bluuebunny/crossref_metadata_2025 huggingface dataset:
The dexamethasone suppression test in bulimic outpatients without major depression
Authors: Bailly D , Regnaut N , Parquet PJ
Published: April 2020

Recent studies have examined the effectiveness of the dexamethasone suppression test (DST) in the evaluation of bulimia. In a series of 18 female bulimic outpatients without major depression, 9 (50%) failed to suppress on the DST. No significant difference was found between suppressors and nonsuppressors in personal and family histories of affective disorder, levels of anxious and depressive symptoms, psychoactive substance abuse, and severity of abnormal eating-related behaviours. In contrast, non-suppression was significantly associated with low weight. There is a trend to differentiate non-suppressors from suppressors in the current diagnosis of anorexia nervosa and in past history of anorexia nervosa. Seven patients received fluvoxamine for 8 weeks. Five patients were suppressors and showed a significant decrease in the frequency of their binges while the 2 non-suppressors did not improve. These preliminary results suggest that DST non-suppression might be typical of bulimic patients with anorexia nervosa and that pretreatment DST results might predict the response of bulimic behaviour to treatment with fluvoxamine.
Reduced immobility time in the tail suspension test (TST) by chronic immobilization stress. Role of corticosterone and brain serotonergic and adrenergic receptors
Authors: De Castro-e-Silva E , Peres MF , Brito P , Cobas C , Saraiva A , Silva V , Chaves A , Barros L , De Oliveira IR
Published: April 2020

Chronically stressed adult male Balb C mice were submitted to the tail suspension test. Chronic immobilization stress (6 h/d for 14 consecutive days) induced a significant reduction in immobility time when compared to non-stressed controls. Pretreatment with LY 53857, a serotonin 5HT2 antagonist, and IPS 339, a selective beta-2 adrenoceptor blocker, reversed immobility time to the levels of non-stressed controls. Chronic administration of corticosterone (100 mg/kg for 7 d) did not modify immobility time as compared to saline treated controls. It is suggested that both serotonergic and adrenergic pathways in the brain may participate in the stress-induced changes occurring in the tail suspension test response and that corticosterone does not appear to play a role in this process.
Alcoholism: a psychobiological perspective
Authors: Dantzer R , Ollat H
Published: April 2020

Like many phenomena which are located at the intersection between different disciplines, the complexity of alcoholism is difficult to comprehend, especially at an experimental level. In particular, pharmacological approaches towards alcoholism have emphasized the anxiety- and stress-reducing properties of ethanol, in spite of the limited clinical support for this hypothesis. In the same manner, the phenomenon of behavioral tolerance has mainly been approached from a pharmacological perspective, with little or no interest paid to the sensory stimuli possibly involved in the conditioning of drug effects. Comparative studies in animals selected for alcohol intake have concentrated on the biological responses to alcohol and have not investigated the possibility of genetic differences in sensitivity to environmental stimuli. Based on recent progress in the elucidation of the individual and environmental factors which play a key role in the development and stabilization of abnormal behavior in conflict situations, it is proposed that alcoholism is the result of a predisposition to react in a certain manner to environmental stimuli and social influences which is strengthened by the pharmacological effects of ethanol. The manner in which this hypothesis can be put to test has been discussed.
Psychodynamique et psychopharmacologie : les enjeux
Authors: Hanin B
Published: April 2020

L'oblet de cette brève revue de la littérature est d'indiquer les principaux axes de recherche et de reflexion sur la complémentarité des approches psychodynamiques et psychologiques.
Dexamethasone suppression test and prediction of treatment response to selective antidepressants
Authors: Ansseau M , Papart P , Pitchot W , Timsit-Berthier M , Legros JJ , von Frenckell R
Published: April 2020

The usefulness of the dexamethasone suppression test (DST) in the prediction of treatment response to selective antidepressants was tested in 56 major depressive inpatients. Following DST, patients were randomly assigned to treatment by either nomifensine, a catecholaminergic antidepressant, or zimeldine, a serotonergic antidepressant during a 3-week period and assessed by means of the second part of the Clinical Global Impressions (CGI-2). No significant difference was present between the 27 DST suppressor and the 29 DST non-suppressor patients in their overall clinical outcome. Moreover, no preferential response to nomifensine or zimeldine was noted in any of the two groups defined according to DST status. Therefore, these results do not support the usefulness of the DST in the prediction of the treatment response to antidepressants in general and to selective antidepressants in particular.
Efficacy and acceptability of tianeptine in the elderly: a review of clinical trials
Authors: Raffaitin F
Published: April 2020

The acceptability and efficacy of tianeptine were evaluated in three open trials in a total of 549 elderly patients, 426 of whom were treated for 3 months and 188 for 1 year. The therapeutic effect was that expected from an effective antidepressant, with a marked response after treatment for one month. In the geriatric trial, where patients were primarily dysthymic, continuation of treatment after 6 months consolidated the improvement already observed. Tianeptine also had a favorable long-term effect in chronic refractory depression. Drop-outs due to side-effects were few (4.4%), despite the high risk population. All pre-treatment complaints improved on tianeptine. The high frequency of somatic complaints expressed before treatment confirmed the extent to which depression is somatised in the elderly. Concomitant physical disease present in 87% of patients did not restrict the use of tianeptine. The fact that tianeptine has a low incidence of anticholinergic effects and no affinity for either H1 or α1 receptors makes it a particularly easy drug to use in elderly subjects who are sensitive to the side-effects of psychotropic agents.
Testing the efficacy of and parents’ preferences for nutrition labels on children’s menus from a full-service chain restaurant: results of an online experiment
Authors: Prowse Rachel J L , Lee Kirsten M , Chen Emily , Zuo Fei , Hammond David , Hobin Erin
Published: April 2020

Objective:

Test the efficacy and perceived effectiveness of nutrition labels on children’s menus from a full-service chain restaurant in an online study.

Design:

Using a between-groups experiment, parents were randomised to view children’s menus displaying one of five children’s nutrition labelling conditions: (i) No Nutrition Information (control); (ii) Calories Only; (iii) Calories + Contextual Statement (CS); (iv) Calories, Sodium + CS; or (v) Calories and Sodium in Traffic Lights + CS. Parents hypothetically ordered up to one entrée, side, beverage and dessert for their child, then rated and ranked all five labelling conditions on the level of perceived effectiveness.

Setting:

Online survey.

Participants:

998 parents with a 3–12 year old child.

Results:

Parents exposed to menus displaying ‘Calories, Sodium + CS’ selected significantly fewer calories ‘overall’ (entrées + side + dessert + beverage) compared to parents exposed to the control condition (−53·1 calories, P < 0·05). Parents selected ‘entrees’ with significantly fewer calories and lower sodium when exposed to menus with ‘Calories + CS’ (−24·3 calories, P < 0·05); ‘Calories, Sodium + CS’ (−25·4 calories, −56·1 mg sodium, P < 0·05 for both); and ‘Calories and Sodium in Traffic Lights + CS’ (−29·1 calories, −58·6 mg sodium, P < 0·05 for both). Parents exposed to menus with ‘Calories, Sodium + CS’ and ‘Calories and Sodium in Traffic Lights + CS’ were more likely to notice and understand nutrition information compared to other nuntrition labelling conditions. Parents perceived the menu with ‘Calories and Sodium in Traffic Lights + CS’ as most effective (P < 0·05).

Conclusions:

Menus disclosing calories, sodium and a contextual statement increased the proportion of parents who noticed and understood nutrition information, and resulted in parents selecting lower calorie and sodium entrées for their children in the hypothetical purchase task.
‘Use of antipsychotics in children and adolescents: a picture from the ARITMO population-based European cohort study’
Authors: Kaguelidou Florentia , Holstiege Jakob , Schink Tania , Bezemer Irene , Poluzzi Elisabetta , Mazzaglia Giampiero , Pedersen Lars , Sturkenboom Miriam , Trifirò Gianluca
Published: April 2020

Aims

Prevalence of the use of antipsychotics (APs) in the paediatric population is globally increasing. The aim of this study was to describe multinational trends and patterns in AP use in children and adolescents in Europe.

Methods

This was a dynamic retrospective cohort study comprising all children and adolescents (⩽18 years of age). Data were extracted from five population-based electronic healthcare databases in Europe (Denmark, Germany, Italy, the Netherlands and United Kingdom) from 2000 to 2010. Yearly prevalence and incidence of AP use was expressed per 1000 person-years (PYs).

Results

Prevalence increased from 1.44 to 3.41/1000 PYs (2008) in Denmark and from 2.07 to 4.35/1000 PYs in the NL (2009), moderately increased from 2.8 to 3.24/1000 in UK (2009) and from 1.53 to 1.74/1000 PYs in Germany (2008) and remained low from 0.61 to 0.34/1000 PYs in Italy (2010). Similarly, incidence rates increased from 0.69 to 1.52/1000 PYs in Denmark and from 0.86 to 1.49/1000 PYs in the NL, stabilised from 2.29 to 2.37/1000 PYs in the UK and from 0.79 to 0.80/1000 PYs in Germany and remained low from 0.32 to 0.2/1000 PYs in Italy. AP use was highest in 15–18 year olds and in boys compared to girls. Yet, the use observed in the 5–9 year olds was found to be comparatively high in the NL. Prescriptions of second generation APs, especially risperidone, were privileged but the first generation APs were still prescribed in the youngest.

Conclusions

A steady increase in AP use in children and adolescents was observed essentially in the NL and Denmark. The use in Germany and Italy was lowest among countries. The use of APs under 9 years of age underlines their off-label use and should be carefully monitored as the risk/benefit ratio of these medications remains unclear in young children. AP use was altogether lower in Europe as compared to that reported in North America.
Concomitants of Depressive Symptoms in Memory Clinic Patients
Authors: Kessler Eva-Marie , Frank Varinia , Klostermann Arne , Peters Oliver , Schäfer Thomas
Published: April 2020

Abstract. This paper investigates how depressive symptoms are related to a comprehensive range of factors including sex, age, education, family history with dementia, subjective cognitive complaints (SCC), objective cognitive impairment, and sleep quality. The sample consisted of 958 memory-clinic patients of a large innercity academic memory clinic in Germany. In line with studies from other countries, 53.1% suffered from minor depression and 11.1% from major depression. In the linear regression (25% explained variance), younger age, lower education, and bad sleep quality were found to be predictors of depressive symptoms, while sleep quality turned out to have the largest effect; SCC and objective memory impairment were insignificant. Results underline the importance of memory clinics as gatekeepers to manage depression beyond the assessment of dementia.
A Simple Model of Chemistry Effects on the Air‐Sea CO2 Exchange Coefficient
Authors: Jørgensen Hans E. , Sørensen Lise Lotte , Larsen Søren E.
Published: April 2020

The transfer of CO2 between air and water can be quantified by the use of a transfer or exchange coefficient. Here we have studied the effect on the exchange coefficient of CO2 from inclusion of the carbonate buffer system in water. The methodology has been to solve the flux budget for the chemical reaction equations in the water column, combining the vertical flux in the air and the flux across the interface by the introduction of a so called resistance model for the whole system where the system has been simplified with respect to variation of certain parameters. The thermal effects on the flow and chemistry modeling have in the present study not been included, although this also plays a significant role on the air‐sea exchange. The model shows the effects on the air‐sea exchange coefficient from the carbonate chemistry in the water column are negligible if the measurements are taken at sufficient depth in the water. Hence, it is found that the skin layer or interface layer contains the largest resistance and therefore controls the flux. It is also shown that measurement of the near‐surface CO2 gradients in ocean water is very difficult, as the gradients of CO2 occur within the first meter from the water surface. In reality, the equilibrium is reached within the first meter from the water surface. The results justify the use of standard methods to estimate the flux of CO2 by measuring a concentration at typical larger than 3 m depth and 10 m above the surface.
Mid‐Latitude Spread‐F Structures Over the Geomagnetic Low‐Mid Latitude Transition Region: An Observational Evidence
Authors: Sivakandan M. , Mondal S. , Sarkhel S. , Chakrabarty D. , Sunil Krishna M. V. , Chaitanya P. Pavan , Patra A. K. , Choudhary R. K. , Pant T. K. , Upadhayaya A. K. , Sori Takuya
Published: April 2020

An observational evidence of a unique plasma depletion event was captured by an O(1D) 630.0 nm airglow imager on 13 June 2018 over a transition region of geomagnetic low‐mid latitude, Hanle, Leh Ladakh, India (32.77°N, 78.97°E; Mlat. ~24.1°N). The observed plasma depletion structures are tilted at an angle of 13° ± 2° west of the geomagnetic north and drifted toward west. Collocated Global Navigation Satellite System‐Total Electron Content measurements confirm that the structures are indeed associated with TEC depletions. Simultaneous ionosonde measurements from Delhi, India (28.70°N, 77.10°E; Mlat. ~20.2°N) shows spread‐F signatures confirming that these structures are associated with the ionospheric irregularities. Interestingly, radar observations over the geomagnetic low‐latitude station Gadanki, India (13.5°N; 79.2°E; Mlat. ~6.5°N) reveal the absence of equatorial plasma bubbles on this night. Therefore, these observations strongly suggest that the observed structures in the airglow images over Hanle are associated with mid‐latitude spread‐F (MSF). These MSF structures are possibly affected by the shear in the zonal plasma drift that forces the field aligned plasma irregularity structures to tilt toward west. These observations, for the first time, bring out the presence of MSF structures over geomagnetic low‐mid latitude transition region. It is suggested that the plasma distribution over low latitudes plays an important role in the occurrence of MSF structures over this transition region. Understanding the source and characteristics of the plasma irregularity structures over this transition region can help in understanding the spatio‐temporal evolution of global L‐band scintillation in a better way.
Quantifying the Effect of Plasmaspheric Hiss on the Electron Loss From the Slot Region
Authors: Kim Kyung‐Chan , Shprits Yuri , Wang Dedong
Published: April 2020

We present global statistical models of both wave amplitude and wave normal angle (WNA) of plasmaspheric hiss using Van Allen Probe‐A observations. They utilize the time history of solar wind parameters, that is, interplanetary magnetic field BZ and solar wind speed, and the AE index for each measurement of hiss waves as inputs. The solar wind parameter‐based model generally results in higher performance than using only the AE index as an input. Both observations and model results reveal a clear dependence of hiss wave distribution on the magnetic local time (MLT): Higher amplitudes with field‐aligned (<30o) WNAs occur more frequently on the dayside than on the nightside. Such a tendency does not depend on magnetic latitude (MLAT), but slightly larger WNAs with a relatively low amplitude frequently appear for larger MLAT (>10o). We also examine how significantly the electron loss rates in the slot region can be changed by incorporating the model output of hiss waves into a diffusive transport simulation. Simulation results show that during a typical timescale (roughly a couple of days) of a corotating interaction region‐driven storm, the nightside hiss waves with larger WNA (>30o) do not contribute to the electron loss in the slot region due to their low amplitude and large WNA, while dayside hiss with WNAs less than 30o and comparatively higher amplitudes leads to a fast drop in flux, especially for electrons of a few hundred keV.
Fault Control on a Thermal Anomaly: Conceptual and Numerical Modeling of a Low‐Temperature Geothermal System in the Southern Alps Foreland Basin (NE Italy)
Authors: Pola Marco , Cacace Mauro , Fabbri Paolo , Piccinini Leonardo , Zampieri Dario , Torresan Filippo
Published: April 2020

The interest on low‐temperature geothermal resources is progressively increasing since their renewability and widespread availability. Despite their frequency, these resources and their development have been only partially investigated. This paper unravels the major physical processes driving a low‐temperature geothermal resource in NE Italy (Euganean Geothermal System) through conceptual and numerical modeling. Dense fracturing associated to regional fault zones and a relay ramp enhances regional to local flow of thermal waters. Their rapid upwelling in the Euganean Geothermal Field is favored by open extensional fractures deforming the relay ramp. The water (65–86 °C) is intensively exploited for balneotherapy, rendering it a profitable resource. Three‐dimensional coupled flow and heat transport numerical simulations based on this conceptual model are performed. Despite the presence of a uniform basal heat flow, a thermal anomaly corresponding to field observations develops in the modeling domain reproducing the relay ramp. Intensive fracturing extending across a wide area and a slightly anomalous heat flow favors a local increase in convection that drives the upwelling of deep‐seated hot waters. The simulations corroborate and refine the conceptual model, revealing that water of up to 115 °C is likely to be found in the unexplored part of the thermal field. This study furthers knowledge on fault‐controlled low‐temperature geothermal resources where the geological setting could enhance local convection without anomalous heat flows, creating temperatures favorable for energy production. Conceptual and numerical modeling based on solid geological and hydrogeological reconstructions can offer a support tool for further detailed explorations of these prominent resources.
Volcano‐Tectonic Interactions at Sabancaya Volcano, Peru: Eruptions, Magmatic Inflation, Moderate Earthquakes, and Fault Creep
Authors: MacQueen Patricia , Delgado Francisco , Reath Kevin , Pritchard Matthew E. , Bagnardi Marco , Milillo Pietro , Lundgren Paul , Macedo Orlando , Aguilar Victor , Ortega Mayra , Anccasi Rosa , Lazarte Zerpa Ivonne Alejandra , Miranda Rafael
Published: April 2020

We present evidence of volcano‐tectonic interactions at Sabancaya volcano that we relate to episodic magma injection and high regional fluid pore pressures. We present a surface deformation time series at Sabancaya including observations from ERS‐1/2, Envisat, Sentinel‐1, COSMO‐SkyMed, and TerraSAR‐X that spans June 1992 to February 2019. These data show deep‐seated inflation northwest of Sabancaya from 1992–1997 and 2013–2019, as well as creep and rupture on multiple faults. Afterslip on the Mojopampa fault following a 2013 MW 5.9 earthquake is anomalously long lived, continuing for at least 6 years. The best fit fault plane for the afterslip is right‐lateral motion on an EW striking fault at 1 km depth. We also model surface deformation from two 2017 earthquakes (MW 4.4 and MW 5.2) on unnamed faults, for which the best fit models are NW striking normal faults at 1–2 km depth. Our best fit model for a magmatic inflation source (13 km depth, volume change of 0.04 to 0.05 km3 yr−1) induces positive Coulomb static stress changes on these modeled fault planes. Comparing these deformation results with evidence from satellite thermal and degassing data, field observations, and seismic records, we interpret strong pre‐eruptive seismicity at Sabancaya as a consequence of magmatic intrusions destabilizing tectonic faults critically stressed by regionally high fluid pressures. High fluid pressure likely also promotes fault creep driven by static stress transfer from the inflation source. We speculate that combining high pore fluid pressures with sufficiently large, offset magmatic inflation can promote strong earthquakes during volcanic unrest.
Spatial and Temporal Variability of the North Atlantic Eddy Field From Two Kilometric‐Resolution Ocean Models
Authors: Ajayi Adekunle , Le Sommer Julien , Chassignet Eric , Molines Jean‐Marc , Xu Xiaobiao , Albert Aurelie , Cosme Emmanuel
Published: April 2020

Ocean circulation is dominated by turbulent geostrophic eddy fields with typical scales ranging from 10 to 300 km. At mesoscales (>50 km), the size of eddy structures varies regionally following the Rossby radius of deformation. The variability of the scale of smaller eddies is not well known due to the limitations in existing numerical simulations and satellite capability. Nevertheless, it is well established that oceanic flows (<50 km) generally exhibit strong seasonality. In this study, we present a basin‐scale analysis of coherent structures down to 10 km in the North Atlantic Ocean using two submesoscale‐permitting ocean models, a NEMO‐based North Atlantic simulation with a horizontal resolution of 1/60 (NATL60) and an HYCOM‐based Atlantic simulation with a horizontal resolution of 1/50 (HYCOM50). We investigate the spatial and temporal variability of the scale of eddy structures with a particular focus on eddies with scales of 10 to 100 km, and examine the impact of the seasonality of submesoscale energy on the seasonality and distribution of coherent structures in the North Atlantic. Our results show an overall good agreement between the two models in terms of surface wave number spectra and seasonal variability. The key findings of the paper are that (i) the mean size of ocean eddies show strong seasonality; (ii) this seasonality is associated with an increased population of submesoscale eddies (10–50 km) in winter; and (iii) the net release of available potential energy associated with mixed layer instability is responsible for the emergence of the increased population of submesoscale eddies in wintertime.
Impact of Afforestation on Atmospheric Recharge to Groundwater in a Semiarid Area
Authors: Huang Tianming , Pang Zhonghe , Yang Shuo , Yin Lihe
Published: April 2020

While the global forest area is generally decreasing, various afforestation projects have been implemented, including the large‐scale Three‐North Afforestation Program (TNAP) and the Conversion of Cropland to Forest Program in China, under which 0.63 million square kilometers of trees have been planted. The large‐scale land use and cover change (LUCC) would affect the redistribution of precipitation and change the water cycle, especially groundwater recharge. The chloride mass balance (CMB) between precipitation and soil water/groundwater is the most widely used technique to estimate the recharge in arid and semiarid areas. However, in the case of decreased recharge following LUCC, a new equilibrium of water and chloride flux is not easily reached and the identification of steady state is the premise to use CMB. This study provided a method to assess the steady state by comparing the history of LUCC and chloride cumulative age at sampling depth and by checking the breaks in the slope of the line for cumulative chloride and soil water. The case study in the Mu Us Sandy Land, affected by the TNAP, shows that soil profiles beneath sparse grassland, shrubland, and woodland have reached steady state. However, new equilibrium has not been reached in the soil profiles beneath the dense shrubland. The estimated recharge rates beneath the plantations represent reductions from 33% to >90% relative to the surrounding bare sandy land (50–54 mm/year). The results highlight the unfavorable effects of some afforestation and ecological rehabilitation approaches in arid and semiarid areas on regional groundwater resources.
The Global Land Carbon Cycle Simulated With ISBA‐CTRIP: Improvements Over the Last Decade
Authors: Delire Christine , Séférian Roland , Decharme Bertrand , Alkama Ramdane , Calvet Jean‐Christophe , Carrer Dominique , Gibelin Anne‐Laure , Joetzjer Emilie , Morel Xavier , Rocher Matthias , Tzanos Diane
Published: April 2020

We present the latest version of the ISBA‐CTRIP land surface system, focusing on the representation of the land carbon cycle. We review the main improvements since the year 2012, mainly added modules for wild fires, carbon leaching through soil and transport of dissolved organic carbon to the ocean, and land cover changes but also improved representation of photosynthesis, respiration, and plant functional types. This version of ISBA‐CTRIP is fully described in terms of land carbon pools, fluxes, and their interactions. Results are compared with the previous version in an off‐line mode forced by observed climate during the historical time period. The two simulations are presented to demonstrate the model performance compared to an ensemble of observed and observation‐derived data sets for gross and net primary productivity, heterotrophic and autotrophic respiration, above and below ground biomass, litter, and soil carbon pools. New developments specific to the new version such as burned area, fire emissions, carbon leaching, and land cover are also validated against observations. The results show clearly that the latest version of ISBA‐CTRIP outperforms the former version and reproduces generally well the observed mean spatial patterns in carbon pools and fluxes, as well as the seasonal cycle of leaf area index. The trends of the global fluxes over the last 50 years agree with other global models and with available estimates. This comparison gives us confidence that the model represents the main processes involved in the terrestrial carbon cycle and can be used to explore future global change projections.
High‐Resolution Gridded Population Projections for China Under the Shared Socioeconomic Pathways
Authors: Chen Yimin , Li Xia , Huang Kangning , Luo Ming , Gao Minyi
Published: April 2020

Gridded population projections consistent with the shared socioeconomic pathways (SSPs) are critical for the studies of climate change impacts and their mitigation. Existing gridded population projections under the SSPs have relatively coarse resolution and issue of overestimation in populated areas, which further bias the analysis of climate change impacts. In this study, we proposed a scheme by integrating high‐resolution historical population maps and machine learning models to predict future built‐up land and population distributions, which were rendered consistent with the SSPs. Using this proposed method in China, we generated a set of 100‐m SSPs population maps for China from 2015 to 2050 at 5‐year intervals. Our projections revealed different spatial structures for the population distribution at the grid level and three modes of provincial population change across the five SSPs from 2015 to 2050. By applying the 100‐m SSPs population grids, we showed that, from 2015 to 2050, exposure to extreme heat in China will increase by 121–136% and 164–191% under the representative concentration pathways 4.5 and 8.5, respectively. We also found a severe spatial bias in the existing 1/8 ° SSPs population grids, i.e., 30–43% of the estimated population is wrongly allocated in cropland, forest, and pastureland. This bias results in substantial underestimation of extreme heat exposure in high‐density metropolitan areas and overestimation in medium and low‐density areas.
Parallel array with axially coded light-sheet microscope
Authors: Loza-Alvarez Pablo
Published: April 2020

A parallel array of frequency modulated light sheets results in a scanning-less light sheet microscope capable of fast volumetric imaging.
MSCs ameliorate hepatocellular apoptosis mediated by PINK1-dependent mitophagy in liver ischemia/reperfusion injury through AMPKα activation
Authors: Zheng Jun , Chen Liang , Lu Tongyu , Zhang Yingcai , Sui Xin , Li Yang , Huang Xuna , He Liying , Cai Jianye , Zhou Chaorong , Liang Jinliang , Chen Guihua , Yao Jia , Yang Yang
Published: April 2020

Hepatocyte apoptosis is the main pathophysiological process underlying liver ischemia/reperfusion (I/R) injury. Mitochondrial abnormalities have a vital role in hepatocellular damage. The hepatoprotective effects of mesenchymal stem cells (MSCs) have been previously demonstrated. In this study, we aim to investigate the effect and potential mechanism of MSCs against liver I/R injury. Effects of MSCs were studied in mice liver I/R injury model and in a hypoxia/reoxygenation (H/R) model of L02 hepatocytes. The potential mechanisms of MSCs on these in vivo and in vitro I/R-induced hepatocellular apoptosis models were studies. Accompanied by the improvement of hepatic damage, MSCs exhibited capabilities of controlling mitochondrial quality, shown by reduced mitochondrial reactive oxygen species (mtROS) overproduction, decreased the accumulation of mitochondrial fragmentation, restored ATP generation and upregulated mitophagy. Furthermore, we descripted a potential mechanism of MSCs on upregulating mitophagy and found that the reduced Parkin and PINK1 expression and inactivated AMPKα pathway were observed in the liver tissue in I/R model. These effects were reversed by MSCs treatment. In vitro study showed that MSC-conditioned medium (MSC-CM) suppressed hepatocellular apoptosis and inhibited mtROS accumulation in the H/R environment. And these effects of MSC-CM were partially blocked after the cells were transfected with PINK1 siRNA or added with dorsomorphin. Collectively, our findings provide a novel pharmacological mechanism that MSCs exert hepatoprotective effect in liver I/R injury via upregulating PINK1-dependent mitophagy. In addition, this effect might be attributed to the modulation of AMPKα activation.
Enhanced fatty acid oxidation provides glioblastoma cells metabolic plasticity to accommodate to its dynamic nutrient microenvironment
Authors: Kant Shiva , Kesarwani Pravin , Prabhu Antony , Graham Stewart F. , Buelow Katie L. , Nakano Ichiro , Chinnaiyan Prakash
Published: April 2020

Despite advances in molecularly characterizing glioblastoma (GBM), metabolic alterations driving its aggressive phenotype are only beginning to be recognized. Integrative cross-platform analysis coupling global metabolomic and gene expression profiling on patient-derived glioma identified fatty acid β-oxidation (FAO) as a metabolic node in GBM. We determined that the biologic consequence of enhanced FAO is directly dependent upon tumor microenvironment. FAO serves as a metabolic cue to drive proliferation in a β-HB/GPR109A dependent autocrine manner in nutrient favorable conditions, while providing an efficient, alternate source of ATP only in nutrient unfavorable conditions. Rational combinatorial strategies designed to target these dynamic roles FAO plays in gliomagenesis resulted in necroptosis-mediated metabolic synthetic lethality in GBM. In summary, we identified FAO as a dominant metabolic node in GBM that provides metabolic plasticity, allowing these cells to adapt to their dynamic microenvironment. Combinatorial strategies designed to target these diverse roles FAO plays in gliomagenesis offers therapeutic potential in GBM.
Default polyfunctional T helper 1 response to ample signal 1 alone
Authors: Danelli Luca , Cornish Georgina , Merkenschlager Julia , Kassiotis George
Published: April 2020

CD4+ T cells integrate well-defined signals from the T-cell receptor (TCR) (signal 1) and a host of costimulatory molecules (signal 2) to initiate clonal expansion and differentiation into diverse functional T helper (Th) subsets. However, our ability to guide the expansion of context-appropriate Th subsets by deploying these signals in vaccination remains limited. Using cell-based vaccines, we selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II (pMHC II) complex in the absence of classic costimulation. Contrary to expectations, amplified signal 1 alone was strongly immunogenic and selectively expanded high-affinity TCR clonotypes, despite delivering intense TCR signals. In contrast to natural infection or standard vaccines, amplified signal 1, presented by a variety of professional and nonprofessional antigen-presenting cells (APCs), induced exclusively polyfunctional Th1 effector and memory cells, which protected against retroviral infection and tumor challenge, and expanded tumor-reactive CD4+ T cells otherwise rendered unresponsive in tumor-bearing hosts. Together, our findings uncover a default Th1 response to ample signal 1 and offer a means to selectively prime such protective responses by vaccination.
Using an integrative machine learning approach utilising homology modelling to clinically interpret genetic variants: CACNA1F as an exemplar
Authors: Sallah Shalaw R. , Sergouniotis Panagiotis I. , Barton Stephanie , Ramsden Simon , Taylor Rachel L. , Safadi Amro , Kabir Mitra , Ellingford Jamie M. , Lench Nick , Lovell Simon C. , Black Graeme C. M.
Published: April 2020

Advances in DNA sequencing technologies have revolutionised rare disease diagnostics and have led to a dramatic increase in the volume of available genomic data. A key challenge that needs to be overcome to realise the full potential of these technologies is that of precisely predicting the effect of genetic variants on molecular and organismal phenotypes. Notably, despite recent progress, there is still a lack of robust in silico tools that accurately assign clinical significance to variants. Genetic alterations in theCACNA1Fgene are the commonest cause of X-linked incomplete Congenital Stationary Night Blindness (iCSNB), a condition associated with non-progressive visual impairment. We combined genetic and homology modelling data to produce CACNA1F-vp, an in silico model that differentiates disease-implicated from benign missenseCACNA1Fchanges. CACNA1F-vp predicts variant effects on the structure of theCACNA1Fencoded protein (a calcium channel) using parameters based upon changes in amino acid properties; these include size, charge, hydrophobicity, and position. The model produces an overall score for each variant that can be used to predict its pathogenicity. CACNA1F-vp outperformed four other tools in identifying disease-implicated variants (area under receiver operating characteristic and precision recall curves = 0.84; Matthews correlation coefficient = 0.52) using a tenfold cross-validation technique. We consider this protein-specific model to be a robust stand-alone diagnostic classifier that could be replicated in other proteins and could enable precise and timely diagnosis.
Muscle overexpression of Klf15 via an AAV8-Spc5-12 construct does not provide benefits in spinal muscular atrophy mice
Authors: Ahlskog Nina , Hayler Daniel , Krueger Anja , Kubinski Sabrina , Claus Peter , Hammond Suzan M. , Wood Matthew J. A. , Yáñez-Muñoz Rafael J. , Bowerman Melissa
Published: April 2020

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the survival motor neuron (SMN) gene. While there are currently two approved gene-based therapies for SMA, availability, high cost, and differences in patient response indicate that alternative treatment options are needed. Optimal therapeutic strategies will likely be a combination of SMN-dependent and -independent treatments aimed at alleviating symptoms in the central nervous system and peripheral muscles. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates key metabolic and ergogenic pathways in muscle. We have recently reported significant downregulation of Klf15 in muscle of presymptomatic SMA mice. Importantly, perinatal upregulation of Klf15 via transgenic and pharmacological methods resulted in improved disease phenotypes in SMA mice, including weight and survival. In the current study, we designed an adeno-associated virus serotype 8 (AAV8) vector to overexpress a codon-optimized Klf15 cDNA under the muscle-specific Spc5-12 promoter (AAV8-Klf15). Administration of AAV8-Klf15 to severe Taiwanese Smn−/−;SMN2 or intermediate Smn2B/− SMA mice significantly increased Klf15 expression in muscle. We also observed significant activity of the AAV8-Klf15 vector in liver and heart. AAV8-mediated Klf15 overexpression moderately improved survival in the Smn2B/− model but not in the Taiwanese mice. An inability to specifically induce Klf15 expression at physiological levels in a time- and tissue-dependent manner may have contributed to this limited efficacy. Thus, our work demonstrates that an AAV8-Spc5-12 vector induces high gene expression as early as P2 in several tissues including muscle, heart, and liver, but highlights the challenges of achieving meaningful vector-mediated transgene expression of Klf15.
Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
Authors: Ngan Hoi-Lam , Poon Peony Hiu Yan , Su Yu-Xiong , Chan Jason Ying Kuen , Lo Kwok-Wai , Yeung Chun Kit , Liu Yuchen , Wong Eileen , Li Hui , Lau Chin Wang , Piao Wenying , Lui Vivian Wai Yan
Published: April 2020

Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated MAPK1 mutations. Residues D321, R135, and E322 are in 3D proximity. MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K’s effect is moderate.
Language in schizophrenia: relation with diagnosis, symptomatology and white matter tracts
Authors: de Boer J. N. , van Hoogdalem M. , Mandl R. C. W. , Brummelman J. , Voppel A. E. , Begemann M. J. H. , van Dellen E. , Wijnen F. N. K. , Sommer I. E. C.
Published: April 2020

Language deviations are a core symptom of schizophrenia. With the advances in computational linguistics, language can be easily assessed in exact and reproducible measures. This study investigated how language characteristics relate to schizophrenia diagnosis, symptom, severity and integrity of the white matter language tracts in patients with schizophrenia and healthy controls. Spontaneous speech was recorded and diffusion tensor imaging was performed in 26 schizophrenia patients and 22 controls. We were able to classify both groups with a sensitivity of 89% and a specificity of 82%, based on mean length of utterance and clauses per utterance. Language disturbances were associated with negative symptom severity. Computational language measures predicted language tract integrity in patients (adjustedR2 = 0.467) and controls (adjustedR2 = 0.483). Quantitative language analyses have both clinical and biological validity, offer a simple, helpful marker of both severity and underlying pathology, and provide a promising tool for schizophrenia research and clinical practice.
The FLAME-accelerated signalling tool (FaST) for facile parallelisation of flexible agent-based models of cell signalling
Authors: Fullstone Gavin , Guttà Cristiano , Beyer Amatus , Rehm Markus
Published: April 2020

Agent-based modelling is particularly adept at modelling complex features of cell signalling pathways, where heterogeneity, stochastic and spatial effects are important, thus increasing our understanding of decision processes in biology in such scenarios. However, agent-based modelling often is computationally prohibitive to implement. Parallel computing, either on central processing units (CPUs) or graphical processing units (GPUs), can provide a means to improve computational feasibility of agent-based applications but generally requires specialist coding knowledge and extensive optimisation. In this paper, we address these challenges through the development and implementation of the FLAME-accelerated signalling tool (FaST), a software that permits easy creation and parallelisation of agent-based models of cell signalling, on CPUs or GPUs. FaST incorporates validated new agent-based methods, for accurate modelling of reaction kinetics and, as proof of concept, successfully converted an ordinary differential equation (ODE) model of apoptosis execution into an agent-based model. We finally parallelised this model through FaST on CPUs and GPUs resulting in an increase in performance of 5.8× (16 CPUs) and 53.9×, respectively. The FaST takes advantage of the communicating X-machine approach used by FLAME and FLAME GPU to allow easy alteration or addition of functionality to parallel applications, but still includes inherent parallelisation optimisation. The FaST, therefore, represents a new and innovative tool to easily create and parallelise bespoke, robust, agent-based models of cell signalling.
Genomic diversifications of five Gossypium allopolyploid species and their impact on cotton improvement
Authors: Chen Z. Jeffrey , Sreedasyam Avinash , Ando Atsumi , Song Qingxin , De Santiago Luis M. , Hulse-Kemp Amanda M. , Ding Mingquan , Ye Wenxue , Kirkbride Ryan C. , Jenkins Jerry , Plott Christopher , Lovell John , Lin Yu-Ming , Vaughn Robert , Liu Bo , Simpson Sheron , Scheffler Brian E. , Wen Li , Saski Christopher A. , Grover Corrinne E. , Hu Guanjing , Conover Justin L. , Carlson Joseph W. , Shu Shengqiang , Boston Lori B. , Williams Melissa , Peterson Daniel G. , McGee Keith , Jones Don C. , Wendel Jonathan F. , Stelly David M. , Grimwood Jane , Schmutz Jeremy
Published: April 2020

Polyploidy is an evolutionary innovation for many animals and all flowering plants, but its impact on selection and domestication remains elusive. Here we analyze genome evolution and diversification for all five allopolyploid cotton species, including economically important Upland and Pima cottons. Although these polyploid genomes are conserved in gene content and synteny, they have diversified by subgenomic transposon exchanges that equilibrate genome size, evolutionary rate heterogeneities and positive selection between homoeologs within and among lineages. These differential evolutionary trajectories are accompanied by gene-family diversification and homoeolog expression divergence among polyploid lineages. Selection and domestication drive parallel gene expression similarities in fibers of two cultivated cottons, involving coexpression networks andN6-methyladenosine RNA modifications. Furthermore, polyploidy induces recombination suppression, which correlates with altered epigenetic landscapes and can be overcome by wild introgression. These genomic insights will empower efforts to manipulate genetic recombination and modify epigenetic landscapes and target genes for crop improvement.
Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals
Authors: Sayre Risa R. , Wambaugh John F. , Grulke Christopher M.
Published: April 2020

Time courses of compound concentrations in plasma are used in chemical safety analysis to evaluate the relationship between external administered doses and internal tissue exposures. This type of experimental data is rarely available for the thousands of non-pharmaceutical chemicals to which people may potentially be unknowingly exposed but is necessary to properly assess the risk of such exposures. In vitro assays and in silico models are often used to craft an understanding of a chemical’s pharmacokinetics; however, the certainty of the quantitative application of these estimates for chemical safety evaluations cannot be determined without in vivo data for external validation. To address this need, we present a public database of chemical time-series concentration data from 567 studies in humans or test animals for 144 environmentally-relevant chemicals and their metabolites (187 analytes total). All major administration routes are incorporated, with concentrations measured in blood/plasma, tissues, and excreta. We also include calculated pharmacokinetic parameters for some studies, and a bibliography of additional source documents to support future extraction of time-series. In addition to pharmacokinetic model calibration and validation, these data may be used for analyses of differential chemical distribution across chemicals, species, doses, or routes, and for meta-analyses on pharmacokinetic studies.
Asymmetric participation of defenders and critics of vaccines to debates on French-speaking Twitter
Authors: Gargiulo Floriana , Cafiero Florian , Guille-Escuret Paul , Seror Valérie , Ward Jeremy K.
Published: April 2020

For more than a decade, doubt about vaccines has become an increasingly important global issue. Polarization of opinions on this matter, especially through social media, has been repeatedly observed, but details about the balance of forces are left unclear. In this paper, we analyse the flow of information on vaccines on the French-speaking realm of Twitter between 2016 and 2017. Two major asymmetries appear. Rather than opposing themselves on each vaccine, defenders and critics focus on different vaccines and vaccine-related topics. Pro-vaccine accounts focus on hopes for new groundbreaking vaccines and on ongoing outbreaks of vaccine-preventable illnesses. Vaccine critics concentrate their posts on a limited number of “controversial” vaccines and adjuvants. Furthermore, vaccine-critical accounts display greater craft and energy, using a wider variety of sources, and a more coordinated set of hashtags. This double asymmetry can have serious consequences. Despite the presence of a large number of pro-vaccine accounts, some arguments raised by efficiently organized and very active vaccine-critical activists are left unanswered.
Improved fidelity of orientation perception: a learning effect dissociable from enhanced discriminability
Authors: Zhang En , Li Wu
Published: April 2020

Visual perception can be influenced by stimulus context, selective attention, and prior experience. Many previous studies have shown complex interactions among these influencing factors, but it remains unclear whether context-induced illusions could be reduced by perceptual training and whether such a change in perceptual fidelity is linked to improved perceptual discriminability. To address this question, we introduced a context-induced tilt illusion into an orientation discrimination training paradigm. This resulted in parallel and long-term improvements in the discriminability and fidelity of orientation perception. The improved discriminability was specific to the task-relevant target stimulus but nonspecific to the task-irrelevant context. By contrast, the improved perceptual fidelity was specific to the task-irrelevant contextual stimulus that induced the illusion, but not specific to the task-relevant target stimulus or task performed on one of its features. These results indicate two dissociable learning effects associated with the same training procedure. Such a dissociation was further supported by the observation that the sizes of the two learning effects were uncorrelated across the subjects. Our findings suggest two parallel learning processes: a task-dependent process giving rise to enhanced discriminability for the task-relevant stimulus attribute, and a context-dependent process leading to improved perceptual fidelity for the attended stimuli.