bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies
Authors: Oda Katsutoshi , Ikeda Yuji , Kashiyama Tomoko , Miyasaka Aki , Inaba Kanako , Fukuda Tomohiko , Asada Kayo , Sone Kenbun , Wada‐Hiraike Osamu , Kawana Kei , Osuga Yutaka , Fujii Tomoyuki 
Published: April 2016

AbstractRecent developments in genomic analysis have unveiled the key signaling pathways in human cancer. However, only a limited number of molecular‐targeted drugs are applicable for clinical use in gynecologic malignancies. TP53 signaling and phosphatidylinositol 3 kinase pathways are frequently mutated in cancer, and have received much attention as molecular targets in human cancers. In this review, we mainly focus on the functions of these pathways, and discuss the molecular‐targeted drugs under clinical trials. The molecular‐targeted drugs described in this review include dual phosphatidylinositol 3 kinase/mTOR inhibitors (NVP‐BEZ235, DS‐7423, SAR245409), an mTOR inhibitor (everolimus), an MEK inhibitor (pimasertib), an autophagy inhibitor (chloroquine), a cyclin‐dependent kinases 4/6 inhibitor (PD0332991), and a poly (ADP‐ribose) polymerase inhibitor (olaparib).
An Updated Review of Methods and Advancements in Microvascular Blood Flow Imaging
Authors: Lal Cerine , Leahy Martin J 
Published: April 2016

AbstractThere has been a consistent growth in research involving imaging of microvasculature over the past few decades. By 2008, publications mentioning the microcirculation had grown more than 2000 per annum. Many techniques have been demonstrated for the measurement of the microcirculation ranging from the earliest invasive techniques to the present high‐speed, high‐resolution noninvasive imaging techniques. Understanding the microvasculature is vital in tackling fundamental research questions as well as to understand the effects of disease progression on the physiological well‐being of an individual. We have previously provided a wide–ranging review covering most of the available techniques and their applications. In this review, we discuss the recent advances made and applications in the field of microcirculation imaging.
Comparative analysis of midgut bacterial communities in three aedine mosquito species from dengue‐endemic and non‐endemic areas ofRajasthan,India
Authors: CHARAN S. S. , PAWAR K. D. , GAVHALE S. D. , TIKHE C. V. , CHARAN N. S. , ANGEL B. , JOSHI V. , PATOLE M. S. , SHOUCHE Y. S. 
Published: April 2016

AbstractDengue viruses are transmitted to humans through the bites of infected female aedine mosquitoes. Differences in the composition and structure of bacterial communities in the midguts of mosquitoes may affect the vector's ability to transmit the disease. To investigate and analyse the role of midgut bacterial communities in viral transmission, midgut bacteria from three species, namelyStegomyia aegypti(=Aedes aegypti),Fredwardsius vittatus(=Aedes vittatus) andStegomyia albopicta(=Aedes albopictus) (all:Diptera:Culicidae), from dengue‐endemic and non‐endemic areas ofRajasthan,India were compared. Construction and analyses of six16S rRNAgene libraries indicated thatSerratiaspp.‐related phylotypes dominated all clone libraries of the three mosquito species from areas in which dengue is not endemic. In dengue‐endemic areas, phylotypes related toAeromonas,Enhydrobacterspp. and uncultivated bacterium dominated the clone libraries ofS.aegypti,F. vittatusandS. albopicta, respectively. Diversity indices analysis and real‐timeTaqManpolymerase chain reaction assays showed bacterial diversity and abundance in the midguts ofS.aegyptito be higher than in the other two species. Significant differences observed among midgut bacterial communities of the three mosquito species from areas in which dengue is and is not endemic, respectively, may be related to the vectorial capacity of mosquitoes to carry dengue viruses and, hence, to the prevalence of disease in some areas.
The role of fungal parasites in tri‐trophic interactions involving lichens and lichen‐feeding snails
Authors: Asplund Johan , Gauslaa Yngvar , Merinero Sonia 
Published: April 2016

Summary

Lichens are hosts for a variety of lichenicolous fungi. By investigating two lichens with specialized parasites, we will test the hypothesis that these parasites reduce lichen fitness by increasing the palatability of their respective hosts.

The palatability of Lobarina scrobiculata and Lobaria pulmonaria with or without galls of the lichenicolous fungi, Plectocarpon scrobiculatae and P. lichenum, respectively, were quantified in a feeding‐preference experiment with grazing snails (Cepaea hortensis). We repeated the experiment for pairs with or without gall in which the carbon‐based secondary compounds (CBSCs) had been reduced nondestructively by acetone rinsing.

Lichens with galls had lower concentration of CBSCs than those without, but this contrast disappeared after acetone rinsing. In the lichen high in nitrogen (N) (the cyanolichen L. scrobiculata), the grazing was low, and the snails did not discriminate between specimens with and without Plectocarpon‐galls. In L. pulmonaria low in N (green algae as main photobiont), the parasite reduced the lichen C : N ratio and the snails strongly preferred specimens with Plectocarpon‐galls, regardless of whether CBSC concentration had been reduced or not.

In conclusion, some lichen parasites can indirectly reduce lichen fitness by increasing its palatability and thus the grazing pressure from snails, whereas other parasites do not affect grazing preferences.
Emotional response to a therapeutic technique: The social Broad Minded Affective Coping
Authors: Holden Natasha , Kelly James , Welford Mary , Taylor Peter J. 
Published: April 2016

ObjectivesIt has been suggested that savouring positive memories can generate positive emotions. Increasing positive emotion can have a range of benefits including reducing attention to and experiences of threat. This study investigated individuals' emotional reactions to a guided mental imagery task focussing on positive social memory called the ‘social Broad Minded Affective Coping (BMAC)’ technique. The study examined possible predictors of individuals’ responses to this intervention.MethodAn internet‐based, within‐group, repeated‐measures design was used. One hundred and twenty‐three participants completed self‐report measures of self‐attacking and social safeness/pleasure. They were then guided through the socialBMAC. Participants completed state measures of positive and negative affect and social safeness/pleasure before and after the intervention. Forty‐nine participants took part in a 2‐week follow‐up.ResultsIt was found that safe/warm positive affect, relaxed positive affect and feelings of social safeness increased following the socialBMAC, whilst negative affect decreased. In addition, it was found that people scoring higher on inadequate self‐attacking benefited most from this intervention. Changes in affect were not maintained at the 2‐week follow‐up.ConclusionThe results provide preliminary support for the efficacy of the socialBMACin activating specific types of mood (those associated with safeness rather than drive/reward). This task has potential as part of therapeutic interventions directed at clinical groups, but further evaluation is needed.Practitioner pointsThe social Broad Minded Affective Coping (BMAC) was related to improvements in forms of positive affect linked to the affiliative system.This task may be helpful in inducing these positive mood states within therapy.Further evaluation comparing theBMACto a control task is needed.Individuals with a greater fear of compassion or more hated‐self‐criticism may gain less from the task, although effects were small.
Genetic analysis of resistance to tomato late blight in Solanum pimpinellifolium accession PI 163245
Authors: Ohlson Erik W. , Foolad Majid R. 
Published: April 2016

AbstractLate blight (LB), caused by Phytophthora infestans, is one of the most devastating diseases of tomato (Solanum lycopersicum) worldwide. Due to the emergence of new and aggressive P. infestans isolates, identifying new genetic resistance to LB is a priority in tomato breeding. Recently, we reported the identification of several Solanum pimpinellifolium accessions with strong LB resistance. In this study, we investigated the utility of resistant accession PI 163245 for tomato breeding by examining heritability (h2) of resistance and the response to selection for resistance. Estimates of h2 based on F2 : F3 and F3 : F4 parent : offspring correlation analyses averaged 0.79 and 0.94, respectively, suggesting the heritable nature of LB resistance in PI 163245. Analysis of response to selection for resistance from F2 to F4 generations indicated a realized h2 of 0.63, confirming the utility of this resistance in tomato breeding. Two methods of estimating the minimum number of loci involved indicated the presence of one major resistance locus. Currently, genetic mapping and breeding efforts are underway to further confirm the viability of this accession for improving tomato LB resistance.
Promotion of Proapoptotic Signals by Lysosomal Photodamage: Mechanistic Aspects and Influence of Autophagy
Authors: Kessel David , Evans Conor L. 
Published: April 2016

AbstractPrior studies demonstrated that a low level (LD10–15) of lysosomal photodamage can sensitize cells to the apoptotic death that results from subsequent mitochondrial photodamage. We have proposed that this process occurs via a calpain‐catalyzed cleavage of the autophagy‐associated protein ATG5 to form a proapoptotic fragment. In this report, we provide evidence for the postulated ATG5 cleavage and show that the sequential photodynamic therapy (PDT) protocol can also partly overcome the adverse effect of hypoxia on the initiation of apoptosis. While autophagy can offer cytoprotection after mitochondrial photodamage, this does not appear to apply when lysosomes are the target. This may account for the ability of very low PDT doses directed at lysosomes to evoke ATG5 cleavage. The resulting proapoptotic effect overcomes intrinsic cytoprotection from mitochondrial photodamage along with a further stimulation of phototoxicity.
Dormancy induction by summer temperatures and/or desiccation in imbibed seeds of trumpet daffodils Narcissus alcaracensis and N. longispathus (Amaryllidaceae)
Authors: Herranz J. M. , Copete E. , Copete M. A. , Márquez J. , Ferrandis P. 
Published: April 2016

AbstractWe analysed the effects of summer temperatures (28/14 °C) and/or desiccation (from 48% to 8% humidity) on imbibed Narcissus alcaracensis and N. longispathus seeds with an elongating embryo. In the N. alcaracensis seeds that overcame dormancy (embryo elongation = 27.14%), exposure to high temperatures induced secondary dormancy and reduced subsequent embryo growth. A further 3‐month cold stratification (5 °C) was required to break secondary dormancy. Desiccation in early embryo growth stages (elongation = 11.42%) also reduced germination. Desiccation in the seeds in a more advanced growth stage (i.e. embryo elongation = 27.14%) induced secondary dormancy, which the further 3‐month cold stratification did not overcome. When desiccation was preceded by high temperatures, seeds better overcame secondary dormancy (i.e. longer embryo elongation and seed germination). Treatments did not affect seed viability. In the N. longispathus seeds that overcame dormancy (embryo elongation = 59.21%), exposure to high temperatures induced secondary dormancy and they needed a further 1‐month stratification at 15/4 °C + 2 months at 5 °C to reactivate the germination process. When embryo elongation was 42.10%, seed desiccation totally impeded subsequent germination. When embryo elongation reached 59.21%, desiccation induced secondary dormancy, which was not overcome by the above‐described stratification treatment. When desiccation was preceded by high temperatures, seeds better overcame dormancy. Stress treatments killed 5–10% of seeds. This study suggests that the seeds of species with complex morphophysiological dormancy (MPD) levels are sensitive to desiccation in early embryo development stages, as opposed to the seeds of species with deep simple epicotyl MPD, which better tolerate water stress.
Long‐Term Effects of the Family Check‐Up in Early Adolescence on Risk of Suicide in Early Adulthood
Authors: Connell Arin M. , McKillop Hannah N. , Dishion Thomas J. 
Published: April 2016

The impact of the Family Check‐Up (FCU), a school‐based prevention program, as delivered in public secondary schools on suicide risk across adolescence, was examined. Students were randomly assigned to a family‐centered intervention (N = 998) in the sixth grade and offered a multilevel intervention that included (1) a universal classroom‐based intervention, (2) the FCU (Dishion, Stormshak, & Kavanagh, 2011), and (3) family management treatment. Engagement with the FCU predicted significant reductions in suicide risk across adolescence and early adulthood.
Oral quercetin administration transiently protects respiratory function in dystrophin‐deficient mice
Authors: Selsby Joshua T. , Ballmann Christopher G. , Spaulding Hannah R. , Ross Jason W. , Quindry John C. 
Published: April 2016

Key point
PGC‐1α pathway activation has been shown to decrease disease severity and can be driven by quercetin.
Oral quercetin supplementation protected respiratory function for 4–6 months during a 12 month dosing regimen.
This transient protection was probably due to a failure to sustain elevated SIRT1 activity and downstream PGC‐1α signalling.
Quercetin supplementation may be a beneficial treatment as part of a cocktail provided continued SIRT1 activity elevation is achieved.
AbstractDuchenne muscular dystrophy (DMD) impacts 1 : 3500 boys and leads to muscle dysfunction culminating in death due to respiratory or cardiac failure. There is an urgent need for effective therapies with the potential for immediate application for this patient population. Quercetin, a flavonoid with an outstanding safety profile, may provide therapeutic relief to DMD patients as the wait for additional therapies continues. This study evaluated the capacity of orally administered quercetin (0.2%) in 2 month old mdx mice to improve respiratory function and end‐point functional and histological outcomes in the diaphragm following 12 months of treatment. Respiratory function was protected for the first 4–6 months of treatment but appeared to become insensitive to quercetin thereafter. Consistent with this, end‐point functional measures were decreased and histopathological measures were more severe in dystrophic muscle compared to C57 and similar between control‐fed and quercetin‐fed mdx mice. To better understand the transient nature of improved respiratory function, we measured PGC‐1α pathway activity, which is suggested to be up‐regulated by quercetin supplementation. This pathway was largely suppressed in dystrophic muscle compared to healthy muscle, and at the 14 month time point dietary quercetin enrichment did not increase expression of downstream effectors. These data support the efficacy of quercetin as an intervention for DMD in skeletal muscle, and also indicate the development of age‐dependent quercetin insensitivity when continued supplementation fails to drive the PGC‐1α pathway. Continued study is needed to determine if this is related to disease severity, age or other factors.
Train stimulation of parallel fibre to Purkinje cell inputs reveals two populations of synaptic responses with different receptor signatures
Authors: Devi Suma Priya Sudarsana , Howe James R. , Auger Céline 
Published: April 2016

Key points
Purkinje cells of the cerebellum receive ∼180,000 parallel fibre synapses, which have often been viewed as a homogeneous synaptic population and studied using single action potentials.
Many parallel fibre synapses might be silent, however, and granule cells in vivo fire in bursts. Here, we used trains of stimuli to study parallel fibre inputs to Purkinje cells in rat cerebellar slices.
Analysis of train EPSCs revealed two synaptic components, phase 1 and 2. Phase 1 is initially large and saturates rapidly, whereas phase 2 is initially small and facilitates throughout the train. The two components have a heterogeneous distribution at dendritic sites and different pharmacological profiles.
The differential sensitivity of phase 1 and phase 2 to inhibition by pentobarbital and NBQX mirrors the differential sensitivity of AMPA receptors associated with the transmembrane AMPA receptor regulatory protein, γ‐2, gating in the low‐ and high‐open probability modes, respectively.
AbstractCerebellar granule cells fire in bursts, and their parallel fibre axons (PFs) form ∼180,000 excitatory synapses onto the dendritic tree of a Purkinje cell. As many as 85% of these synapses have been proposed to be silent, but most are labelled for AMPA receptors. Here, we studied PF to Purkinje cell synapses using trains of 100 Hz stimulation in rat cerebellar slices. The PF train EPSC consisted of two components that were present in variable proportions at different dendritic sites: one, with large initial EPSC amplitude, saturated after three stimuli and dominated the early phase of the train EPSC; and the other, with small initial amplitude, increased steadily throughout the train of 10 stimuli and dominated the late phase of the train EPSC. The two phases also displayed different pharmacological profiles. Phase 2 was less sensitive to inhibition by NBQX but more sensitive to block by pentobarbital than phase 1. Comparison of synaptic results with fast glutamate applications to recombinant receptors suggests that the high‐open‐probability gating mode of AMPA receptors containing the auxiliary subunit transmembrane AMPA receptor regulatory protein γ‐2 makes a substantial contribution to phase 2. We argue that the two synaptic components arise from AMPA receptors with different functional signatures and synaptic distributions. Comparisons of voltage‐ and current‐clamp responses obtained from the same Purkinje cells indicate that phase 1 of the EPSC arises from synapses ideally suited to transmit short bursts of action potentials, whereas phase 2 is likely to arise from low‐release‐probability or ‘silent’ synapses that are recruited during longer bursts.
Offline Predictive Control of Out-of-Plane Shape Deformation for Additive Manufacturing
Authors: Jin Yuan , Joe Qin S. , Huang Qiang 
Published: April 2016

Abstract
Additive manufacturing (AM) is a promising direct manufacturing technology, and the geometric accuracy of AM built products is crucial to fulfill the promise of AM. Prediction and control of three-dimensional (3D) shape deformation, particularly out-of-plane geometric errors of AM built products, have been a challenging task. Although finite-element modeling has been extensively applied to predict 3D deformation and distortion, improving part accuracy based purely on such simulation still needs significant methodology development. We have been establishing an alternative strategy that can be predictive and transparent to specific AM processes based on a limited number of test cases. Successful results have been accomplished in our previous work to control in-plane (x–y plane) shape deformation through offline compensation. In this study, we aim to establish an offline out-of-plane shape deformation control approach based on limited trials of test shapes. We adopt a novel spatial deformation formulation in which both in-plane and out-of-plane geometric errors are placed under a consistent mathematical framework to enable 3D accuracy control. Under this new formulation of 3D shape deformation, we develop a prediction and offline compensation method to reduce out-of-plane geometric errors. Experimental validation is successfully conducted to validate the developed 3D shape accuracy control approach.
Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition
Authors: Landeras-Bueno Sara , Fernández Yolanda , Falcón Ana , Oliveros Juan Carlos , Ortín Juan 
Published: April 2016

ABSTRACTInfluenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and the economy. Therefore, a large effort has been devoted to the development of new anti-influenza virus drugs directed to viral targets, as well as to the identification of cellular targets amenable to anti-influenza virus therapy. Here we have addressed the identification of such potential cellular targets by screening collections of drugs approved for human use. We reasoned that screening with a green fluorescent protein-based recombinant replicon system would identify cellular targets involved in virus transcription/replication and/or gene expression and hence address an early stage of virus infection. By using such a strategy, we identified Montelukast (MK) as an inhibitor of virus multiplication. MK inhibited virus gene expression but did not alter viral RNA synthesisin vitroor viral RNA accumulationin vivo. The low selectivity index of MK prevented its use as an antiviral, but it was sufficient to identify a new cellular pathway suitable for anti-influenza virus intervention. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated with MK or left untreated, we showed that it stimulates the PERK-mediated unfolded protein stress response. The phosphorylation of PERK was partly inhibited in virus-infected cells but stimulated in MK-treated cells. Accordingly, pharmacological inhibition of PERK phosphorylation led to increased viral gene expression, while inhibition of PERK phosphatase reduced viral protein synthesis. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection.IMPORTANCEInfluenza A viruses are responsible for annual epidemics and occasional pandemics with important consequences for human health and the economy. The unfolded protein response is a defense mechanism fired by cells when the demand of protein synthesis and folding is excessive, for instance, during an acute virus infection. In this report, we show that influenza virus downregulates the unfolded protein response mediated by the PERK sensor, while Montelukast, a drug used to treat asthma in humans, specifically stimulated this response and downregulated viral protein synthesis and multiplication. Accordingly, we show that PERK phosphorylation was reduced in virus-infected cells and increased in cells treated with Montelukast. Hence, our studies suggest that modulation of the PERK-mediated unfolded protein response is a target for influenza virus inhibition.