ALBERT

Description: In situ observations of cloud properties made by airborne probes play a critical role in ice cloud research through their role in process studies, parameterization development, and evaluation of simulations and remote sensing retrievals. To determine how cloud properties vary with environmental conditions, in situ data collected during different field projects processed by different groups must be used. However, because of the diverse algorithms and codes that are used to process measurements, it can be challenging to compare the results. Therefore it is vital to understand both the limitations of specific probes and uncertainties introduced by processing algorithms. Since there is currently no universally accepted framework regarding how in situ measurements should be processed, there is a need for a general reference that describes the most commonly applied algorithms along with their strengths and weaknesses. Methods used to process data from bulk water probes, single-particle light-scattering spectrometers and cloud-imaging probes are reviewed herein, with emphasis on measurements of the ice phase. Particular attention is paid to how uncertainties, caveats, and assumptions in processing algorithms affect derived products since there is currently no consensus on the optimal way of analyzing data. Recommendations for improving the analysis and interpretation of in situ data include the following: establishment of a common reference library of individual processing algorithms, better documentation of assumptions used in these algorithms, development and maintenance of sustainable community software for processing in situ observations, and more studies that compare different algorithms with the same benchmark datasets.

Description: It has been known that aerosol particles act as nuclei for ice formation for over a century and a half (see Dufour). Initial attempts to understand the nature of these ice nucleating particles were optical and electron microscope inspection of inclusions at the center of a crystal (see Isono; Kumai). Only within the last few decades has instrumentation to extract ice crystals from clouds and analyze the residual material after sublimation of condensed-phase water been available (see Cziczo and Froyd). Techniques to ascertain the ice nucleating potential of atmospheric aerosols have only been in place for a similar amount of time (see DeMott et al.). In this chapter the history of measurements of ice nucleating particles, both in the field and complementary studies in the laboratory, are reviewed. Remaining uncertainties and artifacts associated with measurements are described and suggestions for future areas of improvement are made.

Description: The life cycle of individual (initially line shaped) contrails behind aircraft and of contrail cirrus (aged contrails mixed with other ice clouds) is described. The full contrail life cycle is covered, from ice formation for given water, heat, and particulate emissions; to changes in the jet, wake, and dispersion phases; through final sublimation or sedimentation. Contrail properties are deduced from various in situ, remote sensing, and model studies. Aerodynamically induced contrails and distrails are explained briefly. Contrails form both in clear air and inside cirrus. Young contrails consume most of the ambient ice supersaturation. Optical properties of contrails are age and humidity dependent. Contrail occurrence and radiative forcing depends on the ambient Earth–atmosphere conditions. Contrail cirrus seems to be optically thicker than assessed previously and may not only increase cirrus coverage but also thicken existing cirrus. Some observational constraints for contrail cirrus occurrence and radiative forcing are derived. Key parameters controlling contrail properties—besides aircraft and fuel properties, ambient pressure, temperature, and humidity—are the number of ice particles per flight distance surviving the wake vortex phase, the contrail depth, and particle sedimentation, wind shear, turbulence, and vertical motions controlling contrail dispersion. The climate impact of contrails depends among other things on the ratio of shortwave to longwave radiative forcing (RF) and on the efficacy with which contrail RF contributes to surface warming. Several open issues are identified, including renucleation from residuals of sublimated contrail ice particles.

Description: Ice-phase precipitation occurs at Earth’s surface and may include various types of pristine crystals, rimed crystals, freezing droplets, secondary crystals, aggregates, graupel, hail, or combinations of any of these. Formation of ice-phase precipitation is directly related to environmental and cloud meteorological parameters that include available moisture, temperature, and three-dimensional wind speed and turbulence, as well as processes related to nucleation, cooling rate, and microphysics. Cloud microphysical parameters in the numerical models are resolved based on various processes such as nucleation, mixing, collision and coalescence, accretion, riming, secondary ice particle generation, turbulence, and cooling processes. These processes are usually parameterized based on assumed particle size distributions and ice crystal microphysical parameters such as mass, size, and number and mass density. Microphysical algorithms in the numerical models are developed based on their need for applications. Observations of ice-phase precipitation are performed using in situ and remote sensing platforms, including radars and satellite-based systems. Because of the low density of snow particles with small ice water content, their measurements and predictions at the surface can include large uncertainties. Wind and turbulence affecting collection efficiency of the sensors, calibration issues, and sensitivity of ground-based in situ observations of snow are important challenges to assessing the snow precipitation. This chapter’s goals are to provide an overview for accurately measuring and predicting ice-phase precipitation. The processes within and below cloud that affect falling snow, as well as the known sources of error that affect understanding and prediction of these processes, are discussed.

Description: Ice fog is a natural, outdoor cloud laboratory that provides an excellent opportunity to study ice microphysical processes. Ice crystals in fog are formed through similar pathways as those in elevated clouds; that is, cloud condensation or ice nuclei are activated in an atmosphere supersaturated with respect to liquid water or ice. The primary differences between surface and elevated ice clouds are related to the sources of water vapor, the cooling mechanisms and dynamical processes leading to supersaturation, and the microphysical characteristics of the nuclei that affect ice fog crystal physical properties. As with any fog, its presence can be a hazard for ground or airborne traffic because of poor visibility and icing. In addition, ice fog plays a role in climate change by modulating the heat and moisture budgets. Ice fog wintertime occurrence in many parts of the world can have a significant impact on the environment. Global climate models need to accurately account for the temporal and spatial microphysical and optical properties of ice fog, as do weather forecast models. The primary handicap is the lack of adequate information on nucleation processes and microphysical algorithms that accurately represent glaciation of supercooled water fog. This chapter summarizes the current understanding of ice fog formation and evolution; discusses operating principles, limitations, and uncertainties associated with the instruments used to measure ice fog microphysical properties; describes the prediction of ice fog by the numerical forecast models and physical parameterizations used in climate models; identifies the outstanding questions to be resolved; and lists recommended actions to address and solve these questions.

Description: State-of-the-art remote sensing techniques applicable to the investigation of ice formation and evolution are described. Ground-based and spaceborne measurements with lidar, radar, and radiometric techniques are discussed together with a global view on past and ongoing remote sensing measurement campaigns concerned with the study of ice formation and evolution. This chapter has the intention of a literature study and should illustrate the major efforts that are currently taken in the field of remote sensing of atmospheric ice. Since other chapters of this monograph mainly focus on aircraft in situ measurements, special emphasis is put on active remote sensing instruments and synergies between aircraft in situ measurements and passive remote sensing methods. The chapter concentrates on homogeneous and heterogeneous ice formation in the troposphere because this is a major topic of this monograph. Furthermore, methods that deliver direct, process-level information about ice formation are elaborated with a special emphasis on active remote sensing methods. Passive remote sensing methods are also dealt with but only in the context of synergy with aircraft in situ measurements.

Description: Ice particle formation in tropospheric clouds significantly changes cloud radiative and microphysical properties. Ice nucleation in the troposphere via homogeneous freezing occurs at temperatures lower than −38°C and relative humidity with respect to ice above 140%. In the absence of these conditions, ice formation can proceed via heterogeneous nucleation aided by aerosol particles known as ice nucleating particles (INPs). In this chapter, new developments in identifying the heterogeneous freezing mechanisms, atmospheric relevance, uncertainties, and unknowns about INPs are described. The change in conventional wisdom regarding the requirements of INPs as new studies discover physical and chemical properties of these particles is explained. INP sources and known reasons for their ice nucleating properties are presented. The need for more studies to systematically identify particle properties that facilitate ice nucleation is highlighted. The atmospheric relevance of long-range transport, aerosol aging, and coating studies (in the laboratory) of INPs are also presented. Possible mechanisms for processes that change the ice nucleating potential of INPs and the corresponding challenges in understanding and applying these in models are discussed. How primary ice nucleation affects total ice crystal number concentrations in clouds and the discrepancy between INP concentrations and ice crystal number concentrations are presented. Finally, limitations of parameterizing INPs and of models in representing known and unknown processes related to heterogeneous ice nucleation processes are discussed.

Description: The goal of this chapter is to synthesize information about what is now known about one of the three main types of clouds, cirrus, and to identify areas where more knowledge is needed. Cirrus clouds, composed of ice particles, form in the upper troposphere, where temperatures are generally below −30°C. Satellite observations show that the maximum-occurrence frequency of cirrus is near the tropics, with a large latitudinal movement seasonally. In situ measurements obtained over a wide range of cirrus types, formation mechanisms, temperatures, and geographical locations indicate that the ice water content and particle size generally decrease with decreasing temperature, whereas the ice particle concentration is nearly constant or increases slightly with decreasing temperature. High ice concentrations, sometimes observed in strong updrafts, result from homogeneous nucleation. The satellite-based and in situ measurements indicate that cirrus ice crystals typically differ from the simple, idealized geometry for smooth hexagonal shapes, indicating complexity and/or surface roughness. Their shapes significantly impact cirrus radiative properties and feedbacks to climate. Cirrus clouds, one of the most uncertain components of general circulation models (GCM), pose one of the greatest challenges in predicting the rate and geographical pattern of climate change. Improved measurements of the properties and size distributions and surface structure of small ice crystals (about 20 μm) and identifying the dominant ice nucleation process (heterogeneous versus homogeneous ice nucleation) under different cloud dynamical forcings will lead to a better representation of their properties in GCM and in modeling their current and future effects on climate.

Description: 〈span〉〈div〉Summary〈/div〉Seismic free oscillations, or normal modes, provide a convenient tool to calculate low-frequency seismograms in heterogeneous Earth models. A procedure called ‘full mode coupling’ allows the seismic response of the Earth to be computed. However, in order to be theoretically exact, such calculations must involve an infinite set of modes. In practice, only a finite subset of modes can be used, introducing an error into the seismograms. By systematically increasing the number of modes beyond the highest frequency of interest in the seismograms, we investigate the convergence of full-coupling calculations. As a rule-of-thumb, it is necessary to couple modes 1–2 mHz above the highest frequency of interest, although results depend upon the details of the Earth model. This is significantly higher than has previously been assumed. Observations of free oscillations also provide important constraints on the heterogeneous structure of the Earth. Historically, this inference problem has been addressed by the measurement and interpretation of splitting functions. These can be seen as secondary data extracted from low frequency seismograms. The measurement step necessitates the calculation of synthetic seismograms, but current implementations rely on approximations referred to as self- or group-coupling and do not use fully accurate seismograms. We therefore also investigate whether a systematic error might be present in currently published splitting functions. We find no evidence for any systematic bias, but published uncertainties must be doubled to properly account for the errors due to theoretical omissions and regularization in the measurement process. Correspondingly, uncertainties in results derived from splitting functions must also be increased. As is well known, density has only a weak signal in low-frequency seismograms. Our results suggest this signal is of similar scale to the true uncertainties associated with currently published splitting functions. Thus, it seems that great care must be taken in any attempt to robustly infer details of Earth's density structure using current splitting functions.〈/span〉

Description: 〈span〉〈div〉Summary〈/div〉In this paper, we propose a new wavelet-based 3-D inversion method for frequency-domain airborne electromagnetic (FDAEM) data. Instead of inverting the model in the space domain using a smoothing constraint, this new method recovers the model in the wavelet domain based on a sparsity constraint. In the wavelet domain, the model is represented by two types of coefficients, which contain both large- and fine-scale informations of the model, meaning the wavelet-domain inversion has inherent multiresolution. In order to accomplish a sparsity constraint, we minimize an L〈sub〉1〈/sub〉-norm measure in the wavelet domain that mostly gives a sparse solution. The final inversion system is solved by an iteratively reweighted least-squares method. We investigate different orders of Daubechies wavelets to accomplish our inversion algorithm, and test them on synthetic frequency-domain AEM data set. The results show that higher order wavelets having larger vanishing moments and regularity can deliver a more stable inversion process and give better local resolution, while the lower order wavelets are simpler and less smooth, and thus capable of recovering sharp discontinuities if the model is simple. At last, we test this new inversion algorithm on a frequency-domain helicopter EM (HEM) field data set acquired in Byneset, Norway. Wavelet-based 3-D inversion of HEM data is compared to L〈sub〉2〈/sub〉-norm-based 3-D inversion's result to further investigate the features of the new method.〈/span〉

Description: 〈span〉〈div〉Summary〈/div〉A monitoring method to grasp the spatio-temporal change in the interplate coupling in a subduction zone based on the spatial gradients of surface displacement rate fields is proposed. I estimated the spatio-temporal change in the interplate coupling along the plate boundary in northeastern (NE) Japan by applying the proposed method to the surface displacement rates based on global positioning system observations. The gradient of the surface velocities is calculated in each swath configured along the direction normal to the Japan Trench for time windows such as 0.5, 1, 2, 3 and 5 yr being shifted by one week during the period of 1997–2016. The gradient of the horizontal velocities is negative and has a large magnitude when the interplate coupling at the shallow part (less than approximately 50 km in depth) beneath the profile is strong, and the sign of the gradient of the vertical velocity is sensitive to the existence of the coupling at the deep part (greater than approximately 50 km in depth). The trench-parallel variation of the spatial gradients of a displacement rate field clearly corresponds to the trench-parallel variation of the amplitude of the interplate coupling on the plate interface, as well as the rupture areas of previous interplate earthquakes. Temporal changes in the trench-parallel variation of the spatial gradient of the displacement rate correspond to the strengthening or weakening of the interplate coupling. We can monitor the temporal change in the interplate coupling state by calculating the spatial gradients of the surface displacement rate field to some extent without performing inversion analyses with applying certain constraint conditions that sometimes cause over- and/or underestimation at areas of limited spatial resolution far from the observation network. The results of the calculation confirm known interplate events in the NE Japan subduction zone, such as the post-seismic slip of the 2003 M8.0 Tokachi-oki and 2005 M7.2 Miyagi-oki earthquakes and the recovery of the interplate coupling around the rupture area of the 1994 M7.6 Sanriku-Haruka-oki earthquake. The results also indicate the semi-periodic occurrence of slow slip events and the expansion of the area of slow slip events before the 2011 Tohoku-oki earthquake (M9.0) approaching the hypocentre of the Tohoku-oki earthquake.〈/span〉

Description: 〈span〉〈div〉Summary〈/div〉We image the internal structure of the San Jacinto fault zone (SJFZ) in the trifurcation area southeast of Anza, California, with seismic records from dense linear and rectangular arrays. The examined data include recordings from more than 20 000 local earthquakes and nine teleseismic events. Automatic detection algorithms and visual inspection are used to identify 〈span〉P〈/span〉 and 〈span〉S〈/span〉 body waves, along with 〈span〉P〈/span〉- and 〈span〉S〈/span〉-types fault zone trapped waves (FZTW). The location at depth of the main branch of the SJFZ, the Clark fault, is identified from systematic waveform changes across lines of sensors within the dense rectangular array. Delay times of 〈span〉P〈/span〉 arrivals from teleseismic and local events indicate damage asymmetry across the fault, with higher damage to the NE, producing a local reversal of the velocity contrast in the shallow crust with respect to the large-scale structure. A portion of the damage zone between the main fault and a second mapped surface trace to the NE generates 〈span〉P〈/span〉- and 〈span〉S〈/span〉-types FZTW. Inversions of high-quality 〈span〉S〈/span〉-type FZTW indicate that the most likely parameters of the trapping structure are width of ∼70 m, 〈span〉S〈/span〉-wave velocity reduction of 60 per cent, 〈span〉Q〈/span〉 value of 60 and depth of ∼2 km. The local reversal of the shallow velocity contrast across the fault with respect to large-scale structure is consistent with preferred propagation of earthquake ruptures in the area to the NW.〈/span〉

Description: 〈span〉〈div〉Summary〈/div〉The computational cost of quasi-〈span〉P〈/span〉 wave extrapolation depends on the complexity of the medium, and specifically the anisotropy. Our effective-model method splits the anisotropic dispersion relation into an isotropic background and a correction factor to handle this dependency. The correction term depends on the slope (measured using the gradient) of current wavefields and the anisotropy. As a result, the computational cost is independent of the nature of anisotropy, which makes the extrapolation efficient. A dynamic implementation of this approach decomposes the original pseudo-differential operator into a Laplacian, handled using the low-rank approximation of the spectral operator, plus an angular dependent correction factor applied in the space domain to correct for anisotropy. We analyse the role played by the correction factor and propose a new spherical decomposition of the dispersion relation. The proposed method provides accurate wavefields in phase and more balanced amplitudes than a previous spherical decomposition. Also, it is free of 〈span〉SV〈/span〉-wave artefacts. Applications to a simple homogeneous transverse isotropic medium with a vertical symmetry axis (VTI) and a modified Hess VTI model demonstrate the effectiveness of the approach. The Reverse Time Migration applied to a modified BP VTI model reveals that the anisotropic migration using the proposed modelling engine performs better than an isotropic migration.〈/span〉

Description: 〈span〉〈div〉Summary〈/div〉Over the past 15 yr, numerical models of convection in Earth’s mantle have made a leap forward: they can now produce self-consistent plate-like behaviour at the surface together with deep mantle circulation. These digital tools provide a new window into the intimate connections between plate tectonics and mantle dynamics, and can therefore be used for tectonic predictions, in principle. This contribution explores this assumption. First, initial conditions at 30, 20, 10 and 0 Ma are generated by driving a convective flow with imposed plate velocities at the surface. We then compute instantaneous mantle flows in response to the guessed temperature fields without imposing any boundary conditions. Plate boundaries self-consistently emerge at correct locations with respect to reconstructions, except for small plates close to subduction zones. As already observed for other types of instantaneous flow calculations, the structure of the top boundary layer and upper-mantle slab is the dominant character that leads to accurate predictions of surface velocities. Perturbations of the rheological parameters have little impact on the resulting surface velocities. We then compute fully dynamic model evolution from 30 and 10 to 0 Ma, without imposing plate boundaries or plate velocities. Contrary to instantaneous calculations, errors in kinematic predictions are substantial, although the plate layout and kinematics in several areas remain consistent with the expectations for the Earth. For these calculations, varying the rheological parameters makes a difference for plate boundary evolution. Also, identified errors in initial conditions contribute to first-order kinematic errors. This experiment shows that the tectonic predictions of dynamic models over 10 My are highly sensitive to uncertainties of rheological parameters and initial temperature field in comparison to instantaneous flow calculations. Indeed, the initial conditions and the rheological parameters can be good enough for an accurate prediction of instantaneous flow, but not for a prediction after 10 My of evolution. Therefore, inverse methods (sequential or data assimilation methods) using short-term fully dynamic evolution that predict surface kinematics are promising tools for a better understanding of the state of the Earth’s mantle.〈/span〉

Description: by Jialiang Guo, Qi Zhang, Jia Li, Yansong Liu, Zhiyong Hou, Wei Chen, Lin Jin, Ye Tian, Linlin Ju, Bo Liu, Tianhua Dong, Fei Zhang, Yingze Zhang Non-union is a major clinical problem in the healing of fractures, especially in patients with osteoporosis. The systemic administration of drugs is time consuming and large doses are demanding and act slowly, whereas local release acts rapidly, increases the quality and quantity of the bone tissue. We hypothesize that local delivery demonstrates better therapeutic effects on an osteoporotic fracture. The aim of this paper is to investigate the effect of the local application of ibandronate loaded with a collagen sponge on regulating bone formation and remodeling in an osteoporotic rat model of fracture healing. We found that the local delivery of ibandronate exhibited excellent effects on improving the bone microarchitecture and suppressed effects on bone remodeling. At 4 weeks, more callus formation and improvement of mechanical character and microstructure were observed in a local delivery via μCT, mechanical test, histological research and serum analysis. The suppression of bone remodeling was compared with a systemic treatment at 12 weeks, and the structural mechanical properties and microarchitecture were also improved with local delivery. This research identifies an earlier, safer and integrated approach for local delivery of ibandronate with collagen and provides a better strategy for the treatment of osteoporotic fracture in rats.

Description: by Maia P. Smith, Marie Standl, Joachim Heinrich, Holger Schulz Background Because of unreliable self-report, accelerometry is increasingly used to objectively monitor physical activity (PA). However, results of accelerometric studies vary depending on the chosen cutpoints between activity intensities. Population-specific activity patterns likely affect the size of these differences. To establish their size and stability we apply three sets of cutpoints, including two calibrated to a single reference, to our accelerometric data and compare PA estimates. Methods 1402 German adolescents from the GINIplus and LISAplus cohorts wore triaxial accelerometers (Actigraph GT3x) for one week (mean 6.23 days, 14.7 hours per day) at the hip. After validation of wear, we applied three sets of cutpoints for youth, including the most common standard (Freedson, 2005) and two calibrated to a single reference, (Romanzini uni- and triaxial, from Romanzini, 2014) to these data, estimating daily sedentary, light, moderate, vigorous and moderate-to-vigorous PA (MPA, VPA, MVPA). Stability of differences was assessed by comparing Romanzini’s two sets of cutpoints. Results Relative agreement between cutpoints was closer for activity of lower intensities (largest difference for sedentary behaviour 9%) but increased for higher intensities (largest difference for light activity 40%, MPA 102%, VPA 88%; all p

Description: by Bertha J. Vandegrift, Chang You, Rosalba Satta, Mark S. Brodie, Amy W. Lasek Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2), the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA) is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2) or estrus (low E2) for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA) of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780) reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.

Description: by Chelsea M. Rochman, J. Mark Parnis, Mark A. Browne, Sebastian Serrato, Eric J. Reiner, Matthew Robson, Thomas Young, Miriam L. Diamond, Swee J. Teh We examined whether environmentally relevant concentrations of different types of microplastics, with or without PCBs, directly affect freshwater prey and indirectly affect their predators. Asian clams ( Corbicula fluminea ) were exposed to environmentally relevant concentrations of polyethylene terephthalate (PET), polyethylene, polyvinylchloride (PVC) or polystyrene with and without polychlorinated biphenyls (PCBs) for 28 days. Their predators, white sturgeon ( Acipenser transmontanus ), were exposed to clams from each treatment for 28 days. In both species, we examined bioaccumulation of PCBs and effects (i.e., immunohistochemistry, histology, behavior, condition, mortality) across several levels of biological organization. PCBs were not detected in prey or predator, and thus differences in bioaccumulation of PCBs among polymers and biomagnification in predators could not be measured. One of the main objectives of this study was to test the hypothesis that bioaccumulation of PCBs would differ among polymer types. Because we could not answer this question experimentally, a bioaccumulation model was run and predicted that concentrations of PCBs in clams exposed to polyethylene and polystyrene would be greater than PET and PVC. Observed effects, although subtle, seemed to be due to microplastics rather than PCBs alone. For example, histopathology showed tubular dilation in clams exposed to microplastics with PCBs, with only mild effects in clams exposed to PCBs alone.

Description: by Deisy Barrios, Raquel Morillo, Ina Guerassimova, Esther Barbero, Héctor Escobar-Morreale, Alexander T. Cohen, Cecilia Becattini, Victor Tapson, Roger Yusen, David Jimenez Background We sought to examine sex-related differences in the characteristics and outcome in patients presenting with acute symptomatic pulmonary embolism (PE). Methods We conducted a retrospective cohort study of 2,096 patients diagnosed with acute PE. The characteristics were recorded at presentation. Treatment was at the discretion of patients’ physicians. The primary study outcome, all-cause mortality, and the secondary outcomes of PE-specific mortality, recurrent venous thromboembolism, and major bleeding were assessed during the first month of follow-up after PE diagnosis. Results Overall, the women were older than the men and had significantly higher rates of immobilization. They had significantly lower rates of chronic obstructive pulmonary disease and cancer. Women had a higher prevalence of syncope and elevated brain natriuretic peptide levels. Thirty-day all-cause mortality was similar between women and men (7.1% versus 6.2%; P = 0.38). Male gender was not independently significantly associated with PE-related death (adjusted odds ratio [OR] 1.02; 95% CI, 0.50 to 2.07; P = 0.96). Restricting the analyses to haemodynamically stable patients (n = 2,021), female gender was an independent predictor of all-cause (adjusted OR 1.56; 95% CI, 1.07 to 2.28; P = 0.02) and PE-specific mortality (adjusted OR 1.85; 95% CI, 1.02 to 3.33; P = 0.04). Compared with men, women were 2.05 times more likely to experience a major bleed. Conclusions Women and men with PE had different clinical characteristics, presentation, and outcomes. Women receiving anticoagulation have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

Description: by Friederike Hammersen, Philip Lewin, Judith Gebauer, Ilonka Kreitschmann-Andermahr, Georg Brabant, Alexander Katalinic, Annika Waldmann This study investigated sleep quality and health-related quality of life (HRQOL) among long-term survivors of Hodgkin (HL) and non-Hodgkin lymphoma (NHL). The aim was to explore the impact of personal and health-related factors on sleep quality as well as associations between sleep quality and HRQOL. For the postal survey, participants with a minimum age of 18 years initially treated between 1998 and 2008 were recruited via the population-based cancer registry in Schleswig-Holstein, Northern Germany. Questionnaires included amongst others the Pittsburg Sleep Quality Index (PSQI) and the 36-Item Short Form Health Survey (SF-36v1). Descriptive and comparative statistics were performed. Additionally, a regression analysis was conducted to identify predictors of sleep quality. In total, we recruited 515 participants (398 NHL, 117 HL) with a mean age of 63.1 years. Approximately half of the survivors were classified as good sleepers. HRQOL scores differed between good and poor sleepers with lower scores in poor sleepers. In a prediction model, self-reported depression, exhaustion, higher age, inability to work, endocrinological disorders and female gender classified as predictors of sleep quality. This study highlights the impact of sleep quality on HRQOL in long-term survivors of NHL and HL. Thus, sleep quality should be routinely assessed during follow-up of cancer survivors with special attention to patients with potential risk factors.

Description: by Nuria García-Marchena, Daniel Silva-Peña, Ana Isabel Martín-Velasco, María Ángeles Villanúa, Pedro Araos, María Pedraz, Rosa Maza-Quiroga, Pablo Romero-Sanchiz, Gabriel Rubio, Estela Castilla-Ortega, Juan Suárez, Fernando Rodríguez de Fonseca, Antonia Serrano, Francisco Javier Pavón The identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs). Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91) and healthy control subjects (control group, N = 55) to examine plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3). The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7%) and psychiatric comorbidity (76.9%). Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3%) [mainly depression (19.9%)] and comorbid substance use disorders (40.7%). Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p

Description: by Stephen P. Cohen, Hongxia Liu, Cristiana T. Argueso, Andy Pereira, Casiana Vera Cruz, Valerie Verdier, Jan E. Leach Plant disease is a major challenge to agriculture worldwide, and it is exacerbated by abiotic environmental factors. During some plant-pathogen interactions, heat stress allows pathogens to overcome host resistance, a phenomenon which could severely impact crop productivity considering the global warming trends associated with climate change. Despite the importance of this phenomenon, little is known about the underlying molecular mechanisms. To better understand host plant responses during simultaneous heat and pathogen stress, we conducted a transcriptomics experiment for rice plants (cultivar IRBB61) containing Xa7 , a bacterial blight disease resistance ( R ) gene, that were infected with Xanthomonas oryzae , the bacterial blight pathogen of rice, during high temperature stress. Xa7- mediated resistance is unusual relative to resistance mediated by other R genes in that it functions better at high temperatures. Using RNA-Seq technology, we identified 8,499 differentially expressed genes as temperature responsive in rice cultivar IRBB61 experiencing susceptible and resistant interactions across three time points. Notably, genes in the plant hormone abscisic acid biosynthesis and response pathways were up-regulated by high temperature in both mock-treated plants and plants experiencing a susceptible interaction and were suppressed by high temperature in plants exhibiting Xa7- mediated resistance. Genes responsive to salicylic acid, an important plant hormone for disease resistance, were down-regulated by high temperature during both the susceptible and resistant interactions, suggesting that enhanced Xa7- mediated resistance at high temperature is not dependent on salicylic acid signaling. A DNA sequence motif similar to known abscisic acid-responsive cis- regulatory elements was identified in the promoter region upstream of genes up-regulated in susceptible but down-regulated in resistant interactions. The results of our study suggest that the plant hormone abscisic acid is an important node for cross-talk between plant transcriptional response pathways to high temperature stress and pathogen attack. Genes in this pathway represent an important focus for future study to determine how plants evolved to deal with simultaneous abiotic and biotic stresses.

Description: by Yang-yang Liu, Han-yan Sun, Wei Li, Yun-lei Xia, Yuan-yu Deng, Ai-xiang Zhang, Huai-gu Chen In China, Fusarium head blight is caused mainly by the Fusarium graminearum species complex (FGSC), which produces trichothecene toxins. The FGSC is divided into three chemotypes: 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), and nivalenol (NIV). In order to predict the geographical changes in the distribution of these chemotype populations in major winter wheat-producing areas in China, the biological characteristics of twenty randomly selected isolates from each of the three chemotypes were studied. No significant difference was exhibited in the growth rate of 3-ADON, 15-ADON, and NIV isolates at 15°C. At 20°C and 25°C, the growth rate of 15-ADON isolates was the highest. At 30°C, the growth rate of NIV and 3-ADON isolates was significantly higher than that of 15-ADON isolates. The 15-ADON isolates produced the highest quantities of perithecia and two to three days earlier than the other two populations at each temperature, and released more ascospores at 18°C. The aggressiveness test on wheat seedlings and ears indicated there was no significant difference between the 3-ADON and 15-ADON isolates. However, the aggressiveness of NIV isolates was significantly lower than that of the 3-ADON and 15-ADON isolates. The DON content in grains from heads inoculated with the 3-ADON isolates was higher than the content of 15-ADON and NIV isolates. The results showed that 15-ADON population had the advantage in perithecia formation and ascospore release, and the 3-ADON population produced more DON in wheat grains. We suggested that distribution of these three chemotype populations may be related to these biological characteristics.

Description: by Marek Zak, Malgorzata Biskup, Pawel Macek, Halina Krol, Szymon Krupnik, Anna Opuchlik Objective Breast cancer treatment, including radical surgery, is also pursued as late as the 7th - 8th decade of women’s lives. Standard physical rehabilitation procedures offered to those women are predominantly focused on attenuating specific functional deficits of the upper limb and trunk. Seldom do they entail any regimens specifically aimed at recovering overall functionality, and reducing exposure to falls-risk.The study aimed to assess potential interrelationships between the self-reported falls, individual functional capabilities and appreciably reducing exposure to falls-risk in a group of post-menopausal, post-surgical breast cancer survivors. Methods The study recruited 102 women (aged 65–79; mean age 70.2), post-surgical breast cancer survivors. The subjects were stratified by age into three groups: Group 1 (65–69 years); Group 2 (70–74 years), and Group 3 (75–79 years). Individual functional capabilities were assessed with Eight-foot up & go test (8UG), chair stand test (CST), and 2-minute step test (2ST). Tinetti POMA test was applied to assess gait and balance disorders. Self-reported falls in the past year were ascertained through a questionnaire. Results Assessment of individual aerobic endurance (2ST) also demonstrated a clear deficit in the mean scores category in all respective age sub-groups, as compared against the reference values. The deficits ranged from 4.86 to 15.90 steps less than the normative values; the oldest subjects demonstrating the largest deficit. The aerobic endurance tests results significantly impacted the ultimate assessment of an individual falls-risk in the oldest group. The analysis of the number of falls sustained within the recent year indicated that 43.67% of the subjects fell victim of such incidents. Conclusion An individual exposure to falls-risk was found to be appreciably more dependent upon individual aerobic endurance rather than overall strength of the lower part of the body in the breast cancer survivors over 75.

Description: by Jae Ha Gwak, So Young Sohn Background Recently, the need for rapid wound-healing has significantly increased because of the increasing number of patients who are diagnosed with diabetes and obesity. These conditions have contributed to a surge in the number of patients with chronic wounds worldwide. Furthermore, many cost-effective wound-healing technologies have been developed in order to keep up with the increased demand. In this paper, we performed a quantitative study of the trends associated with wound-healing technologies using patent data. Methodology We analyzed the trends considering four different groups of patent applicants: firms, universities, research institutes, and individuals using a structural topic model. In addition, we analyzed the knowledge flow between patent applicants using citation analysis, and confirmed the role of applicants in the knowledge-flow network using k-means clustering. As a result, the primary wound-healing technology patents applied for by the four groups varied considerably, and we classified the roles of patent applicants were found in the knowledge-flow network. Conclusions Our results showed the organizations that are leading each area of wound-healing technology. Furthermore, from the results, we identified specific institutions that are efficient for spreading knowledge related to wound-healing technology based on the patents. This information can contribute to the planning of investment strategies and technology policies related to wound-healing.

Description: by Xiyang Liu, Jiewei Jiang, Kai Zhang, Erping Long, Jiangtao Cui, Mingmin Zhu, Yingying An, Jia Zhang, Zhenzhen Liu, Zhuoling Lin, Xiaoyan Li, Jingjing Chen, Qianzhong Cao, Jing Li, Xiaohang Wu, Dongni Wang, Haotian Lin Slit-lamp images play an essential role for diagnosis of pediatric cataracts. We present a computer vision-based framework for the automatic localization and diagnosis of slit-lamp images by identifying the lens region of interest (ROI) and employing a deep learning convolutional neural network (CNN). First, three grading degrees for slit-lamp images are proposed in conjunction with three leading ophthalmologists. The lens ROI is located in an automated manner in the original image using two successive applications of Candy detection and the Hough transform, which are cropped, resized to a fixed size and used to form pediatric cataract datasets. These datasets are fed into the CNN to extract high-level features and implement automatic classification and grading. To demonstrate the performance and effectiveness of the deep features extracted in the CNN, we investigate the features combined with support vector machine (SVM) and softmax classifier and compare these with the traditional representative methods. The qualitative and quantitative experimental results demonstrate that our proposed method offers exceptional mean accuracy, sensitivity and specificity: classification (97.07%, 97.28%, and 96.83%) and a three-degree grading area (89.02%, 86.63%, and 90.75%), density (92.68%, 91.05%, and 93.94%) and location (89.28%, 82.70%, and 93.08%). Finally, we developed and deployed a potential automatic diagnostic software for ophthalmologists and patients in clinical applications to implement the validated model.

Description: by Cissy J. Ballen, Harry W. Greene Taxonomic details of diversity are an essential scaffolding for biology education, yet outdated methods for teaching the tree of life (TOL), as implied by textbook content and usage, are still commonly employed. Here, we show that the traditional approach only vaguely represents evolutionary relationships, fails to denote major events in the history of life, and relies heavily on memorizing near-meaningless taxonomic ranks. Conversely, a clade-based strategy—focused on common ancestry, monophyletic groups, and derived functional traits—is explicitly based on Darwin’s “descent with modification,” provides students with a rational system for organizing the details of biodiversity, and readily lends itself to active learning techniques. We advocate for a phylogenetic classification that mirrors the TOL, a pedagogical format of increasingly complex but always hierarchical presentations, and the adoption of active learning technologies and tactics.

Description: by The PLOS ONE Staff

Description: by David L. Dickinson, Sean P. A. Drummond, Todd McElroy Chronic sleep restriction (SR) increases sleepiness, negatively impacts mood, and impairs a variety of cognitive performance measures. The vast majority of work establishing these effects are tightly controlled in-lab experimental studies. Examining commonly-experienced levels of SR in naturalistic settings is more difficult and generally involves observational methods, rather than active manipulations of sleep. The same is true for analyzing behavioral and cognitive outcomes at circadian unfavorable times. The current study tested the ability of an at-home protocol to manipulate sleep schedules (i.e., impose SR), as well as create a mismatch between a subject’s circadian preference and time of testing. Viability of the protocol was assessed via completion, compliance with the SR, and success at manipulating sleepiness and mood. An online survey was completed by 3630 individuals to assess initial eligibility, 256 agreed via email response to participate in the 3-week study, 221 showed for the initial in-person session, and 184 completed the protocol (175 with complete data). The protocol consisted of 1 week at-home SR (5-6 hours in bed/night), 1 week wash-out, and 1 week well-rested (WR: 8-9 hours in bed/night). Sleep was monitored with actigraphy, diary, and call-ins. Risk management strategies were implemented for subject safety. At the end of each experimental week, subjects reported sleepiness and mood ratings. Protocol completion was 83%, with lower depression scores, higher anxiety scores, and morning session assignment predicting completion. Compliance with the sleep schedule was also very good. Subjects spent approximately 2 hours less time in bed/night and obtained an average of 1.5 hours less nightly sleep during SR, relative to WR, with 82% of subjects obtaining at least 60 minutes less average nightly sleep. Sleepiness and mood were impacted as expected by SR. These findings show the viability of studying experimental chronic sleep restriction outside the laboratory, assuming appropriate safety precautions are taken, thus allowing investigators to significantly increase ecological validity over strictly controlled in-lab studies.

Description: by Orly Dorot, Hermann Steller, Daniel Segal, Mia Horowitz

Description: by Melissa J. Armstrong, C. Daniel Mullins, Gary S. Gronseth, Anna R. Gagliardi Background Patient and consumer engagement in clinical practice guideline development is internationally advocated, but limited research explores mechanisms for successful engagement. Objective To investigate the perspectives of potential patient/consumer guideline representatives on topics pertaining to engagement including guideline development group composition and barriers to and facilitators of engagement. Setting and participants Participants were guideline-naïve volunteers for programs designed to link community members to academic research with diverse ages, gender, race, and degrees of experience interacting with health care professionals. Methods Three focus groups and one key informant interview were conducted and analyzed using a qualitative descriptive approach. Results Participants recommended small, diverse guideline development groups engaging multiple patient/consumer stakeholders with no prior relationships with each other or professional panel members. No consensus was achieved on the ideal balance of patient/consumer and professional stakeholders. Pre-meeting reading/training and an identified contact person were described as keys to successful early engagement; skilled facilitators, understandable speech and language, and established mechanisms for soliciting patient opinions were suggested to enhance engagement at meetings. Conclusions Most suggestions for effective patient/consumer engagement in guidelines require forethought and planning but little additional expense, making these strategies easily accessible to guideline developers desiring to achieve more meaningful patient and consumer engagement.

Description: by Jie Wang, Suying Chang, Liyun Zhao, Wentao Yu, Jian Zhang, Qingqing Man, Li He, Yifan Duan, Hui Wang, Robert Scherpbier, Shi-an Yin Background Poor growth and micronutrient deficiency mainly attack older infants and young children. Some countries have adopted clinically effective measures to combat malnutrition, but the compliance and improvement in efficacy of intervention vehicles in national programs require evaluation. Methods Baseline and follow-up cross-sectional surveys were conducted before and after a nutrition intervention program in 3 national poverty counties in China. Soybean-based complementary food supplements called Yingyangbao (YYB) in Chinese and training materials on child feeding were distributed to households with children aged 6–23 months for 18 months. Representative children were selected by probability proportional to size sampling methods to assess compliance of YYB and the intervention efficacy. A questionnaire was designed to collect data on basic characteristics of children, breastfeeding, 24-hour dietary intake, and consumption and appetite of YYB. Anthropometrics and hemoglobin were measured in the field, and anemia prevalence was evaluated. Venous blood was drawn from children aged 12–35 months to evaluate micronutrient status. Logistic regression was used to identify the risk factors for children’s anemia. Results Of the children involved in the follow-up survey (n = 693), the P 50 ( P 25, P 75) intake of YYB was 6.7 (3.5, 7.0) sachets weekly, and 54.7% of the children liked the taste of YYB. Compared with the baseline situation (n = 823), the proportion of children fed a diverse diet and foods rich in iron or vitamin A increased ( P 〈 0.01) in the follow-up study. The prevalence of stunting and underweight decreased ( P 〈 0.05), the prevalence of anemia decreased from 28.0% to 19.9% ( P 〈 0.01), and the prevalence of vitamin B 12 deficiency decreased from 26.8% to 15.4% ( P 〈 0.01). For children aged 12–23 months, those who liked YYB and consumed 6 or more sachets of YYB weekly were at lower risk for anemia (OR = 0.34, 95% CI 0.13–0.90, P 〈 0.05), but the risk of stunting was associated with a non-diverse diet (OR = 1.48, 95% CI 1.06–2.07, P 〈 0.05). Conclusion The quality of diet and nutritional status of children aged 6–23 months are significantly improved by the intervention of YYB and nutrition education, and good compliance to YYB contributes to a low risk for anemia. Trial Registration Chinese Clinical Trial Registry ChiCTR-OOC-16008846

Description: by Saeam Shin, Sung Ran Cho, Sinyoung Kim, Jong Rak Choi, Kyung-A Lee Optimal timing of apheresis initiation is important for maximizing the hematopoietic stem cell (HSC) yield. This study aimed to identify useful parameters from automatic hematology analyzers for predicting the peripheral blood CD34+ cell count after mobilization. We prospectively enrolled 53 healthy donors and 72 patients, and evaluated 43 cell morphology parameters from Unicel DxH800 (Beckman Coulter, USA) and Advia 2120i (Siemens Healthcare Diagnostics, USA). The correlation of each parameter with the CD34+ cell count in pre-apheresis blood samples was analyzed. The delta neutrophil index (DNI) from Advia 2120i, standard deviation of volume of neutrophils and monocytes (SD-V-NE and SD-V-MO), standard deviation of conductivity of neutrophils and monocytes (SD-C-NE and SD-C-MO), mean conductivity of neutrophils and monocytes (MN-C-NE and MN-C-MO), and standard deviation of axial light loss of neutrophils and monocytes (SD-AL2-NE and SD-AL2-MO) from DxH800 showed significant correlations with the CD34+ cell count. SD-V-NE, SD-C-NE, and SD-C-MO showed good or fair area under the curve values for the prediction of the CD34+ cell count. SD-V-NE, SD-C-NE, and SD-C-MO from DxH800 will provide rapid, useful information for the initiation of apheresis after mobilization.

Description: by Shankar Raj Devkota, Eunju Kwon, Sung Chul Ha, Hyeun Wook Chang, Dong Young Kim Bacillus subtilis SigW is localized to the cell membrane and is inactivated by the tight interaction with anti-sigma RsiW under normal growth conditions. Whereas SigW is discharged from RsiW binding and thus initiates the transcription of its regulon under diverse stress conditions such as antibiotics and alkaline shock. The release and activation of SigW in response to extracytoplasmic signals is induced by the regulated intramembrane proteolysis of RsiW. As a ZAS (Zinc-containing anti-sigma) family protein, RsiW has a CHCC zinc binding motif, which implies that its anti-sigma activity may be regulated by the state of zinc coordination in addition to the proteolytic cleavage of RsiW. To understand the regulation mode of SigW activity by RsiW, we determined the crystal structures of SigW in complex with the cytoplasmic domain of RsiW, and compared the conformation of the CHCC motif in the reduced/zinc binding and the oxidized states. The structures revealed that RsiW inhibits the promoter binding of SigW by interacting with the surface groove of SigW. The interaction between SigW and RsiW is not disrupted by the oxidation of the CHCC motif in RsiW, suggesting that SigW activity might not be regulated by the zinc coordination states of the CHCC motif.

Description: by Aikichi Iwamoto, Rikizo Taira, Yoshiyuki Yokomaku, Tomohiko Koibuchi, Mahbubur Rahman, Yoko Izumi, Kenji Tadokoro Japan has been known as a low HIV-prevalence country with a concentrated epidemic among high-risk groups. However, it has not been determined whether Japan meets the 90-90-90 goals set by the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO). Moreover, to date, the HIV care cascade has not been examined. We estimated the total number of diagnosed people living with HIV/AIDS (PLWHA) (n = 22,840) based on legal reports to the Ministry of Health, Labour and Welfare by subtracting the number of foreigners who left Japan (n = 2,273) and deaths (n = 2,321) from the cumulative diagnosis report (n = 27,434). The number of total undiagnosed PLWHA was estimated by age and sex specific HIV-positive rates observed among first-time blood donors between 2011–2015 in Japan. Our estimates show that 14.4% (n = 3,830) of all PLWHA (n = 26,670) were undiagnosed in Japan at the end of 2015. The number of patients retained in care (n = 20,615: 77.3% of PLWHA), the percentage of those on antiretroviral therapy (n = 18,921: 70.9% of PLWHA) and those with suppressed viral loads (

Description: by David Rodrigues, Diniz Lopes, Madoka Kumashiro When individuals are highly committed to their romantic relationship, they are more likely to engage in pro-relationship maintenance mechanisms. The present research expanded on the notion that commitment redirects self-oriented goals to consider broader relational goals and examined whether commitment interacts with a promotion and prevention focus to activate derogation of attractive alternatives. Three studies used cross-sectional and experimental approaches. Study 1 showed that romantically involved individuals predominantly focused on promotion, but not prevention, reported less initial attraction to an attractive target than single individuals, especially when highly committed to their relationship. Study 2 showed that romantically involved individuals induced in a promotion focus, compared to those in prevention focus, reported less initial attraction, but only when more committed to their relationship. Regardless of regulatory focus manipulation, more committed individuals were also less likely to perceive quality among alternative scenarios and to be attentive to alternative others in general. Finally, Study 3 showed that romantically involved individuals induced in promotion focus and primed with high commitment reported less initial attraction, than those primed with low commitment, or than those induced in prevention focus. Once again, for these latter no differences occurred according to commitment prime. Together, the findings suggest that highly committed promotion focused individuals consider broader relationship goals and activate relationship maintenance behaviors such as derogation of attractive alternatives to promote their relationship.

Description: by Kyosuke Uno, Toh Miyazaki, Kengo Sodeyama, Yoshiaki Miyamoto, Atsumi Nitta Shati/Nat8L significantly increased in the nucleus accumbens (NAc) of mice after repeated methamphetamine (METH) treatment. We reported that Shati/Nat8L overexpression in mouse NAc attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference. We recently found that Shati/Nat8L overexpression in NAc regulates the dopaminergic neuronal system via the activation of group II mGluRs by elevated N -acetylaspartylglutamate following N- acetylaspartate increase due to the overexpression. These findings suggest that Shati/Nat8L suppresses METH-induced responses. However, the mechanism by which METH increases the Shati/Nat8L mRNA expression in NAc is unclear. To investigate the regulatory mechanism of Shati/Nat8L mRNA expression, we performed a mouse Shati/Nat8L luciferase assay using PC12 cells. Next, we investigated the response of METH to Shati/Nat8L expression and CREB activity using mouse brain slices of NAc, METH administration to mice, and western blotting for CREB activity of specific dopamine receptor signals in vivo and ex vivo. We found that METH activates CREB binding to the Shati/Nat8L promoter to induce the Shati/Nat8L mRNA expression. Furthermore, the dopamine D1 receptor antagonist SCH23390, but not the dopamine D2 receptor antagonist sulpiride, inhibited the upregulation of Shati/Nat8L and CREB activities in the mouse NAc slices. Thus, the administration of the dopamine D1 receptor agonist SKF38393 increased the Shati/Nat8L mRNA expression in mouse NAc. These results showed that the Shati/Nat8L mRNA was increased by METH-induced CREB pathway via dopamine D1 receptor signaling in mouse NAc. These findings may contribute to development of a clinical tool for METH addiction.

Description: by Na Zhang, Richard Fielding, Inda Soong, Karen K. K. Chan, Conrad Lee, Alice Ng, Wing Kin Sze, Janice Tsang, Victor Lee, Wendy Wing Tak Lam Objective The eight-item Brief Illness Perception Questionnaire (B-IPQ) supposedly evaluates cognitive and emotional representations of illness. This study examined the validity and reliability of a traditional Chinese version of the B-IPQ in Hong Kong Chinese breast cancer survivors. Methods 358 Chinese breast cancer survivors who had recently ended their primary treatment completed this B-IPQ Chinese version. Confirmatory factor analysis (CFA) tested the factor structure. The internal consistency, construct, predictive and convergent validities of the scale were assessed. Results CFA revealed that the original three-factor (cognitive-emotional representations and illness comprehensibility) structure of the B-IPQ poorly fitted our sample. After deleting one item measuring illness coherence, seven-item gave an optimal two-factor (cognitive-emotional representations) structure for the B-IPQ (B-IPQ-7). Cronbach’s alpha for the two subscales were 0.653 and 0.821, and for the overall seven-item scale of B-IPQ was 0.783. Correlations of illness perception and physical symptom distress, anxiety, depression and known-group comparison between different treatment status suggested acceptable construct validity. The association between baseline illness perception and psychological distress at 3-month follow up supported predictive validity. Conclusions B-IPQ-7 appears to be a moderately valid measure of illness perception in cancer population, potentially useful for assessing illness representations in Chinese women with breast cancer.

Description: by Jing Meng, Zuoshan Li, Lin Shen Individuals with autism-spectrum disorder (ASD) exhibit impairments in response to others’ pain. Evidence suggests that features of autism are not restricted to individuals with ASD, and that autistic traits vary throughout the general population. To investigate the association between autistic traits and the responses to others’ pain in typically developing adults, we employed the Autism-Spectrum Quotient (AQ) to quantify autistic traits in a group of 1670 healthy adults and explored whether 60 participants (30 males and 30 females) with 10% highest AQ scores (High-AQ) would exhibit difficulties in the responses to others’ pain relative to 60 participants (30 males and 30 females) with 10% lowest AQ scores (Low-AQ). This study included a Visual Task and an Auditory Task to test behavioral differences between High-AQ and Low-AQ groups’ responses to others’ pain in both modalities. For the Visual Task, participants were instructed to respond to pictures depicting others’ pain. They were instructed to judge the stimuli type (painful or not), judge others’ pain intensity, and indicate the unpleasantness they personally felt. For the Auditory Task, experimental procedures were identical to the Visual Task except that painful voices were added. Results showed the High-AQ group was less accurate than the Low-AQ group in judging others’ pain. Moreover, relative to Low-AQ males, High-AQ males had significantly longer reaction times in judging others’ pain in the Auditory Task. However, High-AQ and Low-AQ females showed similar reaction times in both tasks. These findings demonstrated identification of others’ pain by healthy adults is related to the extent of autistic traits, gender, and modality.

Description: by Fei Chen, Yuan Zhang, Ashley B. Daugherty, Zunyi Yang, Ryan Shaw, Mengxing Dong, Stefan Lutz, Steven A. Benner One research goal for unnatural base pair (UBP) is to replicate, transcribe and translate them in vivo . Accordingly, the corresponding unnatural nucleoside triphosphates must be available at sufficient concentrations within the cell. To achieve this goal, the unnatural nucleoside analogues must be phosphorylated to the corresponding nucleoside triphosphates by a cascade of three kinases. The first step is the monophosphorylation of unnatural deoxynucleoside catalyzed by deoxynucleoside kinases (dNK), which is generally considered the rate limiting step because of the high specificity of dNKs. Here, we applied a Drosophila melanogaster deoxyribonucleoside kinase (DmdNK) to the phosphorylation of an UBP (a pyrimidine analogue (6-amino-5-nitro-3-(1’-b-d-2’-deoxyribofuranosyl)-2(1H)-pyridone, Z) and its complementary purine analogue (2-amino-8-(1’-b-d-2’-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one, P). The results showed that DmdNK could efficiently phosphorylate only the dP nucleoside. To improve the catalytic efficiency, a DmdNK-Q81E mutant was created based on rational design and structural analyses. This mutant could efficiently phosphorylate both dZ and dP nucleoside. Structural modeling indicated that the increased efficiency of dZ phosphorylation by the DmdNK-Q81E mutant might be related to the three additional hydrogen bonds formed between E81 and the dZ base. Overall, this study provides a groundwork for the biological phosphorylation and synthesis of unnatural base pair in vivo .

Description: by Karina Ribeiro Silva, Isis Côrtes, Sally Liechocki, João Regis Ivar Carneiro, Antônio Augusto Peixoto Souza, Radovan Borojevic, Clarissa Menezes Maya-Monteiro, Leandra Santos Baptista Background/Objectives The pathological condition of obesity is accompanied by a dysfunctional adipose tissue. We postulate that subcutaneous, preperitoneal and visceral obese abdominal white adipose tissue depots could have stromal vascular fractions (SVF) with distinct composition and adipose stem cells (ASC) that would differentially account for the pathogenesis of obesity. Methods In order to evaluate the distribution of SVF subpopulations, samples of subcutaneous, preperitoneal and visceral adipose tissues from morbidly obese women (n = 12, BMI: 46.2±5.1 kg/m 2 ) were collected during bariatric surgery, enzymatically digested and analyzed by flow cytometry (n = 12). ASC from all depots were evaluated for morphology, surface expression, ability to accumulate lipid after induction and cytokine secretion (n = 3). Results A high content of preadipocytes was found in the SVF of subcutaneous depot ( p = 0.0178). ASC from the three depots had similar fibroblastoid morphology with a homogeneous expression of CD34, CD146, CD105, CD73 and CD90. ASC from the visceral depot secreted the highest levels of IL-6, MCP-1 and G-CSF ( p = 0.0278). Interestingly, preperitoneal ASC under lipid accumulation stimulus showed the lowest levels of all the secreted cytokines, except for adiponectin that was enhanced ( p = 0.0278). Conclusions ASC from preperitoneal adipose tissue revealed the less pro-inflammatory properties, although it is an internal adipose depot. Conversely, ASC from visceral adipose tissue are the most pro-inflammatory. Therefore, ASC from subcutaneous, visceral and preperitoneal adipose depots could differentially contribute to the chronic inflammatory scenario of obesity.

Description: by Daijiro Hori, Brittany Dunkerly-Eyring, Yohei Nomura, Debjit Biswas, Jochen Steppan, Jorge Henao-Mejia, Hideo Adachi, Lakshmi Santhanam, Dan E. Berkowitz, Charles Steenbergen, Richard A. Flavell, Samarjit Das Background Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening. Methods and results qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1 -/- mice and wild types (C57BL6J:WT) were followed weekly for pulse wave velocity (PWV) and blood pressure measurements. After 20 weeks, the mice were tested for endothelial function and aortic modulus. There was a progressive increase in PWV and higher systolic blood pressure in miR-181a1/b1 -/- mice compared with WTs. At 21 weeks, aortic modulus was significantly greater in the miR-181a1/b1 -/- group, and serum TGF-β was found to be elevated at this time. A luciferase reporter assay confirmed miR-181b targets TGF-βi (TGF-β induced) in the aortic VSMCs. In contrast, wire myography revealed unaltered endothelial function along with higher nitric oxide production in the miR-181a1/b1 -/- group. Cultured VECs and VSMCs from the mouse aorta showed more secreted TGF-β in VSMCs of the miR-181a1/b1 -/- group; whereas, no change was observed from VECs. Circulating levels of angiotensin II were similar in both groups. Treatment with losartan (0.6 g/L) prevented the increase in PWV, blood pressure, and vascular stiffness in miR-181a1/b1 -/- mice. Immunohistochemistry and western blot for p-SMAD2/3 validated the inhibitory effect of losartan on TGF-β signaling in miR-181a1/b1 -/- mice. Conclusions Decreased miR-181b with aging plays a critical role in ECM remodeling by removing the brake on the TGF-β, pSMAD2/3 pathway.

Description: by Raquel Pascua-Maestro, Sergio Diez-Hermano, Concepción Lillo, Maria D. Ganfornina, Diego Sanchez Environmental insults such as oxidative stress can damage cell membranes. Lysosomes are particularly sensitive to membrane permeabilization since their function depends on intraluminal acidic pH and requires stable membrane-dependent proton gradients. Among the catalog of oxidative stress-responsive genes is the Lipocalin Apolipoprotein D (ApoD), an extracellular lipid binding protein endowed with antioxidant capacity. Within the nervous system, cell types in the defense frontline, such as astrocytes, secrete ApoD to help neurons cope with the challenge. The protecting role of ApoD is known from cellular to organism level, and many of its downstream effects, including optimization of autophagy upon neurodegeneration, have been described. However, we still cannot assign a cellular mechanism to ApoD gene that explains how this protection is accomplished. Here we perform a comprehensive analysis of ApoD intracellular traffic and demonstrate its role in lysosomal pH homeostasis upon paraquat-induced oxidative stress. By combining single-lysosome in vivo pH measurements with immunodetection, we demonstrate that ApoD is endocytosed and targeted to a subset of vulnerable lysosomes in a stress-dependent manner. ApoD is functionally stable in this acidic environment, and its presence is sufficient and necessary for lysosomes to recover from oxidation-induced alkalinization, both in astrocytes and neurons. This function is accomplished by preventing lysosomal membrane permeabilization. Two lysosomal-dependent biological processes, myelin phagocytosis by astrocytes and optimization of neurodegeneration-triggered autophagy in a Drosophila in vivo model, require ApoD-related Lipocalins. Our results uncover a previously unknown biological function of ApoD, member of the finely regulated and evolutionary conserved gene family of extracellular Lipocalins. They set a lipoprotein-mediated regulation of lysosomal membrane integrity as a new mechanism at the hub of many cellular functions, critical for the outcome of a wide variety of neurodegenerative diseases. These results open therapeutic opportunities by providing a route of entry and a repair mechanism for lysosomes in pathological situations.

Description: by Katharine C. Abruzzi, Abigail Zadina, Weifei Luo, Evelyn Wiyanto, Reazur Rahman, Fang Guo, Orie Shafer, Michael Rosbash Locomotor activity rhythms are controlled by a network of ~150 circadian neurons within the adult Drosophila brain. They are subdivided based on their anatomical locations and properties. We profiled transcripts “around the clock” from three key groups of circadian neurons with different functions. We also profiled a non-circadian outgroup, dopaminergic (TH) neurons. They have cycling transcripts but fewer than clock neurons as well as low expression and poor cycling of clock gene transcripts. This suggests that TH neurons do not have a canonical circadian clock and that their gene expression cycling is driven by brain systemic cues. The three circadian groups are surprisingly diverse in their cycling transcripts and overall gene expression patterns, which include known and putative novel neuropeptides. Even the overall phase distributions of cycling transcripts are distinct, indicating that different regulatory principles govern transcript oscillations. This surprising cell-type diversity parallels the functional heterogeneity of the different neurons.

Description: by Yen-Fu Chen, Hsiu-Chuan Lin, Kai-Neng Chuang, Chih-Hsu Lin, Hsueh-Chi Yen, Chen-Hsiang Yeang Ambiguity in genetic codes exists in cases where certain stop codons are alternatively used to encode non-canonical amino acids. In selenoprotein transcripts, the UGA codon may either represent a translation termination signal or a selenocysteine (Sec) codon. Translating UGA to Sec requires selenium and specialized Sec incorporation machinery such as the interaction between the SECIS element and SBP2 protein, but how these factors quantitatively affect alternative assignments of UGA has not been fully investigated. We developed a model simulating the UGA decoding process. Our model is based on the following assumptions: (1) charged Sec-specific tRNAs (Sec-tRNA Sec ) and release factors compete for a UGA site, (2) Sec-tRNA Sec abundance is limited by the concentrations of selenium and Sec-specific tRNA (tRNA Sec ) precursors, and (3) all synthesis reactions follow first-order kinetics. We demonstrated that this model captured two prominent characteristics observed from experimental data. First, UGA to Sec decoding increases with elevated selenium availability, but saturates under high selenium supply. Second, the efficiency of Sec incorporation is reduced with increasing selenoprotein synthesis. We measured the expressions of four selenoprotein constructs and estimated their model parameters. Their inferred Sec incorporation efficiencies did not correlate well with their SECIS-SBP2 binding affinities, suggesting the existence of additional factors determining the hierarchy of selenoprotein synthesis under selenium deficiency. This model provides a framework to systematically study the interplay of factors affecting the dual definitions of a genetic codon.

Description: by Dingqiao Wen, Yun Yu, Luay Nakhleh

Description: by Hojjat Bazzazi, Aleksander S. Popel Vascular endothelial growth factor (VEGF) is a powerful regulator of neovascularization. VEGF binding to its cognate receptor, VEGFR2, activates a number of signaling pathways including ERK1/2. Activation of ERK1/2 is experimentally shown to involve sphingosine kinase 1 (SphK1) activation and its calcium-dependent translocation downstream of ERK1/2. Here we construct a rule-based computational model of signaling downstream of VEGFR2, by including SphK1 and calcium positive feedback mechanisms, and investigate their consequences on ERK1/2 activation. The model predicts the existence of VEGF threshold in ERK1/2 activation that can be continuously tuned by cellular concentrations of SphK1 and sphingosine 1 phosphate (S1P). The computer model also predicts powerful effects of perturbations in plasma and ER calcium pump rates and the current through the CRAC channels on ERK1/2 activation dynamics, highlighting the critical role of intracellular calcium in shaping the pERK1/2 signal. The model is then utilized to simulate anti-angiogenic therapeutic interventions targeting VEGFR2-ERK1/2 axis. Simulations indicate that monotherapies that exclusively target VEGFR2 phosphorylation, VEGF, or VEGFR2 are ineffective in shutting down signaling to ERK1/2. By simulating therapeutic strategies that target multiple nodes of the pathway such as Raf and SphK1, we conclude that combination therapy should be much more effective in blocking VEGF signaling to EKR1/2. The model has important implications for interventions that target signaling pathways in angiogenesis relevant to cancer, vascular diseases, and wound healing.

Description: by Marc Duez, Mathieu Giraud, Ryan Herbert, Tatiana Rocher, Mikaël Salson, Florian Thonier

Description: by Xiao Gao, Xiao Deng, Xin Wen, Ying She, Petra Corianne Vinke, Hong Chen

Description: by Igor Govorov, Signe Löfgren, Roza Chaireti, Margareta Holmström, Katarina Bremme, Miriam Mints

Description: by Andreas Meier, Kai Higashigaito, Katharina Martini, Moritz Wurnig, Burkhardt Seifert, Dagmar I. Keller, Thomas Frauenfelder, Hatem Alkadhi

Description: by Enrique Maguilla, Marcial Escudero

Description: by Shilpy Joshi, Guillaume Davidson, Stéphanie Le Gras, Shuichi Watanabe, Thomas Braun, Gabrielle Mengus, Irwin Davidson The TEAD family of transcription factors (TEAD1-4) bind the MCAT element in the regulatory elements of both growth promoting and myogenic differentiation genes. Defining TEAD transcription factor function in myogenesis has proved elusive due to overlapping expression of family members and their functional redundancy. We show that silencing of either Tead1 , Tead2 or Tead4 did not effect primary myoblast (PM) differentiation, but that their simultaneous knockdown strongly impaired differentiation. In contrast, Tead1 or Tead4 silencing impaired C2C12 differentiation showing their different contributions in PMs and C2C12 cells. Chromatin immunoprecipitation identified enhancers associated with myogenic genes bound by combinations of Tead4, Myod1 or Myog. Tead4 regulated distinct gene sets in C2C12 cells and PMs involving both activation of the myogenic program and repression of growth and signaling pathways. ChIP-seq from mature mouse muscle fibres in vivo identified a set of highly transcribed muscle cell-identity genes and sites bound by Tead1 and Tead4. Although inactivation of Tead4 in mature muscle fibres caused no obvious phenotype under normal conditions, notexin-induced muscle regeneration was delayed in Tead4 mutants suggesting an important role in myogenic differentiation in vivo . By combining knockdown in cell models in vitro with Tead4 inactivation in muscle in vivo , we provide the first comprehensive description of the specific and redundant roles of Tead factors in myogenic differentiation.

Description: by The PLOS ONE Journal Staff

Description: by Christopher Thompson, Sahar Rahim, Jeremiah Arnold, Abigail Hielscher The extracellular matrix (ECM) is abnormal in breast tumors and has been reported to contribute to breast tumor progression. One factor, which may drive ongoing matrix synthesis in breast tumors, is the loss of stromal caveolin-1 (cav-1), a scaffolding protein of caveolae, which has been linked to breast tumor aggressiveness. To determine whether loss of cav-1 results in the abnormal expression of matrix proteins, mammary glands from cav- 1-/- and cav- 1 +/+ mice were investigated for differences in expression of several ECM proteins. In addition, the presence of myofibroblasts, changes in the vessel density, and differences in duct number and size were assessed in the mammary glands of both animal models. Using immunohistochemistry, expression of fibronectin, tenascin-C, collagens and αSMA were significantly increased in the mammary glands of cav-1-/- mice. Second harmonic generation revealed more organized collagen fibers in cav-1 -/- glands and supported immunohistochemical analyses of increased collagen abundance in the glands of cav-1 -/- mice. Analysis of the ductal structure demonstrated a significant increase in the number of proliferating ducts in addition to significant increases in the duct circumference and area in cav-1 -/- glands compared to cav- 1 +/+ glands. Differences in microvessel density weren’t apparent between the animal models. In summary, we found that the loss of cav-1 resulted in increased ECM and α-SMA protein expression in murine mammary glands. Furthermore, we found that an abnormal ductal architecture accompanied the loss of cav-1. These data support a role for cav-1 in maintaining mammary gland structure.

Description: by Wei Dong, Amber Farooqui, Alberto J. Leon, David J. Kelvin Influenza viruses cause mild to severe respiratory infections in humans. Due to efficient means of transmission, the viruses infect human population on a large scale. Apart from vaccines, antiviral drugs are used to control infection; neuraminidase inhibitors are thought to be the first choice of treatment, particularly for severe cases. Rapidly evolving and emerging influenza viruses with increased frequency of viral resistance to these drugs stress the need to explore novel antiviral compounds. In this study, we investigated antiviral activity of ginseng extract and ginsenosides, the ginseng-derived triterpene and saponin compounds, against 2009 pandemic H1N1 virus in vitro and in vivo. Our data showed that treatment of mice with ginsenosides protected the animals from lethal 2009 pandemic H1N1 infection and lowered viral titers in animal lungs. Mechanistic studies revealed that ginsenosides interact with viral hemagglutinin protein and prevent the attachment of virus with α 2–3’ sialic acid receptors present on host cell surfaces. The interference in the viral attachment process subsequently minimizes viral entry into the cells and decreases the severity of the viral infection. We also describe that sugar moieties present in ginsenosides are indispensible for their attachment with viral HA protein. On the basis of our observations, we can say that ginsenosides are promising candidates for the development of antiviral drugs for influenza viruses.

Description: by Vladyslav Oles, Alexander Panchenko, Andrei Smertenko Rise of atmospheric CO 2 is one of the main causes of global warming. Catastrophic climate change can be avoided by reducing emissions and increasing sequestration of CO 2 . Trees are known to sequester CO 2 during photosynthesis, and then store it as wood biomass. Thus, breeding of trees with higher wood yield would mitigate global warming as well as augment production of renewable construction materials, energy, and industrial feedstock. Wood is made of cellulose-rich xylem cells produced through proliferation of a specialized stem cell niche called cambium. Importance of cambium in xylem cells production makes it an ideal target for the tree breeding programs; however our knowledge about control of cambium proliferation remains limited. The morphology and regulation of cambium are different from those of stem cell niches that control axial growth. For this reason, translating the knowledge about axial growth to radial growth has limited use. Furthermore, genetic approaches cannot be easily applied because overlaying tissues conceal cambium from direct observation and complicate identification of mutants. To overcome the paucity of experimental tools in cambium biology, we constructed a Boolean network CARENET (CAmbium REgulation gene NETwork) for modelling cambium activity, which includes the key transcription factors WOX4 and HD-ZIP III as well as their potential regulators. Our simulations predict that: (1) auxin, cytokinin, gibberellin, and brassinosteroids act cooperatively in promoting transcription of WOX4 and HD-ZIP III ; (2) auxin and cytokinin pathways negatively regulate each other; (3) hormonal pathways act redundantly in sustaining cambium activity; (4) individual cambium cells can have diverse molecular identities. CARENET can be extended to include components of other signalling pathways and be integrated with models of xylem and phloem differentiation. Such extended models would facilitate breeding trees with higher wood yield.

Description: by Àngela Domínguez, Núria Soldevila, Diana Toledo, Núria Torner, Luis Force, María José Pérez, Vicente Martín, Lourdes Rodríguez-Rojas, Jenaro Astray, Mikel Egurrola, Francisco Sanz, Jesús Castilla, Working Group of the Project PI12/02079 Pneumococcal pneumonia is a serious cause of morbidity and mortality in the elderly, but investigation of the etiological agent of community-acquired pneumonia (CAP) is not possible in most hospitalized patients. The aim of this study was to estimate the effect of pneumococcal polysaccharide vaccination (PPSV23) in preventing CAP hospitalization and reducing the risk of intensive care unit admission (ICU) and fatal outcomes in hospitalized people aged ≥65 years. We made a multicenter case-control study in 20 Spanish hospitals during 2013–2014 and 2014–2015. We selected patients aged ≥65 years hospitalized with a diagnosis of pneumonia and controls matched by sex, age and date of hospitalization. Multivariate analysis was performed using conditional logistic regression to estimate vaccine effectiveness and unconditional logistic regression to evaluate the reduction in the risk of severe and fatal outcomes. 1895 cases and 1895 controls were included; 13.7% of cases and 14.4% of controls had received PPSV23 in the last five years. The effectiveness of PPSV23 in preventing CAP hospitalization was 15.2% (95% CI -3.1–30.3). The benefit of PPSV23 in avoiding ICU admission or death was 28.1% (95% CI -14.3–56.9) in all patients, 30.9% (95% CI -32.2–67.4) in immunocompetent patients and 26.9% (95% CI -38.6–64.8) in immunocompromised patients. In conclusion, PPSV23 showed a modest trend to avoidance of hospitalizations due to CAP and to the prevention of death or ICU admission in elderly patients hospitalized with a diagnosis of CAP.

Description: by Mirsha Quinto-Sánchez, Celia Cintas, Caio Cesar Silva de Cerqueira, Virginia Ramallo, Victor Acuña-Alonzo, Kaustubh Adhikari, Lucía Castillo, Jorge Gomez-Valdés, Paola Everardo, Francisco De Avila, Tábita Hünemeier, Claudia Jaramillo, Williams Arias, Macarena Fuentes, Carla Gallo, Giovani Poletti, Lavinia Schuler-Faccini, Maria Cátira Bortolini, Samuel Canizales-Quinteros, Francisco Rothhammer, Gabriel Bedoya, Javier Rosique, Andrés Ruiz-Linares, Rolando González-José

Description: by Hiroshi Kishikawa, Kayoko Kimura, Asako Ito, Kyoko Arahata, Sakiko Takarabe, Shogo Kaida, Takanori Kanai, Soichiro Miura, Jiro Nishida

Description: by Kenichi Suda, Leslie Rozeboom, Hui Yu, Kim Ellison, Christopher J. Rivard, Tetsuya Mitsudomi, Fred R. Hirsch Small cell lung cancer (SCLC) is a highly aggressive malignancy with few therapeutic advances in the treatment in recent decades. Based on a recent study that identified the spliceosome as a therapeutic vulnerability in MYC-driven breast cancers, we evaluated the efficacy of a spliceosome inhibitor in SCLC cell lines and analyzed the correlation with MYC status. Among 23 SCLC cell lines examined, eight showed high MYC protein expression (〉 80% positive cells) by immunohistochemistry (IHC), while 10 cell lines demonstrated no staining for MYC. The remaining five cell lines showed weak staining ( 〈 40% positive cells). All four cell lines that were previously demonstrated to have MYC gene amplification were positive for MYC by IHC. Four cell lines with high MYC expression and four with low MYC expression were used in further analysis. A spliceosome inhibitor, pladienolide B, showed high efficacy (IC 50 〈 12nM) in all eight cell lines tested, irrespective of the MYC IHC or MYC gene amplification status. We observed that the four cell lines with higher sensitivity to the spliceosome inhibitor were established from patients with prior chemotherapy. Therefore we chronically treated H1048 cells, that were established from a treatment-naïve patient, with cisplatin for 4 weeks, and found that H1048-cisplatin treated cells became more sensitive to pladienolide B. In conclusion, our in vitro results indicate that spliceosome inhibitors would be promising molecular target drugs in SCLC irrespective of the MYC status, especially in the second-line settings after an effective front-line chemotherapy.

Description: by Philipp A. Reuken, Dorian Torres, Michael Baier, Bettina Löffler, Christoph Lübbert, Norman Lippmann, Andreas Stallmach, Tony Bruns

Description: by Francesca Necchi, Allan Saul, Simona Rondini Serum Bactericidal Activity (SBA) assay is the method of choice to evaluate the complement-mediated functional activity of both infection- and vaccine-induced antibodies. To perform a typical SBA assay, serial dilutions of sera are incubated with target bacterial strains and complement. The conventional SBA assay is based on plating on agar the SBA reaction mix and counting the surviving bacterial colony forming units (CFU) at each serum dilution. Even with automated colony counting, it is labor-intensive, time-consuming and not amenable for large-scale studies. Here, we have developed a luminescence-based SBA (L-SBA) method able to detect surviving bacteria by measuring their ATP. At the end of the SBA reaction, a single commercially available reagent is added to each well of the SBA plate, and the resulting luminescence signal is measured in a microplate reader. The signal obtained is proportional to the ATP present, which is directly proportional to the number of viable bacteria. Bactericidal activity is subsequently calculated. We demonstrated the applicability of L-SBA with multiple bacterial serovars, from 5 species: Citrobacter freundii , Salmonella enterica serovars Typhimurium and Enteritidis, Shigella flexneri serovars 2a and 3a, Shigella sonnei and Neisseria meningitidis . Serum bactericidal titers obtained by the luminescence readout method strongly correlate with the data obtained by the conventional agar plate-based assay, and the new assay is highly reproducible. L-SBA considerably shortens assay time, facilitates data acquisition and analysis and reduces the operator dependency, avoiding the plating and counting of CFUs. Our results demonstrate that L-SBA is a useful high-throughput bactericidal assay.

Description: by Kai Zhang, Hua Zheng, Falin Chen, Ruida Li, Miao Yang, Zhiyun Ouyang, Jun Lan, Xuewu Xiang Nitrogen (N) fertilization is necessary to sustain productivity in eucalypt plantations, but it can increase the risk of greenhouse gas emissions. However, the response of soil greenhouse gas emissions to N fertilization might be influenced by soil characteristics, which is of great significance for accurately assessing greenhouse gas budgets and scientific fertilization in plantations. We conducted a two-year N fertilization experiment (control [CK], low N [LN], middle N [MN] and high N [HN] fertilization) in two eucalypt plantations with different soil characteristics (higher and lower soil organic carbon sites [HSOC and LSOC]) in Guangxi, China, and assessed soil–atmosphere greenhouse gas exchanges. The annual mean fluxes of soil CO 2 , CH 4 , and N 2 O were separately 153–266 mg m -2 h -1 , -55 –-40 μg m -2 h -1 , and 11–95 μg m -2 h -1 , with CO 2 and N 2 O emissions showing significant seasonal variations. N fertilization significantly increased soil CO 2 and N 2 O emissions and decreased CH 4 uptake at both sites. There were significant interactions of N fertilization and SOC level on soil CO 2 and N 2 O emissions. At the LSOC site, the annual mean flux of soil CO 2 emission was only significantly higher than the CK treatment in the HN treatment, but, at the HSOC site, the annual mean flux of soil CO 2 emission was significantly higher for both the LN (or MN) and HN treatments in comparison to the CK treatment. Under the CK and LN treatments, the annual mean flux of N 2 O emission was not significantly different between HSOC and LSOC sites, but under the HN treatment, it was significantly higher in the HSOC site than in the LSOC site. Correlation analysis showed that changes in soil CO 2 and N 2 O emissions were significantly related to soil dissolved organic carbon, ammonia, nitrate and pH. Our results suggested significant interactions of N fertilization and soil characteristics existed in soil–atmosphere greenhouse gas exchanges, which should be considered in assessing greenhouse gas budgets and scientific fertilization strategies in eucalypt plantations.

Description: by Kelvin Kamfwa, Dongyan Zhao, James D. Kelly, Karen A. Cichy Common bean ( Phaseolus vulgaris L.) fixes atmospheric nitrogen (N 2 ) through symbiotic nitrogen fixation (SNF) at levels lower than other grain legume crops. An understanding of the genes and molecular mechanisms underlying SNF will enable more effective strategies for the genetic improvement of SNF traits in common bean. In this study, transcriptome profiling was used to identify genes and molecular mechanisms underlying SNF differences between two common bean recombinant inbred lines that differed in their N-fixing abilities. Differential gene expression and functional enrichment analyses were performed on leaves, nodules and roots of the two lines when grown under N-fixing and non-fixing conditions. Receptor kinases, transmembrane transporters, and transcription factors were among the differentially expressed genes identified under N-fixing conditions, but not under non-fixing conditions. Genes up-regulated in the stronger nitrogen fixer, SA36, included those involved in molecular functions such as purine nucleoside binding, oxidoreductase and transmembrane receptor activities in nodules, and transport activity in roots. Transcription factors identified in this study are candidates for future work aimed at understanding the functional role of these genes in SNF. Information generated in this study will support the development of gene-based markers to accelerate genetic improvement of SNF in common bean.

Description: by Emily Saintas, Liam Abrahams, Gulshan T. Ahmad, Anu-Oluwa M. Ajakaiye, Abdulaziz S. H. A. M. AlHumaidi, Candice Ashmore-Harris, Iain Clark, Usha K. Dura, Carine N. Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M. U. Schöler, Husne Timur, Maxwell D. C. Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E. Hogwood, Pamela E. Lithgow, Michelle Rowe, Lyto Yiangou, Florian Rothweiler, Jindrich Cinatl jr., Richard Zehner, Anthony J. Baines, Michelle D. Garrett, Campbell W. Gourlay, Darren K. Griffin, William J. Gullick, Emma Hargreaves, Mark J. Howard, Daniel R. Lloyd, Jeremy S. Rossman, C. Mark Smales, Anastasios D. Tsaousis, Tobias von der Haar, Mark N. Wass, Martin Michaelis The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-AS r OXALI 4000 ). SK-N-AS r OXALI 4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-AS r OXALI 4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-AS r OXALI 4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-AS r OXALI 4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-AS r OXALI 4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-AS r OXALI 4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin.

Description: by Joaquin Paillamanque, Ana Sanchez-Tusie, Emerson M. Carmona, Claudia L. Treviño, Carolina Sandoval, Francisco Nualart, Nelson Osses, Juan G. Reyes Arachidonic acid (AA), a compound secreted by Sertoli cells (SC) in a FSH-dependent manner, is able to induce the release of Ca 2+ from internal stores in round spermatids and pachytene spermatocytes. In this study, the possible site(s) of action of AA in round spermatids, the signalling pathways associated and the intracellular Ca 2+ stores targeted by AA-induced signalling were pharmacologically characterized by measuring intracellular Ca 2+ using fluorescent Ca 2+ probes. Our results suggest that AA acts by interacting with a fatty acid G protein coupled receptor, initiating a G protein signalling cascade that may involve PLA2 and ERK activation, which in turn opens intracellular ryanodine-sensitive channels as well as NAADP-sensitive channels in acidic intracellular Ca 2+ stores. The results presented here also suggest that AMPK and PKA modulate this AA-induced Ca 2+ release from intracellular Ca 2+ stores in round spermatids. We propose that unsaturated free fatty acid lipid signalling in the seminiferous tubule is a novel regulatory component of rat spermatogenesis.

Description: by Nai-si Huang, Chen-lian Quan, Miao Mo, Jia-jian Chen, Ben-long Yang, Xiao-yan Huang, Jiong Wu Objectives The current study aims to summarize breast anthropomorphic measurement features in Chinese patients with breast diseases and to investigate their potential correlations with demographic factors. Materials and methods Fifteen breast anthropomorphic parameters of 605 Chinese female patients were collected prospectively. Breast ptosis status was scaled by two methods and breast volume was calculated according to a modified formula of BREAST-V. Results Among 1210 breasts, the average breast volume was 340.0±109.1 ml (91.8–919.2 ml). The distance from the nipple to the inframammary fold was 7.5±1.6 cm in the standing position. The width of the breast base was 14.3±1.4 cm (8.5–23.5 cm). The incidence of breast ptosis was 22.8% (274/1204), of which 37 (23.5%) and 79 (31.7%) women had severe ptosis assessed by different criteria. Increased height (OR[odds ratio] = 1.500, P

Description: by Dong-Ping Yang, Hai-Jun Zhou, Changsong Zhou The brain is highly energy consuming, therefore is under strong selective pressure to achieve cost-efficiency in both cortical connectivities and activities. However, cost-efficiency as a design principle for cortical activities has been rarely studied. Especially it is not clear how cost-efficiency is related to ubiquitously observed multi-scale properties: irregular firing, oscillations and neuronal avalanches. Here we demonstrate that these prominent properties can be simultaneously observed in a generic, biologically plausible neural circuit model that captures excitation-inhibition balance and realistic dynamics of synaptic conductance. Their co-emergence achieves minimal energy cost as well as maximal energy efficiency on information capacity, when neuronal firing are coordinated and shaped by moderate synchrony to reduce otherwise redundant spikes, and the dynamical clusterings are maintained in the form of neuronal avalanches. Such cost-efficient neural dynamics can be employed as a foundation for further efficient information processing under energy constraint.

Description: by Miguel Fribourg, Diomedes E. Logothetis, Javier González-Maeso, Stuart C. Sealfon, Belén Galocha-Iragüen, Fernando Las-Heras Andrés, Vladimir Brezina Overall cellular responses to biologically-relevant stimuli are mediated by networks of simpler lower-level processes. Although information about some of these processes can now be obtained by visualizing and recording events at the molecular level, this is still possible only in especially favorable cases. Therefore the development of methods to extract the dynamics and relationships between the different lower-level (microscopic) processes from the overall (macroscopic) response remains a crucial challenge in the understanding of many aspects of physiology. Here we have devised a hybrid computational-analytical method to accomplish this task, the SYStems-based MOLecular kinetic scheme Extractor (SYSMOLE). SYSMOLE utilizes system-identification input-output analysis to obtain a transfer function between the stimulus and the overall cellular response in the Laplace-transformed domain. It then derives a Markov-chain state molecular kinetic scheme uniquely associated with the transfer function by means of a classification procedure and an analytical step that imposes general biological constraints. We first tested SYSMOLE with synthetic data and evaluated its performance in terms of its rate of convergence to the correct molecular kinetic scheme and its robustness to noise. We then examined its performance on real experimental traces by analyzing macroscopic calcium-current traces elicited by membrane depolarization. SYSMOLE derived the correct, previously known molecular kinetic scheme describing the activation and inactivation of the underlying calcium channels and correctly identified the accepted mechanism of action of nifedipine, a calcium-channel blocker clinically used in patients with cardiovascular disease. Finally, we applied SYSMOLE to study the pharmacology of a new class of glutamate antipsychotic drugs and their crosstalk mechanism through a heteromeric complex of G protein-coupled receptors. Our results indicate that our methodology can be successfully applied to accurately derive molecular kinetic schemes from experimental macroscopic traces, and we anticipate that it may be useful in the study of a wide variety of biological systems.

Description: by Lingmei Sun, Kai Liao, Chengcheng Hang, Dayong Wang Objective To investigate the effects of honokiol on induction of reactive oxygen species (ROS), antioxidant defense systems, mitochondrial dysfunction, and apoptosis in Candida albicans . Methods To measure ROS accumulation, 2′,7′-dichlorofluorescein diacetate fluorescence was used. Lipid peroxidation was assessed using both fluorescence staining and a thiobarbituric acid reactive substances (TBARS) assay. Protein oxidation was determined using dinitrophenylhydrazine derivatization. Antioxidant enzymatic activities were measured using commercially available detection kits. Superoxide dismutase (SOD) genes expression was measured using real time RT-PCR. To assess its antifungal abilities and effectiveness on ROS accumulation, honokiol and the SOD inhibitor N,N′-diethyldithiocarbamate (DDC) were used simultaneously. Mitochondrial dysfunction was assessed by measuring the mitochondrial membrane potential (mtΔψ). Honokiol-induced apoptosis was assessed using an Annexin V-FITC apoptosis detection kit. Results ROS, lipid peroxidation, and protein oxidation occurred in a dose-dependent manner in C . albicans after honokiol treatment. Honokiol caused an increase in antioxidant enzymatic activity. In addition, honokiol treatment induced SOD genes expression in C . albicans cells. Moreover, addition of DDC resulted in increased endogenous ROS levels and potentiated the antifungal activity of honokiol. Mitochondrial dysfunction was confirmed by measured changes to mtΔψ. The level of apoptosis increased in a dose-dependent manner after honokiol treatment. Conclusions Collectively, these results indicate that honokiol acts as a pro-oxidant in C . albicans . Furthermore, the SOD inhibitor DDC can be used to potentiate the activity of honokiol against C . albicans .

Description: by Benjamin Udoka Nwosu, Louise Maranda, Ninfa Candela Importance Irritable bowel syndrome (IBS) is associated with significant morbidity in children and adolescents, and the therapeutic efficacy of available treatment options is limited. The role of vitamin D supplementation in pediatric IBS is unclear as the vitamin D status of pediatric patients with IBS is unknown. Equally, the relationship of vitamin D status with psychosomatic symptoms in children and adolescents is unclear. Aim To characterize the vitamin D status of pediatric patients with IBS using a case-control study design. Hypothesis Serum 25-hydroxyvitamin D [25(OH)D] concentration will be similar between patients with IBS and controls. Subjects and methods A retrospective case-controlled study of 116 controls (age 14.6 ± 4.3 y), female (n = 67; 58%) and 55 subjects with IBS (age 16.5 ± 3.1y), female (n = 44; 80%). Overweight was defined as BMI of ≥85 th but

Description: by Yun-Peng Huang, Cheng-Fei Du, Cheng-Kung Cheng, Zheng-Cheng Zhong, Xuan-Wei Chen, Gui Wu, Zhe-Chen Li, Jin-Duo Ye, Jian-Hua Lin, Li Zhen Wang

Description: We investigate the impact of the new LUNA rate for the nuclear reaction 22 Ne( p , ) 23 Na on the chemical ejecta of intermediate-mass stars, with particular focus on the thermally pulsing asymptotic giant branch (TP-AGB) stars that experience hot-bottom burning. To this aim, we use the PARSEC and COLIBRI codes to compute the complete evolution, from the pre-main sequence up to the termination of the TP-AGB phase, of a set of stellar models with initial masses in the range 3.0–6.0 M and metallicities Z i = 0.0005, 0.006 and 0.014. We find that the new LUNA measures have much reduced the nuclear uncertainties of the 22 Ne and 23 Na AGB ejecta that drop from factors of ~=10 to only a factor of few for the lowest metallicity models. Relying on the most recent estimations for the destruction rate of 23 Na, the uncertainties that still affect the 22 Ne and 23 Na AGB ejecta are mainly dominated by the evolutionary aspects (efficiency of mass-loss, third dredge-up, convection). Finally, we discuss how the LUNA results impact on the hypothesis that invokes massive AGB stars as the main agents of the observed O–Na anticorrelation in Galactic globular clusters. We derive quantitative indications on the efficiencies of key physical processes (mass-loss, third dredge-up, sodium destruction) in order to simultaneously reproduce both the Na-rich, O-poor extreme of the anticorrelation and the observational constraints on the CNO abundance. Results for the corresponding chemical ejecta are made publicly available.

Description: We fitted the 3–180 keV spectrum of all the observations of the neutron star low-mass X-ray binary 4U 1636–53 taken with the Rossi X-ray Timing Explorer using a model that includes a thermal Comptonization component. We found that in the low hard state the power-law index of this component, , gradually increases as the source moves in the colour–colour diagram. When the source undergoes a transition from the hard to the soft state drops abruptly; once the source is in the soft state increases again and then decreases gradually as the source spectrum softens further. The changes in , together with changes of the electron temperature, reflect changes of the optical depth in the corona. The lower kilohertz quasi-periodic oscillation (kHz QPO) in this source appears only in observations during the transition from the hard to the soft state, when the optical depth of the corona is high and changes depends strongly upon the position of the source in the colour–colour diagram. Our results are consistent with a scenario in which the lower kHz QPO reflects a global mode in the system that results from the resonance between the disc and/or the neutron star surface, and the Comptonizing corona.

Description: Supermassive stars (SMSs; ~10 5 M ) formed from metal-free gas in the early Universe attract attention as progenitors of supermassive black holes observed at high redshifts. To form SMSs by accretion, central protostars must accrete at as high rates as ~0.1–1 M yr –1 . Such protostars have very extended structures with bloated envelopes, like supergiant stars, and are called supergiant protostars (SGPSs). Under the assumption of hydrostatic equilibrium, SGPSs have density-inverted layers, where the luminosity becomes locally super-Eddington, near the surface. If the envelope matter is allowed to flow out, however, a stellar wind could be launched and hinder the accretion growth of SGPSs before reaching the supermassive regime. We examine whether radiation-driven winds are launched from SGPSs by constructing steady and spherically symmetric wind solutions. We find that the wind velocity does not reach the escape velocity in any case considered. This is because once the temperature falls below ~10 4 K, the opacity plummet drastically owing to the recombination of hydrogen and the acceleration ceases suddenly. This indicates that, in realistic non-steady cases, even if outflows are launched from the surface of SGPSs, they would fall back again. Such a ‘wind’ does not result in net mass-loss and does not prevent the growth of SGPSs. In conclusion, SGPSs will grow to SMSs and eventually collapse to massive black holes of ~10 5 M , as long as the rapid accretion is maintained.

Description: The emergence of cosmic structure is commonly considered one of the most complex phenomena in nature. However, this complexity has never been defined nor measured in a quantitative and objective way. In this work, we propose a method to measure the information content of cosmic structure and to quantify the complexity that emerges from it, based on Information Theory. The emergence of complex evolutionary patterns is studied with a statistical symbolic analysis of the datastream produced by state-of-the-art cosmological simulations of forming galaxy clusters. This powerful approach allows us to measure how many bits of information is necessary to predict the evolution of energy fields in a statistical way, and it offers a simple way to quantify when, where and how the cosmic gas behaves in complex ways. The most complex behaviours are found in the peripheral regions of galaxy clusters, where supersonic flows drive shocks and large energy fluctuations over a few tens of million years. Describing the evolution of magnetic energy requires at least twice as large amount of bits as required for the other energy fields. When radiative cooling and feedback from galaxy formation are considered, the cosmic gas is overall found to double its degree of complexity. In the future, Cosmic Information Theory can significantly increase our understanding of the emergence of cosmic structure as it represents an innovative framework to design and analyse complex simulations of the Universe in a simple, yet powerful way.

Description: Differences in expression levels are an important source of phenotypic variation within and between populations. MicroRNAs (miRNAs) are key players in post-transcriptional gene regulation that are important for plant development and stress responses. We surveyed expression variation of miRNAs and mRNAs of six accessions from two rice subspecies Oryza sativa L. ssp. indica and Oryza sativa L. ssp . japonica using deep sequencing. While more than half (53.7%) of the mature miRNAs exhibit differential expression between grains and seedlings of rice, only 11.0% show expression differences between subspecies, with an additional 2.2% differentiated for the development-by-subspecies interaction. Expression variation is greater for lowly conserved miRNAs than highly conserved miRNAs, whereas the latter show stronger negative correlation with their targets in expression changes between subspecies. Using a permutation test, we identified 51 miRNA–mRNA pairs that correlate negatively or positively in expression level among cultivated rice. Genes involved in various metabolic processes and stress responses are enriched in the differentially expressed genes between rice indica and japonica subspecies. Our results indicate that stabilizing selection is the major force governing miRNA expression in cultivated rice, albeit positive selection may be responsible for much of the between-subspecies expression divergence.

Description: Geographical variation among contiguous populations is frequently attributed to ecological divergence or historical isolation followed by secondary contact. Distinguishing between these effects is key to studies of incipient speciation and could be revealed by different genomic signatures. We used RAD-seq analyses to examine morphologically divergent populations of the endemic lizard ( Gallotia galloti ) from the volcanic island of Tenerife. Previous analyses have suggested ecological and historical causes to explain the morphological diversity. Analyses of 276,483 single nucleotide polymorphisms (SNPs) from 〉20 Mbp of the genome revealed one genetically divergent population from Anaga, a region associated with divergent mtDNA lineages in other Tenerife endemics. This population also has a high number of private alleles, and its divergence can be explained by historical isolation. Bayesian outlier analyses identified a small proportion of SNPs as candidates for selection (0.04%) which were strongly differentiated between xeric and mesic habitat types. Individual testing for specific xeric–mesic selection using an alternative approach also supported ecological divergence in a similarly small proportion of SNPs. The study indicates the roles of both historical isolation and ecological divergence in shaping genomic diversity in G. galloti . However, north–south morphological divergence appears solely associated with the latter and likely involves a relatively small proportion of the genome.

Description: Streptococcus anginosus is a member of the normal oral flora that can become a pathogen causing pyogenic infections in humans. The genome of daptomycin-resistant strain J4206, originally isolated from a patient suffering from breakthrough bacteremia and septic shock at the University of Texas Health Science Center at San Antonio, was determined. The circular genome is 2,001,352 bp long with a GC content of 38.62% and contains multiple mobile genetic elements, including the phage-like chromosomal island SanCI that mediates a mutator phenotype, transposons, and integrative conjugative elements. Daptomycin resistance involves multiple alterations in the cell membrane and cell wall, and unique features were identified in J4206 that may contribute to resistance. A cluster of capsular polysaccharide (CPS) genes for choline metabolism and transport are present that may help neutralize cell surface charges, destabilizing daptomycin binding. Further, unique J4206 genes encoding sortases and LPXTG-target proteins that are involved in cell wall modification were present. The J4206 genome is phylogenetically closely related to the recently reported vancomycin-resistant SA1 strain; however, these genomes differ with SNPs in cardiolipin synthetase, histidine kinase yycG , teichoic acid modification genes, and other genes involved in cell surface modification. Transmission electron microscopy showed that the cell walls of both strains J4206 and SA1 were significantly thicker and more electron dense than daptomycin- and vancomycin-sensitive strain J4211. This comparative genomic study has identified unique genes as well as allelic variants in the J4206 genome that are involved in cell surface modification and thus might contribute to the acquisition of daptomycin resistance.

Description: Chromosome number changes during the evolution of angiosperms are likely to have played a major role in speciation. Their study is of utmost importance, especially now, as a probabilistic model is available to study chromosome evolution within a phylogenetic framework. In the present study, likelihood models of chromosome number evolution were fitted to the largest family of flowering plants, the Asteraceae. Specifically, a phylogenetic supertree of this family was used to reconstruct the ancestral chromosome number and infer genomic events. Our approach inferred that the ancestral chromosome number of the family is n = 9. Also, according to the model that best explained our data, the evolution of haploid chromosome numbers in Asteraceae was a very dynamic process, with genome duplications and descending dysploidy being the most frequent genomic events in the evolution of this family. This model inferred more than one hundred whole genome duplication events; however, it did not find evidence for a paleopolyploidization at the base of this family, which has previously been hypothesized on the basis of sequence data from a limited number of species. The obtained results and potential causes of these discrepancies are discussed.

Description: Elastic reverse time migration (RTM) can yield accurate subsurface information (e.g. PP and PS reflectivity) by imaging the multicomponent seismic data. However, the existing RTM methods are still insufficient to provide satisfactory results because of the finite recording aperture, limited bandwidth and imperfect illumination. Besides, the P - and S -wave separation and the polarity reversal correction are indispensable in conventional elastic RTM. Here, we propose an iterative elastic least-squares RTM (LSRTM) method, in which the imaging accuracy is improved gradually with iteration. We first use the Born approximation to formulate the elastic de-migration operator, and employ the Lagrange multiplier method to derive the adjoint equations and gradients with respect to reflectivity. Then, an efficient inversion workflow (only four forward computations needed in each iteration) is introduced to update the reflectivity. Synthetic and field data examples reveal that the proposed LSRTM method can obtain higher-quality images than the conventional elastic RTM. We also analyse the influence of model parametrizations and misfit functions in elastic LSRTM. We observe that Lamé parameters, velocity and impedance parametrizations have similar and plausible migration results when the structures of different models are correlated. For an uncorrelated subsurface model, velocity and impedance parametrizations produce fewer artefacts caused by parameter crosstalk than the Lamé coefficient parametrization. Correlation- and convolution-type misfit functions are effective when amplitude errors are involved and the source wavelet is unknown, respectively. Finally, we discuss the dependence of elastic LSRTM on migration velocities and its antinoise ability. Imaging results determine that the new elastic LSRTM method performs well as long as the low-frequency components of migration velocities are correct. The quality of images of elastic LSRTM degrades with increasing noise.

Description: Ribosomal RNAs (rRNAs) account for 〉60% of all RNAs in eukaryotic cells and are encoded in the ribosomal DNA (rDNA) arrays. The rRNAs are produced from two sets of loci: the 5S rDNA array resides exclusively on human chromosome 1, whereas the 45S rDNA array resides on the short arm of five human acrocentric chromosomes. The 45S rDNA gives origin to the nucleolus, the nuclear organelle that is the site of ribosome biogenesis. Intriguingly, 5S and 45S rDNA arrays exhibit correlated copy number variation in lymphoblastoid cells (LCLs). Here we examined the genomic architecture and repeat content of the 5S and 45S rDNA arrays in multiple human genome assemblies (including PacBio MHAP assembly) and ascertained contacts between the rDNA arrays and the rest of the genome using Hi-C datasets from two human cell lines (erythroleukemia K562 and lymphoblastoid cells). Our analyses revealed that 5S and 45S arrays each have thousands of contacts in the folded genome, with rDNA-associated regions and genes dispersed across all chromosomes. The rDNA contact map displayed conserved and disparate features between two cell lines, and pointed to specific chromosomes, genomic regions, and genes with evidence of spatial proximity to the rDNA arrays; the data also showed a lack of direct physical interaction between the 5S and 45S rDNA arrays. Finally, the analysis identified an intriguing organization in the 5S array with Alu and 5S elements adjacent to one another and organized in opposite orientation along the array. Portraits of genome folding centered on the ribosomal DNA array could help understand the emergence of concerted variation, the control of 5S and 45S expression, as well as provide insights into an organelle that contributes to the spatial localization of human chromosomes during interphase.

Description: In general, the complex electrical resistivity in the subsurface is anisotropic. Despite this, algorithms for the tomographic inversion of complex resistivity data commonly assume isotropy, mainly due to the lack of anisotropic modelling and inversion schemes, potentially leading to artefacts in the inversion results in the presence of anisotropy. The development of an effective anisotropic complex resistivity inversion algorithm which utilizes the gradient information of some cost function benefits from understanding the characteristics of the problem's sensitivities, that is, the partial derivative of the impedance forward response with respect to the complex conductivities in the different spatial directions, as well as with respect to the different ratios of complex conductivities, that is, the different anisotropy ratios. We here derive expressions for these sensitivities and, based on a 2.5-D finite-element modelling algorithm, we compute and discuss sensitivity distributions as well as measurement response curves of typical surface and cross-borehole measurement configurations for 2-D subsurface anisotropic complex resistivity distributions. Depending on the electrode layout and measurement configuration, the sensitivity with respect to the conductivity in a particular direction shows a unique pattern, while for other directions sensitivity patterns are qualitatively similar. These sensitivity characteristics translate into important equivalences between impedance responses of local anisotropic and isotropic anomalies, for both magnitude and phase. Accordingly, with collinear surface arrays only the complex conductivity in the direction of the electrode layout can be unambiguously resolved, and with cross-borehole arrays only the conductivity in the vertical direction, provided an in-hole current injection is used. Nevertheless, anisotropy ratios involving these resolvable conductivity components are likewise detectable. The distinct shape of the measurement response curves, reflecting the distinct spatial patterns of the corresponding sensitivity distributions, suggest that optimized measurement configurations can be inferred for specific exploration questions involving electrical anisotropy and given electrode layouts. The gained insight into the characteristics of the sensitivity distributions of complex resistivity measurements in case of subsurface anisotropy should guide the implementation of effective anisotropic complex resistivity inversion schemes and lead to a routine use of such schemes in any resistivity and induced polarization surveys whenever subsurface electrical anisotropy could be encountered.

Description: The streaming potential phenomenon is an electrokinetic effect that occurs in porous media. It is characterized by an electrokinetic (EK) coefficient. The aim of this paper is to simulate the EK coefficient in unsaturated conditions using the Lattice Boltzmann method in a 2-D capillary channel. The multiphase flow is simulated with the model of Shan & Chen. The Poisson–Boltzmann equation is solved by implementing the model of Chai & Shi. The streaming potential response shows a non-monotonous behaviour due to the combination of the increase of charge density and decrease of flow velocity with decreasing water saturation. Using a potential of –20 mV at the air–water interface, an enhancement of a factor 5–30 of the EK coefficient, compared to the saturated state, can be observed due to the positive charge excess at this interface which is magnified by the fluid velocity away from the rock surface. This enhancement is correlated to the fractioning of the bubbles, and to the dynamic state of these bubbles, moving or entrapped in the crevices of the channel.

Description: We present the results of two-dimensional hydrodynamic simulations of self-gravitating circumbinary discs around binaries whose parameters match those of the circumbinary planet-hosting systems Kepler-16, Kepler-34 and Kepler-35. Previous work has shown that non-self-gravitating discs in these systems form an eccentric precessing inner cavity due to tidal truncation by the binary, and planets which form at large radii migrate until stalling at this cavity. Whilst this scenario appears to provide a natural explanation for the observed orbital locations of the circumbinary planets, previous simulations have failed to match the observed planet orbital parameters. The aim of this work is to examine the role of self-gravity in modifying circumbinary disc structure as a function of disc mass, prior to considering the evolution of embedded circumbinary planets. In agreement with previous work, we find that for disc masses between one and five times the minimum mass solar nebula (MMSN), disc self-gravity affects modest changes in the structure and evolution of circumbinary discs. Increasing the disc mass to 10 or 20 MMSN leads to two dramatic changes in disc structure. First, the scale of the inner cavity shrinks substantially, bringing its outer edge closer to the binary. Secondly, in addition to the eccentric inner cavity, additional precessing eccentric ring-like features develop in the outer regions of the discs. If planet formation starts early in the disc lifetime, these changes will have a significant impact on the formation and evolution of planets and precursor material.

Description: In this paper, we present a multiwavelength investigation of the star-forming complex IRAS 20286+4105, located in the Cygnus X region. Near-infrared K -band data are used to revisit the cluster/stellar group identified in previous studies. Radio continuum observations at 610 and 1280 MHz show the presence of a H ii region possibly powered by a star of spectral type B0–B0.5. The cometary morphology of the ionized region is explained by invoking the bow-shock model, where the likely association with a nearby supernova remnant is also explored. A compact radio knot with a non-thermal spectral index is detected towards the centre of the cloud. Mid-infrared data from the Spitzer Legacy Survey of the Cygnus X region show the presence of six Class I young stellar objects inside the cloud. Thermal dust emission in this complex is modelled using Herschel far-infrared data to generate dust temperature and column density maps. Herschel images also show the presence of two clumps in this region, the masses of which are estimated to be ~175 and 30 M . The mass–radius relation and the surface density of the clumps mean that they do not qualify as massive star-forming sites. An overall picture of a runaway star ionizing the cloud and a triggered population of intermediate-mass, Class I sources located towards the cloud centre emerges from this multiwavelength study. Variation in the dust emissivity spectral index is shown to exist in this region and is seen to have an inverse relation with the dust temperature.

Description: We present a modification of the method for reconstructing the stellar velocity ellipsoid (SVE) in disc galaxies. Our version does not need any parametrization of the velocity dispersion profiles and uses only one assumption that the ratio z / R remains constant along the profile or along several pieces of the profile. The method was tested on two galaxies from the sample of other authors and for the first time applied to three lenticular galaxies NGC 1167, NGC 3245 and NGC 4150, as well as to one Sab galaxy NGC 338. We found that for galaxies with a high inclination ( $i 〉 55^\circ \text{--}60^\circ$ ) it is difficult or rather impossible to extract the information about SVE, while for galaxies at an intermediate inclination the procedure of extracting is successful. For NGC 1167 we managed to reconstruct SVE, provided that the value of z / R is piecewise constant. We found z / R = 0.7 for the inner parts of the disc and z / R = 0.3 for the outskirts. We also obtained a rigid constraint on the value of the radial velocity dispersion R for highly inclined galaxies, and tested the result using the asymmetric-drift equation, provided that the gas rotation curve is available.

Description: This paper presents new results from the ongoing study of the unusual Lynx–Cancer void galaxy DDO 68, which has star-forming regions of record low metallicity [12+log (O/H) ~7.14]. The results include the following. (i) A new spectrum and photometry have been obtained with the 6-m SAO RAS telescope (BTA) for the luminous blue variable (LBV = DDO68-V1). Photometric data sets were complemented with others based on the Sloan Digital Sky Survey (SDSS) and the Hubble Space Telescope ( HST ) archive images. (ii) We performed an analysis of the DDO 68 supergiant shell (SGS) and the prominent smaller Hα arcs/shells visible in the HST image coupled with kinematic maps in Hα obtained with the Fabry–Perot interferometer (FPI) at the BTA. (iii) We compiled a list of about 50 of the most luminous stars (–9.1 mag 〈 M V 〈 –6.0 mag) identified from the HST images associated with the star-forming regions with known extremely low O/H. This is intended to pave the path for the current science to be investigated with the next generation of giant telescopes. We have confirmed earlier hints of significant variation of the LBV optical light, deriving its amplitude as V 3.7 mag for the first time. New data suggest that in 2008–2010 the LBV reached M V = –10.5 mag and probably underwent a giant eruption. We argue that the structure of star-forming complexes along the SGS (‘Northern Ring’) perimeter provides evidence for sequential induced star-formation episodes caused by the shell gas instabilities and gravitational collapse. The variability of some luminous extremely metal-poor stars in DDO 68 can currently be monitored with medium-size telescopes at sites with superb seeing.

Description: The number, distribution and properties of dwarf satellites are crucial probes of the physics of galaxy formation at low masses and the response of satellite galaxies to the tidal and gas dynamical effects of their more massive parent. To make progress, it is necessary to augment and solidify the census of dwarf satellites of galaxies outside the Local Group. Müller et al. presented 16 dwarf galaxy candidates near M83, but lacking reliable distances, it is unclear which candidates are M83 satellites. Using red-giant-branch stars from the HST /GHOSTS survey in conjunction with ground-based images from VLT/VIMOS, we confirm that one of the candidates, dw1335-29 – with a projected distance of 26 kpc from M83 and a distance modulus of $(m-M)_0 = 28.5^{+0.3}_{-0.1}$ – is a satellite of M83. We estimate an absolute magnitude M V  = –10.1 ± 0.4, an ellipticity of $0.40^{+0.14}_{-0.22}$ , a half-light radius of $656^{+121}_{-170}$  pc and [Fe/H] = $-1.3^{+0.3}_{-0.4}$ . Owing to dw1335-29's somewhat irregular shape and possible young stars, we classify this galaxy as a dwarf irregular or transition dwarf. This is curious, as with a projected distance of 26 kpc from M83, dw1335-29 is expected to lack recent star formation. Further study of M83's dwarf population will reveal if star formation in its satellites is commonplace (suggesting a lack of a hot gas envelope for M83 that would quench star formation) or rare (suggesting that dw1335-29 has a larger M83-centric distance, and is fortuitously projected to small radii).

Description: Conserved non-coding sequences (CNSs) of Eukaryotes are known to be significantly enriched in regulatory sequences. CNSs of diverse lineages follow different patterns in abundance, sequence composition, and location. Here, we report a thorough analysis of CNSs in diverse groups of Eukaryotes with respect to GC content heterogeneity. We examined 24 fungi, 19 invertebrates, and 12 non-mammalian vertebrates so as to find lineage specific features of CNSs. We found that fungi and invertebrate CNSs are predominantly GC rich as in plants we previously observed, whereas vertebrate CNSs are GC poor. This result suggests that the CNS GC content transition occurred from the ancestral GC rich state of Eukaryotes to GC poor in the vertebrate lineage due to the enrollment of GC poor transcription factor binding sites that are lineage specific. CNS GC content is closely linked with the nucleosome occupancy that determines the location and structural architecture of DNAs.

Description: Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral sequence divergence between genomic regions that spend different amounts of time in the male and female germline. For great apes, including human, we show that estimates of divergence are reduced in putatively unconstrained regions near genes relative to unconstrained regions far from genes. Divergence increases with increasing distance from genes on both the X chromosome and autosomes, but increases faster on the X chromosome than autosomes. As a result, ratios of X/A divergence increase with increasing distance from genes and corresponding estimates of male mutation bias are significantly higher in intergenic regions near genes versus far from genes. Future studies in other species will need to carefully consider the effect that genomic location will have on estimates of male mutation bias.

Description: Great genetic variability among teleost immunomes, with gene losses and expansions of central adaptive and innate components, has been discovered through genome sequencing over the last few years. Here, we demonstrate that the innate Myxovirus resistance gene ( Mx ) is lost from the ancestor of Gadiformes and the closely related Stylephorus chordatus , thus predating the loss of Major Histocompatibility Complex class II ( MHCII ) in Gadiformes. Although the functional implication of Mx loss is still unknown, we demonstrate that this loss is one of several ancient events appearing in successive order throughout the evolution of teleost immunity. In particular, we find that the loss of Toll-like receptor 5 predates the loss of Mx involving the entire Paracanthopterygii lineage. Using a time-calibrated phylogeny, we show that loss of MHCII and Mx overlap with major paleoclimatic and geological events indicating that these genetic changes were adaptive responses to the changing environment at the time.

Description: Males and females often display extensive phenotypic differences, and many of these sexual dimorphisms are thought to result from differences between males and females in expression of genes present in both sexes. Sex-biased genes have been shown to exhibit accelerated rates of evolution in a wide array of species, however the cause of this remains enigmatic. In this study, we investigate the extent and evolutionary dynamics of sex-biased gene expression in zebrafish. Our results indicate that both male-biased genes and female-biased genes exhibit accelerated evolution at the protein level. In order to differentiate between adaptive and nonadaptive causes, we tested for codon usage bias and signatures of different selective regimes in our sequence data. Our results show that both male- and female-biased genes show signatures consistent with adaptive evolution. In order to test the generality of our findings across fish, we also analyzed publicly available data on sticklebacks, and found results consistent with our findings in zebrafish.

Description: Host–pathogen interactions may result in either directional selection or in pressure for the maintenance of polymorphism at the molecular level. Hence signatures of both positive and balancing selection are expected in immune genes. Because both overall selective pressure and specific targets may differ between species, large-scale population genomic studies are useful in detecting functionally important immune genes and comparing selective landscapes between taxa. Such studies are of particular interest in amphibians, a group threatened worldwide by emerging infectious diseases. Here, we present an analysis of polymorphism and divergence of 634 immune genes in two lineages of Lissotriton newts: L. montandoni and L. vulgaris graecus . Variation in newt immune genes has been shaped predominantly by widespread purifying selection and strong evolutionary constraint, implying long-term importance of these genes for functioning of the immune system. The two evolutionary lineages differ in the overall strength of purifying selection which can partially be explained by demographic history but may also signal differences in long-term pathogen pressure. The prevalent constraint notwithstanding, 23 putative targets of positive selection and 11 putative targets of balancing selection were identified. The latter were detected by composite tests involving the demographic model and further validated in independent population samples. Putative targets of balancing selection encode proteins which may interact closely with pathogens but include also regulators of immune response. The identified candidates will be useful for testing whether genes affected by balancing selection are more prone to interspecific introgression than other genes in the genome.