bluuebunny/crossref_metadata_2025 huggingface dataset:
Constraints on the Rheology of the Lithosphere From Flexure of the Pacific Plate at the Hawaiian Islands
Authors: Bellas Ashley , Zhong Shijie , Watts Anthony
Published: January 2020

The rheology of oceanic lithosphere is important to our understanding of mantle dynamics and to the emergence and manifestations of plate tectonics. Data from experimental rock mechanics suggest rheology is dominated by three different deformation mechanisms including frictional sliding, low‐temperature plasticity, and high‐temperature creep, from shallow depths at relatively cold temperatures to large depths at relatively high temperatures. However, low‐temperature plasticity is poorly understood. This study further constrains low‐temperature plasticity by comparing observations of flexure at the Hawaiian Islands to predictions from 3‐D viscoelastic loading models with a realistic lithospheric rheology of frictional sliding, low‐temperature plasticity, and high‐temperature creep. We find that previously untested flow laws significantly underpredict the amplitude and overpredict the wavelength of flexure at Hawaii. These flow laws can, however, reproduce observations if they are weakened by a modest reduction (25–40%) in the plastic activation energy. Lithospheric rheology is strongly temperature dependent, and so we explore uncertainties in the thermal structure with different conductive cooling models and convection simulations of plume‐lithosphere interactions. Convection simulations show that thermal erosion from a plume only perturbs the lithospheric temperature significantly at large depths so that when it is added to the thermal structure, it produces a small increase in deflection. In addition, defining the temperature profile by the cooling plate model produces only modest weakening relative to the cooling half‐space model. Therefore, variation of the thermal structure does not appear to be a viable means of bringing laboratory‐derived flow laws for low‐temperature plasticity into agreement with geophysical field observations and modeling.
Tracking of Tropical Intraseasonal Convective Anomalies: 1. Seasonality of the Tropical Intraseasonal Oscillations
Authors: Singh Bohar , Kinter James L.
Published: January 2020

A tracking algorithm based upon a multiple object tracking method is developed to identify, track, and classify Tropical Intraseasonal Oscillations (TISO) on the basis of their direction of propagation. Daily National Oceanic and Atmospheric Administration Outgoing Longwave Radiation anomalies from 1979–2017 are Lanczos band‐pass filtered for the intraseasonal time scale (20–100 days) and spatially averaged with nine neighboring points to get spatially smoothed anomalies over large spatial scales (~105 km2). TISO events are tracked by using a two‐stage Kalman filter predictor‐corrector method. Two dominant components of the TISO (Eastward propagating and Northward propagating) are classified, and it is found that TISO remains active throughout the year. Eastward‐propagating TISO events occur from November to April with a phase speed of ~4 m/s and northward‐propagating TISO events occur from May to October with a phase speed of ~2.5 m/s in both the Indian and Pacific Ocean basins. Composites of the mean background states (wind; sea surface temperature, SST; and moisture) reveal that the co‐occurrence of warm SST and mean westerly zonal wind plays an important role in the direction of propagation and the geographical location of TISO events. In mean state sensitivity experiments with Sp‐CAM4, we have found that the seasonality of TISO in terms of the geographical location of occurrences and direction of propagation is primarily associated with the annual march of the maximum SST and low level zonal wind which tends to follow the SST.
Moho Structure Across the Backarc‐Craton Transition in the Northern U.S. Cordillera
Authors: DiCaprio L. , Maiti T. , Dettmer J. , Eaton D. W.
Published: January 2020

In southern Canada and the northern United States, the present‐day western edge of the North American craton (Laurentia) is marked by a profound change in lithospheric thickness, from
100 km within a hot backarc setting beneath the Cordillera to
200 km beneath the craton. A nearly uniformly flat Moho in the backarc region of southern Canada has been interpreted as a young feature that was produced by lower crustal channel flow. The tectonic environment of the southern Canadian Cordillera extends southward to the Lewis and Clark shear zone in the northern United States, where previously deployed EarthScope Transportable Array stations provide coverage on a
70 km grid. Here, data from Transportable Array stations are used to investigate teleseismic P to S receiver functions of crustal structure across the craton‐backarc transition, coupled with lithospheric structure derived from a recent global tomographic model. These images suggest that, north of the Lewis and Clark shear zone, the shallower Moho beneath the Cordillera has encroached on the craton, creating a narrow complex transition zone. To the south, a step‐like change in crustal thickness is observed, and the complex Moho transition zone is absent. Taken together with other geological and geophysical data, these observations suggest that a young Moho has progressed eastward accompanied by thermal and/or mechanical modification of the Laurentian lithosphere.
A Finite Volume Blowing Snow Model for Use With Variable Resolution Meshes
Authors: Marsh Christopher B. , Pomeroy John W. , Spiteri Raymond J. , Wheater Howard S.
Published: January 2020

Blowing snow is ubiquitous in cold, windswept environments. In some regions, blowing snow sublimation losses can ablate a notable fraction of the seasonal snowfall. It is advantageous to predict alpine snow regimes at the spatial scale of snowdrifts (≈1 to 100 m) because of the role of snow redistribution in governing the duration and volume of snowmelt. However, blowing snow processes are often neglected due to computational costs. Here, a three‐dimensional blowing snow model is presented that is spatially discretized using a variable resolution unstructured mesh. This represents the heterogeneity of the surface explicitly yet, for the case study reported, gained a 62% reduction in computational elements versus a fixed‐resolution mesh and resulted in a 44% reduction in total runtime. The model was evaluated for a subarctic mountain basin using transects of measured snow water equivalent (SWE) in a tundra valley. Including blowing snow processes improved the prediction of SWE by capturing inner‐annual snowdrift formation, more than halved the total mean bias error, and increased the coefficient of variation of SWE from 0.04 to 0.31 better matching the observed CV (0.41). The use of a variable resolution mesh did not dramatically degrade the model performance. Comparison with a constant resolution mesh showed a similar CV and RMSE as the variable resolution mesh. The constant resolution mesh had a smaller mean bias error. A sensitivity analysis showed that snowdrift locations and immediate up‐wind sources of blowing snow are the most sensitive areas of the landscape to wind speed variations.
Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients
Authors: Guo Shiwei , Shi Xiaohan , Shen Jing , Gao Suizhi , Wang Huan , Shen Shuo , Pan Yaqi , Li Bo , Xu Xiongfei , Shao Zhuo , Jin Gang
Published: January 2020

Background

About 25–37% of resectable pancreatic ductal adenocarcinoma (PDAC) had a great chance of early recurrence after radical resection, which is mainly due to preoperative micrometastasis. We herein demonstrated the profiles of ctDNA in resectable PDAC and use of ctDNA to identify patients with potential micrometastasis.

Methods

A total of 113 and 44 resectable PDACs were enrolled in discovery and validation cohorts, separately. A panel containing 50 genes was used to screen ctDNA by an NGS-based assessment with high specificity.

Results

In the discovery cohort, the overall detection rate was 38.05% (43/113). Among positive ctDNA, KRAS mutation had the highest detection rate (23.01%, 26/113), while the others were <5%. Survival analysis showed that plasma KRAS mutations, especially KRAS G12D mutation, had significant association with OS and RFS of resectable PDAC. Plasma KRAS G12D mutation showed a strong correlation with early distant metastasis. In the validation cohort, survival analysis showed similar association between plasma KRAS G12D mutation and poor outcomes.

Conclusions

This study demonstrated that plasma KRAS mutations, especially KRAS G12D mutation, served as a useful predictive biomarker for prognosis of resectable PDAC. More importantly, due to high correlation with micrometastasis, preoperative detection of plasma KRAS G12D mutation helps in optimising surgical selection of resectable PDAC.
Translationally controlled tumor protein promotes liver regeneration by activating mTORC2/AKT signaling
Authors: Lin Zhibin , Zhang Xuan , Wang Jianlin , Liu Wei , Liu Qi , Ye Yuchen , Dai Bin , Guo Dongnan , Zhang Pengcheng , Yang Peijun , Zhang Ruohan , Wang Lin , Dou Kefeng
Published: January 2020

Translationally controlled tumor protein (TCTP), which is a protein characterized by its potent proliferation promoting activity, has been well studied in the area of growth and tumorigenesis. However, the specific role of TCTP in liver regeneration (LR) and its underlying mechanism remains unclear. In order to investigate the contribution of TCTP during LR, heterozygous TCTP mice were generated, and a mimic LR model was applied to TCTP-knockdown (KD) hepatic cell lines. The results revealed that TCTP-KD impaired LR in mice, and manifested as the following aspects: delayed proliferation of hepatocytes, accompanied by disruption of the mRNA expression of markers of the cell cycle, degenerated lipid metabolism, and abnormal immune response. Furthermore, it was found out that TCTP activated PI3K/AKT signaling by regulating mTORC2. Lastly, the increasing rate of serum TCTP positively correlated to the recovery of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) after liver resection in humans. In summary, the present study is the first to reveal the crucial role of intracellular TCTP in LR.
Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages
Authors: Rahman Mohammed Tanjimur , Muppala Santoshi , Wu Jiahui , Krukovets Irene , Solovjev Dmitry , Verbovetskiy Dmitriy , Obiako Chioma , Plow Edward F. , Stenina-Adognravi Olga
Published: January 2020

Thrombospondin-4 (TSP-4) attracted renewed attention recently as a result of assignment of new functions to this matricellular protein in cardiovascular, muscular, and nervous systems. We have previously reported that TSP-4 promotes local vascular inflammation in a mouse atherosclerosis model. A common variant of TSP-4, P387-TSP-4, was associated with increased cardiovascular disease risk in human population studies. In a mouse atherosclerosis model, TSP-4 had profound effect on accumulation of macrophages in lesions, which prompted us to examine its effects on macrophages in more detail. We examined the effects of A387-TSP-4 and P387-TSP-4 on mouse macrophages in cell culture and in vivo in the model of LPS-induced peritonitis. In tissues and in cell culture, TSP-4 expression was associated with inflammation: TSP-4 expression was upregulated in peritoneal tissues in LPS-induced peritonitis, and pro-inflammatory signals, INFγ, GM-CSF, and LPS, induced TSP-4 expression in macrophages in vivo and in cell culture. Deficiency in TSP-4 in macrophages from Thbs4−/− mice reduced the expression of pro-inflammatory macrophage markers, suggesting that TSP-4 facilitates macrophage differentiation into a pro-inflammatory phenotype. Expression of TSP-4, especially more active P387-TSP-4, was associated with higher cellular apoptosis. Cultured macrophages displayed increased adhesion to TSP-4 and reduced migration in presence of TSP-4, and these responses were further increased with P387 variant. We concluded that TSP-4 expression in macrophages increases their accumulation in tissues during the acute inflammatory process and supports macrophage differentiation into a pro-inflammatory phenotype. In a model of acute inflammation, TSP-4 supports pro-inflammatory macrophage apoptosis, a response that is closely related to their pro-inflammatory activity and release of pro-inflammatory signals. P387-TSP-4 was found to be the more active form of TSP-4 in all examined functions.
Down-regulation of long non-coding RNA HOTAIR promotes angiogenesis via regulating miR-126/SCEL pathways in burn wound healing
Authors: Jiang Bimei , Tang Yuting , Wang Hao , Chen Cheng , Yu Wenchang , Sun Hui , Duan Mengting , Lin Xiaofang , Liang Pengfei
Published: January 2020

miR-126, an endothelial-specific microRNA, is associated to vascular integrity and angiogenesis. It is well established that angiogenesis plays a critical role in burn wound healing. However, there was a lack of understanding of the mechanism by which miR-126 regulates angiogenesis during burn wound healing. HOX transcript antisense intergenic RNA (HOTAIR) is a well-characterized long non-coding RNA (lncRNA) involved in cell proliferation, apoptosis, migration, and invasion of cancer cells. Sciellin (SCEL), a precursor to the cornified envelope of human keratinocytes, has been shown to inhibit migration and invasion capabilities of colorectal cancer cells. In this study, a cohort of 20 burn wound tissues and paired adjacent normal tissues were collected. LncRNA and messenger RNA expression profiles were screened by microarray analysis in five pairs of samples with mostly increased miR-126 levels. miR-126 was highly expressed in burn wound tissues and human umbilical vein endothelial cells (HUVECs) exposed to heat stress, whereas HOTAIR and SCEL were down-regulated after thermal injury. Bioinformatic analysis, dual luciferase reporter assay, and quantitative real-time PCR were conducted to validate that HOTAIR and SCEL competitively bind to miR-126 to function as the competitive endogenous RNA. miR-126 promoted endothelial cell proliferation, migration, and angiogenesis, but suppressed apoptosis, while HOTAIR and SCEL exerted opposite effects in HUVECs. The biological functions were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Annexin-V-FITC/PI (propidium iodide/fluorescein isothiocyanate) staining, transwell migration, and tube formation assays. Collectively, our study revealed that HOTAIR/miR-126/SCEL axis contributes to burn wound healing through mediating angiogenesis.
Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy
Authors: Das Mrinmoy , Karnam Anupama , Stephen-Victor Emmanuel , Gilardin Laurent , Bhatt Bharat , Kumar Sharma Varun , Rambabu Naresh , Patil Veerupaxagouda , Lecerf Maxime , Käsermann Fabian , Bruneval Patrick , Narayanaswamy Balaji Kithiganahalli , Benveniste Olivier , Kaveri Srini V. , Bayry Jagadeesh
Published: January 2020

Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target of rapamycin. Mechanistically, IVIG-induced autophagy is F(ab′)2-dependent but sialylation independent, and requires endocytosis of IgG by innate cells. Inhibition of autophagy compromised the ability of IVIG to suppress the inflammatory cytokines in innate immune cells. Moreover, IVIG therapy in inflammatory myopathies such as dermatomyositis, antisynthetase syndrome and immune-mediated necrotizing myopathy induced autophagy in PBMCs and reduced inflammatory cytokines in the circulation, thus validating the translational importance of these results. Our data provide insight on how circulating normal immunoglobulins maintain immune homeostasis and explain in part the mechanism by which IVIG therapy benefits patients with autoimmune and inflammatory diseases.
Correction: Schwann cells support oncogenic potential of pancreatic cancer cells through TGFβ signaling
Authors: Roger Elodie , Martel Sylvie , Bertrand-Chapel Adrien , Depollier Arnaud , Chuvin Nicolas , Pommier Roxane M. , Yacoub Karam , Caligaris Cassandre , Cardot-Ruffino Victoire , Chauvet Véronique , Aires Sophie , Mohkam Kayvan , Mabrut Jean-Yves , Adham Mustapha , Fenouil Tanguy , Hervieu Valérie , Broutier Laura , Castets Marie , Neuzillet Cindy , Cassier Philippe A. , Tomasini Richard , Sentis Stéphanie , Bartholin Laurent
Published: January 2020

The original version of this article contained an error in the name of one of the co-authors (Kayvan Mohkam). This has been corrected in the PDF and HTML versions.
Peptidoglycan reshaping by a noncanonical peptidase for helical cell shape in Campylobacter jejuni
Authors: Min Kyungjin , An Doo Ri , Yoon Hye-Jin , Rana Neha , Park Ji Su , Kim Jinshil , Lee Mijoon , Hesek Dusan , Ryu Sangryeol , Kim B. Moon , Mobashery Shahriar , Suh Se Won , Lee Hyung Ho
Published: January 2020

Assembly of the peptidoglycan is crucial in maintaining viability of bacteria and in defining bacterial cell shapes, both of which are important for existence in the ecological niche that the organism occupies. Here, eight crystal structures for a member of the cell-shape-determining class of Campylobacter jejuni, the peptidoglycan peptidase 3 (Pgp3), are reported. Characterization of the turnover chemistry of Pgp3 reveals cell wall d,d-endopeptidase and d,d-carboxypeptidase activities. Catalysis is accompanied by large conformational changes upon peptidoglycan binding, whereby a loop regulates access to the active site. Furthermore, prior hydrolysis of the crosslinked peptide stem from the saccharide backbone of the peptidoglycan on one side is a pre-requisite for its recognition and turnover by Pgp3. These analyses reveal the noncanonical nature of the transformations at the core of the events that define the morphological shape for C. jejuni as an intestinal pathogen.
The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly
Authors: Pinese Mark , Lacaze Paul , Rath Emma M. , Stone Andrew , Brion Marie-Jo , Ameur Adam , Nagpal Sini , Puttick Clare , Husson Shane , Degrave Dmitry , Cristina Tina Navin , Kahl Vivian F. S. , Statham Aaron L. , Woods Robyn L. , McNeil John J. , Riaz Moeen , Barr Margo , Nelson Mark R. , Reid Christopher M. , Murray Anne M. , Shah Raj C. , Wolfe Rory , Atkins Joshua R. , Fitzsimmons Chantel , Cairns Heath M. , Green Melissa J. , Carr Vaughan J. , Cowley Mark J. , Pickett Hilda A. , James Paul A. , Powell Joseph E. , Kaplan Warren , Gibson Greg , Gyllensten Ulf , Cairns Murray J. , McNamara Martin , Dinger Marcel E. , Thomas David M.
Published: January 2020

Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.
A biphasic growth model for cell pole elongation in mycobacteria
Authors: Hannebelle Mélanie T. M. , Ven Joëlle X. Y. , Toniolo Chiara , Eskandarian Haig A. , Vuaridel-Thurre Gaëlle , McKinney John D. , Fantner Georg E.
Published: January 2020

Mycobacteria grow by inserting new cell wall material in discrete zones at the cell poles. This pattern implies that polar growth zones must be assembled de novo at each division, but the mechanisms that control the initiation of new pole growth are unknown. Here, we combine time-lapse optical and atomic force microscopy to measure single-cell pole growth in mycobacteria with nanometer-scale precision. We show that single-cell growth is biphasic due to a lag phase of variable duration before the new pole transitions from slow to fast growth. This transition and cell division are independent events. The difference between the lag and interdivision times determines the degree of single-cell growth asymmetry, which is high in fast-growing species and low in slow-growing species. We propose a biphasic growth model that is distinct from previous unipolar and bipolar models and resembles “new end take off” (NETO) dynamics of polar growth in fission yeast.
Easy access to medium-sized lactones through metal carbene migratory insertion enabled 1,4-palladium shift
Authors: Yu Yinghua , Chakraborty Pushkin , Song Jinshuai , Zhu Lei , Li Chunsen , Huang Xueliang
Published: January 2020

Reactions that efficiently construct medium-sized lactones are significant, as they overcome the unfavorable entropic factor and transannular interactions for ring closure, and the lactones produced are common structural motifs recurring in many biologically active compounds. Herein, we describe a valuable strategy for medium-sized lactone synthesis by accomplishing site-selective C–H bond functionalization via a palladium carbene migratory insertion enabled 1,4-palladium shift. The overall process achieves the formal dimerization of two readily available benzaldehyde derivatives, providing value-added products medium-sized lactones. Our method is amenable to late-stage modification of approved drugs and other complex molecules. Mechanistic studies including deuterium-labeling experiments and DFT calculation shed light on the reaction pathways.
Neural dynamics of the attentional blink revealed by encoding orientation selectivity during rapid visual presentation
Authors: Tang Matthew F. , Ford Lucy , Arabzadeh Ehsan , Enns James T. , Visser Troy A. W. , Mattingley Jason B.
Published: January 2020

The human brain is inherently limited in the information it can make consciously accessible. When people monitor a rapid stream of visual items for two targets, they typically fail to see the second target if it occurs within 200–500 ms of the first, a phenomenon called the attentional blink (AB). The neural basis for the AB is poorly understood, partly because conventional neuroimaging techniques cannot resolve visual events displayed close together in time. Here we introduce an approach that characterises the precise effect of the AB on behaviour and neural activity. We employ multivariate encoding analyses to extract feature-selective information carried by randomly-oriented gratings. We show that feature selectivity is enhanced for correctly reported targets and suppressed when the same items are missed, whereas irrelevant distractor items are unaffected. The findings suggest that the AB involves both short- and long-range neural interactions between visual representations competing for access to consciousness.
Synergistic effect of quinary molten salts and ruthenium catalyst for high-power-density lithium-carbon dioxide cell
Authors: Baek Kyungeun , Jeon Woo Cheol , Woo Seongho , Kim Jin Chul , Lee Jun Gyeong , An Kwangjin , Kwak Sang Kyu , Kang Seok Ju
Published: January 2020

With a recent increase in interest in metal-gas batteries, the lithium-carbon dioxide cell has attracted considerable attention because of its extraordinary carbon dioxide-capture ability during the discharge process and its potential application as a power source for Mars exploration. However, owing to the stable lithium carbonate discharge product, the cell enables operation only at low current densities, which significantly limits the application of lithium-carbon dioxide batteries and effective carbon dioxide-capture cells. Here, we investigate a high-performance lithium-carbon dioxide cell using a quinary molten salt electrolyte and ruthenium nanoparticles on the carbon cathode. The nitrate-based molten salt electrolyte allows us to observe the enhanced carbon dioxide-capture rate and the reduced discharge-charge over-potential gap with that of conventional lithium-carbon dioxide cells. Furthermore, owing to the ruthernium catalyst, the cell sustains its performance over more than 300 cycles at a current density of 10.0 A g−1 and exhibits a peak power density of 33.4 mW cm−2.
Transcription reinitiation by recycling RNA polymerase that diffuses on DNA after releasing terminated RNA
Authors: Kang Wooyoung , Ha Kook Sun , Uhm Heesoo , Park Kyuhyong , Lee Ja Yil , Hohng Sungchul , Kang Changwon
Published: January 2020

Despite extensive studies on transcription mechanisms, it is unknown how termination complexes are disassembled, especially in what order the essential components dissociate. Our single-molecule fluorescence study unveils that RNA transcript release precedes RNA polymerase (RNAP) dissociation from the DNA template much more often than their concurrent dissociations in intrinsic termination of bacterial transcription. As termination is defined by the release of product RNA from the transcription complex, the subsequent retention of RNAP on DNA constitutes a previously unidentified stage, termed here as recycling. During the recycling stage, post-terminational RNAPs one-dimensionally diffuse on DNA in downward and upward directions, and can initiate transcription again at the original and nearby promoters in the case of retaining a sigma factor. The efficiency of this event, termed here as reinitiation, increases with supplement of a sigma factor. In summary, after releasing RNA product at intrinsic termination, recycling RNAP diffuses on the DNA template for reinitiation most of the time.
Alternative transcription cycle for bacterial RNA polymerase
Authors: Harden Timothy T. , Herlambang Karina S. , Chamberlain Mathew , Lalanne Jean-Benoît , Wells Christopher D. , Li Gene-Wei , Landick Robert , Hochschild Ann , Kondev Jane , Gelles Jeff
Published: January 2020

RNA polymerases (RNAPs) transcribe genes through a cycle of recruitment to promoter DNA, initiation, elongation, and termination. After termination, RNAP is thought to initiate the next round of transcription by detaching from DNA and rebinding a new promoter. Here we use single-molecule fluorescence microscopy to observe individual RNAP molecules after transcript release at a terminator. Following termination, RNAP almost always remains bound to DNA and sometimes exhibits one-dimensional sliding over thousands of basepairs. Unexpectedly, the DNA-bound RNAP often restarts transcription, usually in reverse direction, thus producing an antisense transcript. Furthermore, we report evidence of this secondary initiation in live cells, using genome-wide RNA sequencing. These findings reveal an alternative transcription cycle that allows RNAP to reinitiate without dissociating from DNA, which is likely to have important implications for gene regulation.
TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells
Authors: Corbet Cyril , Bastien Estelle , Santiago de Jesus Joao Pedro , Dierge Emeline , Martherus Ruben , Vander Linden Catherine , Doix Bastien , Degavre Charline , Guilbaud Céline , Petit Laurenne , Michiels Carine , Dessy Chantal , Larondelle Yvan , Feron Olivier
Published: January 2020

Acidosis, a common characteristic of the tumor microenvironment, is associated with alterations in metabolic preferences of cancer cells and progression of the disease. Here we identify the TGF-β2 isoform at the interface between these observations. We document that acidic pH promotes autocrine TGF-β2 signaling, which in turn favors the formation of lipid droplets (LD) that represent energy stores readily available to support anoikis resistance and cancer cell invasiveness. We find that, in cancer cells of various origins, acidosis-induced TGF-β2 activation promotes both partial epithelial-to-mesenchymal transition (EMT) and fatty acid metabolism, the latter supporting Smad2 acetylation. We show that upon TGF-β2 stimulation, PKC-zeta-mediated translocation of CD36 facilitates the uptake of fatty acids that are either stored as triglycerides in LD through DGAT1 or oxidized to generate ATP to fulfill immediate cellular needs. We also address how, by preventing fatty acid mobilization from LD, distant metastatic spreading may be inhibited.
A common wild rice-derived BOC1 allele reduces callus browning in indica rice transformation
Authors: Zhang Kun , Su Jingjing , Xu Min , Zhou Zhihui , Zhu Xiaoyang , Ma Xin , Hou Jingjing , Tan Lubin , Zhu Zuofeng , Cai Hongwei , Liu Fengxia , Sun Hongying , Gu Ping , Li Chen , Liang Yuntao , Zhao Wensheng , Sun Chuanqing , Fu Yongcai
Published: January 2020

Callus browning, a common trait derived from the indica rice cultivar (Oryza sativa L.), is a challenge to transformation regeneration. Here, we report the map-based cloning of BROWNING OF CALLUS1 (BOC1) using a population derived from crossing Teqing, an elite indica subspecies exhibiting callus browning, and Yuanjiang, a common wild rice accession (Oryza rufipogon Griff.) that is less susceptible to callus browning. We show that BOC1 encodes a SIMILAR TO RADICAL-INDUCED CELL DEATH ONE (SRO) protein. Callus browning can be reduced by appropriate upregulation of BOC1, which consequently improves the genetic transformation efficiency. The presence of a Tourist-like miniature inverted-repeat transposable element (Tourist MITE) specific to wild rice in the promoter of BOC1 increases the expression of BOC1 in callus. BOC1 may decrease cell senescence and death caused by oxidative stress. Our study provides a gene target for improving tissue culturability and genetic transformation.
Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs
Authors: Burke Emily E. , Chenoweth Joshua G. , Shin Joo Heon , Collado-Torres Leonardo , Kim Suel-Kee , Micali Nicola , Wang Yanhong , Colantuoni Carlo , Straub Richard E. , Hoeppner Daniel J. , Chen Huei-Ying , Sellers Alana , Shibbani Kamel , Hamersky Gregory R. , Diaz Bustamante Marcelo , Phan BaDoi N. , Ulrich William S. , Valencia Cristian , Jaishankar Amritha , Price Amanda J. , Rajpurohit Anandita , Semick Stephen A. , Bürli Roland W. , Barrow James C. , Hiler Daniel J. , Page Stephanie C. , Martinowich Keri , Hyde Thomas M. , Kleinman Joel E. , Berman Karen F. , Apud Jose A. , Cross Alan J. , Brandon Nicholas J. , Weinberger Daniel R. , Maher Brady J. , McKay Ronald D. G. , Jaffe Andrew E.
Published: January 2020

Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across 9 time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells. We identify widespread changes in the expression of both individual features and global patterns of transcription. We next demonstrate that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without cell sorting. We lastly adapt a previously generated RNA deconvolution approach to single-cell expression data to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue. Using many public datasets, we demonstrate neuronal cultures are maturationally heterogeneous but contain subsets of neurons more mature than previously observed.
Controlled release of H2S and NO gases through CO2-stimulated anion exchange
Authors: Ishihara Shinsuke , Iyi Nobuo
Published: January 2020

Difficulties related to handling gases are a common bottleneck for applications. Although solid materials that release gas molecules under external stimuli exist, they require an external energy or a device for reliable operation. Herein, we report a CO2 stimulus for controlled release of p.p.m.-level functional gases from solid materials. A CO2-preferential anion-exchange property of layered double hydroxides and redox reactions in gas molecules are combined to release various gases (including H2S and NO) under ambient air from HS− and NO2−-incorporated layered double hydroxides, respectively. The profiles of gas release are mainly governed by the difference of pKa between H2CO3 and resulting acids (formed through protonation of interlayer anions), and are not so susceptible to the variation of relative humidity in air. Moreover, structural modulation of solid materials enables fine control of the gas release profiles. The use of safe, ubiquitous, and nearly constant (~400 p.p.m. in atmosphere) CO2 stimulus offers broad applications for functional gases.
Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors
Authors: Wilson D. H. , Jarman E. J. , Mellin R. P. , Wilson M. L. , Waddell S. H. , Tsokkou P. , Younger N. T. , Raven A. , Bhalla S. R. , Noll A. T. R. , Olde Damink S. W. , Schaap F. G. , Chen P. , Bates D. O. , Banales J. M. , Dean C. H. , Henderson D. J. , Sansom O. J. , Kendall T. J. , Boulter L.
Published: January 2020

The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration.
H2S-activatable near-infrared afterglow luminescent probes for sensitive molecular imaging in vivo
Authors: Wu Luyan , Ishigaki Yusuke , Hu Yuxuan , Sugimoto Keisuke , Zeng Wenhui , Harimoto Takashi , Sun Yidan , He Jian , Suzuki Takanori , Jiang Xiqun , Chen Hong-Yuan , Ye Deju
Published: January 2020

Afterglow luminescent probes with high signal-to-background ratio show promise for in vivo imaging; however, such probes that can be selectively delivered into target sites and switch on afterglow luminescence remain limited. We optimize an organic electrochromic material and integrate it into near-infrared (NIR) photosensitizer (silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) and (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]) containing nanoparticles, developing an H2S-activatable NIR afterglow probe (F12+-ANP). F12+-ANP displays a fast reaction rate (1563 ± 141 M−1 s−1) and large afterglow turn-on ratio (~122-fold) toward H2S, enabling high-sensitivity and -specificity measurement of H2S concentration in bloods from healthy persons, hepatic or colorectal cancer patients. We further construct a hepatic-tumor-targeting and H2S-activatable afterglow probe (F12+-ANP-Gal) for noninvasive, real-time imaging of tiny subcutaneous HepG2 tumors (<3 mm in diameter) and orthotopic liver tumors in mice. Strikingly, F12+-ANP-Gal accurately delineates tumor margins in excised hepatic cancer specimens, which may facilitate intraoperative guidance of hepatic cancer surgery.
Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer
Authors: Zhou Stanley , Hawley James R. , Soares Fraser , Grillo Giacomo , Teng Mona , Madani Tonekaboni Seyed Ali , Hua Junjie Tony , Kron Ken J. , Mazrooei Parisa , Ahmed Musaddeque , Arlidge Christopher , Yun Hwa Young , Livingstone Julie , Huang Vincent , Yamaguchi Takafumi N. , Espiritu Shadrielle M. G. , Zhu Yanyun , Severson Tesa M. , Murison Alex , Cameron Sarina , Zwart Wilbert , van der Kwast Theodorus , Pugh Trevor J. , Fraser Michael , Boutros Paul C. , Bristow Robert G. , He Housheng Hansen , Lupien Mathieu
Published: January 2020

Prostate cancer is the second most commonly diagnosed malignancy among men worldwide. Recurrently mutated in primary and metastatic prostate tumors, FOXA1 encodes a pioneer transcription factor involved in disease onset and progression through both androgen receptor-dependent and androgen receptor-independent mechanisms. Despite its oncogenic properties however, the regulation of FOXA1 expression remains unknown. Here, we identify a set of six cis-regulatory elements in the FOXA1 regulatory plexus harboring somatic single-nucleotide variants in primary prostate tumors. We find that deletion and repression of these cis-regulatory elements significantly decreases FOXA1 expression and prostate cancer cell growth. Six of the ten single-nucleotide variants mapping to FOXA1 regulatory plexus significantly alter the transactivation potential of cis-regulatory elements by modulating the binding of transcription factors. Collectively, our results identify cis-regulatory elements within the FOXA1 plexus mutated in primary prostate tumors as potential targets for therapeutic intervention.
Synthesis of a Vocal Sound from the 3,000 year old Mummy, Nesyamun ‘True of Voice’
Authors: Howard D. M. , Schofield J. , Fletcher J. , Baxter K. , Iball G. R. , Buckley S. A.
Published: January 2020

The sound of a 3,000 year old mummified individual has been accurately reproduced as a vowel-like sound based on measurements of the precise dimensions of his extant vocal tract following Computed Tomography (CT) scanning, enabling the creation of a 3-D printed vocal tract. By using the Vocal Tract Organ, which provides a user-controllable artificial larynx sound source, a vowel sound is synthesised which compares favourably with vowels of modern individuals.
Effects of different fertilizer formulas on the growth of loquat rootstocks and stem lignification
Authors: Xu Fangjie , Chu Changbin , Xu Zhihong
Published: January 2020

Grafting is a common method of variety propagation in loquat breeding, the slow growth of rootstocks is a main factor limiting the expansion of this technique. This study aimed to evaluate the effects of seven different fertilizer formulas on the growth of loquat rootstock seedlings, five water-soluble fertilizer formulas, as well as organic fertilizer and controlled-release fertilizer were evaluated. An unfertilized control (CK) was also performed. Growth indicators including plant height, stem thickening and lignification, leaf area, root development, dry matter accumulation, spatial distribution of nutrient elements, and cross-sectional anatomy of stem were measured. The results showed that the addition of microelements in fertilizer could significantly delay the lignification process of the cambium, which exhibiting the greatest improvement in stem thickening. Phosphorus nutrition could significantly promote the occurrence of fibrous roots, while excessive phosphorus supply might disturb the absorption and utilization of nitrogen of roots, intensify the lignification process of the main stem, and then affect the growth of the aboveground part. The findings of this research could provide a theoretical basis for identifying an optimum fertilization formula and technique for promoting the rapid growth and accelerating the lignification process at different stages of loquat rootstock seedling growth.
Effect of Rhizopus nigricans (Rhizopus stolonifera)-based novel starter culture on quality and safety attributes of doenjang, a traditional Korean soybean fermented food product
Authors: Shukla Shruti , Bahuguna Ashutosh , Park Hae-Kyong , Kim Jong-Kyu , Kim Myunghee
Published: January 2020

We aimed to develop a consortium of starter culture of effective microorganisms to prepare doenjang, a traditional Korean fermented food. Different ratios of Bacillus subtilis TKSP 24 (B), Aspergillus oryzae complex (A), Rhizopus nigricans (also named as Rhizopus stolonifera) (R), and Mucor racemosus 15 (M15) were selected as meju starter cultures to produce doenjang with improved quality. Microbial strain combinations (B: A: R and B: M15: R) were mixed separately at three different ratios [1:1:1 (w/w), 1:0.5:1.5 (w/w), and 1:1.5:0.5 (w/w)] to prepare BAR-1, BAR-2, BAR-3, BM15R-1, BM15R-2, and BM15R-3 doenjang samples. Quantitative analyses included free amino acids, free sugar, volatile and non-volatile organic acids, cellular antioxidant activity along with the presence of biogenic amines and aflatoxins, and microbial counts. Total free amino acids responsible for the sweet taste of doenjang were highest in BAR-2 (322.50 mg/100 g) and BM15R-3 (320.07 mg/100 g). Total volatile organic acid was highest in BAR-1 compared to other preparations. All doenjang samples had biogenic amines, especially histamine, below the toxicity level (500 mg/kg). Also, the aflatoxin and hazardous microbial count in the tested doenjang samples were below the level of toxicity. The findings suggest that use of multiple microbial strains in combination with R. nigricans as a starter culture could be a novel and effective approach to improve the nutrition and safety of fermented soybean food products of doenjang.
Differential Expression of PDGF Receptor-α in Human Placental Trophoblasts Leads to Different Entry Pathways by Human Cytomegalovirus Strains
Authors: Naing Zin , Hamilton Stuart T. , van Zuylen Wendy J. , Scott Gillian M. , Rawlinson William D.
Published: January 2020

Human cytomegalovirus (CMV) is the leading non-genetic cause of fetal malformation in developed countries. CMV placental infection is a pre-requisite for materno-fetal transmission of virus, and fetal infection. We investigated the roles of the viral pentameric complex gH/gL/pUL128-pUL131A, and cellular platelet-derived growth factor receptor-α (PDGFRα) for CMV infection in first trimester extravillous-derived (SGHPL-4) and villous-derived (HTR-8/SVneo) trophoblast cells. Infection with four CMV clinical and laboratory strains (Merlin, TB40E, Towne, AD169), and Merlin deletion mutants of UL128-, UL130-, and UL131A-genes, showed a cell type-dependent requirement of the viral pentameric complex for infection of trophoblast cells. The viral pentameric complex was essential for infection of villous trophoblasts, but non-essential for extravillous trophoblasts. Blocking of PDGFRα in extravillous trophoblasts, which naturally express PDGFRα, inhibited entry of pentameric complex-deficient CMV strains, but not the entry of pentameric positive CMV strains. Transient expression of PDGFRα in villous trophoblasts, which are naturally deficient in PDGFRα, promoted the entry of CMV strains lacking gH/gL/pUL128-pUL131A, but had no effect on entry of pentameric positive CMV strains. These results suggest PDGFRα is an important cell receptor for entry of CMV mutant strains lacking gH/gL/pUL128-pUL131A complexes in some placental cells, suggesting these entry pathways could be potential antiviral targets.
Pyramidal tract and alternate motor fibers complementarily mediate motor compensation in patients after hemispherotomy
Authors: Gaubatz Jennifer , Ernst Leon , Prillwitz Conrad C. , David Bastian , Lüchters Guido , Schramm Johannes , Weber Bernd , Surges Rainer , Hattingen Elke , Schlaug Gottfried , Elger Christian E. , Rüber Theodor
Published: January 2020

Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
Adult neurogenesis in the mushroom bodies of red flour beetles (Tribolium castaneum, Herbst) is influenced by the olfactory environment
Authors: Trebels Björn , Dippel Stefan , Schaaf Magdalina , Balakrishnan Karthi , Wimmer Ernst A. , Schachtner Joachim
Published: January 2020

Several studies showed adult persisting neurogenesis in insects, including the red flour beetle Tribolium castaneum, while it is absent in honeybees, carpenter ants, and vinegar flies. In our study, we focus on cell proliferation in the adult mushroom bodies of T. castaneum. We reliably labelled the progenies of the adult persisting mushroom body neuroblasts and determined the proliferation rate under several olfactory conditions within the first week after adult eclosion. We found at least two phases of Kenyon cell proliferation in the early adult beetle. Our results suggest that the generation of Kenyon cells during the first three days after adult eclosion is mainly genetically predetermined and a continuation of the developmental processes (nature), whereas from day four on proliferation seems to be mainly dependent on the odour environment (nurture). Considering that the mushroom bodies are linked to learning and memory, neurogenesis in the mushroom bodies is part of the remodelling of neuronal circuits leading to the adaption to the environment and optimization of behaviour.