bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperative miRNA-dependent PTEN regulation drives resistance to BTK inhibition in B-cell lymphoid malignancies
Authors: Kapoor Isha , Bodo Juraj , Hill Brian T. , Almasan Alexandru 
Published: November 2021

AbstractAberrant microRNA (miR) expression plays an important role in pathogenesis of different types of cancers, including B-cell lymphoid malignancies and in the development of chemo-sensitivity or -resistance in chronic lymphocytic leukemia (CLL) as well as diffuse large B-cell lymphoma (DLBCL). Ibrutinib is a first-in class, oral, covalent Bruton’s tyrosine kinase (BTK) inhibitor (BTKi) that has shown impressive clinical activity, yet many ibrutinib-treated patients relapse or develop resistance over time. We have reported that acquired resistance to ibrutinib is associated with downregulation of tumor suppressor protein PTEN and activation of the PI3K/AKT pathway. Yet how PTEN mediates chemoresistance in B-cell malignancies is not clear. We now show that the BTKi ibrutinib and a second-generation compound, acalabrutinib downregulate miRNAs located in the 14q32 miRNA cluster region, including miR-494, miR-495, and miR-543. BTKi-resistant CLL and DLBCL cells had striking overexpression of miR-494, miR-495, miR-543, and reduced PTEN expression, indicating further regulation of the PI3K/AKT/mTOR pathway in acquired BTKi resistance. Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression. Luciferase reporter gene assay showed that miR-494 directly targeted and suppressed PTEN expression by recognizing two conserved binding sites in the PTEN 3′-UTR, and subsequently activated AKTSer473. Importantly, overexpression of a miR-494 mimic abrogated both PTEN mRNA and protein levels, further indicating regulation of apoptosis by PTEN/AKT/mTOR. Conversely, overexpression of a miR-494 inhibitor in BTKi-resistant cells restored PTEN mRNA and protein levels, thereby sensitizing cells to BTKi-induced apoptosis. Inhibition of miR-494 and miR-495 sensitized cells by cooperative targeting of pten, with additional miRNAs in the 14q32 cluster that target pten able to contribute to its regulation. Therefore, targeting 14q32 cluster miRNAs may have therapeutic value in acquired BTK-resistant patients via regulation of the PTEN/AKT/mTOR signaling axis.
Lateral transduction is inherent to the life cycle of the archetypical Salmonella phage P22
Authors: Fillol-Salom Alfred , Bacigalupe Rodrigo , Humphrey Suzanne , Chiang Yin Ning , Chen John , Penadés José R. 
Published: November 2021

AbstractLysogenic induction ends the stable association between a bacteriophage and its host, and the transition to the lytic cycle begins with early prophage excision followed by DNA replication and packaging (ERP). This temporal program is considered universal for P22-like temperate phages, though there is no direct evidence to support the timing and sequence of these events. Here we report that the long-standing ERP program is an observation of the experimentally favored Salmonella phage P22 tsc229 heat-inducible mutant, and that wild-type P22 actually follows the replication-packaging-excision (RPE) program. We find that P22 tsc229 excises early after induction, but P22 delays excision to just before it is detrimental to phage production. This allows P22 to engage in lateral transduction. Thus, at minimal expense to itself, P22 has tuned the timing of excision to balance propagation with lateral transduction, powering the evolution of its host through gene transfer in the interest of self-preservation.
Competitive binding and molecular crowding regulate the cytoplasmic interactome of non-viral polymeric gene delivery vectors
Authors: Raynold Aji Alex M. , Li Danyang , Chang Lan , Gautrot Julien E. 
Published: November 2021

AbstractIn contrast to the processes controlling the complexation, targeting and uptake of polycationic gene delivery vectors, the molecular mechanisms regulating their cytoplasmic dissociation remains poorly understood. Upon cytosolic entry, vectors become exposed to a complex, concentrated mixture of molecules and biomacromolecules. In this report, we characterise the cytoplasmic interactome associated with polycationic vectors based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) and poly(2-methacrylolyloxyethyltrimethylammonium chloride) (PMETAC) brushes. To quantify the contribution of different classes of low molar mass molecules and biomacromolecules to RNA release, we develop a kinetics model based on competitive binding. Our results identify the importance of competition from highly charged biomacromolecules, such as cytosolic RNA, as a primary regulator of RNA release. Importantly, our data indicate the presence of ribosome associated proteins, proteins associated with translation and transcription factors that may underly a broader impact of polycationic vectors on translation. In addition, we bring evidence that molecular crowding modulates competitive binding and demonstrate how the modulation of such interactions, for example via quaternisation or the design of charge-shifting moieties, impacts on the long-term transfection efficiency of polycationic vectors. Understanding the mechanism regulating cytosolic dissociation will enable the improved design of cationic vectors for long term gene release and therapeutic efficacy.
High-harmonic generation in Weyl semimetal β-WP2 crystals
Authors: Lv Yang-Yang , Xu Jinlong , Han Shuang , Zhang Chi , Han Yadong , Zhou Jian , Yao Shu-Hua , Liu Xiao-Ping , Lu Ming-Hui , Weng Hongming , Xie Zhenda , Chen Y. B. , Hu Jianbo , Chen Yan-Feng , Zhu Shining 
Published: November 2021

AbstractAs a quantum material, Weyl semimetal has a series of electronic-band-structure features, including Weyl points with left and right chirality and corresponding Berry curvature, which have been observed in experiments. These band-structure features also lead to some unique nonlinear properties, especially high-order harmonic generation (HHG) due to the dynamic process of electrons under strong laser excitation, which has remained unexplored previously. Herein, we obtain effective HHG in type-II Weyl semimetal β-WP2 crystals, where both odd and even orders are observed, with spectra extending into the vacuum ultraviolet region (190 nm, 10th order), even under fairly low femtosecond laser intensity. In-depth studies have interpreted that odd-order harmonics come from the Bloch electron oscillation, while even orders are attributed to Bloch oscillations under the “spike-like” Berry curvature at Weyl points. With crystallographic orientation-dependent HHG spectra, we further quantitatively retrieved the electronic band structure and Berry curvature of β-WP2. These findings may open the door for exploiting metallic/semimetallic states as solid platforms for deep ultraviolet radiation and offer an all-optical and pragmatic solution to characterize the complicated multiband electronic structure and Berry curvature of quantum topological materials.
Dopamine D2 receptor regulates cortical synaptic pruning in rodents
Authors: Zhang Ya-Qiang , Lin Wei-Peng , Huang Li-Ping , Zhao Bing , Zhang Cheng-Cheng , Yin Dong-Min 
Published: November 2021

AbstractSynaptic pruning during adolescence is important for appropriate neurodevelopment and synaptic plasticity. Aberrant synaptic pruning may underlie a variety of brain disorders such as schizophrenia, autism and anxiety. Dopamine D2 receptor (Drd2) is associated with several neuropsychiatric diseases and is the target of some antipsychotic drugs. Here we generate self-reporting Drd2 heterozygous (SR-Drd2+/−) rats to simultaneously visualize Drd2-positive neurons and downregulate Drd2 expression. Time course studies on the developing anterior cingulate cortex (ACC) from control and SR-Drd2+/−rats reveal important roles of Drd2 in regulating synaptic pruning rather than synapse formation. Drd2 also regulates LTD, a form of synaptic plasticity which includes some similar cellular/biochemical processes as synaptic pruning. We further demonstrate that Drd2 regulates synaptic pruning via cell-autonomous mechanisms involving activation of mTOR signaling. Deficits of Drd2-mediated synaptic pruning in the ACC during adolescence lead to hyper-glutamatergic function and anxiety-like behaviors in adulthood. Taken together, our results demonstrate important roles of Drd2 in cortical synaptic pruning.
Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing
Authors: Bhattacharya Saikat , Wang Suman , Reddy Divya , Shen Siyuan , Zhang Ying , Zhang Ning , Li Hua , Washburn Michael P. , Florens Laurence , Shi Yunyu , Workman Jerry L. , Li Fudong 
Published: November 2021

AbstractThe RNA recognition motif (RRM) binds to nucleic acids as well as proteins. More than one such domain is found in the pre-mRNA processing hnRNP proteins. While the mode of RNA recognition by RRMs is known, the molecular basis of their protein interaction remains obscure. Here we describe the mode of interaction between hnRNP L and LL with the methyltransferase SETD2. We demonstrate that for the interaction to occur, a leucine pair within a highly conserved stretch of SETD2 insert their side chains in hydrophobic pockets formed by hnRNP L RRM2. Notably, the structure also highlights that RRM2 can form a ternary complex with SETD2 and RNA. Remarkably, mutating the leucine pair in SETD2 also results in its reduced interaction with other hnRNPs. Importantly, the similarity that the mode of SETD2-hnRNP L interaction shares with other related protein-protein interactions reveals a conserved design by which splicing regulators interact with one another.
Optical deciphering of multinary chiral compound mixtures through organic reaction based chemometric chirality sensing
Authors: Hassan Diandra S. , Wolf Christian 
Published: November 2021

AbstractThe advances of high-throughput experimentation technology and chemometrics have revolutionized the pace of scientific progress and enabled previously inconceivable discoveries, in particular when used in tandem. Here we show that the combination of chirality sensing based on small-molecule optical probes that bind to amines and amino alcohols via dynamic covalent or click chemistries and powerful chemometric tools that achieve orthogonal data fusion and spectral deconvolution yields a streamlined multi-modal sensing protocol that allows analysis of the absolute configuration, enantiomeric composition and concentration of structurally analogous—and therefore particularly challenging—chiral target compounds without laborious and time-consuming physical separation. The practicality, high accuracy, and speed of this approach are demonstrated with complicated quaternary and octonary mixtures of varying chemical and chiral compositions. The advantages over chiral chromatography and other classical methods include operational simplicity, increased speed, reduced waste production, low cost, and compatibility with multiwell plate technology if high-throughput analysis of hundreds of samples is desired.
A versatile computational algorithm for time-series data analysis and machine-learning models
Authors: Chomiak Taylor , Rasiah Neilen P. , Molina Leonardo A. , Hu Bin , Bains Jaideep S. , Füzesi Tamás 
Published: November 2021

AbstractHere we introduce Local Topological Recurrence Analysis (LoTRA), a simple computational approach for analyzing time-series data. Its versatility is elucidated using simulated data, Parkinsonian gait, and in vivo brain dynamics. We also show that this algorithm can be used to build a remarkably simple machine-learning model capable of outperforming deep-learning models in detecting Parkinson’s disease from a single digital handwriting test.
The Swiss data cube, analysis ready data archive using earth observations of Switzerland
Authors: Chatenoux Bruno , Richard Jean-Philippe , Small David , Roeoesli Claudia , Wingate Vladimir , Poussin Charlotte , Rodila Denisa , Peduzzi Pascal , Steinmeier Charlotte , Ginzler Christian , Psomas Achileas , Schaepman Michael E. , Giuliani Gregory 
Published: November 2021

AbstractSince the opening of Earth Observation (EO) archives (USGS/NASA Landsat and EC/ESA Sentinels), large collections of EO data are freely available, offering scientists new possibilities to better understand and quantify environmental changes. Fully exploiting these satellite EO data will require new approaches for their acquisition, management, distribution, and analysis. Given rapid environmental changes and the emergence of big data, innovative solutions are needed to support policy frameworks and related actions toward sustainable development. Here we present the Swiss Data Cube (SDC), unleashing the information power of Big Earth Data for monitoring the environment, providing Analysis Ready Data over the geographic extent of Switzerland since 1984, which is updated on a daily basis. Based on a cloud-computing platform allowing to access, visualize and analyse optical (Sentinel-2; Landsat 5, 7, 8) and radar (Sentinel-1) imagery, the SDC minimizes the time and knowledge required for environmental analyses, by offering consistent calibrated and spatially co-registered satellite observations. SDC derived analysis ready data supports generation of environmental information, allowing to inform a variety of environmental policies with unprecedented timeliness and quality.
Albino mice with the point mutation at the tyrosinase locus show high cholesterol diet-induced NASH susceptibility
Authors: Kulathunga Kaushalya , Wakimoto Arata , Hiraishi Yukiko , Yadav Manoj Kumar , Gentleman Kyle , Warabi Eiji , Sakasai Tomoki , Miwa Yoshihiro , Mizuno Seiya , Takahashi Satoru , Hamada Michito 
Published: November 2021

AbstractNon-alcoholic fatty liver disease (NAFLD) constitutes a metabolic disorder with high worldwide prevalence and increasing incidence. The inflammatory progressive state, non-alcoholic steatohepatitis (NASH), leads to liver fibrosis and carcinogenesis. Here, we evaluated whether tyrosinase mutation underlies NASH pathophysiology. Tyrosinase point-mutated B6 (Cg)-Tyrc-2J/J mice (B6 albino) and C57BL/6J black mice (B6 black) were fed with high cholesterol diet (HCD) for 10 weeks. Normal diet-fed mice served as controls. HCD-fed B6 albino exhibited high NASH susceptibility compared to B6 black, a phenotype not previously reported. Liver injury occurred in approximately 50% of B6 albino from one post HCD feeding, with elevated serum alanine aminotransferase and aspartate aminotransferase levels. NASH was induced following 2 weeks in severe-phenotypic B6 albino (sB6), but B6 black exhibited no symptoms, even after 10 weeks. HCD-fed sB6 albino showed significantly higher mortality rate. Histological analysis of the liver revealed significant inflammatory cell and lipid infiltration and severe fibrosis. Serum lipoprotein analysis revealed significantly higher chylomicron and very low-density lipoprotein levels in sB6 albino. Moreover, significantly higher small intestinal lipid absorption and lower fecal lipid excretion occurred together with elevated intestinal NPC1L1 expression. As the tyrosinase point mutation represents the only genetic difference between B6 albino and B6 black, our work will facilitate the identification of susceptible genetic factors for NASH development and expand the understanding of NASH pathophysiology.
Novel phase distributions for large electronically beam-scanning reflectarrays
Authors: Sheikholeslami Ahad , Atlasbaf Zahra 
Published: November 2021

AbstractIn this paper, the hybrid combination of genetic algorithm and particle swarm optimization (GAPSO) is used to optimize the phase distribution (PD) of beam-scanning reflectarray. The GAPSO takes advantage of both conventional algorithms and it could cover their weaknesses. Two novel PDs are proposed in this paper which constant phase elements (CPEs) and ordinary elements (OEs) are two basic kinds of elements used in them. The phases of CPEs are fixed and it is not changed during beam scanning and only OEs’ phase could be adjusted to scan the main beam. In this work GAPSO and two novel PDs are applied to array factor’s PD of a 30 × 30 reflectarray antenna to displace the main beam electronically in the vertical plane from − 40° to 40°. Also, in these two novel PDs, 28.8% of total elements are selected as CPEs. In the first one with only CPEs, the phase of OEs (71.2% of total elements) could adjust, but in the second novel PD with CPEs and phase symmetry plane 35.5% of the total elements’ phase could be changed to scan the beam. Optimization results show that the novel PD and hybrid algorithm have appropriate performance in the electronically beam scanning of reflectarrays.
Readout for simple and precise analog acoustic impact initialization
Authors: Sotner Roman , Polak Ladislav , Jerabek Jan , Lahiri Abhirup , Jaikla Winai 
Published: November 2021

AbstractAn economic concept of acoustic shock wave sensing readout system for simple computer processing is introduced in this work. Its application can be found in precise initialization of the stopwatch from the starter sound, handclap or gun in competitive sport races but also in many other places. The proposed device consists of several low-cost commercially available components and it is powered by a 9 V battery. The proposed device reliably reacts on incoming acoustic shock wave by generation of explicit impulse having controllable duration. It significantly overcomes basic implementations using only a microphone and amplifier (generating parasitic burst instead of defined and distinct impulse) or systems allowing a limited number of adjustable features (gain and/or threshold of the comparator—our concept offers the adjustment of gain, cut-off frequency, threshold level and time duration of active state). In comparison with standard methods, the proposed approach simplifies and makes sensing device less expensive and universal for any powder-based starting gun (without necessity to adapt starting gun). The proposed device, among others, has the following features: impulse duration can be controlled from hundreds of μs up to 2.3 s, the gain range of linear part of processing from 6 to 40 dB and open-collector output compatible with 5 V TTL or 3.3 V CMOS logic. The initialization has been tested in the range from tens of centimeters up to four meters. In order to highlight the important spectral components, the spectral character of the signal can be optimally reduced by a low-pass filter. The quiescent power consumption of the designed simple analog circuit reaches 90 mW. Several use cases, response of the designed system on gunshot signature, talking, hand-clapping and hit on the sensing microphone, are studied and compared to each other. Simulation and experimental results confirm functionality of the realized system.
Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue
Authors: Ramirez-Sanchez Israel , Navarrete-Yañez Viridiana , Garate-Carrillo Alejandra , Lara-Hernandez Modesto , Espinosa-Raya Judith , Moreno-Ulloa Aldo , Gomez-Diaz Benjamin , Cedeño-Garcidueñas Ana Lilia , Ceballos Guillermo , Villarreal Francisco 
Published: November 2021

AbstractWe examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.
Water column structure influences long-distance latitudinal migration patterns and habitat use of bumphead sunfish Mola alexandrini in the Pacific Ocean
Authors: Chang Ching-Tsun , Chiang Wei-Chuan , Musyl Michael K. , Popp Brian N. , Lam Chi Hin , Lin Shian-Jhong , Watanabe Yuuki Y. , Ho Yuan-Hsing , Chen June-Ru 
Published: November 2021

AbstractSatellite-tracking of adult bumphead sunfish, Mola alexandrini, revealed long-distance latitudinal migration patterns covering thousands of kilometers. Horizontal and vertical movements of four bumphead sunfish off Taiwan were recorded with pop-up satellite archival tags in 2019–2020. Two individuals moved northward and traveled to Okinawa Island and Kyushu, Japan and two moved southwards; crossing the equator, to Papua New Guinea and New Caledonia. During daytime, bumphead sunfish descended below the thermocline and ascended to mixed layer depths (MLD) during nighttime. The N–S migrants, however, demonstrated different habitat utilization patterns. Instead of using prevailing currents, the northward movements of sunfish cohorts exhibited extensive use of mesoscale eddies. Fish in anticyclonic eddies usually occupied deeper habitats whereas those in cyclonic eddies used near-surface habitats. On northward excursions, fish spent most of their time in regions with high dissolved oxygen concentrations. Southward movement patterns were associated with major currents and thermal stratification of the water column. In highly stratified regions, fish stayed below the thermocline and frequently ascended to MLD during daytime either to warm muscles or repay oxygen debts. These results for bumphead sunfish present important insights into different habitat use patterns and the ability to undergo long-distance migrations over varying spatial-temporal scales and features.