bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bcl9 and Pygo synergise downstream of Apc to effect intestinal neoplasia in FAP mouse models
Authors: Mieszczanek Juliusz , van Tienen Laurens M. , Ibrahim Ashraf E. K. , Winton Douglas J. , Bienz Mariann 
Published: February 2019

AbstractBcl9 and Pygo are Wnt enhanceosome components that effect β-catenin-dependent transcription. Whether they mediate β-catenin-dependent neoplasia is unclear. Here we assess their roles in intestinal tumourigenesis initiated by Apc loss-of-function (ApcMin), or by Apc1322T encoding a partially-functional Apc truncation commonly found in colorectal carcinomas. Intestinal deletion of Bcl9 extends disease-free survival in both models, and essentially cures Apc1322T mice of their neoplasia. Loss-of-Bcl9 synergises with loss-of-Pygo to shift gene expression within Apc-mutant adenomas from stem cell-like to differentiation along Notch-regulated secretory lineages. Bcl9 loss also promotes tumour retention in ApcMin mice, apparently via relocating nuclear β-catenin to the cell surface, but this undesirable effect is not seen in Apc1322T mice whose Apc truncation retains partial function in regulating β-catenin. Our results demonstrate a key role of the Wnt enhanceosome in β-catenin-dependent intestinal tumourigenesis and reveal the potential of BCL9 as a therapeutic target during early stages of colorectal cancer.
Longitudinal HIV sequencing reveals reservoir expression leading to decay which is obscured by clonal expansion
Authors: Pinzone Marilia Rita , VanBelzen D. Jake , Weissman Sam , Bertuccio Maria Paola , Cannon LaMont , Venanzi-Rullo Emmanuele , Migueles Stephen , Jones R. Brad , Mota Talia , Joseph Sarah B. , Groen Kevin , Pasternak Alexander O. , Hwang Wei-Ting , Sherman Brad , Vourekas Anastasios , Nunnari Giuseppe , O’Doherty Una 
Published: February 2019

AbstractAfter initiating antiretroviral therapy (ART), a rapid decline in HIV viral load is followed by a long period of undetectable viremia. Viral outgrowth assay suggests the reservoir continues to decline slowly. Here, we use full-length sequencing to longitudinally study the proviral landscape of four subjects on ART to investigate the selective pressures influencing the dynamics of the treatment-resistant HIV reservoir. We find intact and defective proviruses that contain genetic elements favoring efficient protein expression decrease over time. Moreover, proviruses that lack these genetic elements, yet contain strong donor splice sequences, increase relatively to other defective proviruses, especially among clones. Our work suggests that HIV expression occurs to a significant extent during ART and results in HIV clearance, but this is obscured by the expansion of proviral clones. Paradoxically, clonal expansion may also be enhanced by HIV expression that leads to splicing between HIV donor splice sites and downstream human exons.
Efficient metal halide perovskite light-emitting diodes with significantly improved light extraction on nanophotonic substrates
Authors: Zhang Qianpeng , Tavakoli Mohammad Mahdi , Gu Leilei , Zhang Daquan , Tang Lei , Gao Yuan , Guo Ji , Lin Yuanjing , Leung Siu-Fung , Poddar Swapnadeep , Fu Yu , Fan Zhiyong 
Published: February 2019

AbstractMetal halide perovskite has emerged as a promising material for light-emitting diodes. In the past, the performance of devices has been improved mainly by optimizing the active and charge injection layers. However, the large refractive index difference among different materials limits the overall light extraction. Herein, we fabricate efficient methylammonium lead bromide light-emitting diodes on nanophotonic substrates with an optimal device external quantum efficiency of 17.5% which is around twice of the record for the planar device based on this material system. Furthermore, optical modelling shows that a high light extraction efficiency of 73.6% can be achieved as a result of a two-step light extraction process involving nanodome light couplers and nanowire optical antennas on the nanophotonic substrate. These results suggest that utilization of nanophotonic structures can be an effective approach to achieve high performance perovskite light-emitting diodes.
A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination
Authors: Zhang Jingjing , Fujiwara Yasuhiro , Yamamoto Shohei , Shibuya Hiroki 
Published: February 2019

AbstractHomologous recombination (HR) repairs DNA double-strand breaks (DSBs) to maintain genomic integrity. Recombinase recruited to the DSBs by the mediator protein BRCA2 catalyzes the homology-directed repair. During meiotic HR, programmed DSBs are introduced genome-wide but their repair mechanisms, including the regulation of BRCA2, have remained largely elusive. Here we identify a meiotic localizer of BRCA2, MEILB2/HSF2BP, that localizes to the site of meiotic DSBs in mice. Disruption ofMeilb2abolishes the localization of RAD51 and DMC1 recombinases in spermatocytes, leading to errors in DSB repair and male sterility. MEILB2 directly binds to BRCA2 and regulates its association to meiotic DSBs. We map the MEILB2-binding domain within BRCA2 that is distinct from the canonical DNA-binding domain but is sufficient to localize to meiotic DSBs in a MEILB2-dependent manner. We conclude that localization of BRCA2 to meiotic DSBs is mediated by MEILB2, which is an integral mechanism to repair abundant meiotic DSBs.
Seagrass can mitigate negative ocean acidification effects on calcifying algae
Authors: Bergstrom Ellie , Silva João , Martins Cíntia , Horta Paulo 
Published: February 2019

AbstractThe ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.
Variations in hydrodynamic characteristics of netting panels with various twine materials, knot types, and weave patterns at small attack angles
Authors: Tang Hao , Hu Fuxiang , Xu Liuxiong , Dong Shuchuang , Zhou Cheng , Wang Xuefang 
Published: February 2019

AbstractIt is essential to conduct hydrodynamic experiments for fishing gear at small attack angles along the flow direction to better understand the hydrodynamic characteristics of netting and application of gear. The hydrodynamic characteristics of netting panels made of different materials at small attack angles were investigated by a self-designed setup; this is essential for the effective use of netting on different types of gears. As confirmed by experiments, the measured drag of designed frame without netting accounted for less than 20% of the total setup drag including experimental netting and remained in a steady state under various current speeds and small attack angles, indicating that the self-designed frame setup is suitable for such trials. The drag coefficient was determined by varying the attack angle, solidity ratio, Reynolds number, knot types, weave pattern, and twine materials at small attack angles. The results indicate that the drag coefficient increased as the attack angle increased, but decreased as the solidity ratio and Reynolds number increased. The drag generated by knot accounted for 21% of the total drag of nylon (PA) netting. For braided knotless netting, the drag coefficient of PA netting was about 8.4% lower than that of polythene netting (PE) and 7% lower than that of polyester netting (PES). Compared with twined netting, the braided netting exhibited a higher resistance to flow, corresponding to higher values of drag coefficient.
Precise Slow Oscillation–Spindle Coupling Promotes Memory Consolidation in Younger and Older Adults
Authors: Muehlroth Beate E. , Sander Myriam C. , Fandakova Yana , Grandy Thomas H. , Rasch Björn , Shing Yee Lee , Werkle-Bergner Markus 
Published: February 2019

AbstractMemory consolidation during sleep relies on the precisely timed interaction of rhythmic neural events. Here, we investigate differences in slow oscillations (SO; 0.5–1 Hz), sleep spindles (SP), and their coupling across the adult human lifespan and ask whether observed alterations relate to the ability to retain associative memories across sleep. We demonstrate that older adults do not show the fine-tuned coupling of fast SPs (12.5–16 Hz) to the SO peak present in younger adults but, instead, are characterized most by a slow SP power increase (9–12.5 Hz) at the end of the SO up-state. This slow SP power increase, typical for older adults, coincides with worse memory consolidation in young age already, whereas the tight precision of SO–fast SP coupling promotes memory consolidation across younger and older adults. Crucially, brain integrity in source regions of SO and SP generation, including the medial prefrontal cortex, thalamus, hippocampus and entorhinal cortex, reinforces this beneficial SO–SP coupling in old age. Our results reveal that cognitive functioning is not only determined by maintaining structural brain integrity across the adult lifespan, but also by the preservation of precisely timed neural interactions during sleep that enable the consolidation of declarative memories.
Prebiotic chemistry in neutral/reduced-alkaline gas-liquid interfaces
Authors: Mompeán Cristina , Marín-Yaseli Margarita R. , Espigares Patricia , González-Toril Elena , Zorzano María-Paz , Ruiz-Bermejo Marta 
Published: February 2019

AbstractThe conditions for the potential abiotic formation of organic compounds from inorganic precursors have great implications for our understanding of the origin of life on Earth and for its possible detection in other environments of the Solar System. It is known that aerosol-interfaces are effective at enhancing prebiotic chemical reactions, but the roles of salinity and pH have been poorly investigated to date. Here, we experimentally demonstrate the uniqueness of alkaline aerosols as prebiotic reactors that produce an undifferentiated accumulation of a variety of multi-carbon biomolecules resulting from high-energy processes (in our case, electrical discharges). Using simulation experiments, we demonstrate that the detection of important biomolecules in tholins increases when plausible and particular local planetary environmental conditions are simulated. A greater diversity in amino acids, carboxylic acids, N-heterocycles, and ketoacids, such as glyoxylic and pyruvic acid, was identified in tholins synthetized from reduced and neutral atmospheres in the presence of alkaline aqueous aerosols than that from the same atmospheres but using neutral or acidic aqueous aerosols.
Induction of MET Receptor Tyrosine Kinase Down-regulation through Antibody-mediated Receptor Clustering
Authors: Li Wenjing , Dick Adam , Lu Fei , Zhang Hui , Sun Hong 
Published: February 2019

AbstractThe proto-oncoprotein MET is a receptor tyrosine kinase that plays a key role in cancer cell growth and invasion. We have used fluorescence-tagged antibodies to activate MET in live serum-starved glioblastoma cells and monitor the fate of antibody-bound MET receptor in single cell-based assays. We found that the antibodies induced rapid and transient formation of highly polarized MET clusters on the plasma membrane and promoted the activation of MET, resembling the initial effects of binding to its ligand, HGF. However, the antibody-induced clustering and activation of MET led to the rapid removal of the receptor from cell surface and altered its intracellular processing, resulted in rapid degradation of the receptor. Consequently, while cells pre-treated with HGF remain competent to respond to further HGF stimulation, cells pre-treated with antibodies are refractory to further HGF stimulation due to antibody-mediated MET depletion. Removal of MET by sustained treatment of antibodies blocked cancer cell migration and invasion. Our studies reveal a novel mechanism to alter the recycling process of MET in glioblastoma cancer cells by promoting the receptor degradation through a proteasome-sensitive and lysosome-dependent pathway through the ligand-independent activation of MET using anti-MET antibodies.
Anomalous orbital structure in two-dimensional titanium dichalcogenides
Authors: Pal Banabir , Cao Yanwei , Liu Xiaoran , Wen Fangdi , Kareev M. , N’Diaye A. T. , Shafer P. , Arenholz E. , Chakhalian J. 
Published: February 2019

AbstractGenerally, lattice distortions play a key role in determining the electronic ground states of materials. Although it is well known that trigonal distortions are generic to most two dimensional transition metal dichalcogenides, the impact of this structural distortion on the electronic structure and topological properties has not been understood conclusively. Here, by using a combination of polarization dependent X-ray absorption spectroscopy (XAS), X-ray photoelectron spectroscopy (XPS) and atomic multiplet cluster calculations, we have investigated the electronic structure of titanium dichalcogenides TiX2 (X = S, Se, Te), where the magnitude of the trigonal distortion increase monotonically from S to Se and Te. Our results reveal the presence of an anomalously large crystal field splitting. This unusual kind of crystal field splitting is likely responsible for the unconventional electronic structure of TiX2 compounds and ultimately controls the degree of the electronic phase protection. Our findings also indicate the drawback of the distorted crystal field picture in explaining the observed electronic ground state and emphasize the key importance of trigonal symmetry, metal-ligand hybridization and electron-electron correlations in defining the electronic structures at the Fermi energy.
Age-dependent differences in learning to control a robot arm using a body-machine interface
Authors: Ranganathan Rajiv , Lee Mei-Hua , Padmanabhan Malavika R. , Aspelund Sanders , Kagerer Florian A. , Mukherjee Ranjan 
Published: February 2019

AbstractBody-machine interfaces, i.e. interfaces that rely on body movements to control external assistive devices, have been proposed as a safe and robust means of achieving movement and mobility; however, how children learn these novel interfaces is poorly understood. Here we characterized the learning of a body-machine interface in young unimpaired adults, two groups of typically developing children (9-year and 12-year olds), and one child with congenital limb deficiency. Participants had to control the end-effector of a robot arm in 2D using movements of the shoulder and torso. Results showed a striking effect of age - children had much greater difficulty in learning the task compared to adults, with a majority of the 9-year old group unable to even complete the task. The 12-year olds also showed poorer task performance compared to adults (as measured by longer movement times and greater path lengths), which were associated with less effective search strategies. The child with congenital limb deficiency showed superior task performance compared to age-matched children, but had qualitatively distinct coordination strategies from the adults. Taken together, these results imply that children have difficulty learning non-intuitive interfaces and that the design of body-machine interfaces should account for these differences in pediatric populations.
Lab-on-Fiber Nanoprobe with Dual High-Q Rayleigh Anomaly-Surface Plasmon Polariton Resonances for Multiparameter Sensing
Authors: Kim Hyun-Tae , Yu Miao 
Published: February 2019

AbstractSurface plasmon resonance (SPR) based sensing is an attractive approach for realizing lab-on-fiber nanoprobes. However, simultaneous measurement of multiple parameters (e.g., refractive index and temperature) with SPR-based nanoprobes, although highly desirable, is challenging. We report a lab-on-fiber nanoprobe with dual high-Q Rayleigh anomaly (RA)-surface plasmon polariton (SPP) resonances for multiparameter sensing. To achieve high-Q RA-SPP resonance the nanoprobe employs a plasmonic crystal cavity enhanced by distributed Bragg reflector (DBR) gratings on the end-face of a single-mode optical fiber. By tailoring the grating periods of the plasmonic crystal cavity and DBRs, two spatially separated high-Q RA-SPP resonance modes are designed within a 50 nm spectral range in C + L band. The fabricated nanoprobe demonstrates two RA-SPP resonances near 1550 nm with high Q-factors up to 198. These two high-Q resonances are further showed to exhibit distinctive responses to the changes of refractive index and temperature, which enables simultaneous measurements of both parameters. The proposed lab-on-fiber nanoprobes will pave the way for realizing compact multiparameter sensing solutions compatible with optical communication infrastructures.
Kidney Stones and Risk of Osteoporotic Fracture in Chronic Kidney Disease
Authors: Han Seung Gyu , Oh Jieun , Jeon Hee Jung , Park Chan , Cho Jeonghwan , Shin Dong Ho 
Published: February 2019

AbstractOsteoporotic fracture associated with calcium dysregulation is more common in patients with kidney stones. However, little is known about the association of kidney stones and bone health status in patients with chronic kidney disease (CKD). This retrospective medical record-based study included 2282 patients with stable stage 3–4 CKD between 2007 and 2017. Of these, 113 patients were diagnosed with kidney stones. Propensity score matching for 226 patients with and without kidney stones showed that osteoporotic fracture occurred more often in patients with kidney stones (33, 29.2%) than in patients without kidney stones (16, 14.2%), resulting in rates of 5.56 and 2.63/100 patient-years, respectively (p < 0.01). In particular, Cox proportional hazard analysis revealed that kidney stones were significantly associated with osteoporotic fracture, even after adjusting for age, sex, body mass index, kidney stones, estimated glomerular filtration rate, excessive alcohol consumption, current smoking, and steroid use in patients with CKD stage 3–4 (hazard ratio, 2.32, 95% CI 1.24–4.34, p = 0.01). This study showed that the presence of kidney stones was a significant predictor for osteoporotic fracture in patients with CKD, suggesting that it should be considered as a clinical risk factor for osteoporotic fracture in them.
Effects of running on adiponectin, insulin and cytokines in cerebrospinal fluid in healthy young individuals
Authors: Schön M. , Kovaničová Z. , Košutzká Z. , Nemec M. , Tomková M. , Jacková L. , Máderová D. , Slobodová L. , Valkovič P. , Ukropec J. , Ukropcová B. 
Published: February 2019

AbstractExercise can prevent the sedentary lifestyle-related risk of metabolic and cognitive decline, but mechanisms and mediators of exercise effects on human brain are relatively unexplored. We measured acute exercise-induced changes in adiponectin, insulin and other bioactive molecules in cerebrospinal fluid (CSF) and serum from young lean individuals. Samples of serum and CSF were obtained before and 1-h after the 90-min run (75–80% HRmax; maximal heart rate), additional serum was taken at finish-line. Body composition, physical fitness, metabolic rate, cognitive functions, food preference, glucose, insulin and albumin were measured. The spectrum of 174 cytokines was assessed by protein arrays, adiponectin was also determined by ELISA and immunoblotting. CSF adiponectin decreased post-exercise by 21.3% (arrays) and 25.8% (ELISA) (p < 0.009). Immunoblotting revealed reduction in a low-molecular-weight-adiponectin (p < 0.005). CSF adiponectin positively correlated with CSF/serum albumin ratio (p < 0.022), an indicator of blood-brain-barrier permeability. CSF and serum adiponectin were positively associated with memory and running-induced changes in insulinemia and CSF insulin. Additionally, running modulated CSF levels of 16 other cytokines. Acute running reduced CSF adiponectin and modulated insulin and albumin in CSF and serum. Associations of adiponectin with memory and metabolism indicate the potential role of this bioactive molecule in mediating exercise-induced adaptive response in human brain.
Comprehensive RNA sequencing and co-expression network analysis to complete the biosynthetic pathway of coumestrol, a phytoestrogen
Authors: Ha Jungmin , Kang Young-Gyu , Lee Taeyoung , Kim Myoyeon , Yoon Min Young , Lee Eunsoo , Yang Xuefei , Kim Donghyun , Kim Yong-Jin , Lee Tae Ryong , Kim Moon Young , Lee Suk-Ha 
Published: February 2019

AbstractCoumestrol (CMS), a coumestan isoflavone, plays key roles in nodulation through communication with rhizobia, and has been used as phytoestrogens for hormone replacement therapy in humans. Because CMS content is controlled by multiple genetic factors, the genetic basis of CMS biosynthesis has remained unclear. We identified soybean genotypes with consistently high (Daewonkong) or low (SS0903-2B-21-1-2) CMS content over 2 years. We performed RNA sequencing of leaf samples from both genotypes at developmental stage R7, when CMS levels are highest. Within the phenylpropanoid biosynthetic pathway, 41 genes were tightly connected in a functional co-expression gene network; seven of these genes were differentially expressed between two genotypes. We identified 14 candidate genes involved in CMS biosynthesis. Among them, seven were annotated as encoding oxidoreductases that may catalyze the transfer of electrons from daidzein, a precursor of CMS. Two of the other genes, annotated as encoding a MYB domain protein and a MLP–like protein, may increase CMS accumulation in response to stress conditions. Our results will help to complete our understanding of the CMS biosynthetic pathway, and should facilitate development of soybean cultivars with high CMS content that could be used to promote the fitness of plants and human beings.
New 2-aryl-6-methyl-3,4-dihydro-β-carbolin-2-iums as potential antifungal agents: Synthesis, bioactivity and structure-activity relationship
Authors: Li Xingqiang , Zhang Bingyu , Zhao Wei , Yang Shanshan , Yang Xinjuan , Zhou Le 
Published: February 2019

AbstractThirty new title compounds along with five known analogues were prepared from commercially available 2-arylhydrazin-1-ium chlorides and α-ketoglutaric acid. The mycelium growth rate method was used to evaluate inhibition activity against six strains of plant pathogenic fungi. Most of the compounds displayed the activity for each the fungi at 150 μΜ, higher than azoxystrobin, a positive drug. Compound 6-2 showed the lowest average IC50 value of 4.58 μg/mL for all the fungi where F. solani exhibited the highest susceptibility to most of the compounds. For F. solani, some compounds were more active with IC50 values of 2.67–8.48 μM than thiabendazole (IC50 = 9.30 μM) and/or carbendazim (IC50 = 3.36 μM). The SAR showed that the activity is significantly affected by substituents on the A-ring and/or D-ring along with the degree of unsaturation of the C-ring. Thus, a series of new β-carboline compounds with potent antifungal potential were found.