bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaginal retraining decreases craving for high-calorie food in overweight and obese women: A randomized controlled trial
Authors: Moritz Steffen , Göritz Anja S. , Schmotz Stella , Weierstall-Pust Roland , Gehlenborg Josefine , Gallinat Jürgen , Kühn Simone
Published: November 2019

Overweight and obesity are epidemic conditions. Obesity is associated with somatic and psychological sequelae, including serious life-shortening disorders (e.g., diabetes). This study aimed to evaluate the efficacy of a newly developed imaginal variant of approach bias modification (i.e., imaginal retraining) for the reduction of craving for high-calorie food. In a randomized controlled trial, 384 women with a body mass index above 25 were allocated to a wait-list control group or to two variants of imaginal retraining (ratio: 1; 0.5; 0.5). The two intervention groups were sent a manual on imaginal retraining. One group was explicitly encouraged and instructed to use electronic reminders (RER); the standard retraining group (RS) was not encouraged to use electronic reminders. Assessments were 6 weeks apart and were carried out online. Craving for high-calorie food represented the primary outcome (based on the Visual Analog Scale, VAS). Secondary outcomes included the Food Cravings Questionnaire (FCQ-T-R). The study was registered as DRKS00017220. Women in the RER group utilized the retraining technique more often than those in the RS condition, and utilization frequency in turn was associated with improvement on craving and eating behavior scales. Both intention-to-treat and per-protocol analyses showed a favorable effect of the RER group, which achieved significance on the primary outcome, as well as on several other outcomes relative to controls at a small to medium effect size. For those participants who measured their weight before and after the assessment using a scale, weight loss in the RER group was significantly greater compared to the control group. Both retraining groups (RER: 39.4%; RS: 31.1%) reduced their subjective amount of eating relative to controls (24.2%). Approximately two-thirds of the sample (68.3%) performed the exercises at least once during the study period. The present results show that, when used regularly, imaginal retraining may reduce craving for high-calorie food in overweight and obese women. Of note, there was also evidence suggestive of weight reduction, although no diet or lifestyle change was recommended in the manual. Because a large subgroup neither read the manual nor performed the exercises, we recommend that future imaginal retraining be conveyed via short video clips.
Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study
Authors: Knorr Ulla , Simonsen Anja Hviid , Roos Peter , Weimann Allan , Henriksen Trine , Christensen Ellen-Margrethe , Vinberg Maj , Mikkelsen Rie Lambæk , Kirkegaard Thomas , Jensen Rasmus Nejst , Akhøj Morten , Forman Julie , Poulsen Henrik Enghusen , Hasselbalch Steen Gregers , Kessing Lars Vedel
Published: November 2019

Bipolar disorder (BD) is a mental disorder characterized by recurrent relapses of affective episodes, cognitive impairment, illness progression, and reduced life expectancy. Increased systemic oxidatively generated nucleoside damage have been found in some neurodegenerative disorders and in BD. As the first, this naturalistic prospective, longitudinal follow-up case-control study investigated cerebrospinal fluid (CSF) oxidative stress markers 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) that relate to RNA and DNA damage, respectively. Patients with BD (n = 86, 51% female) and gender-and-age-matched healthy control individuals (HC; n = 44, 44% female) were evaluated at baseline (T0), during (T1) and after a new affective episode (T2), if it occurred, and after a year (T3). Cerebrospinal and urine oxidative stress markers were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. CSF-8-oxoGuo was statistically significantly higher by 18% (p = 0.003) in BD versus HC at T0, and by 22% (p = 0) at T3. CSF-8-oxoGuo had increased by 15% (p = 0.042) from T0 to T3, and by 14% (p = 0.021) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxodG had increased by 26% (p = 0.054) from T0 to T2 and decreased by 19% (p = 0.041) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxoGuo did not show a statistically significant change in HC during the one-year follow-up. CSF and urine-8-oxoGuo levels correlated moderately. In conclusion, CSF oxidative stress marker of RNA damage 8-oxoGuo showed both state and trait dependence in BD and stability in HC. Central RNA damage may be a potential biomarker for BD.
Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis
Authors: Gagliardi Mara , Cotella Diego , Santoro Claudio , Corà Davide , Barlev Nickolai A. , Piacentini Mauro , Corazzari Marco
Published: November 2019

The incidence of melanoma is increasing over the years with a still poor prognosis and the lack of a cure able to guarantee an adequate survival of patients. Although the new immuno-based coupled to target therapeutic strategy is encouraging, the appearance of targeted/cross-resistance and/or side effects such as autoimmune disorders could limit its clinical use. Alternative therapeutic strategies are therefore urgently needed to efficiently kill melanoma cells. Ferroptosis induction and execution were evaluated in metastasis-derived wild-type and oncogenic BRAF melanoma cells, and the process responsible for the resistance has been dissected at molecular level. Although efficiently induced in all cells, in an oncogenic BRAF- and ER stress-independent way, most cells were resistant to ferroptosis execution. At molecular level we found that: resistant cells efficiently activate NRF2 which in turn upregulates the early ferroptotic marker CHAC1, in an ER stress-independent manner, and the aldo-keto reductases AKR1C1 ÷ 3 which degrades the 12/15-LOX-generated lipid peroxides thus resulting in ferroptotic cell death resistance. However, inhibiting AKRs activity/expression completely resensitizes resistant melanoma cells to ferroptosis execution. Finally, we found that the ferroptotic susceptibility associated with the differentiation of melanoma cells cannot be applied to metastatic-derived cells, due to the EMT-associated gene expression reprogramming process. However, we identified SCL7A11 as a valuable marker to predict the susceptibility of metastatic melanoma cells to ferroptosis. Our results identify the use of pro-ferroptotic drugs coupled to AKRs inhibitors as a new valuable strategy to efficiently kill human skin melanoma cells.
Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases
Authors: Nie Anzheng , Sun Bao , Fu Zhihui , Yu Dongsheng
Published: November 2019

Aminoacyl-tRNA synthetases (ARSs) play a vital role in protein synthesis by linking amino acids to their cognate transfer RNAs (tRNAs). This typical function has been well recognized over the past few decades. However, accumulating evidence reveals that ARSs are involved in a wide range of physiological and pathological processes apart from translation. Strikingly, certain ARSs are closely related to different types of immune responses. In this review, we address the infection and immune responses induced by pathogen ARSs, as well as the potential anti-infective compounds that target pathogen ARSs. Meanwhile, we describe the functional mechanisms of ARSs in the development of immune cells. In addition, we focus on the roles of ARSs in certain immune diseases, such as autoimmune diseases, infectious diseases, and tumor immunity. Although our knowledge of ARSs in the immunological context is still in its infancy, research in this field may provide new ideas for the treatment of immune-related diseases.
Characterization of genetic subclonal evolution in pancreatic cancer mouse models
Authors: Niknafs Noushin , Zhong Yi , Moral John Alec , Zhang Lance , Shao Melody Xiaoshan , Lo April , Makohon-Moore Alvin , Iacobuzio-Donahue Christine A. , Karchin Rachel
Published: November 2019

The KPC mouse model, driven by the Kras and Trp53 transgenes, is well regarded for faithful recapitulation of human pancreatic cancer biology. However, the extent that this model recapitulates the subclonal evolution of this tumor type is unknown. Here we report evidence of continuing subclonal evolution after tumor initiation that largely reflect copy number alterations that target cellular processes of established significance in human pancreatic cancer. The evolutionary trajectories of the mouse tumors show both linear and branching patterns as well as clonal mixing. We propose the KPC model and derivatives have unexplored utility as a functional system to model the mechanisms and modifiers of tumor evolution.
Tumor diversity and the trade-off between universal cancer tasks
Authors: Hausser Jean , Szekely Pablo , Bar Noam , Zimmer Anat , Sheftel Hila , Caldas Carlos , Alon Uri
Published: November 2019

Recent advances have enabled powerful methods to sort tumors into prognosis and treatment groups. We are still missing, however, a general theoretical framework to understand the vast diversity of tumor gene expression and mutations. Here we present a framework based on multi-task evolution theory, using the fact that tumors need to perform multiple tasks that contribute to their fitness. We find that trade-offs between tasks constrain tumor gene-expression to a continuum bounded by a polyhedron whose vertices are gene-expression profiles, each specializing in one task. We find five universal cancer tasks across tissue-types: cell-division, biomass and energy, lipogenesis, immune-interaction and invasion and tissue-remodeling. Tumors that specialize in a task are sensitive to drugs that interfere with this task. Driver, but not passenger, mutations tune gene-expression towards specialization in specific tasks. This approach can integrate additional types of molecular data into a framework of tumor diversity grounded in evolutionary theory.
Tidal wetland resilience to sea level rise increases their carbon sequestration capacity in United States
Authors: Wang Faming , Lu Xiaoliang , Sanders Christian J. , Tang Jianwu
Published: November 2019

Coastal wetlands are large reservoirs of soil carbon (C). However, the annual C accumulation rates contributing to the C storage in these systems have yet to be spatially estimated on a large scale. We synthesized C accumulation rate (CAR) in tidal wetlands of the conterminous United States (US), upscaled the CAR to national scale, and predicted trends based on climate change scenarios. Here, we show that the mean CAR is 161.8 ± 6 g Cm−2 yr−1, and the conterminous US tidal wetlands sequestrate 4.2–5.0 Tg C yr−1. Relative sea level rise (RSLR) largely regulates the CAR. The tidal wetland CAR is projected to increase in this century and continue their C sequestration capacity in all climate change scenarios, suggesting a strong resilience to sea level rise. These results serve as a baseline assessment of C accumulation in tidal wetlands of US, and indicate a significant C sink throughout this century.
The ABCG2 multidrug transporter is a pump gated by a valve and an extracellular lid
Authors: Khunweeraphong Narakorn , Szöllősi Daniel , Stockner Thomas , Kuchler Karl
Published: November 2019

The human ATP-binding cassette transporter ABCG2 is a key to anticancer resistance and physiological detoxification. However, the molecular mechanism of substrate transport remains enigmatic. A hydrophobic di-leucine motif in the ABCG2 core separates a large intracellular cavity from a smaller upper cavity. We show that the di-leucine motif acts as a valve that controls drug extrusion. Moreover, the extracellular structure engages the re-entry helix and all extracellular loops to form a roof architecture on top of the upper cavity. Disulfide bridges and a salt bridge limit roof flexibility, but provide a lid-like function to control drug release. We propose that drug translocation from the central to the upper cavities through the valve is driven by a squeezing motion, suggesting that ABCG2 operates similar to a peristaltic pump. Finally, the roof contains essential residues, offering therapeutic options to block ABCG2 by either targeting the valve or essential residues in the roof.
The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status
Authors: Trigg Ricky M. , Lee Liam C. , Prokoph Nina , Jahangiri Leila , Reynolds C. Patrick , Amos Burke G. A. , Probst Nicola A. , Han Miaojun , Matthews Jamie D. , Lim Hong Kai , Manners Eleanor , Martinez Sonia , Pastor Joaquin , Blanco-Aparicio Carmen , Merkel Olaf , de los Fayos Alonso Ines Garces , Kodajova Petra , Tangermann Simone , Högler Sandra , Luo Ji , Kenner Lukas , Turner Suzanne D.
Published: November 2019

Resistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms in ALK-positive neuroblastoma (NB), we herein employ genome-wide CRISPR activation screens of NB cell lines treated with brigatinib or ceritinib, identifying PIM1 as a putative resistance gene, whose high expression is associated with high-risk disease and poor survival. Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents. These data confirm that PIM1 overexpression decreases sensitivity to ALK inhibitors in NB, and suggests that combined front-line inhibition of ALK and PIM1 is a viable strategy for the treatment of ALK-positive NB independent of MYCN status.
Tsc1-mTORC1 signaling controls striatal dopamine release and cognitive flexibility
Authors: Kosillo Polina , Doig Natalie M. , Ahmed Kamran M. , Agopyan-Miu Alexander H.C.W. , Wong Corinna D. , Conyers Lisa , Threlfell Sarah , Magill Peter J. , Bateup Helen S.
Published: November 2019

Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in TSC1 or TSC2, which encode proteins that negatively regulate mTOR complex 1 (mTORC1). TSC is associated with significant cognitive, psychiatric, and behavioral problems, collectively termed TSC-Associated Neuropsychiatric Disorders (TAND), and the cell types responsible for these manifestations are largely unknown. Here we use cell type-specific Tsc1 deletion to test whether dopamine neurons, which modulate cognitive, motivational, and affective behaviors, are involved in TAND. We show that loss of Tsc1 and constitutive activation of mTORC1 in dopamine neurons causes somatodendritic hypertrophy, reduces intrinsic excitability, alters axon terminal structure, and impairs striatal dopamine release. These perturbations lead to a selective deficit in cognitive flexibility, preventable by genetic reduction of the mTOR-binding protein Raptor. Our results establish a critical role for Tsc1-mTORC1 signaling in setting the functional properties of dopamine neurons, and indicate that dopaminergic dysfunction may contribute to cognitive inflexibility in TSC.
Polar surface structure of oxide nanocrystals revealed with solid-state NMR spectroscopy
Authors: Chen Junchao , Wu Xin-Ping , Hope Michael A. , Qian Kun , Halat David M. , Liu Tao , Li Yuhong , Shen Li , Ke Xiaokang , Wen Yujie , Du Jia-Huan , Magusin Pieter C. M. M. , Paul Subhradip , Ding Weiping , Gong Xue-Qing , Grey Clare P. , Peng Luming
Published: November 2019

Compared to nanomaterials exposing nonpolar facets, polar-faceted nanocrystals often exhibit unexpected and interesting properties. The electrostatic instability arising from the intrinsic dipole moments of polar facets, however, leads to different surface configurations in many cases, making it challenging to extract detailed structural information and develop structure-property relations. The widely used electron microscopy techniques are limited because the volumes sampled may not be representative, and they provide little chemical bonding information with low contrast of light elements. With ceria nanocubes exposing (100) facets as an example, here we show that the polar surface structure of oxide nanocrystals can be investigated by applying 17O and 1H solid-state NMR spectroscopy and dynamic nuclear polarization, combined with DFT calculations. Both CeO4-termination reconstructions and hydroxyls are present for surface polarity compensation and their concentrations can be quantified. These results open up new possibilities for investigating the structure and properties of oxide nanostructures with polar facets.
Human confidence judgments reflect reliability-based hierarchical integration of contextual information
Authors: Schustek Philipp , Hyafil Alexandre , Moreno-Bote Rubén
Published: November 2019

Our immediate observations must be supplemented with contextual information to resolve ambiguities. However, the context is often ambiguous too, and thus it should be inferred itself to guide behavior. Here, we introduce a novel hierarchical task (airplane task) in which participants should infer a higher-level, contextual variable to inform probabilistic inference about a hidden dependent variable at a lower level. By controlling the reliability of past sensory evidence through varying the sample size of the observations, we find that humans estimate the reliability of the context and combine it with current sensory uncertainty to inform their confidence reports. Behavior closely follows inference by probabilistic message passing between latent variables across hierarchical state representations. Commonly reported inferential fallacies, such as sample size insensitivity, are not present, and neither did participants appear to rely on simple heuristics. Our results reveal uncertainty-sensitive integration of information at different hierarchical levels and temporal scales.
Analog errors in quantum annealing: doom and hope
Authors: Pearson Adam , Mishra Anurag , Hen Itay , Lidar Daniel A.
Published: November 2019

Quantum annealing has the potential to provide a speedup over classical algorithms in solving optimization problems. Just as for any other quantum device, suppressing Hamiltonian control errors will be necessary before quantum annealers can achieve speedups. Such analog control errors are known to lead to $$J$$
J
-chaos, wherein the probability of obtaining the optimal solution, encoded as the ground state of the intended Hamiltonian, varies widely depending on the control error. Here, we show that $$J$$
J
-chaos causes a catastrophic failure of quantum annealing, in that the scaling of the time-to-solution metric becomes worse than that of a deterministic (exhaustive) classical solver. We demonstrate this empirically using random Ising spin glass problems run on the two latest generations of the D-Wave quantum annealers. We then proceed to show that this doomsday scenario can be mitigated using a simple error suppression and correction scheme known as quantum annealing correction (QAC). By using QAC, the time-to-solution scaling of the same D-Wave devices is improved to below that of the classical upper bound, thus restoring hope in the speedup prospects of quantum annealing.
An attenuated Zika virus NS4B protein mutant is a potent inducer of antiviral immune responses
Authors: Li Guangyu , Adam Awadalkareem , Luo Huanle , Shan Chao , Cao Zengguo , Fontes-Garfias Camila R. , Sarathy Vanessa V. , Teleki Cody , Winkelmann Evandro R. , Liang Yuejin , Sun Jiaren , Bourne Nigel , Barrett Alan D. T. , Shi Pei-Yong , Wang Tian
Published: November 2019

Live attenuated vaccines (LAVs) are one of the most important strategies to control flavivirus diseases. The flavivirus nonstructural (NS) 4B proteins are a critical component of both the virus replication complex and evasion of host innate immunity. Here we have used site-directed mutagenesis of residues in the highly conserved N-terminal and central hydrophobic regions of Zika virus (ZIKV) NS4B protein to identify candidate attenuating mutations. Three single-site mutants were generated, of which the NS4B-C100S mutant was more attenuated than the other two mutants (NS4B-C100A and NS4B-P36A) in two immunocompromised mouse models of fatal ZIKV disease. The ZIKV NS4B-C100S mutant triggered stronger type 1 interferons and interleukin-6 production, and higher ZIKV-specific CD4+and CD8+T-cell responses, but induced similar titers of neutralization antibodies compared with the parent wild-type ZIKV strain and a previously reported candidate ZIKV LAV with a 10-nucleotide deletion in 3′-UTR (ZIKV-3′UTR-Δ10). Vaccination with ZIKV NS4B-C100S protected mice from subsequent WT ZIKV challenge. Furthermore, either passive immunization with ZIKV NS4B-C100S immune sera or active immunization with ZIKV NS4B-C100S followed by the depletion of T cells affords full protection from lethal WT ZIKV challenge. In summary, our results suggest that the ZIKV NS4B-C100S mutant may serve as a candidate ZIKV LAV due to its attenuated phenotype and high immunogenicity.
Analysis of the Human Protein Atlas Image Classification competition
Authors: Ouyang Wei , Winsnes Casper F. , Hjelmare Martin , Cesnik Anthony J. , Åkesson Lovisa , Xu Hao , Sullivan Devin P. , Dai Shubin , Lan Jun , Jinmo Park , Galib Shaikat M. , Henkel Christof , Hwang Kevin , Poplavskiy Dmytro , Tunguz Bojan , Wolfinger Russel D. , Gu Yinzheng , Li Chuanpeng , Xie Jinbin , Buslov Dmitry , Fironov Sergei , Kiselev Alexander , Panchenko Dmytro , Cao Xuan , Wei Runmin , Wu Yuanhao , Zhu Xun , Tseng Kuan-Lun , Gao Zhifeng , Ju Cheng , Yi Xiaohan , Zheng Hongdong , Kappel Constantin , Lundberg Emma
Published: November 2019

Pinpointing subcellular protein localizations from microscopy images is easy to the trained eye, but challenging to automate. Based on the Human Protein Atlas image collection, we held a competition to identify deep learning solutions to solve this task. Challenges included training on highly imbalanced classes and predicting multiple labels per image. Over 3 months, 2,172 teams participated. Despite convergence on popular networks and training techniques, there was considerable variety among the solutions. Participants applied strategies for modifying neural networks and loss functions, augmenting data and using pretrained networks. The winning models far outperformed our previous effort at multi-label classification of protein localization patterns by ~20%. These models can be used as classifiers to annotate new images, feature extractors to measure pattern similarity or pretrained networks for a wide range of biological applications.
Impact of molecular testing on thyroid nodule neoplastic diagnosis, stratified by 4-cm size, in a surgical series
Authors: Shrestha Rupendra T. , Kizilgul Muhammed , Shahi Maryam , Amin Khalid , Evasovich Maria R. , Burmeister Lynn A.
Published: November 2019

Whether molecular testing adds diagnostic value to the evaluation of thyroid nodules 4-cm or larger is unknown. The impact of molecular testing on cytopathologic-histopathologic diagnosis of neoplasm (adenoma or malignant), stratified by nodule size <or≥ 4-cm, was analyzed from a surgical series. Of 490 index nodules, molecular testing was performed on 18% of 353 nodules <4-cm and 8.8% of 137 nodules ≥4-cm (p = 0.0118). Adenoma was higher (30% vs 14%) and malignancy lower in nodules ≥4-cm vs <4-cm (p < 0.0001). Molecular testing impacted the finding of malignancy in the <4-cm group. Molecular testing of the ≥4-cm AUS and FN cytology subcategory impacted neoplasm discovery (combining adenoma and malignancy), with mutation positive 100% (3/3), mutation negative 38% (3/8), no mutation testing 88% (21/24), p = 0.0122. In conclusion, more adenoma was found in nodules ≥4-cm, including those with benign cytology, which was not explained by available molecular testing results. Molecular testing impacted the finding of malignancy in thyroid nodules <4-cm. The overall number of ≥4-cm nodules with molecular testing in this study was too low to exclude its diagnostic value in this setting. Further study is recommended to include molecular testing in nodules ≥4-cm, including those with benign cytology, to identify follicular adenoma.
Computational screening of nanoparticles coupling to Aβ40 peptides and fibrils
Authors: Sen Soumyo , Vuković Lela , Král Petr
Published: November 2019

Blocking the formation, growth, and breaking of amyloid fibrils by synthetic nanosystems could provide a treatment of neurodegenerative diseases. With this in mind, here atomistic molecular dynamics simulations are used to screen for nanoparticles (NPs), covered with different mixtures of ligands, including positively and negatively charged ligands, Aβ40-cut-peptide, and synthetic inhibitor ligands, in their selective coupling to Aβ40 peptides and their fibrils. The simulations reveal that only Aβ40-cut-peptide-covered NPs have strong and selective coupling to Aβ40 monomers. On the other hand, positive, positive-neutral, Janus, and peptide NPs couple to the beta sheet surfaces of Aβ40 fibrils and only the negative-neutral NPs couple to the fibril tips.
Amazonian Biomass Burning Enhances Tropical Andean Glaciers Melting
Authors: Magalhães Newton de , Evangelista Heitor , Condom Thomas , Rabatel Antoine , Ginot Patrick
Published: November 2019

The melting of tropical glaciers provides water resources to millions of people, involving social, ecological and economic demands. At present, these water reservoirs are threatened by the accelerating rates of mass loss associated with modern climate changes related to greenhouse gas emissions and ultimately land use/cover change. Until now, the effects of land use/cover change on the tropical Andean glaciers of South America through biomass burning activities have not been investigated. In this study, we quantitatively examine the hypothesis that regional land use/cover change is a contributor to the observed glacier mass loss, taking into account the role of Amazonian biomass burning. We demonstrated here, for the first time, that for tropical Andean glaciers, a massive contribution of black carbon emitted from biomass burning in the Amazon Basin does exist. This is favorable due to its positioning with respect to Amazon Basin fire hot spots and the predominant wind direction during the transition from the dry to wet seasons (Aug-Sep-Oct), when most fire events occur. We investigated changes in Bolivian Zongo Glacier albedo due to impurities on snow, including black carbon surface deposition and its potential for increasing annual glacier melting. We showed that the magnitude of the impact of Amazonian biomass burning depends on the dust content in snow. When high concentration of dust is present (e.g. 100 ppm of dust), the dust absorbs most of the radiation that otherwise would be absorbed by the BC. Our estimations point to a melting factor of 3.3 ± 0.8% for black carbon, and 5.0 ± 1.0% for black carbon in the presence of low dust content (e.g. 10 ppm of dust). For the 2010 hydrological year, we reported an increase in runoff corresponding to 4.5% of the annual discharge during the seasonal peak fire season, which is consistent with our predictions.
A real-time spatio-temporal syndromic surveillance system with application to small companion animals
Authors: Hale Alison C. , Sánchez-Vizcaíno Fernando , Rowlingson Barry , Radford Alan D. , Giorgi Emanuele , O’Brien Sarah J. , Diggle Peter J.
Published: November 2019

Lack of disease surveillance in small companion animals worldwide has contributed to a deficit in our ability to detect and respond to outbreaks. In this paper we describe the first real-time syndromic surveillance system that conducts integrated spatio-temporal analysis of data from a national network of veterinary premises for the early detection of disease outbreaks in small animals. We illustrate the system’s performance using data relating to gastrointestinal disease in dogs and cats. The data consist of approximately one million electronic health records for dogs and cats, collected from 458 UK veterinary premises between March 2014 and 2016. For this illustration, the system predicts the relative reporting rate of gastrointestinal disease amongst all presentations, and updates its predictions as new data accrue. The system was able to detect simulated outbreaks of varying spatial geometry, extent and severity. The system is flexible: it generates outcomes that are easily interpretable; the user can set their own outbreak detection thresholds. The system provides the foundation for prompt detection and control of health threats in companion animals.
Prognostic and therapeutic potential of Adenylate kinase 2 in lung adenocarcinoma
Authors: Liu Huibin , Pu Yan , Amina Quhai , Wang Qiang , Zhang Mengmeng , Song Jianzhong , Guo Jun , Mardan Mahmut
Published: November 2019

Adenylate kinase 2 (AK2), an isoenzyme of the AK family, may have momentous extra-mitochondrial functions, especially in tumourigenesis in addition to the well-known control of energy metabolism. In this study, we provided the first evidence that AK2 is overexpressed in lung adenocarcinoma. The positive expression of AK2 is associated with tumor progression, and poor survival in patients with pulmonary adenocarcinoma. Knockdown of AK2 could suppress proliferation, migration, and invasion as well as induce apoptosis and autophagy in human lung adenocarcinoma cells. Remarkably, silencing AK2 exerted the greater tumor suppression roles when combined with hydroxychloroquine, an effective autophagy inhibitor, in vitro and in xenografts mouse models. Our data have probably provided preclinical proof that systematic inhibition of AK2 and autophagy could be therapeutically effective on lung cancer.
Sand mining in the Mekong Delta revisited - current scales of local sediment deficits
Authors: Jordan Christian , Tiede Jan , Lojek Oliver , Visscher Jan , Apel Heiko , Nguyen Hong Quan , Quang Chau Nguyen Xuan , Schlurmann Torsten
Published: November 2019

The delta of the Mekong River in Vietnam has been heavily impacted by anthropogenic stresses in recent years, such as upstream dam construction and sand mining within the main and distributary channels, leading to riverbank and coastal erosion. Intensive bathymetric surveys, conducted within the Tien River branch during the dry and wet season 2018, reveal a high magnitude of sand mining activities. For the year 2018, an analysis of bathymetric maps and the local refilling processes leads to an estimated sand extraction volume of 4.64 $$\pm $$± 0.31 Mm$${}^{3}$$3/yr in the study area, which covered around 20 km. Reported statistics of sand mining for all of the Mekong’s channels within the delta, which have a cumulative length of several hundred kilometres, are 17.77 Mm$${}^{3}$$3/yr for this period. Results from this study highlight that these statistics are likely too conservative. It is also shown that natural sediment supplies from upper reaches of the Mekong are insufficient to compensate for the loss of extracted bed aggregates, illustrating the non-sustainable nature of the local sand mining practices.
Population genetics of Liriomyza trifolii (Diptera: Agromyzidae) and comparison with four Liriomyza species in China based on COI, EF-1a and microsatellites loci
Authors: Chen Jing-Yun , Chang Ya-Wen , Tang Xiao-Tian , Zheng Si-Zhu , Du Yu-Zhou
Published: November 2019

Liriomyza is a large genus that includes polyphagous and invasive species (L. trifolii, L. sativae, and L. huidobrensis), and oligophagous species such as L. Chinensis in China. Effective control of these invasive and oligophagous species is not easy due to the fast invasion rate, interspecific competition, and pesticide resistance. In this study, we investigated population genetics of five Liriomyza species L. trifolii, L. sativae, L. huidobrensis, L. bryoniae, and L. chinensis based on COI and EF-1a genes, and microsatellite DNA. These five Liriomyza species revealed highly conservative characteristics in the COI gene among populations collected from different geographical regions and host plants. By contrast, the mutation rate of the EF-1a gene was higher than COI, and phylogenetic tree based on EF-1a showed that haplotypes of L. trifolii and L. sativae were not distinguished well. Genetic differentiation in microsatellite loci was obvious among the five species. Our results also indicated that geographic isolation had a greater impact on genetic differentiation in L. trifolii than the host plant. Populations of L. trifolii in China showed a high to moderate level of genetic differentiation and they had divided into two groups representing the coastal areas of southern China and northern regions. The genetic diversity of the southern group was higher than the northern group. We speculated that the invasion of L. trifolii likely occurred in southern regions of China and then spread northward. Bottleneck analyses revealed that the L. trifolii population in China was in a steady growth period.
Highly divergent lineage of narrow-headed vole from the Late Pleistocene Europe
Authors: Baca Mateusz , Popović Danijela , Lemanik Anna , Baca Katarzyna , Horáček Ivan , Nadachowski Adam
Published: November 2019

During the Late Pleistocene, narrow-headed voles (Lasiopodomys gregalis) inhabited Eurasia’s vast territories, frequently becoming the dominant small mammal species among steppe-tundra communities. We investigated the relationship between this species’ European and Asiatic populations by sequencing the mtDNA genomes of two extant specimens from Russia and 10 individuals from five Central European sites, dated to the post-LGM period. Phylogenetic analyses based on a large portion of mtDNA genomes highly supported the positioning ofL. gregaliswithinArvicolinae. The phylogeny based on mtDNA cytochromebsequences revealed a deep divergence of European narrow-headed voles from Asiatic ones and their sister position against the extantL. gregalisandL. raddei. The divergence of the European lineage was estimated to a minimum 230 thousand years ago. This suggest, contrary to the current biogeographic hypotheses, that during the interglacial periods narrow-headed vole did not retreat from Europe but survived the unfavourable conditions within the refugial areas. Based on this result, we propose to establish a cryptic species status for the Late Pleistocene European narrow-headed vole and to name this taxonLasiopodomys anglicus.
Real-time prediction of patient immune cell modulation during irreversible electroporation therapy
Authors: Beitel-White N. , Martin R. C. G. , Li Y. , Brock R. M. , Allen I. C. , Davalos R. V.
Published: November 2019

Immunotherapies have demonstrated limited efficacy in pancreatic ductal adenocarcinoma (PDAC) patients despite their success in treating other tumor types. This limitation is largely due to the relatively immunosuppressive environment surrounding the tumor. A focal ablative technique called irreversible electroporation (IRE) has been shown to modulate this environment, enhancing the efficacy of immunotherapy. One enhancing factor related to improved prognosis is a decrease in regulatory T cells (Treg). This decrease has been previously unpredictable for clinicians using IRE, who currently have limited real-time metrics for determining the activation of the patient’s immune response. Here, we report that larger overall changes in output current are correlated with larger decreases in T cell populations 24 hours post-treatment. This result suggests that clinicians can make real-time decisions regarding optimal follow-up therapy based on the range of output current delivered during treatment. This capability could maximize the immunomodulating effect of IRE in synergy with follow-up immunotherapy. Additionally, these results suggest that feedback from a preliminary IRE treatment of the local tumor may help inform clinicians regarding the timing and choice of subsequent therapies, such as resection, immunotherapy, chemotherapy, or follow-up thermal or non-thermal ablation.
Self-harm behaviour and externally-directed aggression in psychiatric outpatients: a multicentre, prospective study (viormed-2 study)
Authors: Scocco Paolo , Macis Ambra , Ferrari Clarissa , Bava Mattia , Bianconi Giorgio , Bulgari Viola , Candini Valentina , Carrà Giuseppe , Cavalera Cesare , Clerici Massimo , Conte Giovanni , Cricelli Marta , Teresa Ferla Maria , Iozzino Laura , Stefana Alberto , de Girolamo Giovanni
Published: November 2019

The aim of the project was to investigate differences between outpatients with Severe Mental Disorders (SMDs) with and without a history of Self-Harm behaviour (SHb) and/or Violent behaviour against other people (Vb) in relation to: (a) socio-demographic and clinical characteristics, (b) violent behaviour during a 1-year FU, (c) predictors of SHb and Vb during the FU. Outpatients with SMDs, with and without a history of Vb were enrolled. They were divided in four groups: patients with lifetime Vb (V), patients with both Vb and SHb (V-SH), patients with only SHb (SH) and patients with no history of SHb and Vb (control group, CONT). The frequency and severity of SHb and Vb during the FU were assessed every two weeks by the MOAS. Overall 246 patients were enrolled. BPRS-E Depression item, the SLOF Social acceptability, the BDHI Indirect Aggression, the BIS Motor Impulsiveness and the STAXI-2 Control-Out showed significant correlations with all the four groups (p < 0.030). V and V-SH patient groups reached higher scores in all MOAS sub-scales. Age among the SH group and BPRS-E affect-anxiety subscale among the V group significantly predicted aggression against people. In people with SMDs a history of SHb or Vb is associated with different medium-term outcomes.
Covalent Epitope Decoration of Carbon Electrodes using Solid Phase Peptide Synthesis
Authors: Candelaria Lindsay , Kalugin Peter N. , Kowalski Brian M. , Kalugin Nikolai G.
Published: November 2019

Long-term, minimally perturbative brain electrophysiology requires electrodes to seamlessly integrate into surrounding tissue. In this work, we demonstrate electrodes composed of covalently functionalized graphite, decorated with various functional affinity and epitope tags, and use them to detect changes in electrical potential on the surfaces of illuminated quantum dots and near fluorescing molecules. Affinity and epitope tagging of carbon was achieved using direct attachment of biotin and solid phase peptide synthesis (SPPS) of histidine (His)- and human influenza hemagglutinin (HA)-tags. Surface modification was confirmed with Auger, Energy-Dispersive X-ray (EDX), Raman, and fluorescence spectroscopy. Photoresponse was detected with compatible binding protein-surface tag combinations, confirming desired tag and electrode functionality. These results provide a path to organic, biofunctionalized, fully molecularly-defined electrodes for neuronal applications, and to a wide range of other secondary reactions and modifications of carbon; potential uses include affinity chromatography, DNA sequencing technologies, biomolecular sensors, and surfaces and scaffolds for targeted interfaces with biological tissues.
Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis
Authors: Chandran Aneesh , Williams Kerstin , Mendum Tom , Stewart Graham , Clark Simon , Zadi Sirine , Lanni Faye , McLeod Neil , Williams Ann , Villarreal-Ramos Bernardo , Vordermeier Martin , Maroudam Veerasamy , Prasad Aravind , Bharti Neeraj , Banerjee Ruma , Manjari Kasibhatla Sunitha , McFadden Johnjoe
Published: November 2019

Bovine tuberculosis (BTB) caused by Mycobacterium bovis remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain of the M. bovis pathogen, BCG, is not used to control bovine tuberculosis in cattle at present, due to its variable efficacy and because it interferes with the PPD test. Diagnostic tests capable of Differentiating Infected from Vaccinated Animals (DIVA) have been developed that detect immune responses to M. bovis antigens absent in BCG; but these are too expensive and insufficiently sensitive to be used for BTB control worldwide. To address these problems we aimed to generate a synergistic vaccine and diagnostic approach that would permit the vaccination of cattle without interfering with the conventional PPD-based surveillance. The approach was to widen the pool of M. bovis antigens that could be used as DIVA targets, by identifying antigenic proteins that could be deleted from BCG without affecting the persistence and protective efficacy of the vaccine in cattle. Using transposon mutagenesis we identified genes that were essential and those that were non-essential for persistence in bovine lymph nodes. We then inactivated selected immunogenic, but non-essential genes in BCG Danish to create a diagnostic-compatible triple knock-out ΔBCG TK strain. The protective efficacy of the ΔBCG TK was tested in guinea pigs experimentally infected with M. bovis by aerosol and found to be equivalent to wild-type BCG. A complementary diagnostic skin test was developed with the antigenic proteins encoded by the deleted genes which did not cross-react in vaccinated or in uninfected guinea pigs. This study demonstrates the functionality of a new and improved BCG strain which retains its protective efficacy but is diagnostically compatible with a novel DIVA skin test that could be implemented in control programmes.
The circadian clock uses different environmental time cues to synchronize emergence and locomotion of the solitary bee Osmia bicornis
Authors: Beer Katharina , Schenk Mariela , Helfrich-Förster Charlotte , Holzschuh Andrea
Published: November 2019

Life on earth adapted to the daily reoccurring changes in environment by evolving an endogenous circadian clock. Although the circadian clock has a crucial impact on survival and behavior of solitary bees, many aspects of solitary bee clock mechanisms remain unknown. Our study is the first to show that the circadian clock governs emergence in Osmia bicornis, a bee species which overwinters as adult inside its cocoon. Therefore, its eclosion from the pupal case is separated by an interjacent diapause from its emergence in spring. We show that this bee species synchronizes its emergence to the morning. The daily rhythms of emergence are triggered by temperature cycles but not by light cycles. In contrast to this, the bee’s daily rhythms in locomotion are synchronized by light cycles. Thus, we show that the circadian clock of O. bicornis is set by either temperature or light, depending on what activity is timed. Light is a valuable cue for setting the circadian clock when bees have left the nest. However, for pre-emerged bees, temperature is the most important cue, which may represent an evolutionary adaptation of the circadian system to the cavity-nesting life style of O. bicornis.
NV center based nano-NMR enhanced by deep learning
Authors: Aharon Nati , Rotem Amit , McGuinness Liam P. , Jelezko Fedor , Retzker Alex , Ringel Zohar
Published: November 2019

The growing field of nano nuclear magnetic resonance (nano-NMR) seeks to estimate spectra or discriminate between spectra of minuscule amounts of complex molecules. While this field holds great promise, nano-NMR experiments suffer from detrimental inherent noise. This strong noise masks to the weak signal and results in a very low signal-to-noise ratio. Moreover, the noise model is usually complex and unknown, which renders the data processing of the measurement results very complicated. Hence, spectra discrimination is hard to achieve and in particular, it is difficult to reach the optimal discrimination. In this work we present strong indications that this difficulty can be overcome by deep learning (DL) algorithms. The DL algorithms can mitigate the adversarial effects of the noise efficiently by effectively learning the noise model. We show that in the case of frequency discrimination DL algorithms reach the optimal discrimination without having any pre-knowledge of the physical model. Moreover, the DL discrimination scheme outperform Bayesian methods when verified on noisy experimental data obtained by a single Nitrogen-Vacancy (NV) center. In the case of frequency resolution we show that this approach outperforms Bayesian methods even when the latter have full pre-knowledge of the noise model and the former has none. These DL algorithms also emerge as much more efficient in terms of computational resources and run times. Since in many real-world scenarios the noise is complex and difficult to model, we argue that DL is likely to become a dominant tool in the field.
Enhancing violations of Leggett-Garg inequalities in nonequilibrium correlated many-body systems by interactions and decoherence
Authors: Mendoza-Arenas J. J. , Gómez-Ruiz F. J. , Rodríguez F. J. , Quiroga L.
Published: November 2019

We identify different schemes to enhance the violation of Leggett-Garg inequalities in open many-body systems. Considering a nonequilibrium archetypical setup of quantum transport, we show that particle interactions control the direction and amplitude of maximal violation, and that in the strongly-interacting and strongly-driven regime bulk dephasing enhances the violation. Through an analytical study of a minimal model we unravel the basic ingredients to explain this decoherence-enhanced quantumness, illustrating that such an effect emerges in a wide variety of systems.