sistema político-cultural, el polisistema, como teoría, cobra nuevo valor y aplicabilidad. En este nuevo contexto, el traductor actúa sobre el sistema receptor como tal, pero también como intelectual y militante. Una derivación obvia es que la traducción deja de pensarse como mera actividad accesoria y pasa a conformar una red de relaciones en la que traductor, militante e intelectual son facetas de un mismo sujeto, aquí definido como internacional. Se toma como ejemplo de sistema político y cultural el anarquismo de principios de siglo xx y se destaca la figura de Diego Abad de Santillán, quien, desde su actividad como dirigente, periodista, escritor y traductor, canaliza a través de su persona las relaciones entre diversos subsistemas de una especie de macrosistema internacional de los movimientos anarquistas.

L’archi -road movie, ou le routage des sens

Scipedia content — Mon, 03 Apr 2017 16:00:17 +0200

Cada film abre un mundo (o un cinemundo, como dice Jean-Luc Nancy). Por esto, el camino, y el road-movie como género, son más que meros tropos, más que simples metáforas para la película: son los sensorimotor schemata del cine pavimentando su propio camino. El problema de la sincronización por lo tanto se reformula como routing de los sentidos, cada vez en un sentido singular, como su colisión, donde sus trayectorias se cruzan. El artículo analiza el curso filmado por los ojos y oídos de un número de films como Blow Out (Brian De Palma, 1981), Lost Highway (David Lynch, 1997), and Deathproof (Quentin Tarantino, 2007).

El enigma de Walter Benjamin

Scipedia content — Mon, 03 Apr 2017 16:00:12 +0200

El siguiente ensayo inicia reconstruyendo el relato de los últimos días de la vida de Walter Benjamin, en el contexto histórico de la Segunda Guerra Mundial, y la existencia de un misterioso manuscrito perdido en su frustrada huida por la frontera franco-española en 1940, en la segunda parte se intenta descifrar la enigmática fisionomía del pensador berlinés, cuya perspectiva múltiple, tanto en lo teórico como en lo político, lo convierten en un autor incomprendido, pero tremendamente fascinante, en la tercera parte se explora uno de sus textos más herméticos, conocido como las tesis Sobre el concepto de historia, con la intención de poner de manifiesto el carácter crítico de su discurso, como clave para comprender los enigmas del mundo moderno y su necesaria transformación revolucionaria.

J. M. Coetzee: en el callejón de Samuel Beckett

Scipedia content — Mon, 03 Apr 2017 16:00:04 +0200

El autor muestra la influencia de Samuel Beckett en la obra del escritor sudafricano. Analiza las dos primeras novelas de J. M. Coetzee, Dusklands (1974) e In the Hearth of the Country (1977), para explicar cómo sus protagonistas comparten el solipsismo de los personajes becketianos, sin embargo, su destino cambia bajo la lógica del Colonialismo. A partir de este grado cero de la escritura, los personajes del novelista sudafricano inician un viaje que, en términos filosóficos, va de la parodia del ego cartesiano hacia el horizonte de reconocimiento hegeliano.

La constitución de la memoria cultural

Scipedia content — Mon, 03 Apr 2017 16:00:00 +0200

En la primera mitad del siglo xx, el sociólogo Maurice Halbwachs y el crítico literario y filósofo Walter Benjamin, publicaron trabajos pioneros sobre la dimensión social de la memoria así como las primeras consideraciones sobre la transmisión de la propia experiencia y de lo que un miembro de una colectividad escuchó. Pese a que los dos destaquen la importancia de la comunicación oral, se deja vislumbrar en los textos de ambos el germen para lo que a partir de la década de 1980 empezó a llamarse “memoria cultural”, una memoria que no sólo se crea con base en relatos orales y la interacción cotidiana —es decir, el medio de la voz— sino a través del uso de diversos soportes. Estos permiten almacenar y divulgar las versiones del pasado en espacios más grandes que los que constituyen los entornos de la memoria de los que hablaba Halbwachs. Jan Assmann describe los procesos de estabilización de la memoria cultural en que intervienen las diversas instituciones y medios, en tanto que Astrid Erll explora los procesos de dinamización de la memoria cultural que se producen en nuestras sociedades actuales mediáticas a través de la remediatización y premedia-tización, así como la mayor accesibilidad de los medios electrónicos para un amplio público. Así se posibilita articular latencias de la memoria y cuestionar las versiones hegemónicas del pasado.

De la desesperanza a la plenitud: la revelación epifánica en la poesía de Álvaro Mutis

Scipedia content — Mon, 03 Apr 2017 15:59:56 +0200

The boundaries between prose and verse, the presence of different characters’ voices, wich act as semi-heteronyms and orbit the texts giving a certain distance to the poetic self, the journey into the past as a revelatory experience and the insuffiency of word as the means of expression are the principal subjects of Álvaro Mutiss poetry. In this essay, the concept of epiphany, understood as a representation of the perfect order or as an indecipherable formula of an enigma in the face of the agonistic circumstances of disaster, unifies the colombians poetic work.

Tiempo y mirada en la obra de Hiroshi Sugimoto y Wolfgang Tillmans

Scipedia content — Mon, 03 Apr 2017 15:59:52 +0200

Este texto expone algunas relaciones entre tiempo y técnica en la fotografía, en términos de Walter Benjamin y José Luis Brea, pero también de la misma práctica. A partir de dichas relaciones, el texto propone concepciones de tiempo y mirada en el acto fotográfico que confrontan el mito que lo coloca en el papel de técnica instantánea que guarda el pasado. Hiroshi Sugimoto y Wolfgang Tillmans son ejemplos de estas concepciones propuestas, pues reflexionan en la práctica sobre tiempo y técnica.

Los detectives salvajes: figuras, cesuras, retornos

Scipedia content — Mon, 03 Apr 2017 15:59:49 +0200

En este artículo se propone una lectura de Los detectives salvajes de Roberto Bolaño (1998) a partir del análisis de algunos procesos de intempestividad y espectralidad que atraviesan, fisuran y cada vez interrumpen la multiplicidad de relatos de la novela. Concentramos la atención en un gesto, el de la poeta Cesárea Tinajero, uno de los personajes clave del libro, para ver cómo se desprende, de manera genealógica, la investigación bolañiana sobre los márgenes de la historia y sus fantasmas. Cesárea deja el Distrito Federal, deja a los es-tridentistas y a la Revolución mexicana y vuelve al desierto de Sonora. Nos importan los diferenciales de tiempo: los de un gesto pasado que sigue irrumpiendo en un presente que lo narra. Finalmente, se intenta pensar este retorno dialéctico y anacrónico, así como ese desierto, como pre-figuración del lugar donde Bolaño, en su última, póstuma novela (2666 ) hizo refluir el horror de un siglo entero: santa Teresa, re-inscripción de Ciudad Juárez y de su feminicidio imparable.

El primer Manierismo toscano y P. P. Pasolini

Scipedia content — Mon, 03 Apr 2017 15:59:44 +0200

La mística al revés en el cuento “Rito” de Juan García Ponce

Scipedia content — Mon, 03 Apr 2017 15:59:40 +0200

La mística no siempre ha transitado por el mismo camino ni en el mismo sentido. En algunas obras de literatura se presenta como una mística al revés. En el cuento “Rito”, de Juan García Ponce, se lleva a cabo un proceso místico transitando los caminos del mal. A partir de la desnudez del cuerpo de una mujer joven y hermosa, del erotismo y del acto sexual se pretende que el Espíritu de la Divinidad se manifieste. En este cuento está presente la transgresión y la perversión de las normas sociales de comportamiento dentro del matrimonio. Los personajes del cuento, Liliana y Arturo, son esposos. Sin embargo, les gusta practicar un rito en el cual se invita a cenar a un individuo desconocido. De lo que se trata es de poner en práctica “las leyes de la hospitalidad” que el escritor francés Pierre Klossowski propone en sus novelas Roberte, esta noche y en La revocación del Edicto de Nantes. En el nivel profano, el esposo, como Señor de la casa, debe acceder al nivel místico de Anfitrión, a su vez, la Señora de la casa, como esposa, debe acceder al nivel místico de Anfitriona. Para ello, el esposo debe ofrecer a su esposa al invitado, como Tercero desconocido. El esposo, como Anfitrión, contempla el acto sexual de su esposa con el invitado: ella es la Anfitriona, y el Tercero desconocido funciona como el elemento angelical que comunica lo profano con lo sagrado. En el acto sexual y en la desnudez del cuerpo de la hermosa mujer se manifiesta el Espíritu de la Divinidad.

“Nacimiento de la pasión que se busca en el núcleo de su vida’’. Aproximaciones al sufismo desde un poemario de Francisco Magaña

Scipedia content — Mon, 03 Apr 2017 15:59:37 +0200

En el año de 1992 Francisco Magaña publica su tercer poemario, Calendas, la mirada, en la colección “El ala del tigre” de la Universidad Nacional Autónoma de Mexico. La añoranza por un tiempo pasado se propone desde el título y es reforzada por el epígrafe de apertura, perteneciente al poeta místico persa Jalal ai-Din Rumi: “Estuvimos en el cielo, éramos amigos / de los ángeles, Padre, déjanos / regresar allí, pues ésa es nuestra / tierra”. Son abundantes los intertextos e hipertextos que presenta este poemario con temas propios del sufismo. El llamado a la contemplación, la relación con la música y la danza, las imágenes del samá, la infancia y el amor como vía de unión con lo divino, son algunos de los tópicos más recurrentes en este poemario, en el cual, el poeta tabasqueño, más que participar en una experiencia mística propia del sufismo, escribe maravillado el descubrimiento de esta tradición.

Vivian Maier, la mirada de autor y la mirada social

Scipedia content — Mon, 03 Apr 2017 15:59:33 +0200

El descubrimiento reciente del archivo fotográfico de Vivian Maier, de más de 150, 000 imágenes de Nueva York y Chicago de los años cincuenta, sesenta y setenta del siglo xx, nos descubre la vida callejera de la modernidad norteamericana. Este Atlas inmenso que nos legó una mujer que vivió y murió en el anonimato, nos permiten llevar a cabo una reflexión benjaminiana acerca de un momento del pasado que se manifiesta como el germen de nuestra reciente catástrofe. La fotografía de Maier no es el “pretexto” para emprender esta tarea, sino la prueba forense de un detective callejero, tal y como Benjamin concibió a la fotografía de finales del siglo xix .

El viaje como expresión del misticismo en Segundo sueño de Sergio Fernández

Scipedia content — Mon, 03 Apr 2017 15:59:25 +0200

En este artículo se analiza la relación que puede establecerse entre los sueños de anábasis del poema de sor Juana Inés de la Cruz, Primero sueño, y la novela de Sergio Fernández, Segundo sueño, en una concordancia donde el alma, durante su viaje por las esferas supra lunares, o en la transmutación de los elementos naturales —la lluvia, la nieve y el lodo—, experimenta el misterio de su encuentro con lo divino como un proceso de iniciación. En el poema, la búsqueda del conocimiento supremo es una trampa, en la novela, la encrucijada se halla en el erotismo transgresor. Estos dos viajes de anábasis traducen el guiño que anuncia la sucesión en una caída. En ambos casos, la desmesura del alma, máscara de un héroe trágico, derrite las alas de Ícaro y propicia la muerte de Faetón, el auriga inexperto del carro divino.

Vos que me empezaste y quiero que me acabes en la mitad de vos. La mística de la poesía de Juan Gelman

Scipedia content — Mon, 03 Apr 2017 15:59:22 +0200

La mística es una experiencia que muy pocas personas consiguen tener, y aun para esas personas es difícil expresar lo que significó y continúa significando en su vida. Relatos de místicos antiguos y contemporáneos se encuentran dispersos por todo el mundo y no se atienen a una sola religión. Así pues, es posible encontrar relatos de experiencias místicas de practicantes de diversas religiones como el islamismo, el judaismo o el catolicismo. Juan Gelman, poeta, ensayista y periodista argentino, es una de las figuras más importantes de la literatura de América Latina contemporánea. Con sus textos periodísticos y poemas, pudo denunciar las injusticias de la política de su país, y además fue una personalidad que relató descarnadamente uno de los procesos más cruentos ocurridos en Argentina: la dictadura militar. Gelman también se acercó al fenómeno de la experiencia mística. Ya fuese por un sentimiento de identificación (al sentirse extranjero) o por la búsqueda de ‘lo místico’ (aquello que lo trasciende como ser humano), Gelman es un autor latinoamericano cuya etapa de poesía mística es fundamental para comprender este fenómeno por medio de la literatura. En este ensayo se propone explorar la veta de Juan Gelman como buscador de la experiencia mística y relator de ella. Se rastreará esto a partir del material de esta índole que el autor dejó plasmado en sus obras Citas y Comentarios, Com/posiciones y dibaxu, además de la revisión que él mismo hizo de los místicos de tradición judía.