bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hsp90 isoforms from S. cerevisiae differ in structure, function and client range
Authors: Girstmair Hannah , Tippel Franziska , Lopez Abraham , Tych Katarzyna , Stein Frank , Haberkant Per , Schmid Philipp Werner Norbert , Helm Dominic , Rief Matthias , Sattler Michael , Buchner Johannes 
Published: August 2019

AbstractThe molecular chaperone Hsp90 is an important regulator of proteostasis. It has remained unclear why S. cerevisiae possesses two Hsp90 isoforms, the constitutively expressed Hsc82 and the stress-inducible Hsp82. Here, we report distinct differences despite a sequence identity of 97%. Consistent with its function under stress conditions, Hsp82 is more stable and refolds more efficiently than Hsc82. The two isoforms also differ in their ATPases and conformational cycles. Hsc82 is more processive and populates closed states to a greater extent. Variations in the N-terminal ATP-binding domain modulate its dynamics and conformational cycle. Despite these differences, the client interactomes are largely identical, but isoform-specific interactors exist both under physiological and heat shock conditions. Taken together, changes mainly in the N-domain create a stress-specific, more resilient protein with a shifted activity profile. Thus, the precise tuning of the Hsp90 isoforms preserves the basic mechanism but adapts it to specific needs.
Ventral midbrain stimulation induces perceptual learning and cortical plasticity in primates
Authors: Arsenault John T. , Vanduffel Wim 
Published: August 2019

AbstractPractice improves perception and enhances neural representations of trained visual stimuli, a phenomenon known as visual perceptual learning (VPL). While attention to task-relevant stimuli plays an important role in such learning, Pavlovian stimulus-reinforcer associations are sufficient to drive VPL, even subconsciously. It has been proposed that reinforcement facilitates perceptual learning through the activation of neuromodulatory centers, but this has not been directly confirmed in primates. Here, we paired task-irrelevant visual stimuli with microstimulation of a dopaminergic center, the ventral tegmental area (VTA), in macaques. Pairing VTA microstimulation with a task-irrelevant visual stimulus increased fMRI activity and improved classification of fMRI activity patterns selectively for the microstimulation-paired stimulus. Moreover, pairing VTA microstimulation with a task-irrelevant visual stimulus improved the subject’s capacity to discriminate that stimulus. This is the first causal demonstration of the role of neuromodulatory centers in VPL in primates.
The pause-initiation limit restricts transcription activation in human cells
Authors: Gressel Saskia , Schwalb Björn , Cramer Patrick 
Published: August 2019

AbstractEukaryotic gene transcription is often controlled at the level of RNA polymerase II (Pol II) pausing in the promoter-proximal region. Pausing Pol II limits the frequency of transcription initiation (‘pause-initiation limit’), predicting that the pause duration must be decreased for transcriptional activation. To test this prediction, we conduct a genome-wide kinetic analysis of the heat shock response in human cells. We show that the pause-initiation limit restricts transcriptional activation at most genes. Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. The transcription of enhancer elements is generally not pause limited and can be activated without CDK9 activity. Our results define the kinetics of Pol II transcriptional regulation in human cells at all gene classes during a natural transcription response.
Single-handed supramolecular double helix of homochiral bis(N-amidothiourea) supported by double crossed C−I···S halogen bonds
Authors: Yan Xiaosheng , Zou Kunshan , Cao Jinlian , Li Xiaorui , Zhao Zhixing , Li Zhao , Wu Anan , Liang Wanzhen , Mo Yirong , Jiang Yunbao 
Published: August 2019

AbstractThe natural DNA double helix consists of two strands of nucleotides that are held together by multiple hydrogen bonds. Here we propose to build an artificial double helix from fragments of two strands connected by covalent linkages therein, but with halogen bonding as the driving force for self-assembling the fragments to the double helix. We succeed in building such a double helix in both solution and solid state, by using a bilateral N-(p-iodobenzoyl)alanine based amidothiourea which in its folded cis-form allows double and crossed C−I···S halogen bonds that lead to right- or left-handed double helix when the two alanine residues are of the same L,L- or D,D-configuration. The double helix forms in dilute CH3CN solution of the micromolar concentration level, e.g., 5.6 μM from 2D NOESY experiments and exhibits a high thermal stability in solution up to 75 °C, suggesting cooperative and thereby strong intermolecular double crossed halogen bonding that makes the double helix stable. This is supported by the observed homochiral self-sorting in solution.
MpsAB is important for Staphylococcus aureus virulence and growth at atmospheric CO2 levels
Authors: Fan Sook-Ha , Ebner Patrick , Reichert Sebastian , Hertlein Tobias , Zabel Susanne , Lankapalli Aditya Kumar , Nieselt Kay , Ohlsen Knut , Götz Friedrich 
Published: August 2019

AbstractThe mechanisms behind carbon dioxide (CO2) dependency in non-autotrophic bacterial isolates are unclear. Here we show that the Staphylococcus aureus mpsAB operon, known to play a role in membrane potential generation, is crucial for growth at atmospheric CO2 levels. The genes mpsAB can complement an Escherichia coli carbonic anhydrase (CA) mutant, and CA from E. coli can complement the S. aureus delta-mpsABC mutant. In comparison with the wild type, S. aureus mps mutants produce less hemolytic toxin and are less virulent in animal models of infection. Homologs of mpsA and mpsB are widespread among bacteria and are often found adjacent to each other on the genome. We propose that MpsAB represents a dissolved inorganic carbon transporter, or bicarbonate concentrating system, possibly acting as a sodium bicarbonate cotransporter.
HSP90 inhibitors stimulate DNAJB4 protein expression through a mechanism involving N6-methyladenosine
Authors: Miao Weili , Li Lin , Zhao Yonghui , Dai Xiaoxia , Chen Xuemei , Wang Yinsheng 
Published: August 2019

AbstractSmall-molecule inhibitors for the 90-kDa heat shock protein (HSP90) have been extensively exploited in preclinical studies for the therapeutic interventions of human diseases accompanied with proteotoxic stress. By using an unbiased quantitative proteomic method, we uncover that treatment with three HSP90 inhibitors results in elevated expression of a large number of heat shock proteins. We also demonstrate that the HSP90 inhibitor-mediated increase in expression of DNAJB4 protein occurs partly through an epitranscriptomic mechanism, and is substantially modulated by the writer, eraser, and reader proteins of N6-methyladenosine (m6A). Furthermore, exposure to ganetespib leads to elevated modification levels at m6A motif sites in the 5′-UTR of DNAJB4 mRNA, and the methylation at adenosine 114 site in the 5′-UTR promotes the translation of the reporter gene mRNA. This m6A-mediated mechanism is also at play upon heat shock treatment. Cumulatively, we unveil that HSP90 inhibitors stimulate the translation of DNAJB4 through an epitranscriptomic mechanism.
Stable and bright formamidinium-based perovskite light-emitting diodes with high energy conversion efficiency
Authors: Miao Yanfeng , Ke You , Wang Nana , Zou Wei , Xu Mengmeng , Cao Yu , Sun Yan , Yang Rong , Wang Ying , Tong Yunfang , Xu Wenjie , Zhang Liangdong , Li Renzhi , Li Jing , He Haiping , Jin Yizheng , Gao Feng , Huang Wei , Wang Jianpu 
Published: August 2019

AbstractSolution-processable perovskites show highly emissive and good charge transport, making them attractive for low-cost light-emitting diodes (LEDs) with high energy conversion efficiencies. Despite recent advances in device efficiency, the stability of perovskite LEDs is still a major obstacle. Here, we demonstrate stable and bright perovskite LEDs with high energy conversion efficiencies by optimizing formamidinium lead iodide films. Our LEDs show an energy conversion efficiency of 10.7%, and an external quantum efficiency of 14.2% without outcoupling enhancement through controlling the concentration of the precursor solutions. The device shows low efficiency droop, i.e. 8.3% energy conversion efficiency and 14.0% external quantum efficiency at a current density of 300 mA cm−2, making the device more efficient than state-of-the-art organic and quantum-dot LEDs at high current densities. Furthermore, the half-lifetime of device with benzylamine treatment is 23.7 hr under a current density of 100 mA cm−2, comparable to the lifetime of near-infrared organic LEDs.
Caspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling
Authors: Xu Zhi-Xiang , Tan Ji-Wei , Xu Haifei , Hill Cassandra J. , Ostrovskaya Olga , Martemyanov Kirill A. , Xu Baoji 
Published: August 2019

AbstractCaspase-2 is the most evolutionarily conserved member in the caspase family of proteases and is constitutively expressed in most cell types including neurons; however, its physiological function remains largely unknown. Here we report that caspase-2 plays a critical role in synaptic plasticity and cognitive flexibility. We found that caspase-2 deficiency led to deficits in dendritic spine pruning, internalization of AMPA receptors and long-term depression. Our results indicate that caspase-2 degrades Rictor, a key mTOR complex 2 (mTORC2) component, to inhibit Akt activation, which leads to enhancement of the GSK3β activity and thereby long-term depression. Furthermore, we found that mice lacking caspase-2 displayed elevated levels of anxiety, impairment in reversal water maze learning, and little memory loss over time. These results not only uncover a caspase-2–mTORC2–Akt–GSK3β signaling pathway, but also suggest that caspase-2 is important for memory erasing and normal behaviors by regulating synaptic number and transmission.
Measuring the ionisation fraction in a jet from a massive protostar
Authors: Fedriani R. , Caratti o Garatti A. , Purser S. J. D. , Sanna A. , Tan J. C. , Garcia-Lopez R. , Ray T. P. , Coffey D. , Stecklum B. , Hoare M. 
Published: August 2019

AbstractIt is important to determine if massive stars form via disc accretion, like their low-mass counterparts. Theory and observation indicate that protostellar jets are a natural consequence of accretion discs and are likely to be crucial for removing angular momentum during the collapse. However, massive protostars are typically rarer, more distant and more dust enshrouded, making observational studies of their jets more challenging. A fundamental question is whether the degree of ionisation in jets is similar across the mass spectrum. Here we determine an ionisation fraction of ~5–12% in the jet from the massive protostar G35.20-0.74N, based on spatially coincident infrared and radio emission. This is similar to the values found in jets from lower-mass young stars, implying a unified mechanism of shock ionisation applies in jets across most of the protostellar mass spectrum, up to at least ~10 solar masses.
Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation
Authors: Walker Jemma Victoria , Zhuang Heng , Singer Donald , Illsley Charlotte Sara , Kok Wai Ling , Sivaraj Kishor K. , Gao Yan , Bolton Chloe , Liu Yuying , Zhao Mengyuan , Grayson Portia Rebecca Clare , Wang Shuang , Karbanová Jana , Lee Tim , Ardu Stefano , Lai Qingguo , Liu Jihui , Kassem Moustapha , Chen Shuo , Yang Kai , Bai Yuxing , Tredwin Christopher , Zambon Alexander C. , Corbeil Denis , Adams Ralf , Abdallah Basem M. , Hu Bing 
Published: August 2019

AbstractStem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs and epithelial SCs. WithNotchsignaling as the key regulator, we disclose molecular proof and lineage tracing evidence showing the distinct MSCs contribute to incisor MTACs and the other mesenchymal cell lineages. MTACs can feedback and regulate the homeostasis and activation of CL-MSCs through Delta-like 1 homolog (Dlk1), which balances MSCs-MTACs number and the lineage differentiation.Dlk1’s function on SCs priming and self-renewal depends on its biological forms and its gene expression is under dynamic epigenetic control. Our findings can be validated in clinical samples and applied to accelerate tooth wound healing, providing an intriguing insight of how to direct SCs towards tissue regeneration.
Extending Cardiac Functional Assessment with Respiratory-Resolved 3D Cine MRI
Authors: Liu Jing , Wang Yan , Wen Zhaoying , Feng Li , Lima Ana Paula Santos , Mahadevan Vaikom S. , Bolger Ann , Saloner David , Ordovas Karen 
Published: August 2019

AbstractThis study aimed to develop a cardiorespiratory-resolved 3D magnetic resonance imaging (5D MRI: x-y-z-cardiac-respiratory) approach based on 3D motion tracking for investigating the influence of respiration on cardiac ventricular function. A highly-accelerated 2.5-minute sparse MR protocol was developed for a continuous acquisition of cardiac images through multiple cardiac and respiratory cycles. The heart displacement along respiration was extracted using a 3D image deformation algorithm, and this information was used to cluster the acquired data into multiple respiratory phases. The proposed approach was tested in 15 healthy volunteers (7 females). Cardiac function parameters, including the end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF), were measured for the left and right ventricle in both end-expiration and end-inspiration. Although with the proposed 5D cardiac MRI, there were no significant differences (p > 0.05, t-test) between end-expiration and end-inspiration measurements of the cardiac function in volunteers, incremental respiratory motion parameters that were derived from 3D motion tracking, such as the depth, expiration and inspiration distribution, correlated (p < 0.05, correlation coefficient, Mann-Whitney) with those volume-based parameters of cardiac function and varied between genders. The obtained initial results suggested that this new approach allows evaluation of cardiac function during specific respiratory phases. Thus, it can enable investigation of effects related to respiratory variability and better assessment of cardiac function for studying respiratory and/or cardiac dysfunction.
Anthocyanins, delphinidin-3-O-glucoside and cyanidin-3-O-glucoside, inhibit immune checkpoints in human colorectal cancer cells in vitro and in silico
Authors: Mazewski Candice , Kim Morgan Sanha , Gonzalez de Mejia Elvira 
Published: August 2019

AbstractThe objective was to assess anti-progression and stimulatory immune response effects among anthocyanins (ANC) and their metabolites on human colorectal cancer cells in vitro and in silico. Pure phenolics including delphinidin-3-O-glucoside (D3G) and its metabolites, delphinidin (DC) and gallic acid (GA), were tested alone or in combination, on HCT-116 and HT-29 human colorectal cancer cells (100–600 µg/mL). HCT-116 and HT-29 50% inhibition concentrations (µg/mL) were 396 ± 23 and 329 ± 17 for D3G; 242 ± 16 and >600 for DC; and 154 ± 5 and 81 ± 5 for GA, respectively. Using molecular docking, cyanidin-3-O-glucoside (C3G) showed the highest potential to inhibit immune checkpoints: programmed cell death protein-1 (PD-1) (−6.8 kcal/mol) and programmed death-ligand-1 (PD-L1) (−9.6 kcal/mol). C3G, D3G, DC, GA, and D3G-rich extracts decreased PD-L1 protein expression in HCT-116 cells. C3G decreased PD-L1 fluorescence intensity by 39%. ANC decreased PD-1 expression in peripheral blood mononuclear cells in monoculture by 41% and 55%, and co-culture with HCT-116 and HT-29 cells by 39% and 26% (C3G) and 50% and 51% (D3G), respectively. D3G and C3G, abundant in plant foods, showed potential for binding with and inhibiting immune checkpoints, PD-1 and PD-L1, which can activate immune response in the tumor microenvironment and induce cancer cell death.
Cucumber mosaic virus-induced gene silencing in banana
Authors: Tzean Yuh , Lee Ming-Chi , Jan Hsiao-Hsuan , Chiu Yi-Shu , Tu Tsui-Chin , Hou Bo-Han , Chen Ho-Ming , Chou Chun-Nan , Yeh Hsin-Hung 
Published: August 2019

AbstractBanana (Musa spp.) is one of the world’s most important staple and cash crops. Despite accumulating genetic and transcriptomic data, low transformation efficiency in agronomically important Musa spp. render translational researches in banana difficult by using conventional knockout approaches. To develop tools for translational research in bananas, we developed a virus induced-gene silencing (VIGS) system based on a banana-infecting cucumber mosaic virus (CMV) isolate, CMV 20. CMV 20 genomic RNA 1, 2, and 3, were separately cloned in Agrobacterium pJL89 binary vectors, and a cloning site was introduced on RNA 2 immediately after the 2a open reading frame to insert the gene targeted for silencing. An efficient Agrobacterium inoculation method was developed for banana, which enabled the CMV 20 VIGS vector infection rate to reach 95% in our experiments. CMV 20-based silencing of Musa acuminata cv. Cavendish (AAA group) glutamate 1-semialdehyde aminotransferase (MaGSA) produced a typical chlorotic phenotype and silencing of M. acuminata phytoene desaturase (MaPDS) produced a photobleachnig phenotype. We show this approach efficiently reduced GSA and PDS transcripts to 10% and 18% of the control, respectively. The high infection rate and extended silencing of this VIGS system will provide an invaluable tool to accelerate functional genomic studies in banana.
Self-assembled hyaluronan nanocapsules for the intracellular delivery of anticancer drugs
Authors: Cadete Ana , Olivera Ana , Besev Magnus , Dhal Pradeep K. , Gonçalves Lídia , Almeida António J. , Bastiat Guillaume , Benoit Jean-Pierre , de la Fuente María , Garcia-Fuentes Marcos , Alonso María José , Torres Dolores 
Published: August 2019

AbstractPreparation of sophisticated delivery systems for nanomedicine applications generally involve multi-step procedures using organic solvents. In this study, we have developed a simple self-assembling process to prepare docetaxel-loaded hyaluronic acid (HA) nanocapsules by using a self-emulsification process without the need of organic solvents, heat or high shear forces. These nanocapsules, which comprise an oily core and a shell consisting of an assembly of surfactants and hydrophobically modified HA, have a mean size of 130 nm, a zeta potential of −20 mV, and exhibit high docetaxel encapsulation efficiency. The nanocapsules exhibited an adequate stability in plasma. Furthermore, in vitro studies performed using A549 lung cancer cells, showed effective intracellular delivery of docetaxel. On the other hand, blank nanocapsules showed very low cytotoxicity. Overall, these results highlight the potential of self-emulsifying HA nanocapsules for intracellular drug delivery.
Evaluation of AGP Fucosylation as a Marker for Hepatocellular Carcinoma of Three Different Etiologies
Authors: Liang Jing , Zhu Jianhui , Wang Mengmeng , Singal Amit G. , Odewole Mobolaji , Kagan Sofia , Renteria Veronica , Liu Suyu , Parikh Neehar D. , Lubman David M. 
Published: August 2019

AbstractA mass spectrometric analysis platform has been developed to determine whether glycosylation patterns of alpha-1 acid glycoprotein (AGP) could be used as a marker for early detection of hepatocellular carcinoma (HCC) in different etiologies, i.e. non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALC), and hepatitis C virus (HCV). MALDI-MS profiling of N-glycans of AGP purified from 20 μL of patient serum in HCC (n = 72) and liver cirrhosis (n = 58) showed that a unique trifucosylated tetra-antennary glycan (m/z 3490.76) was predominantly identified in HCCs but was absent in healthy subjects and the majority of cirrhosis patients. Receiver operation characteristic (ROC) curve analysis showed that the trifucosylated N-glycan of AGP (triFc_AGP) could differentiate HCC from cirrhosis with an area under the curve (AUC) of 0.707, 0.726 and 0.751 for NASH, ALC and HCV, respectively. When combining triFc_AGP with INR and AFP, the panel had the greatest benefit in detection of NASH-related HCCs, with a significantly improved AUC of 0.882 for all NASH HCCs and 0.818 for early NASH HCCs compared to AFP alone (0.761 and 0.641, respectively). Moreover, triFc_AGP could serve as a potential marker for monitoring AFP-negative HCC patients.
Design of integer‐N PLL frequency synthesiser for E‐band frequency for high phase noise performance in 5G communication systems
Authors: Berber Zakia , Kameche Samir , Benkhelifa Elhadj 
Published: August 2019

A phase‐locked loop (PLL) frequency synthesiser is designed for 5G E‐band frequency. ADF4155‐PLL chip with an external (loop filter, prescaler, VCO and an external reference oscillator) is simulated using the ADIsimPLL tool. With a third‐order passive filter having 1 MHz loop bandwidth and 45° phase margin, simulation results show that the proposed synthesiser achieves a total phase noise (PN) of −81.50 and −115.7 dBc/Hz at 100 kHz and 10 MHz, respectively, for (71–76 GHz) and −80.39 and −114.7 dBc/Hz at 100 kHz and 10 MHz, respectively, for the highest (81–86 GHz) 5G frequency range even if −160 dBc/Hz VCO noise floor and −170dBc/Hz reference PN floor are integrated in the design. Also, the performance of the system in terms of RMS jitter and reference spurs are verified. The proposed synthesiser for 5G application presents very low reference spurs (−113, −112 dBc) at 50 MHz offset frequency and low RMS jitter (0.39, 0.40 ps) for 70 and 80 GHz frequency band, respectively.