Phosphorylation of WHIRLY1 by CIPK14 shifts its localization and dual functions in Arabidopsis.

Mol Plant. 2017 Apr 12;:

Authors: Ren Y, Li Y, Jiang Y, Wu B, Miao Y

Abstract
Plastid-to-nucleus retrograde signaling is critical for normal growth and development in plants. The dual-function and dual-located ssDNA binding protein WHIRLY1 (WHY1) has been supposed to coordinate the retrograde signaling from plastids to the nucleus. However, the regulatory mechanism governing the functional switch of WHY1 for mediating plastid-to-nucleus retrograde signaling remains unknown. Here we report that the Calcineurin B-Like-Interacting Protein Kinase14 (CIPK14) interacts with and phosphorylates WHY1 in Arabidopsis. Phosphorylation of WHY1 results in increased accumulation in the nucleus and enhanced binding with the promoter of WRKY53, which encodes a key transcription factor regulating leaf senescence in Arabidopsis. Transgenic plants overexpressing CIPK14 showed increased nuclear isoform but decreased plastid isoform of WHY1, among which 95% transgenic lines showed the stay-green phenotype and 5% lines with variegated pale-green phenotype. Interestingly, the phenotypes of both types of transgenic plants could be recovered by overexpression of plastid-form WHY1. In contrast, knockdown of CIPK14 caused early senescence and even seedling-lethal phenotypes along with elevated expression of the senescence-related genes such as WRKY53, SAG12 and NDHF but decreased expression of MER11, RAD50 and POR genes, which could be rescued by overexpression of CIPK14 but neither by overexpressing the plastid-form or nuclear-form WHY1, whereas the stay-green plants overexpressing CIPK14 showed reduced expression of WRKY53, SAG12, NDHF and large plastid rRNA. Consistently, the accumulation of nuclear-form WHY1 was significantly reduced in the CIPK14 knockdown lines, resulting in a low ratio of nuclear/plastid-form WHY1. Taken together, our results demonstrates that CIPK14 regulates the phosphorylation and organelle distributions of WHY1, which may function as a cellular switch between leaf senescence and plastid development for coordinating the intercellular signaling in Arabidopsis.

PMID: 28412544 [PubMed - as supplied by publisher]

Endotoxin induced TLR4 signaling downregulates CYP19A1 expression through CEBPB in buffalo granulosa cells.

Toxicol In Vitro. 2017 Apr 13;:

Authors: Rao Y, Ravinder, Singh D

Abstract
Estrogen is essential for growth and development of ovarian follicles. Infections associated with E. coli or Endotoxin (LPS) suppress estradiol production by the downregulation of CYP19A1 expression. However, the molecular mechanism of its down regulation is not yet known. To elucidate the molecular mechanisms of LPS-mediated downregulation of CYP19A1 gene expression, we studied the effect of LPS and TLR4 signaling pathway inhibitor (OxPAPC, OxPAPC-Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine) on CYP19A1 expression, and expression of CEBPB and CEBPB binding on CYP19A1 proximal promoter (CYP19A1 PII) in buffalo granulosa cells in vitro. The results showed that LPS (1μg/ml) significantly declined the expression of CYP19A1 gene. In further experiments, inhibitor studies confirmed the involvement of TLR4 in LPS induced CYP19A1 gene down regulation in buffalo granulosa cells. LPS promoted higher levels of CEBPB at cellular and nuclear level in granulosa cells. Chromatin immunoprecipitation results showed, that LPS induces higher amount of CEBPB binding on the CYP19A1 PII. Further, TLR4 inhibitor attenuated the LPS induced implications. In conclusion, our results demonstrated that CEBPB could be a potential regulator for LPS mediated downregulation of CYP19A1 and decline of 17-beta estradiol levels in buffalo granulosa cells.

PMID: 28412504 [PubMed - as supplied by publisher]

RNA-Binding Proteins Revisited - The Emerging Arabidopsis mRNA Interactome.

Trends Plant Sci. 2017 Apr 12;:

Authors: Köster T, Marondedze C, Meyer K, Staiger D

Abstract
RNA-protein interaction is an important checkpoint to tune gene expression at the RNA level. Global identification of proteins binding in vivo to mRNA has been possible through interactome capture - where proteins are fixed to target RNAs by UV crosslinking and purified through affinity capture of polyadenylated RNA. In Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked samples have been identified. As in mammals and yeast, the mRNA interactomes came with a few surprises. For example, a plethora of the proteins caught on RNA had not previously been linked to RNA-mediated processes, for example proteins of intermediary metabolism. Thus, the studies provide unprecedented insights into the composition of the mRNA interactome, highlighting the complexity of RNA-mediated processes.

PMID: 28412036 [PubMed - as supplied by publisher]

Interferon-α for Induction and Maintenance of Remission in Eosinophilic Granulomatosis with Polyangiitis: A Single-center Retrospective Observational Cohort Study.

J Rheumatol. 2017 Apr 15;:

Authors: Seeliger B, Förster M, Happe J, Forberg T, Moeser A, Neumann T, Kroegel C

Abstract
OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by frequent relapses following induction therapy. Interferon-α (IFN-α) can reverse the underlying Th2-driven immune response and has successfully induced remission in previous reports. We undertook this study to investigate its efficacy and safety in patients with EGPA.
METHODS: We conducted a retrospective monocentric cohort study including 30 patients (16 women) with active EGPA under IFN-α treatment. Primary endpoints were remission induction, occurrence of relapses, prednisolone (PSL) dosage at time of remission, and adverse events. Remission was defined by a Birmingham Vasculitis Activity Score (BVAS) of 0. Pulmonary function tests were recorded at baseline and at time of remission. Health-related quality of life was analyzed by questionnaire at baseline and following 12 months of treatment.
RESULTS: At baseline, the median BVAS was 6 (interquartile range 4-13.5) and remission or partial response was achieved in 25/30 patients. After initiation of IFN-α treatment, the median PSL dosages could be reduced from 17.5 mg/day at baseline to 5.5 mg/day at time of remission. Following remission, 17 relapses (5 major) in 16 patients were observed. Pulmonary function tests improved and the time of hospitalization decreased. Adverse events at initiation of treatment were common, but mostly transient. Severe adverse events occurred during treatment in 4 patients (autoimmune hepatitis, n = 1; drug-induced neuropathy, n = 3).
CONCLUSION: IFN-α treatment results in high rate of remission and maintenance in EGPA with significant reduction in oral corticosteroids, although reversible adverse events may occur. IFN-α represents an alternative therapeutic option in cases of refractory to standard treatment.

PMID: 28412705 [PubMed - as supplied by publisher]

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections.

Curr Opin Virol. 2017 Apr 12;24:1-8

Authors: Bauer L, Lyoo H, van der Schaar HM, Strating JR, van Kuppeveld FJ

Abstract
Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs.

PMID: 28411509 [PubMed - as supplied by publisher]

GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

Stroke. 2017 Apr 14;:

Authors: Fernández-Cadenas I, Mendióroz M, Giralt D, Nafria C, Garcia E, Carrera C, Gallego-Fabrega C, Domingues-Montanari S, Delgado P, Ribó M, Castellanos M, Martínez S, Freijo M, Jiménez-Conde J, Rubiera M, Alvarez-Sabín J, Molina CA, Font MA, Grau Olivares M, Palomeras E, Perez de la Ossa N, Martinez-Zabaleta M, Masjuan J, Moniche F, Canovas D, Piñana C, Purroy F, Cocho D, Navas I, Tejero C, Aymerich N, Cullell N, Muiño E, Serena J, Rubio F, Davalos A, Roquer J, Arenillas JF, Martí-Fábregas J, Keene K, Chen WM, Worrall B, Sale M, Arboix A, Krupinski J, Montaner J, GRECOS Study Group

Abstract
BACKGROUND AND PURPOSE: Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS.
METHODS: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method.
RESULTS: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10(-)(03)), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10(-)(09)) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03).
CONCLUSIONS: The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.

PMID: 28411264 [PubMed - as supplied by publisher]

Knowledge and attitude regarding pharmacogenetics among formerly pregnant women in the Netherlands and their interest in pharmacogenetic research.

BMC Pregnancy Childbirth. 2017 Apr 14;17(1):120

Authors: Daud ANA, Bergsma EL, Bergman JEH, De Walle HEK, Kerstjens-Frederikse WS, Bijker BJ, Hak E, Wilffert B

Abstract
BACKGROUND: Pharmacogenetics is an emerging field currently being implemented to improve safety when prescribing drugs. While many women who take drugs during pregnancy would likely benefit from such personalized drug therapy, data is lacking on the awareness towards pharmacogenetics among women. We aim to determine the level of knowledge and acceptance of formerly pregnant women in the Netherlands regarding pharmacogenetics and its implementation, and their interest in pharmacogenetic research.
METHODS: A population-based survey using postal questionnaires was conducted among formerly pregnant women in the Northern parts of the Netherlands. A total of 986 women were invited to participate.
RESULTS: Of the 219 women who returned completed questionnaires (22.2% response rate), only 22.8% had heard of pharmacogenetics, although the majority understood the concept (64.8%). Women who had experience with drug side-effects were more likely to know about pharmacogenetics [OR = 2.06, 95% CI 1.16, 3.65]. Of the respondents, 53.9% were positive towards implementing pharmacogenetics in their future drug therapy, while 46.6% would be willing to participate in pharmacogenetic research. Among those who were either not willing or undecided in this regard, their concerns were about the consequences of the pharmacogenetic test, including the privacy and anonymity of their genetic information.
CONCLUSION: The knowledge and attitude regarding the concept of pharmacogenetics among our population of interest is good. Also, their interest in pharmacogenetic research provides opportunities for future research related to drug use during pregnancy and fetal outcome.

PMID: 28410576 [PubMed - in process]

Clostridium difficile and cystic fibrosis: management strategies and the role of faecal transplantation.

Paediatr Respir Rev. 2017 Mar 14;:

Authors: Dunwoody R, Steel A, Landy J, Simmonds N

Abstract
Clostridium difficile is a bacterial infection that colonises the gut in susceptible hosts. It is associated with exposure to healthcare settings and antibiotic use. It could be assumed that cystic fibrosis (CF) patients are a high-risk group for C.difficile. However, despite high carriage rates, CF patients have low rates of active disease. There are guidelines for the treatment of C.difficile, however little is published specific to treating C.difficile in CF. This article provides an overview of the current management strategies for C.difficile in CF, including a description of the first faecal transplantation in this patient population.

PMID: 28411069 [PubMed - as supplied by publisher]

Phenotypes of Rapid Cystic Fibrosis Lung Disease Progression during Adolescence and Young Adulthood.

Am J Respir Crit Care Med. 2017 Apr 14;:

Authors: Szczesniak RD, Li D, Su W, Brokamp C, Pestian J, Seid M, Clancy JP

Abstract
RATIONALE: Individuals with cystic fibrosis are at risk for prolonged drops in lung function, clinically termed rapid decline, during discreet periods of the disease.
OBJECTIVES: To identify phenotypes of rapid pulmonary decline and determine how these phenotypes are related to patient characteristics.
METHODS: A longitudinal cohort study of cystic fibrosis patients aged 6-21 years was conducted using the Cystic Fibrosis Foundation Patient Registry. A statistical approach for clustering longitudinal profiles, sparse functional principal components analysis, was used to classify patients into distinct phenotypes by evaluating trajectories of FEV1 decline. Phenotypes were compared with respect to baseline and mortality characteristics.
MEASUREMENTS AND MAIN RESULTS: Three distinct phenotypes of rapid decline were identified, corresponding to early, middle and late timing of maximal FEV1 loss, in the overall cohort (n=18,387). The majority of variation (first functional principal component: 94%) among patient profiles was characterized by differences in mean longitudinal FEV1 trajectories. Average degree of rapid decline was similar among phenotypes (roughly -3% predicted/year); however, average timing differed, with early, middle and late phenotypes experiencing rapid decline at 12.9, 16.3 and 18.5 years of age, respectively. Individuals with the late phenotype had the highest initial FEV1 but experienced the greatest loss of lung function. The early phenotype was more likely to have respiratory infections and acute exacerbations at baseline or to develop them subsequently, compared to other phenotypes.
CONCLUSIONS: By identifying phenotypes and associated risk factors, timing of interventions may be more precisely targeted for subgroups at highest risk of lung function loss.

PMID: 28410569 [PubMed - as supplied by publisher]

Genetic Variation at the Sulfonylurea Receptor, Type 2 Diabetes, and Coronary Heart Disease.

Diabetes. 2017 Apr 14;:

Authors: Emdin CA, Klarin D, Natarajan P, CARDIOGRAM Exome consortium, Florez JC, Kathiresan S, Khera AV

Abstract
Despite widespread clinical use in the treatment of type 2 diabetes, the impact of sulfonylurea therapy on cardiovascular outcomes remains uncertain. Studies of naturally occurring genetic variation can be used to anticipate the expected clinical consequences of a pharmacologic therapy. A common missense variant in the gene encoding a component of the sulfonylurea receptor (ABCC8 p.A1369S) promotes closure of the target channel of sulfonylurea therapy and is associated with increased insulin secretion, thus mimicking the effects of sulfonylurea therapy. Using individual-level data from 120 286 participants in the UK Biobank and summary association results from four large-scale genome wide association studies, we examined the impact of this variant on cardiometabolic traits, type 2 diabetes and coronary heart disease. The p.A1369S variant was associated with a significantly lower risk of type 2 diabetes (OR 0.93 95%CI 0.91, 0.95; p=1.2×10(-11)). The variant was associated with increased body mass index (0.062 CI 0.037, 0.086 kg/m(2); p=8.1×10(-7)) but lower waist-to-hip ratio adjusted for body mass index, a marker of abdominal fat distribution. Furthermore, p.A1369S was associated with a reduced risk of coronary heart disease (OR 0.98 CI 0.96, 0.99; p=5.9×10(-4)). These results suggest that, despite a known association with increased weight, long-term sulfonylurea therapy may reduce the risk of coronary heart disease.

PMID: 28411266 [PubMed - as supplied by publisher]

Transdifferentiation as a Mechanism of Treatment Resistance in a Mouse Model of Castration-resistant Prostate Cancer.

Cancer Discov. 2017 Apr 14;:

Authors: Zou M, Toivanen R, Mitrofanova A, Floc'h N, Hayati S, Sun Y, Le Magnen C, Chester D, Mostaghel EA, Califano A, Rubin MA, Shen MM, Abate-Shen C

Abstract
Current treatments for castration-resistant prostate cancer (CPRC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here we provide novel insights into treatment response for the anti-androgen abiraterone by analyses of a genetically-engineered mouse model (GEMM) with combined inactivation of Trp53 and Pten, which are frequently co-mutated in human CRPC. These NPp53 mice fail to respond to abiraterone, and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans. Cross-species computational analyses identify master regulators of adverse response that are conserved with human CRPC-NE, including the neural differentiation factor SOX11, which promotes neuroendocrine differentiation in cells derived from NPp53 tumors. Furthermore, abiraterone-treated NPp53 prostate tumors contain regions of focal and/or overt neuroendocrine differentiation, distinguished by their proliferative potential. Notably, lineage-tracing in vivo provides definitive and quantitative evidence that focal and overt neuroendocrine regions arise by transdifferentiation of luminal adenocarcinoma cells. These findings underscore principal roles for TP53 and PTEN inactivation in abiraterone resistance and progression from adenocarcinoma to CRPC-NE by transdifferentiation.

PMID: 28411207 [PubMed - as supplied by publisher]

M3 muscarinic acetylcholine receptor facilitates the endocytosis of mu opioid receptor mediated by morphine independently of the formation of heteromeric complexes.

Cell Signal. 2017 Apr 11;:

Authors: Lopez-Gimenez JF, Alvarez-Curto E, Milligan G

Abstract
Morphine inefficiency to induce the internalization of mu opioid (MOP) receptors observed in numerous experimental models constitutes a paradigm of G-protein coupled receptor (GPCR) functional selectivity. We recently described that activation of Gαq/11 proteins through 5-HT2A serotonin receptors co-expressed in the same cells facilitates MOP receptor endocytosis promoted by morphine. In order to explore whether a different Gαq/11 coupled GPCR would emulate this effect, a double stable Flp-In T-REx HEK293 cell line permanently expressing MOP-YFP receptors along with FLAG-M3-Cerulean receptors expressed in an inducible manner was generated. Fluorescence microscopy examination of these cells revealed a co-distribution of both receptors mainly compartmentalized in plasma membrane. Concurrent stimulation with carbachol and morphine promoted MOP receptor internalization, desensitization and down-regulation and this facilitation was not dependent on PKC activation. Co-immunoprecipitation experiments demonstrated that FLAG-M3-Cerulean/MOP-YFP receptors interact forming heteromeric complexes in a time depending manner, i.e. the strongest interaction was detected after 96h of FLAG-M3-Cerulean induced expression. Under these experimental conditions, treatment of cells with carbachol plus morphine resulted in the internalization of both receptors within separated endocytic vesicles as visualized by confocal microscopy. This trafficking segregation observed for FLAG-M3-Cerulean and MOP-YFP receptors upon agonist stimulation suggests that this protein-protein interaction presents temporal and dynamic properties. Moreover, MOP-YFP receptor internalization facilitated by FLAG-M3-Cerulean receptors is independent of the constitution of heteromeric complexes.

PMID: 28411124 [PubMed - as supplied by publisher]

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Stem Cell Reports. 2017 Apr 11;8(4):1086-1100

Authors: Panopoulos AD, D'Antonio M, Benaglio P, Williams R, Hashem SI, Schuldt BM, DeBoever C, Arias AD, Garcia M, Nelson BC, Harismendy O, Jakubosky DA, Donovan MKR, Greenwald WW, Farnam K, Cook M, Borja V, Miller CA, Grinstein JD, Drees F, Okubo J, Diffenderfer KE, Hishida Y, Modesto V, Dargitz CT, Feiring R, Zhao C, Aguirre A, McGarry TJ, Matsui H, Li H, Reyna J, Rao F, O'Connor DT, Yeo GW, Evans SM, Chi NC, Jepsen K, Nariai N, Müller FJ, Goldstein LSB, Izpisua Belmonte JC, Adler E, Loring JF, Berggren WT, D'Antonio-Chronowska A, Smith EN, Frazer KA

Abstract
Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines.

PMID: 28410642 [PubMed - in process]

Natural selection drove metabolic specialization of the chromatophore in Paulinella chromatophora.

BMC Evol Biol. 2017 Apr 14;17(1):99

Authors: Valadez-Cano C, Olivares-Hernández R, Resendis-Antonio O, DeLuna A, Delaye L

Abstract
BACKGROUND: Genome degradation of host-restricted mutualistic endosymbionts has been attributed to inactivating mutations and genetic drift while genes coding for host-relevant functions are conserved by purifying selection. Unlike their free-living relatives, the metabolism of mutualistic endosymbionts and endosymbiont-originated organelles is specialized in the production of metabolites which are released to the host. This specialization suggests that natural selection crafted these metabolic adaptations. In this work, we analyzed the evolution of the metabolism of the chromatophore of Paulinella chromatophora by in silico modeling. We asked whether genome reduction is driven by metabolic engineering strategies resulted from the interaction with the host. As its widely known, the loss of enzyme coding genes leads to metabolic network restructuring sometimes improving the production rates. In this case, the production rate of reduced-carbon in the metabolism of the chromatophore.
RESULTS: We reconstructed the metabolic networks of the chromatophore of P. chromatophora CCAC 0185 and a close free-living relative, the cyanobacterium Synechococcus sp. WH 5701. We found that the evolution of free-living to host-restricted lifestyle rendered a fragile metabolic network where >80% of genes in the chromatophore are essential for metabolic functionality. Despite the lack of experimental information, the metabolic reconstruction of the chromatophore suggests that the host provides several metabolites to the endosymbiont. By using these metabolites as intracellular conditions, in silico simulations of genome evolution by gene lose recover with 77% accuracy the actual metabolic gene content of the chromatophore. Also, the metabolic model of the chromatophore allowed us to predict by flux balance analysis a maximum rate of reduced-carbon released by the endosymbiont to the host. By inspecting the central metabolism of the chromatophore and the free-living cyanobacteria we found that by improvements in the gluconeogenic pathway the metabolism of the endosymbiont uses more efficiently the carbon source for reduced-carbon production. In addition, our in silico simulations of the evolutionary process leading to the reduced metabolic network of the chromatophore showed that the predicted rate of released reduced-carbon is obtained in less than 5% of the times under a process guided by random gene deletion and genetic drift. We interpret previous findings as evidence that natural selection at holobiont level shaped the rate at which reduced-carbon is exported to the host. Finally, our model also predicts that the ABC phosphate transporter (pstSACB) which is conserved in the genome of the chromatophore of P. chromatophora strain CCAC 0185 is a necessary component to release reduced-carbon molecules to the host.
CONCLUSION: Our evolutionary analysis suggests that in the case of Paulinella chromatophora natural selection at the holobiont level played a prominent role in shaping the metabolic specialization of the chromatophore. We propose that natural selection acted as a "metabolic engineer" by favoring metabolic restructurings that led to an increased release of reduced-carbon to the host.

PMID: 28410570 [PubMed - in process]

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Semantics derived automatically from language corpora contain human-like biases.

Science. 2017 Apr 14;356(6334):183-186

Authors: Caliskan A, Bryson JJ, Narayanan A

Abstract
Machine learning is a means to derive artificial intelligence by discovering patterns in existing data. Here, we show that applying machine learning to ordinary human language results in human-like semantic biases. We replicated a spectrum of known biases, as measured by the Implicit Association Test, using a widely used, purely statistical machine-learning model trained on a standard corpus of text from the World Wide Web. Our results indicate that text corpora contain recoverable and accurate imprints of our historic biases, whether morally neutral as toward insects or flowers, problematic as toward race or gender, or even simply veridical, reflecting the status quo distribution of gender with respect to careers or first names. Our methods hold promise for identifying and addressing sources of bias in culture, including technology.

PMID: 28408601 [PubMed - in process]

Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review.

J Clin Virol. 2017 Mar 21;91:12-17

Authors: Moretti M, Lava SAG, Zgraggen L, Simonetti GD, Kottanattu L, Bianchetti MG, Milani GP

Abstract
BACKGROUND AND OBJECTIVES: Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity.
STUDY DESIGN: Stimulated by our experience with two cases, we performed a review of the literature.
RESULTS: The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered.
CONCLUSIONS: In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy.

PMID: 28410496 [PubMed - as supplied by publisher]

Genetic Testing for Opioid Pain Management: A Primer.

Pain Ther. 2017 Apr 13;:

Authors: Agarwal D, Udoji MA, Trescot A

Abstract
Patients see their primary care physicians (PCPs) for a variety of medical conditions, chronic pain being one of the most common. An increased use of prescription medications (especially opioids) has led to an increase in adverse drug reactions and has heightened our awareness of the variability in response to medications. Opioids and other pain adjuvants are widely used, and drug-drug interactions involving these analgesics can be problematic and potentially lethal. Pharmacogenetics has improved our understanding of drug efficacy and response, opened doors to individual tailoring of medical management, and created a series of ethical and economic considerations. Since it is a relatively new field, genetic testing has not been fully integrated into the primary care setting. The purpose of this paper is to review the metabolism of commonly prescribed opioids, discuss the economic and ethical issues, and provide PCPs with an understanding of how to incorporate genetic testing into routine use to improve clinical practice and patient management.

PMID: 28409480 [PubMed - as supplied by publisher]