bluuebunny/crossref_metadata_2025 huggingface dataset:
Energetic Electron Precipitation: Multievent Analysis of Its Spatial Extent During EMIC Wave Activity
Authors: Capannolo L. , Li W. , Ma Q. , Shen X.‐C. , Zhang X.‐J. , Redmon R. J. , Rodriguez J. V. , Engebretson M. J. , Kletzing C. A. , Kurth W. S. , Hospodarsky G. B. , Spence H. E. , Reeves G. D. , Raita T.
Published: March 2019

Electromagnetic ion cyclotron (EMIC) waves can drive precipitation of tens of keV protons and relativistic electrons, and are a potential candidate for causing radiation belt flux dropouts. In this study, we quantitatively analyze three cases of EMIC‐driven precipitation, which occurred near the dusk sector observed by multiple Low‐Earth‐Orbiting (LEO) Polar Operational Environmental Satellites/Meteorological Operational satellite programme (POES/MetOp) satellites. During EMIC wave activity, the proton precipitation occurred from few tens of keV up to hundreds of keV, while the electron precipitation was mainly at relativistic energies. We compare observations of electron precipitation with calculations using quasi‐linear theory. For all cases, we consider the effects of other magnetospheric waves observed simultaneously with EMIC waves, namely, plasmaspheric hiss and magnetosonic waves, and find that the electron precipitation at MeV energies was predominantly caused by EMIC‐driven pitch angle scattering. Interestingly, each precipitation event observed by a LEO satellite extended over a limited L shell region (ΔL ~ 0.3 on average), suggesting that the pitch angle scattering caused by EMIC waves occurs only when favorable conditions are met, likely in a localized region. Furthermore, we take advantage of the LEO constellation to explore the occurrence of precipitation at different L shells and magnetic local time sectors, simultaneously with EMIC wave observations near the equator (detected by Van Allen Probes) or at the ground (measured by magnetometers). Our analysis shows that although EMIC waves drove precipitation only in a narrow ΔL, electron precipitation was triggered at various locations as identified by POES/MetOp over a rather broad region (up to ~4.4 hr MLT and ~1.4 L shells) with similar patterns between satellites.
A Technique to Infer Magnetic Topology at Mars and Its Application to the Terminator Region
Authors: Xu Shaosui , Weber Tristan , Mitchell David L. , Brain David A. , Mazelle Christian , DiBraccio Gina A. , Espley Jared
Published: March 2019

Magnetic topology is important for understanding the Martian plasma environment, including particle precipitation, energy transport, cold ion escape, and wave‐particle interaction. In this study, we combine two independent but complementary methods in order to determine magnetic topology based on superthermal electron energy and pitch angle distributions. This approach removes ambiguities that result from using either energy or pitch angle alone, providing a more accurate and comprehensive determination of magnetic topology than previous studies. By applying this combined technique, we are able to identify seven magnetic topologies, including four types of closed field lines, two types of open field lines, and draped. All seven topologies are present in the Mars environment and are mapped in longitude, latitude, solar zenith angle, and altitude with the combined technique near the terminator. We find that closed field lines with double‐sided loss cones are frequently present over stronger crustal field regions at higher altitudes. We also show that the cross‐terminator closed field lines are more spatially confined over strong crustal regions, likely connecting nearby magnetic crustal patches. In contrast, cross‐terminator closed loops over weak crustal regions have more distantly separated foot points, most likely connecting distant crustal patches.
Statistical Analysis of Hiss Waves in Plasmaspheric Plumes Using Van Allen Probe Observations
Authors: Kim Kyung‐Chan , Shprits Yuri
Published: March 2019

Plasmaspheric hiss waves commonly observed in high‐density regions in the Earth's magnetosphere are known to be one of the main contributors to the loss of radiation belt electrons. There has been a lot of effort to investigate the distributions of hiss waves in the plasmasphere, while relatively little attention has been given to those in the plasmaspheric plume. In this study, we present for the first time a statistical analysis of the occurrence and the spatial distribution of wave amplitudes and wave normal angles for hiss waves in plumes using Van Allen Probes observations during the period of October 2012 to December 2016. Statistical results show that a wide range of hiss wave amplitudes in plumes from a few picotesla to >100 pT is observed, but a modest (<20 pT) wave amplitude is more commonly observed regardless of geomagnetic activity in both the midnight‐to‐dawn and dusk sector. By contrast, stronger amplitude hiss occurs preferentially during geomagnetically active times in the dusk sector. The wave normal angles are distributed over a broad range from 0° to 90° with a bimodal distribution: a quasi‐field‐aligned population (<20°) with an occurrence rate of <60% and an oblique one (>50°) with a relative low occurrence rate of ≲20%. Therefore, from a statistical point of view, we confirm that the hiss intensity (a few tens of picotesla) and field‐aligned hiss wave adopted in previous simulation studies are a reasonable assumption but stress that the activity dependence of the wave amplitude should be considered.
Sensitivity of Seismic Velocity Changes to the Tidal Strain at Different Lapse Times: Data Analyses of a Small Seismic Array at Izu‐Oshima Volcano
Authors: Takano Tomoya , Nishimura Takeshi , Nakahara Hisashi , Ueda Hideki , Fujita Eisuke
Published: March 2019

We investigate seismic velocity changes in response to the tidal strain at Izu‐Oshima volcano, Japan, by analyzing the data of permanent seismic stations and a small seismic array to evaluate the characteristics of strain sensitivity of velocity changes. We estimate the seismic velocity changes by phase differences between cross‐correlations functions of ambient noises at the frequency of 2–4 Hz stacked for time periods with different tidal strain amplitudes. The seismic velocity changes decrease and increase during dilatation and contraction periods, respectively, when analyzing the cross‐correlations functions at early lapse times ranging from 2 to 7 s. The strain sensitivity of seismic velocity changes is estimated to beat the early lapse times. However, we find that strain sensitivity of the seismic velocity changes decreases when analyzing the cross‐correlation functions at later lapse times from 7 s to 35 s. Applying an array analysis to the cross‐correlation functions, we observe apparent velocities of about 1 km/s at the early lapse times and those of higher than 1 km/s at the late lapse times. Since the group velocity of Rayleigh waves is 1.1 km/s at Izu‐Oshima volcano, the apparent velocities at the late lapse times may indicate the scattered or reflected body waves incident from a deeper region. Decrease of strain sensitivity with the lapse times therefore results from the emergence of body waves on the late lapse times. These results highlight the need to pay attention to wave types of cross‐correlation functions and their paths to interpret seismic velocity changes.
Improved Surface Layer Simulation Using Refined Vertical Resolution in the GFDL Atmospheric General Circulation Model
Authors: Shin Hyeyum Hailey , Ming Yi , Zhao Ming , Chen Xi , Lin Shian‐Jiann
Published: March 2019

Surface layer (SL) variables (e.g., 2‐m temperature [T2] and 10‐m wind [U10]) are diagnosed by applying the flux‐profile relationships based on Monin‐Obukhov similarity theory to the lowest model height (LMH). This assumes that the LMH is in the SL, which is approximately the bottom 10% of the boundary layer, but atmospheric general circulation models rarely satisfy this in stable boundary layers (SBLs). To assess errors in the diagnostic variables due to the LMH solely linked to the diagnostic algorithm, offline tests of the flux‐profile relationships are performed with LMH from a few meters to 60 m for three SBL regimes: weakly stable, very stable, and transition stability regimes. The results show that T2 and U10 are underestimated by O(0.1–1 °C) and O(0.1–1 m/s), respectively, if the LMH is higher than the SL height. The stronger the SL stability is, the larger the temperature biases are. The negative wind biases increase with the surface stress. Based on these findings, we analyze the impacts of the LMH on the climatologies of the diagnostic parameters in the Geophysical Fluid Dynamics Laboratory (GFDL) Atmosphere Model 4.0/Land Model 4.0. The results show reduced negative biases in T2 and U10 by lowering the LMH. The decrease of the overall bias over land is mainly due to the sensitivity of the diagnostic method to the LMH in SBLs, as shown in the offline tests. The overall increase in T2 and U10 over the oceans results from the increase in the actual near‐surface temperature and wind rather than from the diagnostic method.
Forecasting Seismicity from Wastewater Disposal in Oklahoma
Authors: Cook Terri
Published: March 2019

Mandated wastewater injection reductions in effect since 2016 are inadequate for preventing future, large-magnitude earthquakes in the state, according to a new induced seismicity model.
Unused Fiber-Optic Cables Repurposed as Seismic Sensors
Authors: Cartier Kimberly
Published: March 2019

So-called dark fiber can serve as regional seismic activity monitors and also detect earthquakes thousands of kilometers away, according to new research.
Squaramide-based synthetic chloride transporters activate TFEB but block autophagic flux
Authors: Zhang Shaoyi , Wang Yan , Xie Wei , Howe Ethan N. W. , Busschaert Nathalie , Sauvat Allan , Leduc Marion , Gomes-da-Silva Lígia C. , Chen Guo , Martins Isabelle , Deng Xiaxing , Maiuri Luigi , Kepp Oliver , Soussi Thierry , Gale Philip A. , Zamzami Naoufal , Kroemer Guido
Published: March 2019

Cystic fibrosis is a disease caused by defective function of a chloride channel coupled to a blockade of autophagic flux. It has been proposed to use synthetic chloride transporters as pharmacological agents to compensate insufficient chloride fluxes. Here, we report that such chloride anionophores block autophagic flux in spite of the fact that they activate the pro-autophagic transcription factor EB (TFEB) coupled to the inhibition of the autophagy-suppressive mTORC1 kinase activity. Two synthetic chloride transporters (SQ1 and SQ2) caused a partially TFEB-dependent relocation of the autophagic marker LC3 to the Golgi apparatus. Inhibition of TFEB activation using a calcium chelator or calcineurin inhibitors reduced the formation of LC3 puncta in cells, yet did not affect the cytotoxic action of SQ1 and SQ2 that could be observed after prolonged incubation. In conclusion, the squaramide-based synthetic chloride transporters studied in this work (which can also dissipate pH gradients) are probably not appropriate for the treatment of cystic fibrosis yet might be used for other indications such as cancer.
Inhibiting 4E-BP1 re-activation represses podocyte cell cycle re-entry and apoptosis induced by adriamycin
Authors: Li Fang , Mao Xing , Zhuang Qiyuan , Zhao Zhonghua , Zhang Zhigang , Wu Huijuan
Published: March 2019

Podocyte loss is one of the determining factors for the progression toward glomerulosclerosis. Podocyte is terminally differentiated and does not typically proliferate following injury and loss. However, recent evidence suggested that during renal injury, podocyte could re-enter the cell cycle, sensitizing the cells to injury and death, but the molecular mechanisms underlying it, as well as the cell fate determination still remained unclear. Here, using NPHS2 Cre; mT/mG transgenic mice and primary podocytes isolated from the mice, we investigated the effect of mammalian target of rapamycin complex 1 (mTORC1)/4E-binding protein 1 (4E-BP1) signaling pathway on cell cycle re-entry and apoptosis of podocyte induced by adriamycin. It was found that podocyte cell cycle re-entry could be induced by adriamycin as early as the 1st week in vivo and the 2nd hour in vitro, accompanied with 4E-BP1 activation and was followed by podocyte loss or apoptosis from the 4th week in vivo or the 4th hour in vitro. Importantly, targeting 4E-BP1 activation by the RNA interference of 4E-BP1 or pharmacologic rapamycin (inhibitor of mTORC1, blocking mTORC1-dependent phosphorylation of its substrate 4E-BP1) treatment was able to inhibit the increases of PCNA, Ki67, and the S-phase fraction of cell cycle in primary podocyte during 2–6 h of adriamycin treatment, and also attenuated the following apoptotic cell death of podocyte detected from the 4th hour, suggesting that 4E-BP1 could be a regulator to manipulate the amount of cell cycle re-entry provided by differentiated podocyte, and thus regulate the degree of podocyte apoptosis, bringing us a new potential podocyte-protective substance that can be used for therapy.
Loss of SET reveals both the p53-dependent and the p53-independent functions in vivo
Authors: Kon Ning , Wang Donglai , Gu Wei
Published: March 2019

Our previous study showed that the oncoprotein SET acts as a new reader of unacetylated p53 for transcriptional repression. To further elucidate the physiological significance of SET in vivo, we generated set knockout mice. Set knockout mice died during embryonic development between day 11.5 and day 12.5 post coitum, exhibiting cardiac edema and open neural tube, among other developmental defects. Further analyses revealed that loss of SET leads to upregulation of p53 target genes including p21 and puma without any obvious effect on p53 stability in set knockout embryos. Notably, the developmental defects of set knockout mice were significantly, but nonetheless partially, rescued by concomitant deletion of p53. The failure to obtain fully live set/p53 double knockout mice suggested that p53-independent targets of SET also contribute to the embryonic lethality of set knockout mice. Indeed, we found that FOXO1 acts as an important target of SET and that SET-mediated regulation of FOXO1 is also acetylation-dependent. Taken together, these data underscore the importance of SET oncoprotein during embryonic development and reveal both of the p53-dependent and the p53-independent functions of SET in vivo.
Aqueous proton-selective conduction across two-dimensional graphyne
Authors: Shi Le , Xu Ao , Pan Ding , Zhao Tianshou
Published: March 2019

The development of direct methanol fuel cells is hindered by the issue of methanol crossover across membranes, despite the remarkable features resulting from the use of liquid fuel. Here we investigate the proton-selective conduction behavior across 2D graphyne in an aqueous environment. The aqueous proton conduction mechanism transitions from bare proton penetration to a mixed vehicular and Grotthuss transportation when the side length of triangular graphyne pores increases to 0.95 nm. A further increase in the side length to 1.2 nm results in the formation of a patterned aqueous/vacuum interphase, enabling protons to be conducted through the water wires via Grotthuss mechanism with low energy barriers. More importantly, it is found that 2D graphyne with the side length of less than 1.45 nm can effectively block methanol crossover, suggesting that 2D graphyne with an appropriate pore size is an ideal material to achieve zero-crossover proton-selective membranes.
Author Correction: RGS7 is recurrently mutated in melanoma and promotes migration and invasion of human cancer cells
Authors: Qutob Nouar , Masuho Ikuo , Alon Michal , Emmanuel Rafi , Cohen Isadora , Di Pizio Antonella , Madore Jason , Elkahloun Abdel , Ziv Tamar , Levy Ronen , Gartner Jared J. , Hill Victoria K. , Lin Jimmy C. , Hevroni Yael , Greenberg Polina , Brodezki Alexandra , Rosenberg Steven A. , Kosloff Mickey , Hayward Nicholas K. , Admon Arie , Niv Masha Y. , Scolyer Richard A. , Martemyanov Kirill A. , Samuels Yardena
Published: March 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone
Authors: Bekeschus Sander , Lippert Maxi , Diepold Kristina , Chiosis Gabriela , Seufferlein Thomas , Azoitei Ninel
Published: March 2019

HSP90 is a ubiquitously expressed molecular chaperone implicated in the correct folding and maturation of a plethora of proteins including protein kinases and transcription factors. While disruption of chaperone activity was associated with augmented cancer cell death and decreased tumor growth both in vitro and in vivo, the regulation of HSP90 is not clearly understood. Here we report that treatment of cancer cells with cold physical plasma, an emerging and less aggressive tumor therapy, resulted in ROS generation which subsequently triggered the cleavage of HSP90. Notably, cleavage of HSP90 was followed by the degradation of PKD2, a crucial regulator of tumor growth and angiogenesis. Pre-sensitization of cancer cells with subliminal doses of PU-H71, an HSP90 inhibitor currently under clinical evaluation, followed by treatment with cold-plasma, synergistically and negatively impacted on the viability of cancer cells. Taken together, cold-plasma can be used in conjunction with pharmacologic treatment in order to target the expression and activity of HSP90 and the downstream client proteins implicated in various cancer cell capabilities.
A new genus and two new species of freshwater mussels (Unionidae) from western Indochina
Authors: Konopleva Ekaterina S. , Pfeiffer John M. , Vikhrev Ilya V. , Kondakov Alexander V. , Gofarov Mikhail Yu. , Aksenova Olga V. , Lunn Zau , Chan Nyein , Bolotov Ivan N.
Published: March 2019

The systematics of Oriental freshwater mussels (Bivalvia: Unionidae) is poorly known. Here, we present an integrative revision of the genus Trapezoideus Simpson, 1900 to further understanding of freshwater mussel diversity in the region. We demonstrate that Trapezoideus as currently circumscribed is non-monophyletic, with its former species belonging to six other genera, one of which is new to science and described here. We recognize Trapezoideus as a monotypic genus, comprised of the type species, T. foliaceus. Trapezoideus comptus, T. misellus, T. pallegoixi, and T. peninsularis are transferred to the genus Contradens, T. subclathratus is moved to Indonaia, and T. theca is transferred to Lamellidens. Trapezoideus prashadi is found to be a junior synonym of Arcidopsis footei. Trapezoideus dallianus, T. nesemanni, T. panhai, T. peguensis, and two species new to science are placed in Yaukthwagen. nov. This genus appears to be endemic of the Western Indochina Subregion. The two new species, Yaukthwa paiensissp. nov. and Y. inlenensissp. nov., are both endemic to the Salween River basin. Our results highlight that Southeast Asia is a species-rich freshwater mussel diversity hotspot with numerous local endemic species, which are in need of special conservation efforts.
Lack of IL-17 Receptor A signaling aggravates lymphoproliferation in C57BL/6 lpr mice
Authors: Corneth Odilia B. J. , Schaper Fleur , Luk Franka , Asmawidjaja Patrick S. , Mus Adriana M. C. , Horst Gerda , Heeringa Peter , Hendriks Rudi W. , Westra Johanna , Lubberts Erik
Published: March 2019

Defects in Fas function correlate with susceptibility to systemic autoimmune diseases like autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosus (SLE). C57BL/6 lpr (B6/lpr) mice are used as an animal model of ALPS and develop a mild SLE phenotype. Involvement of interleukin-17A (IL-17A) has been suggested in both phenotypes. Since IL-17 receptor A is part of the signaling pathway of many IL-17 family members we investigated the role of IL-17 receptor signaling in disease development in mice with a B6/lpr background. B6/lpr mice were crossed with IL-17 receptor A deficient (IL-17RA KO) mice and followed over time for disease development. IL-17RA KO/lpr mice presented with significantly enhanced lymphoproliferation compared with B6/lpr mice, which was characterized by dramatic lymphadenomegaly/splenomegaly and increased lymphocyte numbers, expansion of double-negative (DN) T-cells and enhanced plasma cell formation. However, the SLE phenotype was not enhanced, as anti-nuclear antibody (ANA) titers and induction of glomerulonephritis were not different. In contrast, levels of High Mobility Group Box 1 (HMGB1) and anti-HMGB1 autoantibodies were significantly increased in IL-17RA KO/lpr mice compared to B6/lpr mice. These data show that lack of IL-17RA signaling aggravates the lymphoproliferative phenotype in B6/lpr mice but does not affect the SLE phenotype.
Biochemical and structural characterization of tomato polyphenol oxidases provide novel insights into their substrate specificity
Authors: Kampatsikas Ioannis , Bijelic Aleksandar , Rompel Annette
Published: March 2019

Polyphenol oxidases (PPOs) contain the structurally similar enzymes tyrosinases (TYRs) and catechol oxidases (COs). Two cDNAs encoding pro-PPOs from tomato (Solanum lycopersicum) were cloned and heterologously expressed in Escherichia coli. The two pro-PPOs (SlPPO1-2) differ remarkably in their activity as SlPPO1 reacts with the monophenols tyramine (kcat = 7.94 s−1) and phloretin (kcat = 2.42 s−1) and was thus characterized as TYR, whereas SlPPO2 accepts only diphenolic substrates like dopamine (kcat = 1.99 s−1) and caffeic acid (kcat = 20.33 s−1) rendering this enzyme a CO. This study, for the first time, characterizes a plant TYR and CO originating from the same organism. Moreover, X-ray structure analysis of the latent holo- and apo-SlPPO1 (PDB: 6HQI and 6HQJ) reveals an unprecedented high flexibility of the gatekeeper residue phenylalanine (Phe270). Docking studies showed that depending on its orientation the gatekeeper residue could either stabilize and correctly position incoming substrates or hinder their entrance into the active site. Furthermore, phloretin, a substrate of SIPPO1 (Km = 0.11 mM), is able to approach the active centre of SlPPO1 with both phenolic rings. Kinetic and structural results indicate that phloretin could act as a natural substrate and connote the participation of PPOs in flavonoid-biosynthesis.
A Mathematical Analysis of Aerobic Glycolysis Triggered by Glucose Uptake in Cones
Authors: Camacho Erika T. , Brager Danielle , Elachouri Ghizlane , Korneyeva Tatyana , Millet-Puel Géraldine , Sahel José-Alain , Léveillard Thierry
Published: March 2019

Patients affected by retinitis pigmentosa, an inherited retinal disease, experience a decline in vision due to photoreceptor degeneration leading to irreversible blindness. Rod-derived cone viability factor (RdCVF) is the most promising mutation-independent treatment today. To identify pathologic processes leading to secondary cone photoreceptor dysfunction triggering central vision loss of these patients, we model the stimulation by RdCVF of glucose uptake in cones and glucose metabolism by aerobic glycolysis. We develop a nonlinear system of enzymatic functions and differential equations to mathematically model molecular and cellular interactions in a cone. We use uncertainty and sensitivity analysis to identify processes that have the largest effect on the system and their timeframes. We consider the case of a healthy cone, a cone with low levels of glucose, and a cone with low and no RdCVF. The three key processes identified are metabolism of fructose-1,6-bisphosphate, production of glycerol-3-phosphate and competition that rods exert on cone resources. The first two processes are proportional to the partition of the carbon flux between glycolysis and the pentose phosphate pathway or the Kennedy pathway, respectively. The last process is the rods’ competition for glucose, which may explain why rods also provide the RdCVF signal to compensate.
Clinical Features and Outcomes of Patients with Sarcoidosis-associated Pulmonary Hypertension
Authors: Parikh Kishan S. , Dahhan Talal , Nicholl Leigh , Ruopp Nicole , Pomann Gina-Maria , Fortin Terry , Tapson Victor F. , Rajagopal Sudarshan
Published: March 2019

The presence of pulmonary hypertension (PH) significantly worsens outcomes in patients with advanced sarcoidosis, but its optimal management is unknown. We aimed to characterize a large sarcoidosis-associated pulmonary hypertension (SAPH) cohort to better understand patient characteristics, clinical outcomes, and management strategies including treatment with PH therapies. Patients at Duke University Medical Center with biopsy-proven sarcoidosis and SAPH confirmed by right heart catheterization (RHC) were identified from 1990–2010. Subjects were followed for up to 11 years and assessed for differences by treatment strategy for their SAPH, including those who were not treated with PH-specific therapies. Our primary outcomes of interest were change in 6-minute walk distance (6MWD) and change in N-terminal pro-brain natriuretic peptide (NT-proBNP) by after therapy. We included 95 patients (76% women, 86% African American) with SAPH. Overall, 70% of patients had stage IV pulmonary sarcoidosis, and 77% had functional class III/IV symptoms. Median NT-proBNP value was elevated (910 pg/mL), and right ventricular dysfunction was moderate/severe in 55% of patients. Median values for mean pulmonary artery pressure (49 mmHg) and pulmonary vascular resistance (8.5 Woods units) were consistent with severe pulmonary hypertension. The mortality rate over median 3-year follow-up was 32%. Those who experienced a clinical event and those who did not had similar overall echocardiographic findings, hemodynamics, 6MWD and NT-proBNP at baseline, and unadjusted analysis showed that only follow-up NT-proBNP was associated with all-cause hospitalization or mortality. A sign test to evaluate the difference between NT-Pro-BNP before and after PH therapy produced evidence that a significant difference existed between the median pre- and post-NT-Pro-BNP (−387.0 (IQR: −1373.0-109), p = 0.0495). Use of PH-specific therapy may be helpful in selected patients with SAPH and pre-capillary pulmonary vascular disease. Prospective trials are needed to characterize responses to PH-specific therapy in this subset of patients with SAPH.
Acetaminophen influences social and economic trust
Authors: Roberts Ian D. , Krajbich Ian , Way Baldwin M.
Published: March 2019

Acetaminophen has long been assumed to selectively alleviate physical pain, but recent research has started to reveal its broader psychological effects. Building on this work, we find suggestive evidence that acetaminophen affects the basic social process of trust across a national survey and five lab experiments. In a national community sample (MIDUS II), acetaminophen usage was negatively associated with neighborhood trust and feelings of social integration. In a series of lab experiments (N = 767), acetaminophen reduced the influence of self-generated expectations on investments in a trust game. When we manipulated trust game investor expectations, acetaminophen increased investments regardless of expectations. These results provide the first demonstration that an over-the-counter drug can impact trust-related behavior. Overall, the findings paint a complex picture of how situational factors may influence drug effects.
Three-dimensional Stereoscopic Visualization Shortens Operative Time in Laparoscopic Gastrectomy for Gastric Cancer
Authors: Itatani Yoshiro , Obama Kazutaka , Nishigori Tatsuto , Ganeko Riki , Tsunoda Shigeru , Hosogi Hisahiro , Hisamori Shigeo , Hashimoto Kyoichi , Sakai Yoshiharu
Published: March 2019

Laparoscopic gastrectomy for gastric cancer is now widely accepted and has become a standard surgery. This study investigated the advantages of three-dimensional (3D) stereoscopic visualization for laparoscopic gastrectomy over a conventional two-dimensional (2D) planar screen. The primary outcome of this study was operative time. Ninety-four consecutive cases of gastric cancer patients who underwent laparoscopic total gastrectomy (LTG) (25 cases) or laparoscopic distal gastrectomy (LDG) (69 cases) were enrolled in this study before and after the introduction of the 3D system. Operative time was significantly shorter in the 3D groups for both LTG (351 vs. 406 min, P = 0.026) and LDG (269 vs. 344 min, P < 0.01). During intracorporeal procedures, dissection time was significantly shorter in the 3D groups for both LTG (183 vs. 232 min, P = 0.011) and LDG (161 vs. 213 min, P < 0.01), although the time needed for anastomosis was similar between the groups. However, operators preferred intracorporeal knot-tying as a ligature for anastomosis under 3D (LTG, P = 0.012; LDG, P < 0.01). These data suggest that 3D stereoscopic visualization shortens the operative time of laparoscopic gastrectomy by reducing the intracorporeal dissection time.
Identifying genes associated with invasive disease in S. pneumoniae by applying a machine learning approach to whole genome sequence typing data
Authors: Obolski Uri , Gori Andrea , Lourenço José , Thompson Craig , Thompson Robin , French Neil , Heyderman Robert S. , Gupta Sunetra
Published: March 2019

Streptococcus pneumoniae, a normal commensal of the upper respiratory tract, is a major public health concern, responsible for substantial global morbidity and mortality due to pneumonia, meningitis and sepsis. Why some pneumococci invade the bloodstream or CSF (so-called invasive pneumococcal disease; IPD) is uncertain. In this study we identify genes associated with IPD. We transform whole genome sequence (WGS) data into a sequence typing scheme, while avoiding the caveat of using an arbitrary genome as a reference by substituting it with a constructed pangenome. We then employ a random forest machine-learning algorithm on the transformed data, and find 43 genes consistently associated with IPD across three geographically distinct WGS data sets of pneumococcal carriage isolates. Of the genes we identified as associated with IPD, we find 23 genes previously shown to be directly relevant to IPD, as well as 18 uncharacterized genes. We suggest that these uncharacterized genes identified by us are also likely to be relevant for IPD.
Purification and Characterization of a Nonspecific Lipid Transfer Protein 1 (nsLTP1) from Ajwain (Trachyspermum ammi) Seeds
Authors: Nazeer Meshal , Waheed Humera , Saeed Maria , Ali Saman Yousuf , Choudhary M. Iqbal , Ul-Haq Zaheer , Ahmed Aftab
Published: March 2019

Ajwain(Trachyspermum ammi)belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 is comprised of 91 amino acids, with eight conserved cysteine residues. The amino acid sequence based predicted three dimensional (3D) structure is composed of four α-helices stabilized by four disulfide bonds, and a longC-terminal tail. The predicted model was verified by using different computational tools; i.e. ERRAT, verify 3D web server, and PROCHECK. The docking of ajwain nsLTP1 with ligands; myristic acid (MYR), and oleic acid (OLE) was performed, and molecular dynamics (MD) simulation was used to validate the docking results. The findings suggested that amino acids; Leu11, Leu12, Ala55, Ala56, Val15, Tyr59, and Leu62 are pivotal for the binding of lipid molecules with ajwain nsLTP1.
Energy expenditure and body temperature variations in llamas living in the High Andes of Peru
Authors: Riek Alexander , Stölzl Anna , Marquina Bernedo Rodolfo , Ruf Thomas , Arnold Walter , Hambly Catherine , Speakman John R. , Gerken Martina
Published: March 2019

Some large herbivores exhibit seasonal adjustments in their energy metabolism. Therefore, our aim was to determine if the llama (one of the most extensively kept livestock breeds) exhibits seasonal adjustment of their energy expenditure, body temperature and locomotion, under its natural high altitude Andean habitat. For this purpose, energy expenditure, body temperature and locomotion were measured in seven non-pregnant llama dams for ten months on the Andean High Plateau (4400 m above sea level). Daily energy expenditure was measured as field metabolic rate using the doubly labelled water method at four different measurement times. Additionally, a telemetry system was used to continuously record activity, body temperature (3 min intervals) as well as the position (hourly) of each animal. The results show that llamas adjusted their body temperature and daily energy expenditure according to environmental conditions. Furthermore, llamas under high altitude Andean climatic conditions exhibited a pronounced daily rhythm in body temperature and activity, with low values at sunrise and increasing values towards sunset. Llamas also had remarkably low energy expenditure compared to other herbivores. Thus, despite the domestication process, llamas have not lost the ability to adjust their body temperature and daily energy expenditure under adverse environmental conditions, similar to some wild herbivores.
Identification of two independent X-autosome translocations in closely related mammalian (Proechimys) species
Authors: Oliveira da Silva Willam , Rodrigues da Costa Marlyson Jeremias , Pieczarka Julio Cesar , Rissino Jorge , Pereira Jorge C. , Ferguson-Smith Malcolm Andrew , Nagamachi Cleusa Yoshiko
Published: March 2019

Multiple sex chromosome systems have been described for several mammalian orders, with different species from the same genus sharing the same system (e.g., X1X2Y or XY1Y2). This is important because the translocated autosome may be influenced by the evolution of the recipient sex chromosome, and this may be related to speciation. It is often thought that the translocation of an autosome to a sex chromosome may share a common origin among phylogenetically related species. However, the neo-X chromosomes of Proechimys goeldii (2n = 24♀, 25♂/NFa = 42) and Proechimys gr. goeldii (2n = 16♀, 17♂/NFa = 14) have distinct sizes and morphologies that have made it difficult to determine whether they have the same or different origins. This study investigates the origins of the XY1Y2 sex chromosome determination system in P. goeldii (PGO) and P. gr. goeldii (PGG) and elucidates the chromosomal rearrangements in this low-diploid-number group of Proechimys species. Toward this end, we produced whole-chromosome probes for P. roberti (PRO; 2n = 30♂/NFa = 54) and P. goeldii (2n = 25♂/NFa = 42) and used them in comparative chromosomal mapping. Our analysis reveals that multiple translocations and inversions are responsible for the karyotype diversity of these species, with only three whole-chromosomes conserved between PRO and PGO and eight between PGO and PGG. Our data indicate that multiple sex chromosome systems have originated twice in Proechimys. As small populations are prone to the fixation of chromosomal rearrangements, we speculate that biological features of Rodentia contribute to this fixation. We also highlight the potential of these rodents as a model for studying sex chromosome evolution.
Label-Free Multi Parameter Optical Interrogation of Endothelial Activation in Single Cells using a Lab on a Disc Platform
Authors: King Damien , Glynn MacDara , Cindric Sandra , Kernan David , O’Connell Tríona , Hakimjavadi Roya , Kearney Sinéad , Ackermann Tobias , Berbel Xavier Munoz , Llobera Andreu , Simonsen Ulf , Laursen Britt E. , Redmond Eileen M. , Cahill Paul A. , Ducrée Jens
Published: March 2019

Cellular activation and inflammation leading to endothelial dysfunction is associated with cardiovascular disease (CVD). We investigated whether a single cell label-free multi parameter optical interrogation system can detect endothelial cell and endothelial progenitor cell (EPC) activation in vitro and ex vivo, respectively. Cultured human endothelial cells were exposed to increasing concentrations of tumour necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS) before endothelial activation was validated using fluorescence-activated cell sorting (FACS) analysis of inflammatory marker expression (PECAM-1, E-selectin and ICAM-1). A centrifugal microfluidic system and V-cup array was used to capture individual cells before optical measurement of light scattering, immunocytofluorescence, auto-fluorescence (AF) and cell morphology was determined. In vitro, TNF-α promoted specific changes to the refractive index and cell morphology of individual cells concomitant with enhanced photon activity of fluorescently labelled inflammatory markers and increased auto-fluorescence (AF) intensity at three different wavelengths, an effect blocked by inhibition of downstream signalling with Iκβ. Ex vivo, there was a significant increase in EPC number and AF intensity of individual EPCs from CVD patients concomitant with enhanced PECAM-1 expression when compared to normal controls. This novel label-free ‘lab on a disc’ (LoaD) platform can successfully detect endothelial activation in response to inflammatory stimuli in vitro and ex vivo.
Identification and characterization of core abscisic acid (ABA) signaling components and their gene expression profile in response to abiotic stresses in Setaria viridis
Authors: Duarte Karoline Estefani , de Souza Wagner Rodrigo , Santiago Thaís Ribeiro , Sampaio Bruno Leite , Ribeiro Ana Paula , Cotta Michelle Guitton , da Cunha Bárbara Andrade Dias Brito , Marraccini Pierre Roger René , Kobayashi Adilson Kenji , Molinari Hugo Bruno Correa
Published: March 2019

Abscisic acid (ABA) is an essential phytohormone that regulates growth, development and adaptation of plants to environmental stresses. In Arabidopsis and other higher plants, ABA signal transduction involves three core components namely PYR/PYL/RCAR ABA receptors (PYLs), type 2C protein phosphatases (PP2Cs) and class III SNF-1-related protein kinase 2 (SnRK2s). In the present study, we reported the identification and characterization of the core ABA signaling components in Setaria viridis, an emerging model plant for cereals and feedstock crops presenting C4 metabolism, leading to the identification of eight PYL (SvPYL1 to 8), twelve PP2C (SvPP2C1 to 12) and eleven SnRK2 (SvSnRK2.1 through SvSnRK2.11) genes. In order to study the expression profiles of these genes, two different S. viridis accessions (A10.1 and Ast-1) were submitted to drought, salinity and cold stresses, in addition to application of exogenous ABA. Differential gene expression profiles were observed in each treatment and plant genotype, demonstrating variations of ABA stress responses within the same species. These differential responses to stresses were also assessed by physiological measurements such as photosynthesis, stomatal conductance and transpiration rate. This study allows a detailed analysis of gene expression of the core ABA signaling components in Setaria viridis submitted to different treatments and provides suitable targets for genetic engineering of C4 plants aiming tolerance to abiotic stresses.
Å-Indentation for non-destructive elastic moduli measurements of supported ultra-hard ultra-thin films and nanostructures
Authors: Cellini Filippo , Gao Yang , Riedo Elisa
Published: March 2019

During conventional nanoindentation measurements, the indentation depths are usually larger than 1–10 nm, which hinders the ability to study ultra-thin films (<10 nm) and supported atomically thin two-dimensional (2D) materials. Here, we discuss the development of modulated Å-indentation to achieve sub-Å indentations depths during force-indentation measurements while also imaging materials with nanoscale resolution. Modulated nanoindentation (MoNI) was originally invented to measure the radial elasticity of multi-walled nanotubes. Now, by using extremely small amplitude oscillations (<<1 Å) at high frequency, and stiff cantilevers, we show how modulated nano/Å-indentation (MoNI/ÅI) enables non-destructive measurements of the contact stiffness and indentation modulus of ultra-thin ultra-stiff films, including CVD diamond films (~1000 GPa stiffness), as well as the transverse modulus of 2D materials. Our analysis demonstrates that in presence of a standard laboratory noise floor, the signal to noise ratio of MoNI/ÅI implemented with a commercial atomic force microscope (AFM) is such that a dynamic range of 80 dB –– achievable with commercial Lock-in amplifiers –– is sufficient to observe superior indentation curves, having indentation depths as small as 0.3 Å, resolution in indentation <0.05 Å, and in normal load <0.5 nN. Being implemented on a standard AFM, this method has the potential for a broad applicability.
The Clinical Effect of Arthroscopic Rotator Cuff Repair techniques: A Network Meta-Analysis and Systematic Review
Authors: Xu Binwu , Chen Long , Zou Jun , Gu Yurong , Hao Liang , Peng Kun
Published: March 2019

Rotator cuff tears are common and are associated with shoulder pain, disability, and dysfunction. Previous studies that have reported different arthroscopic techniques are controversial. A network meta-analysis with indirect and direct evidence was performed to compare the effectiveness of arthroscopic techniques for the treatment of rotator cuff tears. PUBMED, the Cochrane Register of Controlled Trials, EMBASE and Scopus were searched based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and related studies that evaluated arthroscopic techniques for the treatment of rotator cuff tears were identified in May 2018. The primary outcome measure was the retear rate. The secondary outcome measures included the constant score and the range of motion (forward flexion and external rotation). Twenty-one trials comprising 1815 shoulders were included in the study. This study indicated that single-row (SR) repair resulted in a higher retear rate than suture bridge (SB) and double-row (DR) repairs. Moreover, the SR and DR repairs resulted in higher incidences of retear than SB repair. The ranking of the treatments based on the constant score and external rotation was SB repair, SR repair and DR repair, whereas the treatment ranking according to forward flexion was SB repair, DR repair and SR repair. In summary, this network meta-analysis provides evidence that SB repairs might be the best choice to improve the postoperative recovery of function and decrease the retear rate.
Birth experience in newborn infants is associated with changes in nociceptive sensitivity
Authors: Kasser Severin , Hartley Caroline , Rickenbacher Hanna , Klarer Noemi , Depoorter Antoinette , Datta Alexandre N. , Cobo Maria M. , Goksan Sezgi , Hoskin Amy , Magerl Walter , Huhn Evelyn A. , Green Gabrielle , Slater Rebeccah , Wellmann Sven
Published: March 2019

Vaginal birth prepares the fetus for postnatal life. It confers respiratory, cardiovascular and homeostatic advantages to the newborn infant compared with elective cesarean section, and is reported to provide neonatal analgesia. We hypothesize that infants born by vaginal delivery will show lower noxious-evoked brain activity a few hours after birth compared to those born by elective cesarean section. In the first few hours of neonatal life, we record electrophysiological measures of noxious-evoked brain activity following the application of a mildly noxious experimental stimulus in 41 infants born by either vaginal delivery or by elective cesarean section. We demonstrate that noxious-evoked brain activity is related to the mode of delivery and significantly lower in infants born by vaginal delivery compared with those born by elective cesarean section. Furthermore, we found that the magnitude of noxious-evoked brain activity is inversely correlated with fetal copeptin production, a surrogate marker of vasopressin, and dependent on the experience of birth-related distress. This suggests that nociceptive sensitivity in the first few hours of postnatal life is influenced by birth experience and endogenous hormonal production.
Long-lived association between Avalonia and the Meguma terrane deduced from zircon geochronology of metasedimentary granulites
Authors: Shellnutt J. Gregory , Owen J. Victor , Yeh Meng-Wan , Dostal Jaroslav , Nguyen Dieu T.
Published: March 2019

The Acadian Orogeny of the Northern Appalachians was caused by accretion of the peri-Gondwanan terranes Avalonia and Meguma to the eastern margin of Laurentia during the Devonian. The lithotectonic relationship between Avalonia and Meguma prior to accretion is uncertain. Radioisotopic dating of detrital zircons from metasedimentary granulite xenoliths from the structural basement to the Meguma terrane indicates that Avalonia and Meguma were proximal and likely contiguous as they transited the Rheic Ocean. The zircon ages range from the Cryogenian to Late Silurian with a minor Paleoproterozoic peak. Mesoproterozoic zircons are also identified and, coupled with the Ordovician to Silurian zircons, distinguish the rocks from those of the Meguma terrane. Furthermore, three distinct metamorphic events are identified at 399.0 ± 2.1 Ma, 376.9 ± 1.6 Ma, and 353.8 ± 3.3 Ma. We conclude that the granulite facies metamorphism experienced by the metasedimentary rocks occurred 10 to 20 million years after deposition of their protoliths during the initial stages of the Acadian Orogeny whereas the younger events are related to syn- and post-collisional episodes. The implication is that Avalonia and the Meguma terrane jointly transited from Gondwana.
Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control
Authors: Petrov Petar , Sarapulov Alexey V. , Eöry Lel , Scielzo Cristina , Scarfò Lydia , Smith Jacqueline , Burt David W. , Mattila Pieta K.
Published: March 2019

Missing in Metastasis (MIM), or Metastasis Suppressor 1 (MTSS1), is a highly conserved protein, which links the plasma membrane to the actin cytoskeleton. MIM has been implicated in various cancers, however, its modes of action remain largely enigmatic. Here, we performed an extensive in silico characterisation of MIM to gain better understanding of its function. We detected previously unappreciated functional motifs including adaptor protein (AP) complex interaction site and a C-helix, pointing to a role in endocytosis and regulation of actin dynamics, respectively. We also identified new functional regions, characterised with phosphorylation sites or distinct hydrophilic properties. Strong negative selection during evolution, yielding high conservation of MIM, has been combined with positive selection at key sites. Interestingly, our analysis of intra-molecular co-evolution revealed potential regulatory hotspots that coincided with reduced potentially pathogenic polymorphisms. We explored databases for the mutations and expression levels of MIM in cancer. Experimentally, we focused on chronic lymphocytic leukaemia (CLL), where MIM showed high overall expression, however, downregulation on poor prognosis samples. Finally, we propose strong conservation of MTSS1 also on the transcriptional level and predict novel transcriptional regulators. Our data highlight important targets for future studies on the role of MIM in different tissues and cancers.