bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractSurface 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.
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

AbstractCystic 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

AbstractPodocyte 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

AbstractOur 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

AbstractThe 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.
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

AbstractHSP90 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

AbstractThe 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

AbstractDefects 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

AbstractPolyphenol 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

AbstractPatients 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

AbstractThe 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

AbstractAcetaminophen 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

AbstractLaparoscopic 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

AbstractStreptococcus 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

AbstractAjwain(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.