bluuebunny/crossref_metadata_2025_split huggingface dataset:
Japanese Encephalitis Virus‐induced let‐7a/b interacted with the NOTCH‐TLR7 pathway in microglia and facilitated neuronal death via caspase activation
Authors: Mukherjee Sriparna , Akbar Irshad , Kumari Bharti , Vrati Sudhanshu , Basu Anirban , Banerjee Arup 
Published: December 2018

AbstractMicroRNAs (miRNAs) released from the activated microglia upon neurotropic virus infection may exacerbate the neuronal damage. Here, we identified let‐7a and let‐7b (let‐7a/b) as one of the essential miRNAs over‐expressed upon Japanese Encephalitis virus (JEV) infection and released in the culture supernatant of the JEV‐infected microglial cells through extracellular vesicles. The let‐7a/b was previously reported to modulate inflammation in microglial cells through Toll‐like receptor 7 (TLR7) pathways; although their role in accelerating JEV pathogenesis remain unexplored. Therefore, we studied the role of let‐7a/b in modulating microglia‐mediated inflammation during JEV infection and investigated the effect of let‐7a/b‐containing exosomes on primary neurons. To this end, we examined let‐7a/b and NOTCH signaling pathway in TLR7 knockdown (KD) mice. We observed that TLR7 KD or inhibition of let‐7a/b suppressed the JEV‐induced NOTCH activation possibly via NF‐κB dependent manner and subsequently, attenuated JEV‐induced TNFα production in microglial cells. Furthermore, exosomes secreted from let‐7a/b over‐expressed microglia when transferred to uninfected mice brain induced caspase activation. Exosomes secreted from virus‐infected or let‐7a/b over‐expressed microglia when co‐incubated with mouse neuronal (Neuro2a) cells or primary cortical neurons also facilitated caspase activation leading to neuronal death. Thus, our results provide evidence for the multifaceted role of let‐7a/b miRNAs in JEV pathogenesis. Let‐7a/b can interact with TLR7 and NOTCH signaling pathway and enhance TNFα release from microglia. On the other hand, the exosomes secreted by JEV‐infected microglia can activate caspases in uninfected neuronal cells which possibly contribute to bystander neuronal death.
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Cover Image for this issue: doi: 10.1111/jnc.14506.
A case of ochronosis successfully treated with the picosecond laser
Authors: Méndez Baca Isela , Al‐Niaimi Firas , Colina Claudia , Anuzita Alexander 
Published: December 2018

SummaryExogenous ochronosis is a cutaneous condition characterized by blue‐black pigmentation resulting as a complication of long‐term application of skin‐lightening creams containing hydroquinone and other substances such as quinine, phenol and mercury derivatives. We report a case of a 55‐year‐old woman who developed exogenous ochronosis as a result of prolonged use of topical hydroquinone for 5 years, characterized by greyish hyperpigmented patches on the nose and cheeks. The diagnosis was confirmed histologically. Treatment with picosecond laser resulted in marked clinical improvement together with improvement in overall texture and quality of the skin.
Employee Stock Option Exercise and Firm Cost
Authors: CARPENTER JENNIFER N. , STANTON RICHARD , WALLACE NANCY 
Published: December 2018

ABSTRACTWe develop an empirical model of employee stock option exercise that is suitable for valuation and allows for behavioral channels. We estimate exercise rates as functions of option, stock, and employee characteristics using all employee exercises at 88 public firms, 27 of them in the S&P 500. Increasing vesting frequency from annual to monthly reduces option value by 11% to 16%. Men exercise faster, reducing value by 2% to 4%, while top employees exercise slower, increasing value by 2% to 7%. Finally, we develop an analytic valuation approximation that is more accurate than methods used in practice.
Scriptural Coping: An Empirical Test of Hermeneutic Theory
Authors: DeAngelis Reed T. , Bartkowski John P. , Xu Xiaohe 
Published: December 2018

AbstractThis study develops and tests a theory of scriptural coping. Using elements from hermeneutic theory as our guide, we contend that (1) specific life exigencies will increase the likelihood of someone turning to scripture for relevant insights and (2) reading scripture for relevant insights will moderate associations between exigencies and psychological well‐being. Analyzing nationally representative data from the 2012 General Social Survey (n = 1,551), we find that poor self‐rated health and low socioeconomic status increase the likelihood of someone reading scripture for insight into attaining health and wealth, respectively. Moreover, reading scripture for health insights amplifies the positive association between poor health and depressive symptoms, thereby suggesting a stress‐exacerbating effect of scriptural coping. Scripture is a polysemous resource, one that can alternatively provide comfort or trigger negative coping in the face of psychosocial stress. We discuss the implications and limitations of these findings and outline avenues for future research.
Effects of the potassium‐sparing diuretic amiloride on chemotherapy response in canine osteosarcoma cells
Authors: Poon Andrew C. , Inkol Jordon M. , Luu Anita K. , Mutsaers Anthony J. 
Published: December 2018

BackgroundOsteosarcoma (OSA) is a common bone tumor of mesenchymal origin in dogs. Chemotherapy delays metastasis, yet most dogs die of this disease within 1 year of diagnosis. The high metabolic demand of cancer cells promotes proton pump upregulation, leading to acidification of the tumor microenvironment and chemoresistance. The potassium‐sparing diuretic amiloride is among a class of proton pump inhibitors prescribed for refractory heart failure treatment in dogs.ObjectiveWe hypothesized that amiloride treatment improves chemotherapy response by reducing acidification in canine OSA cells. Our objective was to assess the in vitro effects of amiloride on cell viability, apoptosis, and metabolism.MethodsIn vitro study. Assessments of cell viability and apoptosis were performed after single agent or combination treatment, along with calculations of pharmacological synergism using the combination index. Protein signaling during apoptosis was evaluated by Western blotting. Metabolic profiling was performed using a Seahorse bioanalyzer.ResultsAmiloride strongly synergized with doxorubicin in combination treatment and exhibited additive or antagonistic effects with carboplatin in canine OSA cells. Combination treatment with doxorubicin significantly upregulated p53‐mitochondrial signaling to activate apoptosis and downregulate Akt phosphorylation. Amiloride‐treated cells further exhibited metabolic switching with reductions in glycolytic capacity and maximal respiration.Conclusion and Clinical ImportanceAmiloride synergized with doxorubicin to potentiate apoptosis in canine OSA cells. These results justify further investigation into repurposing of amiloride as an oncology drug for the treatment of OSA in dogs.
The fascinating biology behind phage display: filamentous phage assembly
Authors: Loh Belinda , Kuhn Andreas , Leptihn Sebastian 
Published: December 2018

SummaryWith the recently awarded Nobel Prize to the inventor of Phage Display, George Smith, the technique has once more gained attention. However, one should not forget about the biology behind the method. Almost always ignored is how the structure of this bacterial virus is assembled. In contrast to lytic phages, filamentous phages are constantly being extruded through the bacterial membranes without lysis. Such filamentous phages are found in all aquatic environments, such as rivers and lakes, in the deep sea, in arctic ice, in hot springs and, associated with their hosts, in plants and animals including humans. While most filamentous phages infect Gram‐negative hosts, inoviruses of Gram‐positive hosts have also been described. Despite being among the minority within the phage family with an estimate of less than 5%, filamentous phages are real parasites as they exist at the expense of the host, but do not kill it. In contrast to lytic bacteriophages, filamentous phages are assembled in the host’s membrane and extruded across the cellular envelope while the bacterium continues to grow. In this review, we focus on this complex and yet poorly understood process of assembly and secretion of filamentous phages.
Waterlogging‐induced adventitious root formation in cucumber is regulated by ethylene and auxin through reactive oxygen species signalling
Authors: Qi Xiaohua , Li Qianqian , Ma Xiaotian , Qian Chunlu , Wang Huihui , Ren Nannan , Shen Chenxi , Huang Shumiao , Xu Xuewen , Xu Qiang , Chen Xuehao 
Published: December 2018

AbstractDevelopment of adventitious roots (ARs) at the base of the shoot is an important adaptation of plants to waterlogging stress; however, its physiological mechanisms remain unclear. Here, we investigated the regulation of AR formation under waterlogged conditions by hormones and reactive oxygen species (ROS) in Cucumis sativus L., an agriculturally and economically important crop in China. We found that ethylene, auxin, and ROS accumulated in the waterlogged cucumber plants. On the other hand, application of the ethylene receptor inhibitor 1‐methylcyclopropene (1‐MCP), the auxin transport inhibitor 1‐naphthylphthalamic acid (NPA), or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the number of ARs induced by waterlogging. Auxin enhanced the expression of ethylene biosynthesis genes, which led to ethylene entrapment in waterlogged plants. Both ethylene and auxin induced the generation of ROS. Auxin‐induced AR formation was inhibited by 1‐MCP, although ethylene‐induced AR formation was not inhibited by NPA. Both ethylene‐ and auxin‐induced AR formation were counteracted by DPI. These results indicate that auxin‐induced AR formation is dependent on ethylene, whereas ethylene‐induced AR formation is independent of auxin. They also show that ROS signals mediate both ethylene‐ and auxin‐induced AR formation in cucumber plants.
The reality of “food porn”: Larger brain responses to food‐related cues than to erotic images predict cue‐induced eating
Authors: Versace Francesco , Frank David W. , Stevens Elise M. , Deweese Menton M. , Guindani Michele , Schembre Susan M. 
Published: December 2018

AbstractWhile some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue‐induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food‐related cues than to erotic images are more susceptible to cue‐induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue‐induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.
Integrating a Proactive Technique Into a Holistic Cyber Risk Management Approach
Authors: Marotta Angelica , McShane Michael 
Published: December 2018

AbstractCyber threats are an emerging risk posing a range of challenges to organizations of all sizes. Corporate risk managers need to understand that cyber risk management must not be a silo in the IT department. Cyber threats are the result of intelligent adaptive agents that cannot be managed by traditional risk management techniques only. The article describes the honeypot concept, which is a proactive measure for identifying and gathering information about attackers in order to develop suitable and effective countermeasures. In addition, this article proposes the integration of the honeypot concept into a cyber risk management approach based on the five preparedness mission areas of the Federal Emergency Management Agency (FEMA).
Artificial Intelligence: Implications for Social Inflation and Insurance
Authors: Kelley Kevin H. , Fontanetta Lisa M. , Heintzman Mark , Pereira Nikki 
Published: December 2018

AbstractArtificial intelligence (AI) has the ability to enhance the insurance industry's value chain by altering relationships, reinventing business platforms, and expanding hidden data. Insurance companies will apply AI to greatly enhance large data analytics, evolve algorithms with transactional data faster, and combine data in new ways to discover better underwriting risks and appropriately price the risk of various insureds based on the true value of their business risks. This article explores how AI will have a significant impact on the workforce, jobs, and furthermore how the elimination of jobs will potentially exacerbate social equality gaps on a global scale, leading to a shift in culture and increased social inflation, thus impacting the insurance industry as well as its customers.
Bayesian Non-Parametric Survival Regression for Optimizing Precision Dosing of Intravenous Busulfan in Allogeneic Stem Cell Transplantation
Authors: Xu Yanxun , Thall Peter F. , Hua William , Andersson Borje S. 
Published: December 2018

SummaryAllogeneic stem cell transplantation is now part of standard care for acute leukaemia. To reduce toxicity of the pretransplant conditioning regimen, intravenous busulfan is usually used as a preparative regimen for acute leukaemia patients undergoing allogeneic stem cell transplantation. Systemic busulfan exposure, characterized by the area under the plasma concentration versus time curve, AUC, is strongly associated with clinical outcome. An AUC that is too high is associated with severe toxicities, whereas an AUC that is too low carries increased risks of recurrence of disease and failure to engraft. Consequently, an optimal AUC-interval needs to be determined for therapeutic use. To address the possibility that busulfan pharmacokinetics and pharmacodynamics vary significantly with patients’ characteristics, we propose a tailored approach to determine optimal covariate-specific AUC-intervals. To estimate these personalized AUC-intervals, we apply a flexible Bayesian non-parametric regression model based on a dependent Dirichlet process and Gaussian process. Our analyses of a data set of 151 patients identified optimal therapeutic intervals for AUC that varied substantively with age and whether the patient was in complete remission or had active disease at transplant. Extensive simulations to evaluate the dependent Dirichlet process–Gaussian process model in similar settings showed that its performance compares favourably with alternative methods. We provide an R package, DDPGPSurv, that implements the dependent Dirichlet process–Gaussian process model for a broad range of survival regression analyses.
Characterization of LRL5 as a key regulator of root hair growth in maize
Authors: Wang Chun‐Xia , Qi Chuang‐Ye , Luo Jin‐Hong , Liu Lin , He Yan , Chen Li‐Qun 
Published: December 2018

SummaryRoot hair, a special type of tubular‐shaped cell, outgrows from the root epidermal cell and plays important roles in the acquisition of nutrients and water, as well as interactions with biotic and abiotic stresses. Studies in the model plant Arabidopsis have revealed that root‐hair initiation and elongation are hierarchically regulated by a group of basic helix−loop−helix (bHLH) transcription factors (TFs). However, knowledge regarding the regulatory pathways of these bHLH TFs in controlling root hair growth remains limited. In this study, RNA‐seq analysis was conducted to profile the transcriptome in the elongating maize root hair and >1000 genes with preferential expression in root hair were identified. A consensus cis‐element previously featured as the potential bHLH‐TF binding sites was present in the regulatory regions for the majority of the root hair‐preferentially expressed genes. In addition, an individual change in ZmLRL5, the highest‐expressed bHLH‐TF in maize root hair resulted in a dramatic reduction in the elongation of root hair, and rendered the growth of root hair hypersensitive to translational inhibition. Moreover, RNA‐seq, yeast‐one‐hybrid and ribosome profile analysis suggested that ZmLRL5 may function as a key player in orchestrating the translational process by directly regulating the expression of translational processes/ribosomal genes during maize root hair growth.
Identification and characterization of a core set of ROS wave‐associated transcripts involved in the systemic acquired acclimation response of Arabidopsis to excess light
Authors: Zandalinas Sara I. , Sengupta Soham , Burks David , Azad Rajeev K. , Mittler Ron 
Published: December 2018

SummarySystemic acquired acclimation (SAA) plays a key role in optimizing growth and preventing damage associated with fluctuating or abrupt changes in the plant environment. To be effective, SAA has to occur at a rapid rate and depend on rapid signaling pathways that transmit signals from affected tissues to all parts of the plant. Although recent studies have identified several different rapid systemic signaling pathways that could mediate SAA, very little information is known about the extent of their involvement in mediating transcriptomic responses. Here we reveal that the systemic transcriptomic response of plants to excess light stress is extensive in its context and involves an early (2 min) and transient stage of transcript expression that includes thousands of genes. This early response is dependent on the respiratory burst oxidase homolog D protein, and the function of the reactive oxygen species (ROS) wave. We further identify a core set of transcripts associated with the ROS wave and suggest that some of these transcripts are involved in linking ROS with calcium signaling. Priming of a systemic leaf to become acclimated to a particular stress during SAA involves thousands of transcripts that display a rapid and transient expression pattern driven by the ROS wave.
Use of intravenous immunoglobulin G to treat spontaneous heparin‐induced thrombocytopenia
Authors: Irani Mehraboon , Siegal Eric , Jella Abhay , Aster Richard , Padmanabhan Anand 
Published: December 2018

BACKGROUNDSpontaneous heparin‐induced thrombocytopenia (HIT) is a rare but serious prothrombotic syndrome characterized by thrombosis, thrombocytopenia, and strong platelet‐activating HIT antibodies in the absence of heparin exposure, and is frequently characterized by a suboptimal response to standard therapies. Here, we present the first report of intravenous immunoglobulin G (IVIG) use in a patient with spontaneous HIT.STUDY DESIGN AND METHODSPatient information, including demographic, clinical, and laboratory results, were obtained from the electronic medical record. Laboratory testing was performed in the serotonin release assay, platelet factor 4 (PF4)‐dependent P‐selectin expression assay, and PF4/polyvinylsulfonate enzyme‐linked immunosorbent assay to study the impact of IVIG on HIT antibody‐mediated platelet activation. The patient was also genotyped for a polymorphism in the IgG receptor on platelets, FcγRIIa, at amino acid position 131.RESULTSA 30‐year‐old man had a thrombotic stroke and thrombocytopenia and strong HIT serologies in the absence of proximate heparin use. Direct thrombin inhibitor therapy was not associated with a prompt response. Due to severity and extent of thrombosis and persistent thrombocytopenia, he was treated with high‐dose IVIG. This treatment was associated with rapid and sustained normalization of platelet counts and a gradual improvement in thrombotic complications. Platelet activation induced by HIT antibodies in the PF4‐dependent P‐selectin expression assay (low PF4) was significantly lower after IVIG treatment, correlating well with platelet rise. Consistent with the severity of thrombosis, the patient was found to possess the 131HR polymorphism in FcγRIIa.CONCLUSIONThese results suggest that IVIG may be a useful adjunctive therapy in spontaneous HIT.
Eosinophilic cerebrospinal fluid pleocytosis associated with neural Angiostrongylus vasorum infection in a dog
Authors: Alcoverro Emili , Bersan Erika , Sanchez‐Masian Daniel , Piviani Martina 
Published: December 2018

AbstractA 1‐year‐old, female intact Pug dog was presented to the Small Animal Teaching Hospital of the University of Liverpool with a 4‐week history of progressive multifocal intracranial signs. Magnetic resonance imaging (MRI) detected multiple hemorrhagic lesions in the brain. The Baermann and zinc sulfate flotation tests with centrifugation, performed on fecal samples, were positive for lungworm larvae and an antigenic test confirmed Angiostrongylus vasorum infection. Anthelmintic treatment was started with a consequent marked clinical improvement. Seventy days later, the dog was clinically normal, and no larvae were detected on the Baermann test. Repeat MRI of the brain revealed marked improvement of the hemorrhagic lesions. Cerebrospinal fluid analysis (CSF) showed marked eosinophilic pleocytosis, and anthelmintic treatment was restarted. A follow‐up CSF analysis 4 months after the first presentation revealed resolution of the eosinophilic pleocytosis. This is the first case report of marked eosinophilic pleocytosis associated with neural A vasorum infection in a dog. The CSF eosinophilic pleocytosis persisted for several weeks after treatment, even in the absence of concurrent clinical signs and with a negative A vasorum Baermann test.
Effect of oral afoxolaner on naturally occurring infestations of peacocks by the louse Goniodes pavonis
Authors: Yarto Jaramillo Enrique , Osorio Marquez Rufino , Rangel Díaz Josué , Romero Núñez Camilo , Miranda Contreras Laura , Heredia Cardenas Rafael 
Published: December 2018

BackgroundEctoparasitism of ornamental birds, including captive species kept in zoos, represents a serious health problem. Up to 13 different species of lice have been reported to affect peacocks worldwide and heavy infestation may cause anaemia. Because of this, alternatives to the prevailing treatments have been sought including use of isoxazolines. This class of drugs has been used successfully in poultry without adverse effects on health or production.ObjectiveTo evaluate the effect of afoxolaner on the peacock louse (Goniodes pavonis).AnimalsTwenty‐three peacocks (Pavo cristatus) with naturally occurring infestation with G. pavonis.Methods and materialsThe peacocks were divided in two groups; one was treated once orally with 2.5 mg/kg afoxolaner and the other group received no treatment. Samples were collected using the acetate tape technique, for identification of lice by microscopy. Concomitantly, blood samples were taken to evaluate the haematocrit before and after the intervention.ResultsTreatment with afoxolaner significantly decreased the number of peacocks positive for lice (P = 0.02) compared to the control group, in which the number of positive birds did not decrease. The haematocrit improved in the afoxolaner‐treated group from a baseline of 46.4%–54.7% at 35 days post‐treatment, whereas it decreased in untreated birds (44.6%–40.7%). No adverse effects attributed to afoxolaner treatment were observed.Conclusions and clinical importanceOral administration of afoxolaner is an effective treatment for G. pavonis infestation of peacocks.