bluuebunny/crossref_metadata_2025_split huggingface dataset:
Out-of-sequence skeletal growth causing oscillatory zoning in arc olivines
Authors: Salas Pablo , Ruprecht Philipp , Hernández Laura , Rabbia Osvaldo 
Published: July 2021

AbstractPrimitive olivines from the monogenetic cones Los Hornitos, Central-South Andes, preserve dendritic, skeletal, and polyhedral growth textures. Consecutive stages of textural maturation occur along compositional gradients where high Fo–Ni cores of polyhedral olivines (Fo92.5, Ni ~3500 ppm) contrast with the composition of dendritic olivines (Fo < 91.5, Ni < 3000 ppm), indicating sequential nucleation. Here we present a new growth model for oscillatory Fo–Ni olivine zoning that contrasts with the standard interpretation of continuous, sequential core-to-rim growth. Olivine grows rapidly via concentric addition of open-structured crystal frames, leaving behind compositional boundary layers that subsequently fill-in with Fo–Ni-depleted olivine, causing reversals. Elemental diffusion modeling reveals growth of individual crystal frames and eruption at the surface occurred over 3.5–40 days. Those timescales constrain magma ascent rates of 40–500 m/h (0.011 to 0.14 m/s) from the deep crust. Compared to ocean island basalts, where dendritic and skeletal olivines have been often described, magmas erupted at arc settings, experiencing storage and degassing, may lack such textures due to fundamentally different ascent histories.
Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome
Authors: Wang Li , Chen Kangjing , Chen Zhucheng 
Published: July 2021

AbstractChromatin remodeler ALC1 (amplification in liver cancer 1) is crucial for repairing damaged DNA. It is autoinhibited and activated by nucleosomal epitopes. However, the mechanisms by which ALC1 is regulated remain unclear. Here we report the crystal structure of human ALC1 and the cryoEM structure bound to the nucleosome. The structure shows the macro domain of ALC1 binds to lobe 2 of the ATPase motor, sequestering two elements for nucleosome recognition, explaining the autoinhibition mechanism of the enzyme. The H4 tail competes with the macro domain for lobe 2-binding, explaining the requirement for this nucleosomal epitope for ALC1 activation. A dual-arginine-anchor motif of ALC1 recognizes the acidic pocket of the nucleosome, which is critical for chromatin remodeling in vitro. Together, our findings illustrate the structures of ALC1 and shed light on its regulation mechanisms, paving the way for the discovery of drugs targeting ALC1 for the treatment of cancer.
Genetic dissection identifies Necdin as a driver gene in a mouse model of paternal 15q duplications
Authors: Tamada Kota , Fukumoto Keita , Toya Tsuyoshi , Nakai Nobuhiro , Awasthi Janak R. , Tanaka Shinji , Okabe Shigeo , Spitz François , Saitow Fumihito , Suzuki Hidenori , Takumi Toru 
Published: July 2021

AbstractMaternally inherited duplication of chromosome 15q11-q13 (Dup15q) is a pathogenic copy number variation (CNV) associated with autism spectrum disorder (ASD). Recently, paternally derived duplication has also been shown to contribute to the development of ASD. The molecular mechanism underlying paternal Dup15q remains unclear. Here, we conduct genetic and overexpression-based screening and identify Necdin (Ndn) as a driver gene for paternal Dup15q resulting in the development of ASD-like phenotypes in mice. An excess amount of Ndn results in enhanced spine formation and density as well as hyperexcitability of cortical pyramidal neurons. We generate 15q dupΔNdn mice with a normalized copy number of Ndn by excising its one copy from Dup15q mice using a CRISPR-Cas9 system. 15q dupΔNdn mice do not show ASD-like phenotypes and show dendritic spine dynamics and cortical excitatory-inhibitory balance similar to wild type animals. Our study provides an insight into the role of Ndn in paternal 15q duplication and a mouse model of paternal Dup15q syndrome.
Display of the human mucinome with defined O-glycans by gene engineered cells
Authors: Nason Rebecca , Büll Christian , Konstantinidi Andriana , Sun Lingbo , Ye Zilu , Halim Adnan , Du Wenjuan , Sørensen Daniel M. , Durbesson Fabien , Furukawa Sanae , Mandel Ulla , Joshi Hiren J. , Dworkin Leo Alexander , Hansen Lars , David Leonor , Iverson Tina M. , Bensing Barbara A. , Sullam Paul M. , Varki Ajit , Vries Erik de , de Haan Cornelis A. M. , Vincentelli Renaud , Henrissat Bernard , Vakhrushev Sergey Y. , Clausen Henrik , Narimatsu Yoshiki 
Published: July 2021

AbstractMucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids. Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins. Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells. Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
Metagenomic and metatranscriptomic profiling of Lactobacillus casei Zhang in the human gut
Authors: Wang Jicheng , Zhang Jiachao , Liu Wenjun , Zhang Heping , Sun Zhihong 
Published: July 2021

AbstractLittle is known about the replication and dynamic transcription of probiotics during their “passenger” journey in the human GI tract, which has therefore limited the understanding of their probiotic mechanisms. Here, metagenomic and metatranscriptomic sequencing was used to expose the in vivo expression patterns of the probiotic Lactobacillus casei Zhang (LcZ), which was compared with its in vitro growth transcriptomes, as well as the dynamics of the indigenous microbiome response to probiotic consumption. Extraction of the strain-specific reads revealed that replication and transcripts from the ingested LcZ were increased, while those from the resident L. casei strains remained unchanged. Mapping of all sequencing reads to LcZ genome showed that gene expression in vitro and in vivo differed dramatically. Approximately 39% of mRNAs and 45% of sRNAs of LcZ well-expressed were repressed after ingestion into human gut. The expression of ABC transporter genes and amino acid metabolism genes was induced at day 14 of ingestion, and genes for sugar and SCFA metabolism were activated at day 28 of ingestion. Expression of rli28c sRNA with peaked expression during the in vitro stationary phase was also activated in the human gut; this sRNA repressed LcZ growth and lactic acid production in vitro. However, the response of the human gut microbiome to LcZ was limited and heterogeneous. These findings implicate the ingested probiotic has to change its transcription patterns to survive and adapt in the human gut, and the time-dependent activation patterns indicate highly dynamic cross-talk between the probiotic and human gut microbes.
A Bayesian approach to extracting free-energy profiles from cryo-electron microscopy experiments
Authors: Giraldo-Barreto Julian , Ortiz Sebastian , Thiede Erik H. , Palacio-Rodriguez Karen , Carpenter Bob , Barnett Alex H. , Cossio Pilar 
Published: July 2021

AbstractCryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule’s conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles. In this work, we propose the cryo-BIFE method (cryo-EM Bayesian Inference of Free-Energy profiles), which uses a path collective variable to extract free-energy profiles and their uncertainties from cryo-EM images. We test the framework on several synthetic systems where the imaging parameters and conditions were controlled. We found that for realistic cryo-EM environments and relevant biomolecular systems, it is possible to recover the underlying free energy, with the pose accuracy and SNR as crucial determinants. We then use the method to study the conformational transitions of a calcium-activated channel with real cryo-EM particles. Interestingly, we recover not only the most probable conformation (used to generate a high-resolution reconstruction of the calcium-bound state) but also a metastable state that corresponds to the calcium-unbound conformation. As expected for turnover transitions within the same sample, the activation barriers are on the order of $$k_BT$$

k
B

T

. We expect our tool for extracting free-energy profiles from cryo-EM images to enable more complete characterization of the thermodynamic ensemble of biomolecules.
Surface model of the human red blood cell simulating changes in membrane curvature under strain
Authors: Kuchel Philip W. , Cox Charles D. , Daners Daniel , Shishmarev Dmitry , Galvosas Petrik 
Published: July 2021

AbstractWe present mathematical simulations of shapes of red blood cells (RBCs) and their cytoskeleton when they are subjected to linear strain. The cell surface is described by a previously reported quartic equation in three dimensional (3D) Cartesian space. Using recently available functions in Mathematica to triangularize the surfaces we computed four types of curvature of the membrane. We also mapped changes in mesh-triangle area and curvatures as the RBCs were distorted. The highly deformable red blood cell (erythrocyte; RBC) responds to mechanically imposed shape changes with enhanced glycolytic flux and cation transport. Such morphological changes are produced experimentally by suspending the cells in a gelatin gel, which is then elongated or compressed in a custom apparatus inside an NMR spectrometer. A key observation is the extent to which the maximum and minimum Principal Curvatures are localized symmetrically in patches at the poles or equators and distributed in rings around the main axis of the strained RBC. Changes on the nanometre to micro-meter scale of curvature, suggest activation of only a subset of the intrinsic mechanosensitive cation channels, Piezo1, during experiments carried out with controlled distortions, which persist for many hours. This finding is relevant to a proposal for non-uniform distribution of Piezo1 molecules around the RBC membrane. However, if the curvature that gates Piezo1 is at a very fine length scale, then membrane tension will determine local curvature; so, curvatures as computed here (in contrast to much finer surface irregularities) may not influence Piezo1 activity. Nevertheless, our analytical methods can be extended address these new mechanistic proposals. The geometrical reorganization of the simulated cytoskeleton informs ideas about the mechanism of concerted metabolic and cation-flux responses of the RBC to mechanically imposed shape changes.
Shear-induced chemical segregation in a Fe-based bulk metallic glass at room temperature
Authors: Louzguine-Luzgin D. V. , Trifonov A. S. , Ivanov Yu. P. , Lu A. K. A. , Lubenchenko A. V. , Greer A. L. 
Published: July 2021

AbstractShear-induced segregation, by particle size, is known in the flow of colloids and granular media, but is unexpected at the atomic level in the deformation of solid materials, especially at room temperature. In nanoscale wear tests of an Fe-based bulk metallic glass at room temperature, without significant surface heating, we find that intense shear localization under a scanned indenter tip can induce strong segregation of a dilute large-atom solute (Y) to planar regions that then crystallize as a Y-rich solid solution. There is stiffening of the material, and the underlying chemical and structural effects are characterized by transmission electron microscopy. The key influence of the soft Fe–Y interatomic interaction is investigated by ab-initio calculation. The driving force for the induced segregation, and its mechanisms, are considered by comparison with effects in other sheared media.
Ganoderma lucidum promotes sleep through a gut microbiota-dependent and serotonin-involved pathway in mice
Authors: Yao Chunyan , Wang Zhiyuan , Jiang Huiyong , Yan Ren , Huang Qianfei , Wang Yin , Xie Hui , Zou Ying , Yu Ying , Lv Longxian 
Published: July 2021

AbstractGanoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative tranquilizing effects. However, the component of G. lucidum that promotes sleep has not been clearly identified. Here, the effect and mechanism of the acidic part of the alcohol extract of G. lucidum mycelia (GLAA) on sleep were studied in mice. Administration of 25, 50 and 100 mg/kg GLAA for 28 days promoted sleep in pentobarbital-treated mice by shortening sleep latency and prolonging sleeping time. GLAA administration increased the levels of the sleep-promoting neurotransmitter 5-hydroxytryptamine and the Tph2, Iptr3 and Gng13 transcripts in the sleep-regulating serotonergic synapse pathway in the hypothalamus during this process. Moreover, GLAA administration reduced lipopolysaccharide and raised peptidoglycan levels in serum. GLAA-enriched gut bacteria and metabolites, including Bifidobacterium, Bifidobacterium animalis, indole-3-carboxylic acid and acetylphosphate were negatively correlated with sleep latency and positively correlated with sleeping time and the hypothalamus 5-hydroxytryptamine concentration. Both the GLAA sleep promotion effect and the altered faecal metabolites correlated with sleep behaviours disappeared after gut microbiota depletion with antibiotics. Our results showed that GLAA promotes sleep through a gut microbiota-dependent and serotonin-associated pathway in mice.
Phylogeography of Prunus armeniaca L. revealed by chloroplast DNA and nuclear ribosomal sequences
Authors: Li Wen-Wen , Liu Li-Qiang , Zhang Qiu-Ping , Zhou Wei-Quan , Fan Guo-Quan , Liao Kang 
Published: July 2021

AbstractTo clarify the phytogeography of Prunus armeniaca L., two chloroplast DNA fragments (trnL-trnF and ycf1) and the nuclear ribosomal DNA internal transcribed spacer (ITS) were employed to assess genetic variation across 12 P. armeniaca populations. The results of cpDNA and ITS sequence data analysis showed a high the level of genetic diversity (cpDNA: HT = 0.499; ITS: HT = 0.876) and a low level of genetic differentiation (cpDNA: FST = 0.1628; ITS: FST = 0.0297) in P. armeniaca. Analysis of molecular variance (AMOVA) revealed that most of the genetic variation in P. armeniaca occurred among individuals within populations. The value of interpopulation differentiation (NST) was significantly higher than the number of substitution types (GST), indicating genealogical structure in P. armeniaca. P. armeniaca shared genotypes with related species and may be associated with them through continuous and extensive gene flow. The haplotypes/genotypes of cultivated apricot populations in Xinjiang, North China, and foreign apricot populations were mixed with large numbers of haplotypes/genotypes of wild apricot populations from the Ili River Valley. The wild apricot populations in the Ili River Valley contained the ancestral haplotypes/genotypes with the highest genetic diversity and were located in an area considered a potential glacial refugium for P. armeniaca. Since population expansion occurred 16.53 kyr ago, the area has provided a suitable climate for the population and protected the genetic diversity of P. armeniaca.
Uncertainty of chemical status in surface waters
Authors: Loga Małgorzata , Przeździecki Karol 
Published: July 2021

AbstractThis article addresses the issue of estimating Pom—the probability of misclassifying the chemical status confidence of a water body status assessment. The main concerns of the authors were chemical quality elements with concentrations in water bodies which are close to or even smaller than the limit of quantification (LOQ). Their values must be set to half of this limit to calculate the mean value. This procedure leads to very low standard deviation values and unrealistic values of Pom for chemical indicators. In turn, this may lead to the false conclusion that not only is the chemical status good but also that this status assessment is perfect. Therefore, for a more reliable calculation of Pom, the authors suggested a modified calculation in which the value of half the LOQ for calculating the mean value was kept, but zero as the concentration value for the standard deviation calculation was adopted. The proposed modification has been applied to the Hierarchical Approach procedure for Pom estimation of the chemical status of Polish rivers and lakes. The crucial finding is that current chemical status assessments may be incorrect in the case of approximately 25% of river water bodies and 30% of lake water bodies categorised as good, and 20% of both types of water bodies classified as below good.
Plasma concentrations of granulocyte colony-stimulating factor (G-CSF) in patients with substance use disorders and comorbid major depressive disorder
Authors: Galván Sandra Torres , Flores-López María , Romero-Sanchiz Pablo , Requena-Ocaña Nerea , Porras-Perales Oscar , Nogueira-Arjona Raquel , Mayoral Fermín , Araos Pedro , Serrano Antonia , Muga Roberto , Pavón Francisco Javier , García-Marchena Nuria , de Fonseca Fernando Rodríguez 
Published: July 2021

AbstractGranulocyte colony–stimulating factor (G-CSF) has raised much interest because of its role in cocaine addiction in preclinical models. We explored the plasma concentrations of G-CSF in patients diagnosed with substance use disorder (SUD) and highly comorbid psychiatric disorders. In particular, we investigated the association between G-CSF concentrations and comorbid major depressive disorder (MDD) in patients with cocaine and alcohol use disorders (CUD and AUD, respectively). Additionally, patients with MDD but not SUD were included in the study. Three hundred and eleven participants were enrolled in this exploratory study: 136 control subjects, 125 patients with SUD (SUD group) from outpatient treatment programs for cocaine (N = 60, cocaine subgroup) and alcohol (N = 65, alcohol subgroup), and 50 patients with MDD but not SUD (MDD group) from primary-care settings. Participants were assessed based on DSM-IV-TR criteria, and a blood sample was collected to examine the plasma concentrations of G-CSF. G-CSF concentrations were negatively correlated with age in the entire sample (r = − 0.233, p < 0.001) but not in the patients with MDD. G-CSF concentrations were lower in patients with SUD than in controls (p < 0.05), specifically in the cocaine subgroup (p < 0.05). Patients with SUD and comorbid MDD had lower G-CSF concentrations than patients with SUD but not comorbid MDD or controls (p < 0.05). In contrast, patients with MDD but not SUD showed no differences compared with their controls. The negative association between G-CSF concentrations and age in the sample was not observed in patients with MDD. G-CSF concentrations were decreased in patients with SUD and comorbid MDD but not in patients with MDD. Therefore, G-CSF may be useful to improve the stratification of patients with dual diagnosis seeking treatment. Further investigation is needed to explore the impact of sex and type of drug on the expression of G-CSF.
A kinome-centered CRISPR-Cas9 screen identifies activated BRAF to modulate enzalutamide resistance with potential therapeutic implications in BRAF-mutated prostate cancer
Authors: Palit Sander A. L. , van Dorp Jeroen , Vis Daniel , Lieftink Cor , Linder Simon , Beijersbergen Roderick , Bergman Andries M. , Zwart Wilbert , van der Heijden Michiel S. 
Published: July 2021

AbstractResistance to drugs targeting the androgen receptor (AR) signaling axis remains an important challenge in the treatment of prostate cancer patients. Activation of alternative growth pathways is one mechanism used by cancer cells to proliferate despite treatment, conferring drug resistance. Through a kinome-centered CRISPR-Cas9 screen in CWR-R1 prostate cancer cells, we identified activated BRAF signaling as a determinant for enzalutamide resistance. Combined pharmaceutical targeting of AR and MAPK signaling resulted in strong synergistic inhibition of cell proliferation. The association between BRAF activation and enzalutamide resistance was confirmed in two metastatic prostate cancer patients harboring activating mutations in the BRAF gene, as both patients were unresponsive to enzalutamide. Our findings suggest that co-targeting of the MAPK and AR pathways may be effective in patients with an activated MAPK pathway, particularly in patients harboring oncogenic BRAF mutations. These results warrant further investigation of the response to AR inhibitors in BRAF-mutated prostate tumors in clinical settings.
Experimental investigation of optically controlled topological transition in bismuth-mica structure
Authors: Zaitsev Anton , Zykov Dmitry , Demchenko Petr , Novoselov Mikhail , Nazarov Ravshanjon , Masyukov Maxim , Makarova Elena , Tukmakova Anastasiia , Asach Aleksei , Novotelnova Anna , Kablukova Natallya , Khodzitsky Mikhail 
Published: July 2021

AbstractThe hyperbolic materials are strongly anisotropic media with a permittivity/permeability tensor having diagonal components of different sign. They combine the properties of dielectric and metal-like media and are described with hyperbolic isofrequency surfaces in wave-vector space. Such media may support unusual effects like negative refraction, near-field radiation enhancement and nanoscale light confinement. They were demonstrated mainly for microwave and infrared frequency ranges on the basis of metamaterials and natural anisotropic materials correspondingly. For the terahertz region, the tunable hyperbolic media were demonstrated only theoretically. This paper is dedicated to the first experimental demonstration of an optically tunable terahertz hyperbolic medium in 0.2–1.0 THz frequency range. The negative phase shift of a THz wave transmitted through the structure consisting of 40 nm (in relation to THz wave transmitted through substrate) to 120 nm bismuth film (in relation to both THz waves transmitted through substrate and air) on 21 µm mica substrate is shown. The optical switching of topological transition between elliptic and hyperbolic isofrequency contours is demonstrated for the effective structure consisting of 40 nm Bi on mica. For the case of 120 nm Bi on mica, the effective permittivity is only hyperbolic in the studied range. It is shown that the in-plane component of the effective permittivity tensor may be positive or negative depending on the frequency of THz radiation and continuous-wave optical pumping power (with a wavelength of 980 nm), while the orthogonal one is always positive. The proposed optically tunable structure may be useful for application in various fields of the modern terahertz photonics.