bluuebunny/crossref_metadata_2025 huggingface dataset:
A Wedge Mechanism for Summer Surface Water Inflow Into the Ross Ice Shelf Cavity
Authors: Malyarenko A. , Robinson N. J. , Williams M. J. M. , Langhorne P. J.
Published: January 2019

Ocean heat supply to ice shelves has a significant impact on the long‐term evolution of ice shelves. Intrusions of warm surface waters into the frontal region of the cavity, known as “Mode 3” circulation, are capable of melting the ice shelf base. However, ablation of the vertical walls of the ice shelf front has, to date, received little attention. Here we propose a mechanism for Mode 3 circulation that is aided by ice shelf front ablation: Direct contact of warm Antarctic Surface Water with the ice wall generates meltwater that buoyantly ascends the vertical face and leads to formation of a “wedge” of fresher water immediately adjacent to the wall. This wedge, which thins with distance from the ice shelf front, allows isopycnals to curve gently downward, creating an efficient conduit by which surface waters moved by other forces such as tidal flow and eddies enter an ice shelf cavity with minimal mixing. Here we use new and existing observational data from the Ross Sea and the Ross Ice Shelf cavity to demonstrate the existence of the wedge. Our analysis and a review of the literature suggest that the freshwater wedge structure is a pervasive feature of the Western Ross Sea in summer and enhances other inflow mechanisms.
Surface Layer Turbulence Parameters Derived From 1‐s Wind Observations on the West Florida Shelf
Authors: Mayer Dennis A. , Zhang Jun A. , Weisberg Robert H.
Published: January 2019

One‐second wind data on the West Florida Shelf were used to examine turbulent scales from large eddies to small eddies in the atmospheric surface layer within a frequency band from 0.02 to 0.3 Hz (periods from ~1 min to ~3 s). Data were collected at two at‐sea locations spanning 6.5 months. Three events in three wind ranges were examined in exploring the one‐dimensional turbulent power spectra: >14 m/s, wind range I; those between 10 and 14 m/s, wind range II; and those between 5 and 10 m/s, wind range III. Events consisted of ensembles of abutting 30‐min subsets spanning 5.5 to 23 hr. The mean vector wind time scale of T0 = 30 min was found to be reasonable for the West Florida Shelf region. The first wind range provided the best results, more or less in line with a Kolmogorov −5/3 power law whose mean vector wind speed over 21 subsets (10.5 hr) was nearly 15 m/s. The one‐dimensional turbulent power spectra provided an estimate of the dissipation rate (ε) from which other turbulent quantities could be computed: u*, τ, and Cd (the frictional velocity, the surface stress, and the drag coefficient, respectively). The salient point here is that these quantities were larger than those from previous observational studies. Where the power law was not operant intrinsic turbulent spatial scales ranged from 1 to 0.1 m and provide evidence of anisotropy for frequencies greater than 0.1 Hz.
Perturbations to Global Energy Budget Due to Absorbing and Scattering Aerosols
Authors: Suzuki Kentaroh , Takemura Toshihiko
Published: January 2019

Impacts of absorbing and scattering aerosols on global energy balance are investigated with a global climate model. A series of sensitivity experiments perturbing emissions of black carbon and sulfate aerosols individually is conducted with the model to explore how components of global energy budget change in response to the instantaneous radiative forcing due to the two types of aerosols. It is demonstrated how differing vertical structures of the instantaneous radiative forcing between the two aerosols induce distinctively different proportions of fast and slow climate responses through different energy redistribution into atmosphere and surface. These characteristics are quantified in the form of the whole picture of global energy budget perturbations normalized by the top‐of‐atmosphere instantaneous radiative forcing. The energy budget perturbation per “unit” instantaneous forcing thus quantified reveals relative magnitudes of changes to different component fluxes in restoring atmospheric and surface energy balances through fast and slow responses. The normalized picture then directly links the “initial forcing” to the eventual climate “responses,” thereby explaining how starkly different responses of the global‐mean temperature and precipitation are induced by the two types of aerosols. The study underscores a critical need for better quantifications of the forcings' vertical structure and atmospheric rapid adjustment for reliable estimates of climatic impact of absorbing and scattering aerosols. In particular, cloud responses through the indirect and semidirect effects and the sensible heat decrease in response to stabilized atmosphere due to the black carbon heating are identified as key uncertain components in the global energy budget perturbation.
High‐Resolution Modeling of ENSO‐Induced Precipitation in the Tropical Andes: Implications for Proxy Interpretation
Authors: Kiefer J. , Karamperidou C.
Published: January 2019

Sediment records from Lake Pallcacocha, Ecuador, have been interpreted as proxies of El Niño–Southern Oscillation (ENSO) variability, owing to increased precipitation in the area during El Niño events. However, the lake's watershed receives precipitation from processes arising from both the eastern and western Andes, where ENSO has different impacts; this has led to ambiguity in observed regional ENSO signals and has consequently challenged the suitability of the lake's records as ENSO proxies. Here, a mesoscale weather prediction model is used to investigate the regional circulation dynamics and precipitation response during different ENSO events, namely, Eastern Pacific (EP), Central Pacific (CP), coastal El Niño (COA), and La Niña (LN). The region receives more accumulated precipitation during COA and LN compared to EP and CP events. However, during EP and COA events, the region is prone to extreme precipitation associated with convective bursts originating from the Pacific. During CP and LN, moisture originates from the Atlantic and may reach the area as broader‐scale less‐intense precipitation. Statistical analysis of modeled precipitation reveals consistency between the number of threshold‐exceeding precipitation events in the high Andean elevations and the number of events identified in the late Holocene Pallcacocha record. These results illustrate the importance of considering ENSO flavors when interpreting paleoclimate proxies, highlight the role of COA events in understanding eastern Pacific proxy records, and support the hypothesis that Holocene changes in the number of events recorded in the lake sediment may indicate a change in the relative frequency of ENSO flavors.
Initial Deformation of the Northern Tibetan Plateau: Insights From Deposition of the Lulehe Formation in the Qaidam Basin
Authors: Cheng Feng , Garzione Carmala N. , Jolivet Marc , Guo Zhaojie , Zhang Daowei , Zhang Changhao , Zhang Qiquan
Published: January 2019

The Paleogene Lulehe Formation marks the onset of deposition in the Qaidam basin and preserves evidence of the initial topographic growth of northern Tibet. However, limited outcrops impede understanding of the sedimentary features of the Lulehe Formation as well as the tectonic relationship between the basin and surrounding topography. To fill this gap, we investigated core samples along the basin margin and conducted flexural modeling to estimate the topographic load of the Qilian Shan and Eastern Kunlun Shan during the deposition of the Lulehe Formation. Core samples reveal that the Lulehe Formation mainly consists of distal fluvial to marginal lacustrine deposits and proximal fluvial deposits along the southern margin of the basin while characterized by proximal alluvial fan deposits along the northern margin of the basin. Together with evidence for faulting shown on the seismic profiles, we infer that simultaneous deformation within the Qilian Shan and Altyn Tagh Shan during the Paleogene resulted in accumulation of coarse detrital deposits in the northwestern and northeastern Qaidam basin. The simultaneous deformation within the Altyn Tagh Shan and Qilian Shan since the Paleogene supports the idea that deformation in these two regions is kinematically linked. One‐ and two‐load beam flexural modeling indicates that the topographic load generated by both the Eastern Kunlun Shan and the Qilian Shan is responsible for the subsidence of the Qaidam basin during deposition of the Lulehe Formation. Our results highlight the initial relative high topography in the northern Tibetan plateau during the early Cenozoic.
Peering into Pores: What Happens When Water Meets Soil?
Authors: Zhang Chao , Lu Ning
Published: January 2019

New research sheds light on the long-standing puzzle of how and why soil water density differs from free water density.
Waves of Deadly Brine Can Slosh After Submarine Landslides
Authors: Kornei Katherine
Published: January 2019

Brine pools—hypersaline, low-oxygen waters deadly to many forms of ocean life—can experience waves hundreds of meters high when hit by a landslide, potentially overspilling their deep-sea basins.
Placebo aiTBS attenuates suicidal ideation and frontopolar cortical perfusion in major depression
Authors: Baeken Chris , Wu Guo-Rong , van Heeringen Kees
Published: January 2019

The application of repetitive transcranial magnetic stimulation has been shown to rapidly decrease suicidal ideation in major depressive disorder (MDD). However, the neural working mechanisms behind this prompt attenuation of suicidal thoughts remains to be determined. Here, we examined how placebo-accelerated intermittent theta burst stimulation (aiTBS) may influence brain perfusion and suicidal thoughts using arterial spin labeling (ASL). In a randomized double-blind sham-controlled crossover trial, 45 MDD patients received aiTBS applied to the left dorsolateral prefrontal cortex (Trial registration: http://clinicaltrials.gov/show/NCT01832805). With each ASL scan measurement, suicidal ideation was assessed with the Beck Scale for Suicidal Ideation (BSI) and depression severity with the Beck Depression Inventory (BDI). Compared with active stimulation, the attenuation of suicidal ideation after 4 days of placebo aiTBS was related to significant frontopolar prefrontal perfusion decreases. These findings were unrelated to changes in depression severity scores. Although both active and sham aiTBS resulted in prompt decreases in suicidal ideation, specifically sham aiTBS significantly attenuated frontopolar perfusion in relation to reductions in BSI scores. Our findings show that in accelerated neurostimulation paradigms, placebo responses are related to perfusion decreases in brain areas associated with higher cognitive processes, resulting in suicidal ideation attenuation.
Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress
Authors: Jianguo Li , Xueyang Jia , Cui Wang , Changxin Wu , Xuemei Qin
Published: January 2019

The gut microbiota has been increasingly correlated with depressive disorder. It was recently shown that the transplantation of the gut microbiota from depressed patients to animals can produce depressive-like behaviors, suggesting that the gut microbiota plays a causal role in the development of depression. In addition, metabolic disorder, which is strongly associated with depression, is exacerbated by changes in the composition of the gut microbiota and is alleviated by treatment with antidepressants. However, the key players and pathways that link the gut microbiota to the pathogenesis of depression remain largely unknown. To evaluate the relationships between depression and metabolic disorders in feces and plasma, we monitored changes in fecal and plasma metabolomes during the development of depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS). In these animals, the fecal metabolome was altered first and subjected to changes in the plasma metabolome. Changes in the abundance of fecal metabolites were associated with depressive-like behaviors and with altered levels of neurotransmitters in the hippocampus. Furthermore, the analysis of the fecal metabolome and the fecal microbiota in CUMS rats demonstrated consistent changes in the levels of several amino acids, including L-threonine, isoleucine, alanine, serine, tyrosine, and oxidized proline. Finally, we observed significant correlations between these amino acids and the altered fecal microbiota. The results of this study suggest that changes in amino acid metabolism by the gut microbiota contribute to changes in circulating amino acids and are associated with the behavior indices of depression.
ADGRL3 (LPHN3) variants predict substance use disorder
Authors: Arcos-Burgos Mauricio , Vélez Jorge I. , Martinez Ariel F. , Ribasés Marta , Ramos-Quiroga Josep A. , Sánchez-Mora Cristina , Richarte Vanesa , Roncero Carlos , Cormand Bru , Fernández-Castillo Noelia , Casas Miguel , Lopera Francisco , Pineda David A. , Palacio Juan D. , Acosta-López Johan E. , Cervantes-Henriquez Martha L. , Sánchez-Rojas Manuel G. , Puentes-Rozo Pedro J. , Molina Brooke S. G. ,   MTA Cooperative Group, Boden Margaret T. , Wallis Deeann , Lidbury Brett , Newman Saul , Easteal Simon , Swanson James , Patel Hardip , Volkow Nora , Acosta Maria T. , Castellanos Francisco X. , de Leon Jose , Mastronardi Claudio A. , Muenke Maximilian
Published: January 2019

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.
TTC3 contributes to TGF-β1-induced epithelial−mesenchymal transition and myofibroblast differentiation, potentially through SMURF2 ubiquitylation and degradation
Authors: Kim June-Hyung , Ham Sangwoo , Lee Yunjong , Suh Gee Young , Lee Yun-Song
Published: January 2019

Transforming growth factor-β (TGF-β) acts as a key cytokine in epithelial−mesenchymal transition (EMT) and myofibroblast differentiation, which are important for normal tissue repair and fibrotic diseases. Ubiquitylation and proteasomal degradation of TGF-β signaling proteins acts as a regulatory mechanism for the precise control of TGF-β signaling. SMAD-specific ubiquitin E3 ligase (SMAD ubiquitination regulatory factor 2, SMURF2) controls TGF-β signaling proteins including the TGF-β receptor (TGFR) and SMAD2/3. Here, we report that tetratricopeptide repeat domain 3 (TTC3), a ubiquitin E3 ligase, positively regulates TGF-β1-induced EMT and myofibroblast differentiation, through inducing ubiquitylation and proteasomal degradation of SMURF2. In human bronchial epithelial cells (BEAS-2B) and normal human lung fibroblasts, TTC3 knockdown suppressed TGF-β1-induced EMT and myofibroblast differentiation, respectively. Similarly, when TTC3 expression was suppressed, the TGF-β1-stimulated elevation of p-SMAD2, SMAD2, p-SMAD3, and SMAD3 were inhibited. In contrast, overexpression of TTC3 caused both EMT and myofibroblast differentiation in the absence of TGF-β1 treatment. TGF-β1 reduced SMURF2 levels and TTC3 overexpression led to a further decrease in SMURF2 levels, while TTC3 knockdown inhibited TGF-β1-induced SMURF2 reduction. In cell and in vitro ubiquitylation assays demonstrated TTC3-mediated SMURF2 ubiquitylation, and coimmunoprecipitation assays established the binding between SMURF2 and TTC3. TGF-β1-induced TTC3 expression was inhibited by the knockdown of SMAD2 and SMAD3. Finally, Ttc3 mRNA levels were significantly increased and Smurf2 protein levels were significantly decreased in the lungs of mice treated with bleomycin as compared with the lungs of control mice. Collectively, these data suggest that TTC3 may contribute to TGF-β1-induced EMT and myofibroblast differentiation, potentially through SMURF2 ubiquitylation/proteasomal degradation and subsequent inhibition of SMURF2-mediated suppression of SMAD2 and SMAD3, which in turn induces TTC3 expression.
Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children
Authors: Chotsiri Palang , Zongo Issaka , Milligan Paul , Compaore Yves Daniel , Somé Anyirékun Fabrice , Chandramohan Daniel , Hanpithakpong Warunee , Nosten François , Greenwood Brian , Rosenthal Philip J. , White Nicholas J. , Ouédraogo Jean-Bosco , Tarning Joel
Published: January 2019

Young children are the population most severely affected by Plasmodium falciparum malaria. Seasonal malaria chemoprevention (SMC) with amodiaquine and sulfadoxine-pyrimethamine provides substantial benefit to this vulnerable population, but resistance to the drugs will develop. Here, we evaluate the use of dihydroartemisinin-piperaquine as an alternative regimen in 179 children (aged 2.33–58.1 months). Allometrically scaled body weight on pharmacokinetic parameters of piperaquine result in lower drug exposures in small children after a standard mg per kg dosage. A covariate-free sigmoidal EMAX-model describes the interval to malaria re-infections satisfactorily. Population-based simulations suggest that small children would benefit from a higher dosage according to the WHO 2015 guideline. Increasing the dihydroartemisinin-piperaquine dosage and extending the dose schedule to four monthly doses result in a predicted relative reduction in malaria incidence of up to 58% during the high transmission season. The higher and extended dosing schedule to cover the high transmission period for SMC could improve the preventive efficacy substantially.
Bisnorgammacerane traces predatory pressure and the persistent rise of algal ecosystems after Snowball Earth
Authors: van Maldegem Lennart M. , Sansjofre Pierre , Weijers Johan W. H. , Wolkenstein Klaus , Strother Paul K. , Wörmer Lars , Hefter Jens , Nettersheim Benjamin J. , Hoshino Yosuke , Schouten Stefan , Sinninghe Damsté Jaap S. , Nath Nilamoni , Griesinger Christian , Kuznetsov Nikolay B. , Elie Marcel , Elvert Marcus , Tegelaar Erik , Gleixner Gerd , Hallmann Christian
Published: January 2019

Eukaryotic algae rose to ecological relevance after the Neoproterozoic Snowball Earth glaciations, but the causes for this consequential evolutionary transition remain enigmatic. Cap carbonates were globally deposited directly after these glaciations, but they are usually organic barren or thermally overprinted. Here we show that uniquely-preserved cap dolostones of the Araras Group contain exceptional abundances of a newly identified biomarker: 25,28-bisnorgammacerane. Its secular occurrence, carbon isotope systematics and co-occurrence with other demethylated terpenoids suggest a mechanistic connection to extensive microbial degradation of ciliate-derived biomass in bacterially dominated ecosystems. Declining 25,28-bisnorgammacerane concentrations, and a parallel rise of steranes over hopanes, indicate the transition from a bacterial to eukaryotic dominated ecosystem after the Marinoan deglaciation. Nutrient levels already increased during the Cryogenian and were a prerequisite, but not the ultimate driver for the algal rise. Intense predatory pressure by bacterivorous protists may have irrevocably cleared self-sustaining cyanobacterial ecosystems, thereby creating the ecological opportunity that allowed for the persistent rise of eukaryotic algae to global importance.
Mechanism of IRSp53 inhibition by 14-3-3
Authors: Kast David J. , Dominguez Roberto
Published: January 2019

Filopodia are precursors of dendritic spines and polarized cell migration. The I-BAR-domain protein IRSp53 is a key regulator of filopodia dynamics that couples Rho-GTPase signaling to cytoskeleton and membrane remodeling, playing essential roles in neuronal development and cell motility. Here, we describe the structural-functional basis for 14-3-3-dependent inhibition of IRSp53. Phosphoproteomics, quantitative binding and crystallographic studies demonstrate that 14-3-3 binds to two pairs of phosphorylation sites in IRSp53. Using bicistronic expression, we obtain an IRSp53 heterodimer in which only one subunit is phosphorylated, and show that each subunit of IRSp53 independently binds one 14-3-3 dimer. A FRET-sensor assay using natively phosphorylated IRSp53 reveals opposite conformational changes upon binding of activatory (Cdc42, Eps8) or inhibitory (14-3-3) inputs. Finally, we show that 14-3-3 inhibits IRSp53 binding to membranes. Collectively, our findings support a mechanism whereby phosphorylation-dependent inhibition of IRSp53 by 14-3-3 counters membrane binding and interactions with Cdc42 and downstream cytoskeletal effectors.
Infrared-pump electronic-probe of methylammonium lead iodide reveals electronically decoupled organic and inorganic sublattices
Authors: Guo Peijun , Mannodi-Kanakkithodi Arun , Gong Jue , Xia Yi , Stoumpos Constantinos C. , Cao Duyen H. , Diroll Benjamin T. , Ketterson John B. , Wiederrecht Gary P. , Xu Tao , Chan Maria K. Y. , Kanatzidis Mercouri G. , Schaller Richard D.
Published: January 2019

Organic-inorganic hybrid perovskites such as methylammonium lead iodide (CH3NH3PbI3) are game-changing semiconductors for solar cells and light-emitting devices owing to their defect tolerance and exceptionally long carrier lifetimes and diffusion lengths. Determining whether the dynamically disordered organic cations with large dipole moment benefit the optoelectronic properties of CH3NH3PbI3 has been an outstanding challenge. Herein, via transient absorption measurements employing an infrared pump pulse tuned to a methylammonium vibration, we observe slow, nanosecond-long thermal dissipation from the selectively excited organic mode to the inorganic sublattice. The resulting transient electronic signatures, during the period of thermal-nonequilibrium when the induced thermal motions are mostly concentrated on the organic sublattice, reveal that the induced atomic motions of the organic cations do not alter the absorption or the photoluminescence response of CH3NH3PbI3, beyond thermal effects. Our results suggest that the attractive optoelectronic properties of CH3NH3PbI3 mainly derive from the inorganic lead-halide framework.
Molecular weight fractionation by confinement of polymer in one-dimensional pillar[5]arene channels
Authors: Ogoshi Tomoki , Sueto Ryuta , Yagyu Masafumi , Kojima Ryosuke , Kakuta Takahiro , Yamagishi Tada-aki , Doitomi Kazuki , Tummanapelli Anil Kumar , Hirao Hajime , Sakata Yoko , Akine Shigehisa , Mizuno Motohiro
Published: January 2019

Confinement of polymers in nano-spaces can induce unique molecular dynamics and properties. Here we show molecular weight fractionation by the confinement of single polymer chains of poly(ethylene oxide) (PEO) in the one-dimensional (1D) channels of crystalline pillar[5]arene. Pillar[5]arene crystals are activated by heating under reduced pressure. The activated crystals are immersed in melted PEO, causing the crystals to selectively take up PEO with high mass fraction. The high mass fractionation is caused by the greater number of attractive CH/π interactions between PEO C-H groups and the π-electron-rich 1D channel of the pillar[5]arene with increasing PEO chain length. The molecular motion of the confined PEO (PEO chain thickness of ~3.7 Å) in the 1D channel of pillar[5]arenes (diameter of ~4.7 Å) is highly restricted compared with that of neat PEO.
Author Correction: A scalable peptide-GPCR language for engineering multicellular communication
Authors: Billerbeck Sonja , Brisbois James , Agmon Neta , Jimenez Miguel , Temple Jasmine , Shen Michael , Boeke Jef D. , Cornish Virginia W.
Published: January 2019

The original version of this Article omitted a declaration from the Competing Interests statement, which should have included the following: ‘J.D.B. is a founder and Director of the following: Neochromosome, Inc., the Center of Excellence for Engineering Biology, and CDI Labs, Inc. and serves on the Scientific Advisory Board of the following: Modern Meadow, Inc., Recombinetics, Inc., and Sample6, Inc.’. This has now been corrected in both the PDF and HTML versions of the Article.
Author Correction: Aberrant activation of non-coding RNA targets of transcriptional elongation complexes contributes to TDP-43 toxicity
Authors: Chung Chia-Yu , Berson Amit , Kennerdell Jason R. , Sartoris Ashley , Unger Travis , Porta Sílvia , Kim Hyung-Jun , Smith Edwin R. , Shilatifard Ali , Van Deerlin Vivianna , Lee Virginia M. -Y. , Chen-Plotkin Alice , Bonini Nancy M.
Published: January 2019

The original version of this Article contained an error in the author affiliations. The affiliation of Alice Chen-Plotkin with the Department of Neurology, Perelman School of Medicine, Philadelphia, PA, 19104 USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.
Author Correction: Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer
Authors: Nong Jingying , Gong Yuhua , Guan Yanfang , Yi Xin , Yi Yuting , Chang Lianpeng , Yang Ling , Lv Jialin , Guo Zhirong , Jia Hongyan , Chu Yuxing , Liu Tao , Chen Ming , Byers Lauren , Roarty Emily , Lam Vincent K. , Papadimitrakopoulou Vassiliki A. , Wistuba Ignacio , Heymach John V. , Glisson Bonnie , Liao Zhongxing , Lee J. Jack , Futreal P. Andrew , Zhang Shucai , Xia Xuefeng , Zhang Jianjun , Wang Jinghui
Published: January 2019

The original version of this Article contained an error in Fig. 2, in which the left y-axis labels ‘tDNA’ and ‘ctDNA’ were inadvertently inverted. This has been corrected in the PDF and HTML versions of the Article.
Author Correction: Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis
Authors: Dorival Jonathan , Risser Fanny , Jacob Christophe , Collin Sabrina , Dräger Gerald , Paris Cédric , Chagot Benjamin , Kirschning Andreas , Gruez Arnaud , Weissman Kira J.
Published: January 2019

In the original version of this Article, the final concentration of riboflavin in the supplemented LB medium for recombinant LkcE expression was incorrectly stated as 1 g L−1 (this was the concentration of the stock solution) and should have read 10–50 mg L−1. This error has been corrected in both the PDF and HTML versions of the Article.
Accounting for errors in quantum algorithms via individual error reduction
Authors: Otten Matthew , Gray Stephen K.
Published: January 2019

We discuss a surprisingly simple scheme for accounting (and removal) of error in observables determined from quantum algorithms. A correction to the value of the observable is calculated by first measuring the observable with all error sources active and subsequently measuring the observable with each error source reduced separately. We apply this scheme to the variational quantum eigensolver, simulating the calculation of the ground state energy of equilibrium H2 and LiH in the presence of several noise sources, including amplitude damping, dephasing, thermal noise, and correlated noise. We show that this scheme provides a decrease in the needed quality of the qubits by up to two orders of magnitude. In near-term quantum computing, where full fault-tolerant error correction is too expensive, this scheme provides a route to significantly more accurate calculations.
Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Hidalgo Bertha A. , Sofer Tamar , Qi Qibin , Schneiderman Neil , Chen Y.-D. Ida , Kaplan Robert C. , Avilés-Santa M. Larissa , North Kari E. , Arnett Donna K. , Szpiro Adam , Cai Jianwen , Yu Bing , Boerwinkle Eric , Papanicolaou George , Laurie Cathy C. , Rotter Jerome I. , Stilp Adrienne M.
Published: January 2019

Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, Cuban, and Dominican). We estimated the SNP-diabetes association in the six groups and in the combined sample. We found that the risk alleles occur in two non-reference haplotypes in HCHS/SOL, as in the SIGMA Mexicans. The haplotype frequencies were very similar between SIGMA Mexicans and the HCHS/SOL Mainland groups, but different in the Caribbean groups. The SLC16A11 sequence variants were significantly associated with risk for diabetes in the Mexican origin group (P = 0.025), replicating the SIGMA findings. However, these variants were not significantly associated with diabetes in a combined analysis of all groups, although the power to detect such effects was 85% (assuming homogeneity of effects among the groups). Additional analyses performed separately in each of the five non-Mexican origin groups were not significant. We also analyzed (1) exclusion of young controls and, (2) SNP by BMI interactions, but neither was significant in the HCHS/SOL data. The previously reported effects of SLC16A11 variants on diabetes in Mexican samples was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. Lack of replication in the HCHS/SOL non-Mexicans, and in the entire HCHS/SOL sample combined may represent underlying genetic heterogeneity. These results indicate a need for future genetic research to consider heterogeneity of the Hispanic/Latino population in the assessment of disease risk, but add to the evidence suggesting SLC16A11 as a potential therapeutic target for type 2 diabetes.
Remyelination promoting therapies in multiple sclerosis animal models: a systematic review and meta-analysis
Authors: Hooijmans Carlijn R. , Hlavica Martin , Schuler Florian A. F. , Good Nicolas , Good Andrin , Baumgartner Lisa , Galeno Gianluca , Schneider Marc P. , Jung Tarzis , de Vries Rob , Ineichen Benjamin V.
Published: January 2019

An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.
Expression of recombinant glutamic acid decarboxylase in insect larvae and its application in an immunoassay for the diagnosis of autoimmune diabetes mellitus
Authors: Trabucchi Aldana , Bombicino Silvina S. , Targovnik Alexandra M. , Marfía Juan I. , Sabljic Adriana V. , Faccinetti Natalia I. , Guerra Luciano L. , Iacono Ruben F. , Miranda María V. , Valdez Silvina N.
Published: January 2019

Autoimmune Diabetes Mellitus (DM) is a chronic disease caused by the selective destruction of insulin producing beta cells in human pancreas. DM is characterized by the presence of autoantibodies that bind a variety of islet-cell antigens. The 65 kDa isoform of glutamate decarboxylase (GAD65) is a major autoantigen recognized by these autoantibodies. Autoantibodies to GAD65 (GADA) are considered predictive markers of the disease when tested in combination with other specific autoantibodies. In order to produce reliable immunochemical tests for large scale screening of autoimmune DM, large amounts of properly folded GAD65 are needed. Herein, we report the production of human GAD65 using the baculovirus expression system in two species of larvae, Rachiplusia nu and Spodoptera frugiperda. GAD65 was identified at the expected molecular weight, properly expressed with high yield and purity in both larvae species and presenting appropriate enzymatic activity. The immunochemical ability of recombinant GAD65 obtained from both larvae to compete with [35S]GAD65 was assessed qualitatively by incubating GADA-positive patients’ sera in the presence of 1 μM of the recombinant enzyme. All sera tested became virtually negative after incubation with antigen excess. Besides, radiometric quantitative competition assays with GADA-positive patients’ sera were performed by adding recombinant GAD65 (0.62 nM–1.4 µM). All dose response curves showed immunochemical identity between proteins. In addition, a bridge-ELISA for the detection of GADA was developed using S. frugiperda-GAD65. This assay proved to have 77.3% sensitivity and 98.2% of specificity. GAD65 could be expressed in insect larvae, being S. frugiperda the best choice due to its high yield and purity. The development of a cost effective immunoassay for the detection of GADA was also afforded.
Biodegradation of naphthalene, BTEX, and aliphatic hydrocarbons by Paraburkholderia aromaticivorans BN5 isolated from petroleum-contaminated soil
Authors: Lee Yunho , Lee Yunhee , Jeon Che Ok
Published: January 2019

To isolate bacteria responsible for the biodegradation of naphthalene, BTEX (benzene, toluene, ethylbenzene, and o-, m-, and p-xylene), and aliphatic hydrocarbons in petroleum-contaminated soil, three enrichment cultures were established using soil extract as the medium supplemented with naphthalene, BTEX, or n-hexadecane. Community analyses showed that Paraburkholderia species were predominant in naphthalene and BTEX, but relatively minor in n-hexadecane. Paraburkholderia aromaticivorans BN5 was able to degrade naphthalene and all BTEX compounds, but not n-hexadecane. The genome of strain BN5 harbors genes encoding 29 monooxygenases including two alkane 1-monooxygenases and 54 dioxygenases, indicating that strain BN5 has versatile metabolic capabilities, for diverse organic compounds: the ability of strain BN5 to degrade short chain aliphatic hydrocarbons was verified experimentally. The biodegradation pathways of naphthalene and BTEX compounds were bioinformatically predicted and verified experimentally through the analysis of their metabolic intermediates. Some genomic features including the encoding of the biodegradation genes on a plasmid and the low sequence homologies of biodegradation-related genes suggest that biodegradation potentials of strain BN5 may have been acquired via horizontal gene transfers and/or gene duplication, resulting in enhanced ecological fitness by enabling strain BN5 to degrade all compounds including naphthalene, BTEX, and short aliphatic hydrocarbons in contaminated soil.
Immune cell characteristics and cytokine responses in adult HIV-negative tuberculous meningitis: an observational cohort study
Authors: van Laarhoven Arjan , Dian Sofiati , van Dorp Suzanne , Purnama Feby , Koeken Valerie A. C. M. , Diandini Emira , Utami Fitria , Livia Resvi , Apriani Lika , Ardiansyah Edwin , ter Horst Rob , Netea Mihai G. , Achmad Tri Hanggono , Hill Philip C. , Ruslami Rovina , Alisjahbana Bachti , Ussher James E. , Indrati Agnes , Verrall Ayesha , Ganiem Ahmad Rizal , van Crevel Reinout
Published: January 2019

Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe disease and 38% died in 6 months. Blood from TBM patients analysed by flow cytometry showed lower αβT and γδT cells, NK cells and MAIT cells compared to 26 pulmonary tuberculosis patients (2.4-4-fold, all p < 0.05) and 27 healthy controls (2.7-7.6-fold, p < 0.001), but higher neutrophils and classical monocytes (2.3-3.0-fold, p < 0.001). CSF leukocyte activation was higher than in blood (1.8-9-fold). CSF of TBM patients showed a predominance of αβT and NK cells, associated with better survival. Cytokine production after ex-vivo stimulation of whole blood showed a much broader range in TBM compared to both control groups (p < 0.001). Among TBM patients, high ex-vivo production of TNF-α, IL-6 and IL-10 correlated with fever, lymphocyte count and monocyte HLA-DR expression (all p < 0.05). TBM patients show a strong myeloid blood response, with a broad variation in immune function. This may influence the response to adjuvant treatment and should be considered in future trials of host-directed therapy.
Bacterial DNA translocation contributes to systemic inflammation and to minor changes in the clinical outcome of liver transplantation
Authors: Rodríguez-Laiz Gonzalo P. , Zapater Pedro , Melgar Paola , Alcázar Cándido , Franco Mariano , Giménez Paula , Pascual Sonia , Bellot Pablo , Palazón José M. , Rodríguez María , Carnicer Fernando , Más-Serrano Patricio , González-Navajas José M. , Gómez Luís , Such José , Lluís Félix , Francés Rubén ,   on behalf of the Liver Transplantation Group, de Santiago Carlos , Navarro José , Martínez Francisco , Galiana María , Salas Esteban , Palomar Inmaculada , Irurzun Javier , Bernabé Juan Matías , Perdiguero Miguel , Díaz María , Lozano Teresa , Merino Esperanza , Almanza Susana , Mataix José M , Orts Pedro , Jaime Francisco
Published: January 2019

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.
Nanoparticle administration method in cell culture alters particle-cell interaction
Authors: Moore Thomas L. , Urban Dominic A. , Rodriguez-Lorenzo Laura , Milosevic Ana , Crippa Federica , Spuch-Calvar Miguel , Balog Sandor , Rothen-Rutishauser Barbara , Lattuada Marco , Petri-Fink Alke
Published: January 2019

As a highly interdisciplinary field, working with nanoparticles in a biomedical context requires a robust understanding of soft matter physics, colloidal behaviors, nano-characterization methods, biology, and bio-nano interactions. When reporting results, it can be easy to overlook simple, seemingly trivial experimental details. In this context, we set out to understand howin vitrotechnique, specifically the way we administer particles in 2D culture, can influence experimental outcomes. Gold nanoparticles coated with poly(vinylpyrrolidone) were added to J774A.1 mouse monocyte/macrophage cultures as either a concentrated bolus, a bolus then mixed via aspiration, or pre-mixed in cell culture media. Particle-cell interaction was monitored via inductively coupled plasma-optical emission spectroscopy and we found that particles administered in a concentrated dose interacted more with cells compared to the pre-mixed administration method. Spectroscopy studies reveal that the initial formation of the protein corona upon introduction to cell culture media may be responsible for the differences in particle-cell interaction. Modeling of particle deposition using thein vitrosedimentation, diffusion and dosimetry model helped to clarify what particle phenomena may be occurring at the cellular interface. We found that particle administration methodin vitrohas an effect on particle-cell interactions (i.e. cellular adsorption and uptake). Initial introduction of particles in to complex biological media has a lasting effect on the formation of the protein corona, which in turn mediates particle-cell interaction. It is of note that a minor detail, the way in which we administer particles in cell culture, can have a significant effect on what we observe regarding particle interactionsin vitro.
Valve-like dynamics of gas flow through a packed crystal mush and cyclic strombolian explosions
Authors: Barth Anna , Edmonds Marie , Woods Andrew
Published: January 2019

Strombolian volcanic explosions are commonly attributed to the rise and burst of conduit-filling gas slugs. The magmas associated with strombolian activity, however, are typically not only volatile-rich but also highly crystalline, with mush regions in the shallow plumbing system, where an exsolved volatile phase may also be abundant. Through analogue experiments, we explore a new mechanism to form gas slugs and strombolian explosions. A steady flux of gas is supplied to the base of a particle-rich liquid layer, generating a localised gas intrusion, which initially grows through plastic deformation. Once the pressure in the intrusion overcomes the effective tensile strength of the particle pack, a localised channel opens, allowing gas to propagate upwards. As the pressure in the intrusion falls, the gas pocket collapses. The continued supply of gas leads to the formation of a new intrusion, and the cycle repeats. With higher gas fluxes, continuous channelised gas flow occurs. Highly crystalline shallow portions of basaltic conduits may act as a flow valve, transforming a steady gas flux into a series of discrete gas slugs which cause explosions.
Circadian transcription factor HSF1 regulates differential HSP70 gene transcription during the arousal-torpor cycle in mammalian hibernation
Authors: Tsukamoto Daisuke , Hasegawa Tomoko , Hirose Shin-ichi , Sakurai Yukina , Ito Michihiko , Takamatsu Nobuhiko
Published: January 2019

Mammalian hibernation is a seasonal phenomenon. The hibernation season consists of torpor periods with a reduced body temperature (Tb), interrupted by euthermic arousal periods (interbout arousal, IBA). The physiological changes associated with hibernation are assumed to be under genetic control. However, the molecular mechanisms that govern hibernation-associated gene regulation are still unclear. We found that HSP70 transcription is upregulated in the liver of nonhibernating (summer-active) chipmunks compared with hibernating (winter-torpid) ones. In parallel, HSF1, the major transcription factor for HSP70 expression, is abundant in the liver-cell nuclei of nonhibernating chipmunks, and disappears from the nuclei of hibernating ones. Moreover, during IBA, HSF1 reappears in the nuclei and drives HSP70 transcription. In mouse liver, HSF1 is regulated by the daily Tb rhythm, and acts as a circadian transcription factor. Taken together, chipmunks similarly use the Tb rhythm to regulate gene expression via HSF1 during the torpor-arousal cycle in the hibernation season.
Eco-friendly 2-Thiobarbituric acid as a corrosion inhibitor for API 5L X60 steel in simulated sweet oilfield environment: Electrochemical and surface analysis studies
Authors: Usman Bashir J. , Gasem Zuhair M. , Umoren Saviour A. , Solomon Moses M.
Published: January 2019

The corrosion inhibition efficiency of 2-Thiobarbituric acid (TBA) for metal substrate (API X60 steel) in 3.5% NaCl solution saturated with CO2gas was probed using various techniques namely, LPR (linear polarization resistance), EIS (electrochemical impedance spectroscopy), and PDP (potentiodynamic polarization). The effects of TBA concentration (25–100 ppm), solution pH (4 and 6), temperature (25–80 °C), and immersion time (2–72 h) on the inhibition efficiency were examined. SEM (scanning electron microscopy) and XPS (X–ray photoelectron spectroscopy) were deployed to explore the corrosion retardation mechanism. TBA exhibited protection efficiencies exceeding 90% for all experimental conditions considered. The excellent anticorrosion performance by TBA was retained up to 72 hours of immersion time. PDP results exhibited that TBA behaved as a mixed type inhibitor. Results from kinetics and thermodynamics analyses indicate that TBA chemically adsorbed on the steel surface following Langmuir isotherm model. The composition of the adsorbed TBA film has been analyzed by XPS.
Asymmetry-enriched electronic and optical properties of bilayer graphene
Authors: Huang Bor-Luen , Chuu Chih-Piao , Lin Ming-Fa
Published: January 2019

The electronic and optical response of Bernal stacked bilayer graphene with geometry modulation and gate voltage are studied. The broken symmetry in sublattices, one dimensional periodicity perpendicular to the domain wall and out-of-plane axis introduces substantial changes of wavefunctions, such as gapless topological protected states, standing waves with bonding and anti-bonding characteristics, rich structures in density of states and optical spectra. The wavefunctions present well-behaved standing waves in pure system and complicated node structures in geometry-modulated system. The optical absorption spectra show forbidden optical excitation channels, prominent asymmetric absorption peaks, and dramatic variations in absorption structures. These results provide that the geometry-modulated structure with tunable gate voltage could be used for electronic and optical manipulation in future graphene-based devices.