bluuebunny/crossref_metadata_2025 huggingface dataset:
The cross-national epidemiology of specific phobia in the World Mental Health Surveys
Authors: Wardenaar K. J. , Lim C. C. W. , Al-Hamzawi A. O. , Alonso J. , Andrade L. H. , Benjet C. , Bunting B. , de Girolamo G. , Demyttenaere K. , Florescu S. E. , Gureje O. , Hisateru T. , Hu C. , Huang Y. , Karam E. , Kiejna A. , Lepine J. P. , Navarro-Mateu F. , Oakley Browne M. , Piazza M. , Posada-Villa J. , ten Have M. L. , Torres Y. , Xavier M. , Zarkov Z. , Kessler R. C. , Scott K. M. , de Jonge P.
Published: February 2017

Background

Although specific phobia is highly prevalent, associated with impairment, and an important risk factor for the development of other mental disorders, cross-national epidemiological data are scarce, especially from low- and middle-income countries. This paper presents epidemiological data from 22 low-, lower-middle-, upper-middle- and high-income countries.

Method

Data came from 25 representative population-based surveys conducted in 22 countries (2001–2011) as part of the World Health Organization World Mental Health Surveys initiative (n = 124 902). The presence of specific phobia as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition was evaluated using the World Health Organization Composite International Diagnostic Interview.

Results

The cross-national lifetime and 12-month prevalence rates of specific phobia were, respectively, 7.4% and 5.5%, being higher in females (9.8 and 7.7%) than in males (4.9% and 3.3%) and higher in high- and higher-middle-income countries than in low-/lower-middle-income countries. The median age of onset was young (8 years). Of the 12-month patients, 18.7% reported severe role impairment (13.3–21.9% across income groups) and 23.1% reported any treatment (9.6–30.1% across income groups). Lifetime co-morbidity was observed in 60.5% of those with lifetime specific phobia, with the onset of specific phobia preceding the other disorder in most cases (72.6%). Interestingly, rates of impairment, treatment use and co-morbidity increased with the number of fear subtypes.

Conclusions

Specific phobia is common and associated with impairment in a considerable percentage of cases. Importantly, specific phobia often precedes the onset of other mental disorders, making it a possible early-life indicator of psychopathology vulnerability.
A constraint-based approach for planning unmanned aerial vehicle activities
Authors: Guettier Christophe , Lucas François
Published: February 2017

Unmanned Aerial Vehicles (UAV) represent a major advantage in defense, disaster relief and first responder applications. UAV may provide valuable information on the environment if their Command and Control (C2) is shared by different operators. In a C2 networking system, any operator may request and use the UAV to perform a remote sensing operation. These requests have to be scheduled in time and a consistent navigation plan must be defined for the UAV. Moreover, maximizing UAV utilization is a key challenge for user acceptance and operational efficiency. The global planning problem is constrained by the environment, targets to observe, user availability, mission duration and on-board resources. This problem follows previous research works on automatic mission Planning & Scheduling for defense applications. The paper presents a full constraint-based approach to simultaneously satisfy observation requests, and resolve navigation plans.
Introduction to the special issue on constraint satisfaction for planning and scheduling
Authors: Salido Miguel A. , Barták Roman
Published: February 2017

The areas of Artificial Intelligence planning and scheduling have seen important advances thanks to the application of constraint satisfaction models and techniques. Especially, solutions to many real-world problems need to integrate plan synthesis capabilities with resource allocation, which can be efficiently managed by using constraint satisfaction techniques. Constraint satisfaction plays an important role in solving such real life problems, and integrated techniques that manage planning and scheduling with constraint satisfaction are particularly useful.
Milk kefir: nutritional, microbiological and health benefits
Authors: Rosa Damiana D. , Dias Manoela M. S. , Grześkowiak Łukasz M. , Reis Sandra A. , Conceição Lisiane L. , Peluzio Maria do Carmo G.
Published: February 2017

Kefir is fermented milk produced from grains that comprise a specific and complex mixture of bacteria and yeasts that live in a symbiotic association. The nutritional composition of kefir varies according to the milk composition, the microbiological composition of the grains used, the time/temperature of fermentation and storage conditions. Kefir originates from the Caucasus and Tibet. Recently, kefir has raised interest in the scientific community due to its numerous beneficial effects on health. Currently, several scientific studies have supported the health benefits of kefir, as reported historically as a probiotic drink with great potential in health promotion, as well as being a safe and inexpensive food, easily produced at home. Regular consumption of kefir has been associated with improved digestion and tolerance to lactose, antibacterial effect, hypocholesterolaemic effect, control of plasma glucose, anti-hypertensive effect, anti-inflammatory effect, antioxidant activity, anti-carcinogenic activity, anti-allergenic activity and healing effects. A large proportion of the studies that support these findings were conducted in vitro or in animal models. However, there is a need for systematic clinical trials to better understand the effects of regular use of kefir as part of a diet, and for their effect on preventing diseases. Thus, the present review focuses on the nutritional and microbiological composition of kefir and presents relevant findings associated with the beneficial effects of kefir on human and animal health.
Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges
Authors: Jeanes Yvonne M. , Reeves Sue
Published: February 2017

Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.
Modelling seed germination response to temperature inEucalyptusL'Her. (Myrtaceae) species in the context of global warming
Authors: Cochrane Anne
Published: February 2017

Seed germination is vital for persistence of many plant species, and is linked to local environmental conditions. Small increases in temperature during this critical life history transition may threaten species by altering germination timing and success. Such changes in turn may influence population dynamics, community composition and the geographic distributions of species. In this investigation, a bi-directional temperature gradient plate was used to profile thermal constraints for germination in 26 common, threatened and geographically restrictedEucalyptusspecies (Myrtaceae) from southern Western Australia. These observed data were used to populate models to predict optimum germination responses (mean time to germination, germination timing and success) under current (1950–2000 averages) and future (2070 high greenhouse gas emission climate scenario) mean monthly minimum and maximum temperatures. Many species demonstrated wide physiological tolerance for high germination temperatures and an ability to germinate outside current and forecast future autumn–winter wet season temperatures, suggesting that climatic distribution is a poor proxy for thermal tolerance forEucalyptusseed germination. Germination for some species is predicted to decline under forecast conditions, but the majority will maintain or improve germination particularly during the cooler winter months of the year. Although thermal tolerance may benefit persistence of manyEucalyptusspecies in southern Western Australia as warming becomes more severe, large rainfall declines are also forecast which may prove more detrimental to plant survival. Nonetheless, this framework has the potential to identify seed resilience to heat stress in an early life history phase and hence species vulnerability to one characteristic of forecast environmental change.
Store-directed price promotions and communications strategies improve healthier food supply and demand: impact results from a randomized controlled, Baltimore City store-intervention trial
Authors: Budd Nadine , Jeffries Jayne K , Jones-Smith Jessica , Kharmats Anna , McDermott Ann Yelmokas , Gittelsohn Joel
Published: February 2017

Objective

Small food store interventions show promise to increase healthy food access in under-resourced areas. However, none have tested the impact of price discounts on healthy food supply and demand. We tested the impact of store-directed price discounts and communications strategies, separately and combined, on the stocking, sales and prices of healthier foods and on storeowner psychosocial factors.

Design

Factorial design randomized controlled trial.

Setting

Twenty-four corner stores in low-income neighbourhoods of Baltimore City, MD, USA.

Subjects

Stores were randomized to pricing intervention, communications intervention, combined pricing and communications intervention, or control. Stores that received the pricing intervention were given a 10–30 % price discount by wholesalers on selected healthier food items during the 6-month trial. Communications stores received visual and interactive materials to promote healthy items, including signage, taste tests and refrigerators.

Results

All interventions showed significantly increased stock of promoted foodsv. control. There was a significant treatment effect for daily unit sales of healthy snacks (β=6·4, 95 % CI 0·9, 11·9) and prices of healthy staple foods (β=–0·49, 95 % CI –0·90, –0·03) for the combined groupv. control, but not for other intervention groups. There were no significant intervention effects on storeowner psychosocial factors.

Conclusions

All interventions led to increased stock of healthier foods. The combined intervention was effective in increasing sales of healthier snacks, even though discounts on snacks were not passed to the consumer. Experimental research in small stores is needed to understand the mechanisms by which store-directed price promotions can increase healthy food supply and demand.
Dietary advice provided to those undergoing pelvic radiotherapy
Authors: Pallin Nickola , Richardson Jane
Published: February 2017

Background

In those receiving radiotherapy for pelvic cancers, up to 80% develop gastrointestinal symptoms, with dietary interventions recommended to reduce these symptoms. However, research outlining the current dietary support provided to patients undergoing radiotherapy for pelvic cancer is lacking.

Aim

To identify the gastrointestinal symptoms experienced by those undergoing pelvic radiotherapy and to identify the dietary support provided to these patients.

Methods and materials

A service evaluation was undertaken in one NHS Trust hospital whereby patients undergoing radical pelvic radiotherapy during a 15-week recruitment period were invited to complete an anonymous questionnaire. Participants were recruited using purposive sampling and the data were analysed descriptively using SPSS.

Results

In total, 31 patients responded achieving a response rate of 48%. The most frequent reported gastrointestinal symptoms were gas and flatulence followed by diarrhoea, nausea and abdominal pain. The main dietary changes implemented by the respondents and recommended by health care professionals included reducing fibre intake, reducing certain vegetables, reducing caffeine and increasing water.

Findings

The results illustrate the impact of gastrointestinal side effects on patients’ dietary intake. The results highlight that nutritional guidance need to be standardised, especially for the management of diarrhoea and gas and flatulence as these were the most common occurring side effects. With radiographers most frequently giving nutritional advice they must be provided with guidance to support those undergoing pelvic radiotherapy.
Quantum criticality at the superconductor-insulator transition revealed by specific heat measurements
Authors: Poran S. , Nguyen-Duc T. , Auerbach A. , Dupuis N. , Frydman A. , Bourgeois Olivier
Published: February 2017

The superconductor–insulator transition (SIT) is considered an excellent example of a quantum phase transition that is driven by quantum fluctuations at zero temperature. The quantum critical point is characterized by a diverging correlation length and a vanishing energy scale. Low-energy fluctuations near quantum criticality may be experimentally detected by specific heat, cp, measurements. Here we use a unique highly sensitive experiment to measure cp of two-dimensional granular Pb films through the SIT. The specific heat shows the usual jump at the mean field superconducting transition temperature "Equation missing" marking the onset of Cooper pairs formation. As the film thickness is tuned towards the SIT, "Equation missing" is relatively unchanged, while the magnitude of the jump and low-temperature specific heat increase significantly. This behaviour is taken as the thermodynamic fingerprint of quantum criticality in the vicinity of a quantum phase transition.
Dynamical barrier and isotope effects in the simplest substitution reaction via Walden inversion mechanism
Authors: Zhao Zhiqiang , Zhang Zhaojun , Liu Shu , Zhang Dong H
Published: February 2017

Reactions occurring at a carbon atom through the Walden inversion mechanism are one of the most important and useful classes of reactions in chemistry. Here we report an accurate theoretical study of the simplest reaction of that type: the H+CH4 substitution reaction and its isotope analogues. It is found that the reaction threshold versus collision energy is considerably higher than the barrier height. The reaction exhibits a strong normal secondary isotope effect on the cross-sections measured above the reaction threshold, and a small but reverse secondary kinetic isotope effect at room temperature. Detailed analysis reveals that the reaction proceeds along a path with a higher barrier height instead of the minimum-energy path because the umbrella angle of the non-reacting methyl group cannot change synchronously with the other reaction coordinates during the reaction due to insufficient energy transfer from the translational motion to the umbrella mode.
Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
Authors: Burk Katja , Mire Erik , Bellon Anaïs , Hocine Mélanie , Guillot Jeremy , Moraes Filipa , Yoshida Yutaka , Simons Michael , Chauvet Sophie , Mann Fanny
Published: February 2017

Local endocytic events involving receptors for axon guidance cues play a central role in controlling growth cone behaviour. Yet, little is known about the fate of internalized receptors, and whether the sorting events directing them to distinct endosomal pathways control guidance decisions. Here, we show that the receptor Plexin-D1 contains a sorting motif that interacts with the adaptor protein GIPC1 to facilitate transport to recycling endosomes. This sorting process promotes colocalization of Plexin-D1 with vesicular pools of active R-ras, leading to its inactivation. In the absence of interaction with GIPC1, missorting of Plexin-D1 results in loss of signalling activity. Consequently, Gipc1 mutant mice show specific defects in axonal projections, as well as vascular structures, that rely on Plexin-D1 signalling for their development. Thus, intracellular sorting steps that occur after receptor internalization by endocytosis provide a critical level of control of cellular responses to guidance signals.
Allograft inflammatory factor 1 is a regulator of transcytosis in M cells
Authors: Kishikawa Sari , Sato Shintaro , Kaneto Satoshi , Uchino Shigeo , Kohsaka Shinichi , Nakamura Seiji , Kiyono Hiroshi
Published: February 2017

M cells in follicle-associated epithelium (FAE) are specialized antigen-sampling cells that take up intestinal luminal antigens. Transcription factor Spi-B regulates M-cell maturation, but the molecules that promote transcytosis within M cells are not fully identified. Here we show that mouse allograft inflammatory factor 1 (Aif1) is expressed by M cells and contributes to M-cell transcytosis. FAE in Aif1−/− mice has suppressed uptake of particles and commensal bacteria, compared with wild-type mice. Translocation of Yersinia enterocolitica, but not of Salmonella enterica serovar Typhimurium, leading to the generation of antigen-specific IgA antibodies, is also diminished in Aif1-deficient mice. Although β1 integrin, which acts as a receptor for Y. enterocolitica via invasin protein, is expressed on the apical surface membranes of M cells, its active form is rarely found in Aif1−/− mice. These findings show that Aif1 is important for bacterial and particle transcytosis in M cells.
Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses
Authors: Toyama Yuki , Kano Hanaho , Mase Yoko , Yokogawa Mariko , Osawa Masanori , Shimada Ichio
Published: February 2017

Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation.
Identification of protein biomarkers and signaling pathways associated with prostate cancer radioresistance using label-free LC-MS/MS proteomic approach
Authors: Chang Lei , Ni Jie , Beretov Julia , Wasinger Valerie C. , Hao Jingli , Bucci Joseph , Malouf David , Gillatt David , Graham Peter H. , Li Yong
Published: February 2017

Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ≤ 0.05, fold differences >1.5, ≥80% power). Among these proteins, nineteen are common among three paired CaP cell lines and associated with metastasis, progression and radioresistance. The PI3K/Akt, VEGF and glucose metabolism pathways were identified as the main pathways associated with CaP radioresistance. In addition, the identified potential protein markers were further validated in CaP-RR cell lines and subcutaneous (s.c) animal xenografts by western blotting and immunohistochemistry, respectively and protein aldolase A (ALDOA) was selected for a radiosensitivity study. We found the depletion of ALDOA combined with radiotherapy effectively reduced colony formation, induced more apoptosis and increased radiosensitivity in CaP-RR cells. Our findings indicate that CaP radioresistance is caused by multifactorial traits and downregulation of ALDOA increases radiosensitivity in CaP-RR cells, suggesting that controlling these identified proteins or signaling pathways in combination with radiotherapy may hold promise to overcome CaP radioresistance.
Correction: Corrigendum: Glomerular filtration rate in patients with atrial fibrillation and 1-year outcomes
Authors: Boriani Giuseppe , Laroche Cécile , Diemberger Igor , Popescu Mircea Ioachim , Rasmussen Lars Hvilsted , Petrescu Lucian , Crijns Harry J. G. M. , Tavazzi Luigi , Maggioni Aldo P. , Lip Gregory Y. H.
Published: February 2017

Scientific Reports 6: Article number: 30271; published online: 28 July 2016; updated: 22 February 2017 This Article contains errors in the Acknowledgements section: “Abbott Vascular Int. (2011–2014), Amgen (2012–2018), AstraZeneca (2014–2017), Bayer (2013–2018), Boehringer Ingelheim (2013–2016), Boston Scientific (2010–2012), The Bristol Myers Squibb and Pfizer Alliance (2014–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Gedeon Richter Plc.
TRPV1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation
Authors: He Lin-Hai , Liu Meng , He Yang , Xiao E. , Zhao Lu , Zhang Ting , Yang Hua-Qian , Zhang Yi
Published: February 2017

Fracture healing, in which osteoclasts and osteoblasts play important roles, has drawn much clinical attention. Osteoclast deficiency or decreased osteoblast activity will impair fracture healing. TRPV1 is a member of the Ca2+ permeable cation channel subfamily, and pharmacological inhibition of TRPV1 prevents ovariectomy-induced bone loss, which makes TRPV1 a potential target for osteoporosis. However, whether long term TRPV1 inhibition or TRPV1 deletion will affect the fracture healing process is unclear. In this study, we found that the wild-type mice showed a well-remodeled fracture callus, whereas TRPV1 knockout mice still had an obvious fracture gap with unresorbed soft-callus 4 weeks post-fracture. The number of osteoclasts was reduced in the TRPV1 knockout fracture callus, and osteoclast formation and resorption activity were also impaired in vitro. TRPV1 deletion decreased the calcium oscillation frequency and peak cytoplasmic concentration in osteoclast precursors, subsequently reducing the expression and nuclear translocation of NFATc1 and downregulating DC-stamp, cathepsin K, and ATP6V. In addition, TRPV1 deletion caused reduced mRNA and protein expression of Runx2 and ALP in bone marrow stromal cells (BMSCs) and reduced calcium deposition in vitro. Our results suggest that TRPV1 deletion impairs fracture healing, and inhibited osteoclastogenesis and osteogenesis.
Correction: Corrigendum: Succeed escape: Flow shear promotes tumbling of Escherichia coli near a solid surface
Authors: Molaei Mehdi , Sheng Jian
Published: February 2017

Scientific Reports 6: Article number: 35290; published online: 18 October 2016; updated on: 22 February 2017 The Acknowledgements section in this Article is incomplete. “Research was supported in part by NSF under the grant no. CBET-1341901, NIH under the grant no. 1-R21-EB008844-01, and GoMRI (Gulfof Mexico Research Initiatives) under the grant no.
Transcriptomic responses of the olive fruit fly Bactrocera oleae and its symbiont Candidatus Erwinia dacicola to olive feeding
Authors: Pavlidi Nena , Gioti Anastasia , Wybouw Nicky , Dermauw Wannes , Ben-Yosef Michael , Yuval Boaz , Jurkevich Edouard , Kampouraki Anastasia , Van Leeuwen Thomas , Vontas John
Published: February 2017

The olive fruit fly,Bactrocera oleae, is the most destructive pest of olive orchards worldwide. The monophagous larva has the unique capability of feeding on olive mesocarp, coping with high levels of phenolic compounds and utilizing non-hydrolyzed proteins present, particularly in the unripe, green olives. On the molecular level, the interaction betweenB. oleaeand olives has not been investigated as yet. Nevertheless, it has been associated with the gut obligate symbiotic bacteriumCandidatus Erwinia dacicola. Here, we used aB.oleaemicroarray to analyze the gene expression of larvae during their development in artificial diet, unripe (green) and ripe (black) olives. The expression profiles ofCa. E. dacicolawere analyzed in parallel, using the Illumina platform. Several genes were found overexpressed in the olive fly larvae when feeding in green olives. Among these, a number of genes encoding detoxification and digestive enzymes, indicating a potential association with the ability ofB. oleaeto cope with green olives. In addition, a number of biological processes seem to be activated inCa. E. dacicoladuring the development of larvae in olives, with the most notable being the activation of amino-acid metabolism.
Topologically protected localised states in spin chains
Authors: Estarellas Marta P. , D’Amico Irene , Spiller Timothy P.
Published: February 2017

We consider spin chain families inspired by the Su, Schrieffer and Hegger (SSH) model. We demonstrate explicitly the topologically induced spatial localisation of quantum states in our systems. We present detailed investigations of the effects of random noise, showing that these topologically protected states are very robust against this type of perturbation. Systems with such topological robustness are clearly good candidates for quantum information tasks and we discuss some potential applications. Thus, we present interesting spin chain models which show promising applications for quantum devices.
Nonreciprocal nonlinear wave scattering by loss-compensated active hyperbolic structures
Authors: Shramkova O. V. , Tsironis G. P.
Published: February 2017

The combinatorial frequency generation (CFG) in active periodic semiconductor-dielectric structures has been explored through illumination by a pair of pump waves with dissimilar frequencies and incidence angles. We study the influence of gain on linear refraction properties of the stack and on the efficiency of the mixing processes by the system with the resistive character of nonlinearity. We demonstrate that the introduction of gain dielectric material inside the stack not only compensates for losses caused by the collisions of the electrons in semiconductor media but also improves the efficiency of the CFG. We show that in systems with weak asymmetry of linear response we can get significant nonreciprocity of nonlinear interaction.
Variable salinity responses of 12 alfalfa genotypes and comparative expression analyses of salt-response genes
Authors: Sandhu Devinder , Cornacchione Monica V. , Ferreira Jorge F. S. , Suarez Donald L.
Published: February 2017

Twelve alfalfa genotypes that were selected for biomass under salinity, differences in Na and Cl concentrations in shoots and K/Na ratio were evaluated in this long-term salinity experiment. The selected plants were cloned to reduce genetic variability within each genotype. Salt tolerance (ST) index of the genotypes ranged from 0.39 to 1. The most salt-tolerant genotypes SISA14-1 (G03) and AZ-90ST (G10), the top performers for biomass, exhibited the least effect on shoot number and height. SISA14-1 (G03) accumulated low Na and Cl under salinity. Most genotypes exhibited a net reduction in shoot Ca, Mg, P, Fe, and Cu, while Mn and Zn increased under salinity. Salinity reduced foliar area and stomatal conductance; while net photosynthetic rate and transpiration were not affected. Interestingly, salinity increased chlorophyll and antioxidant capacity in most genotypes; however neither parameter correlated well to ST index. Salt-tolerant genotypes showed upregulation of theSOS1, SOS2, SOS3, HKT1, AKT1, NHX1, P5CS1, HSP90.7, HSP81.2, HSP71.1, HSPC025, OTS1, SGF29andSAL1genes. Gene expression analyses allowed us to classify genotypes based on their ability to regulate different components of the salt tolerance mechanism. Pyramiding different components of the salt tolerance mechanism may lead to superior salt-tolerant alfalfa genotypes.
Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats
Authors: Xiong Xingjiang , Yang Xiaochen , Duan Lian , Liu Wei , Zhang Yun , Liu Yongmei , Wang Pengqian , Li Shengjie , Li Xiaoke
Published: February 2017

Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension.
Magneto-transport Spectroscopy of the First and Second Two-dimensional Subbands in Al0.25Ga0.75N/GaN Quantum Point Contacts
Authors: Lu Fangchao , Tang Ning , Shang Liangliang , Guan Hongming , Xu Fujun , Ge Weikun , Shen Bo
Published: February 2017

Magnetic transport spectroscopy is investigated in quantum point contacts (QPCs) fabricated in Al0.25Ga0.75N/GaN heterostructures. The magnetic field perpendicular to the two-dimensional electron gas (2DEG) is shown to depopulate the quasi-one-dimensional energy levels in the first two-dimensional (2D) subband faster than those in the second one. In GaN based heterostructures, the energy levels in the second 2D subband is generally concealed in the fast course of depletion and hence rarely detected. The perpendicular magnetic field facilitates the observation of the second 2D subband, and provides a method to study the properties of these energy levels. A careful analysis on the rate of the magnetic depletion with respect to the level index and confinement is carried out, from which the profile of the lateral confinement in GaN based QPCs is found to be triangular. The stability diagram at "Equation missing"T shows the energy separation between the first and second 2D subband to be in the range of 32 to 42 meV.
Preoperative red cell distribution width and neutrophil-to-lymphocyte ratio predict survival in patients with epithelial ovarian cancer
Authors: Li Zheng , Hong Na , Robertson Melissa , Wang Chen , Jiang Guoqian
Published: February 2017

Several parameters of preoperative complete blood count (CBC) and inflammation-associated blood cell markers derived from them have been reported to correlate with prognosis in patients with epithelial ovarian cancer (EOC), but their prognostic importance and optimal cutoffs are still needed be elucidated. Clinic/pathological parameters, 5-year follow-up data and preoperative CBC parameters were obtained retrospectively in 654 EOC patients underwent primary surgery at Mayo Clinic. Cutoffs for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were optimized by receiver operating characteristic (ROC) curve. Prognostic significance for overall survival (OS) and recurrence free survival (RFS) were determined by Cox proportional hazards models and Kaplan-Meier method. Associations of RDW and NLR with clinic/pathological parameters were analyzed using non-parametric tests. RDW with cutoff 14.5 and NLR with cutoff 5.25 had independent prognostic significance for OS, while combined RDW and NLR scores stratified patients into low (RDW-low and NLR-low), intermediate (RDW-high or NLR-high) and high risk (RDW-high and NLR-high) groups, especially in patients with high-grade serous ovarian cancer (HGSOC). Moreover, high NLR was associated with poor RFS as well. Elevated RDW was strongly associated with age, whereas high NLR was strongly associated with stage, preoperative CA125 level and ascites at surgery.
Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors
Authors: Peiris Diluka , Spector Alexander F. , Lomax-Browne Hannah , Azimi Tayebeh , Ramesh Bala , Loizidou Marilena , Welch Hazel , Dwek Miriam V.
Published: February 2017

Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6.83 Hz; glycosylated cells Bmax: 7.35 Hz). The sensitivity of cells to DXR and to growth factors was evaluated using an MTT assay. Maintenance of SKBR-3 cells in tunicamycin (an inhibitor of N-linked glycosylation) resulted in an increase in sensitivity to DXR (0.1 μM DXR P < 0.001) and a decrease in sensitivity to IGF-1 alone and to IGF-1 supplemented with EGF (P < 0.001). This report illustrates the importance of N-linked glycosylation in modulating the response of cancer cells to chemotherapeutic and biological treatments and highlights the potential of glycosylation inhibitors as future combination treatments for breast cancer.
Radiation exposure in the remote period after the Chernobyl accident caused oxidative stress and genetic effects in Scots pine populations
Authors: Volkova Polina Yu. , Geras’kin Stanislav A. , Kazakova Elizaveta A.
Published: February 2017

Even 30 years after the Chernobyl accident, biological effects of irradiation are observed in the chronically exposed Scots pine populations. Chronic radiation exposure at dose rates above 50 mGy∙yr−1caused oxidative stress and led to the increase of antioxidants concentrations in these populations. Genetic variability was examined for 6 enzymes and 14 enzymatic loci of 6 Scots pine populations. Dose rates over 10 mGy∙yr−1caused the increased frequency of mutations and changes in genetic structure of Scots pine populations. However, the same dose rates had no effect on enzymatic activities. The results indicate that even relatively low dose rates of radiation can be considered as an ecological factor which should be taken into account for ecological management and radiation protection of biota species.
Identification of novel cancer therapeutic targets using a designed and pooled shRNA library screen
Authors: Oliver David , Ji Hao , Liu Piaomu , Gasparian Alexander , Gardiner Ellen , Lee Samuel , Zenteno Adrian , Perinskaya Lillian O. , Chen Mengqian , Buckhaults Phillip , Broude Eugenia , Wyatt Michael D. , Valafar Homayoun , Peña Edsel , Shtutman Michael
Published: February 2017

Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation. We developed a bootstrap likelihood ratio test for the interpretation of the effects of multiple shRNAs over multiple cell line passages. Our analysis identified 44 genes whose depletion preferentially inhibited the growth of cancer cells. Among these genes ribosomal protein RPL35A, putative RNA helicase DDX24, and coatomer complex I (COPI) subunit ARCN1 most significantly inhibited growth of multiple cancer cell lines without affecting normal cell growth and survival. Further investigation revealed that the growth inhibition caused by DDX24 depletion is independent of p53 status underlining its value as a drug target. Overall, our study establishes a new approach for the analysis of proliferation-based shRNA selection strategies and identifies new targets for the development of cancer therapeutics.
The miRNAome of Catharanthus roseus: identification, expression analysis, and potential roles of microRNAs in regulation of terpenoid indole alkaloid biosynthesis
Authors: Shen Ethan M. , Singh Sanjay K. , Ghosh Jayadri S. , Patra Barunava , Paul Priyanka , Yuan Ling , Pattanaik Sitakanta
Published: February 2017

MicroRNAs (miRNAs) regulate numerous crucial biological processes in plants. However, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including Catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (TIAs). Using small RNA-sequencing, we identified 181 conserved and 173 novel miRNAs (cro-miRNAs) in C. roseus seedlings. Genome-wide expression analysis revealed that a set of cro-miRNAs are differentially regulated in response to methyl jasmonate (MeJA). In silico target prediction identified 519 potential cro-miRNA targets that include several auxin response factors (ARFs). The presence of cleaved transcripts of miRNA-targeted ARFs in C. roseus cells was confirmed by Poly(A) Polymerase-Mediated Rapid Amplification of cDNA Ends (PPM-RACE). We showed that auxin (indole acetic acid, IAA) repressed the expression of key TIA pathway genes in C. roseus seedlings. Moreover, we demonstrated that a miRNA-regulated ARF, CrARF16, binds to the promoters of key TIA pathway genes and repress their expression. The C. roseus miRNAome reported here provides a comprehensive account of the cro-miRNA populations, as well as their abundance and expression profiles in response to MeJA. In addition, our findings underscore the importance of miRNAs in posttranscriptional control of the biosynthesis of specialized metabolites.
High-Intensity Aerobic Exercise Improves Both Hepatic Fat Content and Stiffness in Sedentary Obese Men with Nonalcoholic Fatty Liver Disease
Authors: Oh Sechang , So Rina , Shida Takashi , Matsuo Tomoaki , Kim Bokun , Akiyama Kentaro , Isobe Tomonori , Okamoto Yoshikazu , Tanaka Kiyoji , Shoda Junichi
Published: February 2017

We compared the effects of 12-week programs of resistance training (RT), high-intensity interval aerobic training (HIAT), and moderate-intensity continuous aerobic training (MICT). The primary goal was to evaluate the therapeutic effects of the exercise modalities for the management of nonalcoholic fatty liver disease (NAFLD). A total of 61 sedentary obese men with NAFLD were randomized into one of the following exercise regimens (RT, HIAT, or MICT). Hepatic fat content was decreased to a similar extent in the RT, HIAT, and MICT groups (−14.3% vs. −13.7% vs. −14.3%) without significant changes in weight and visceral fat. The gene expression levels of fatty acid synthesis were significantly decreased in the subjects’ monocytes. Hepatic stiffness was decreased only in the HIAT group (−16.8%). The stiffness change was associated with restored Kupffer cell phagocytic function (+17.8%) and decreased levels of inflammation such as leptin (−13.2%) and ferritin (−14.1%). RT, HIAT, and MICT were equally effective in reducing hepatic fat content, but only HIAT was effective in improving hepatic stiffness and restoring Kupffer cell function. These benefits appeared to be independent of detectable weight and visceral fat reductions; the benefits were acquired through the modulation ofin vivofatty acid metabolism and obesity-related inflammatory conditions.
Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers
Authors: Skene Debra J. , Middleton Benita , Fraser Cara K. , Pennings Jeroen L. A. , Kuchel Timothy R. , Rudiger Skye R. , Bawden C. Simon , Morton A. Jennifer
Published: February 2017

The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients.
PVN Blockade of p44/42 MAPK Pathway Attenuates Salt-induced Hypertension through Modulating Neurotransmitters and Attenuating Oxidative Stress
Authors: Gao Hong-Li , Yu Xiao-Jing , Liu Kai-Li , Shi Xiao-Lian , Qi Jie , Chen Yan-Mei , Zhang Yan , Bai Juan , Yi Qiu-Yue , Feng Zhi-Peng , Chen Wen-Sheng , Cui Wei , Liu Jin-Jun , Zhu Guo-Qing , Kang Yu-Ming
Published: February 2017

The imbalance of neurotransmitters and excessive oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether blockade of p44/42 MAPK pathway in the hypothalamic paraventricular nucleus (PVN) ameliorates the development of hypertension through modulating neurotransmitters and attenuating oxidative stress. Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 6 weeks and were treated with bilateral PVN infusion of PD-98059 (0.025 μg/h), a p44/42 MAPK inhibitor, or vehicle via osmotic minipump. HS resulted in higher mean arterial pressure (MAP) and Fra-like (Fra-LI) activity, and plasma and PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. PD-98059 infusion reduced NE, TH, NOX2 and NOX4 in the PVN, and induced Cu/Zn-SOD and GAD67 in the PVN. It suggests that PVN blockade of p44/42 MAPK attenuates hypertension through modulating neurotransmitters and attenuating oxidative stress.
Antitumorigenic effect of atmospheric-pressure dielectric barrier discharge on human colorectal cancer cells via regulation of Sp1 transcription factor
Authors: Han Duksun , Cho Jin Hyoung , Lee Ra Ham , Bang Woong , Park Kyungho , Kim Minseok S. , Shim Jung-Hyun , Chae Jung-Il , Moon Se Youn
Published: February 2017

Human colorectal cancer cell lines (HT29 and HCT116) were exposed to dielectric barrier discharge (DBD) plasma at atmospheric pressure to investigate the anticancer capacity of the plasma. The dose- and time-dependent effects of DBDP on cell viability, regulation of transcription factor Sp1, cell-cycle analysis, and colony formation were investigated by means of MTS assay, DAPI staining, propidium iodide staining, annexin V–FITC staining, Western blot analysis, RT-PCR analysis, fluorescence microscopy, and anchorage-independent cell transformation assay. By increasing the duration of plasma dose times, significant reductions in the levels of both Sp1 protein and Sp1 mRNA were observed in both cell lines. Also, expression of negative regulators related to the cell cycle (such as p53, p21, and p27) was increased and of the positive regulator cyclin D1 was decreased, indicating that the plasma treatment led to apoptosis and cell-cycle arrest. In addition, the sizes and quantities of colony formation were significantly suppressed even though two cancer promoters, such as TPA and epidermal growth factor, accompanied the plasma treatment. Thus, plasma treatment inhibited cell viability and colony formation by suppressing Sp1, which induced apoptosis and cell-cycle arrest in these two human colorectal cancer cell lines.
Prevention of tumorigenesis in mice by exercise is dependent on strain background and timing relative to carcinogen exposure
Authors: Kelly Scott A. , Zhao Liyang , Jung Kuo-Chen , Hua Kunjie , Threadgill David W. , Kim Yunjung , de Villena Fernando Pardo Manuel , Pomp Daniel
Published: February 2017

Among cancer diagnoses, colorectal cancer (CRC) is prevalent, with a lifetime risk of developing CRC being approximately 5%. Population variation surrounding the mean risk of developing CRCs has been associated with both inter-individual differences in genomic architecture and environmental exposures. Decreased risk of CRC has been associated with physical activity, but protective responses are variable. Here, we utilized a series of experiments to examine the effects of genetic background (strain), voluntary exercise (wheel running), and their interaction on azoxymethane (AOM)-induced intestinal tumor number and size in mice. Additionally, we investigated how the timing of exercise relative to AOM exposure, and amount of exercise, affected tumor number and size. Our results indicated that voluntary exercise significantly reduced tumor number in a strain dependent manner. Additionally, among strains where exercise reduced tumor number (A/J, CC0001/Unc) the timing of voluntary exercise relative to AOM exposure was crucial. Voluntary exercise prior to or during AOM treatment resulted in a significant reduction in tumor number, but exercise following AOM exposure had no effect. The results indicate that voluntary exercise should be used as a preventative measure to reduce risk for environmentally induced CRC with the realization that the extent of protection may depend on genetic background.