bluuebunny/crossref_metadata_2025 huggingface dataset:
CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2
Authors: Hoffmann Donata , Corleis Björn , Rauch Susanne , Roth Nicole , Mühe Janine , Halwe Nico Joel , Ulrich Lorenz , Fricke Charlie , Schön Jacob , Kraft Anna , Breithaupt Angele , Wernike Kerstin , Michelitsch Anna , Sick Franziska , Wylezich Claudia , Hoffmann Bernd , Thran Moritz , Thess Andreas , Mueller Stefan O. , Mettenleiter Thomas C. , Petsch Benjamin , Dorhoi Anca , Beer Martin
Published: June 2021

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. The efficacy of spike encoding mRNA vaccines (CVnCoV and CV2CoV) against the ancestral strain and the VOC B.1.351 was tested in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice develop elevated SARS-CoV-2 RBD-specific antibody and neutralization titers which are readily detectable, but significantly reduced against VOC B.1.351. The mRNA vaccines fully protect from disease and mortality caused by either viral strain. SARS-CoV-2 remains undetected in swabs, lung, or brain in these groups. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV and CV2CoV show complete disease protection against the novel VOC B.1.351 in our studies.
SETBP1 accumulation induces P53 inhibition and genotoxic stress in neural progenitors underlying neurodegeneration in Schinzel-Giedion syndrome
Authors: Banfi Federica , Rubio Alicia , Zaghi Mattia , Massimino Luca , Fagnocchi Giulia , Bellini Edoardo , Luoni Mirko , Cancellieri Cinzia , Bagliani Anna , Di Resta Chiara , Maffezzini Camilla , Ianielli Angelo , Ferrari Maurizio , Piazza Rocco , Mologni Luca , Broccoli Vania , Sessa Alessandro
Published: June 2021

The investigation of genetic forms of juvenile neurodegeneration could shed light on the causative mechanisms of neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome caused by mutations in the SETBP1 gene, inducing the accumulation of its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here we introduce a human SGS model that displays disease-relevant phenotypes. We show that SGS neural progenitors exhibit aberrant proliferation, deregulation of oncogenes and suppressors, unresolved DNA damage, and resistance to apoptosis. Mechanistically, we demonstrate that high SETBP1 levels inhibit P53 function through the stabilization of SET, which in turn hinders P53 acetylation. We find that the inheritance of unresolved DNA damage in SGS neurons triggers the neurodegenerative process that can be alleviated either by PARP-1 inhibition or by NAD + supplementation. These results implicate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis.
Molecular separation of ions from aqueous solutions using modified nanocomposites
Authors: Ghaforinejad Hamed , Marjani Azam , Mazaheri Hossein , Joshaghani Ali Hassani
Published: June 2021

Herein, two novel porous polymer matrix nanocomposites were synthesized and used as adsorbents for heavy metal uptake. Methacrylate-modified large mesoporous silica FDU-12 was incorporated in poly(methyl methacrylate) matrix through an in-situ polymerization approach. For another, amine-modified FDU-12 was composited with Nylon 6,6 via a facile solution blending protocol. Various characterization techniques including small-angle X-ray scattering, FTIR spectroscopy, field emission-scanning electron microscopy, transmission electron microscopy, porosimetry, and thermogravimetric analysis have been applied to investigate the physical and chemical properties of the prepared materials. The adsorption of Pb(II) onto the synthesized nanocomposites was studied in a batch system. After study the effect of solution pH, adsorbent amount, contact time, and initial concentration of metal ion on the adsorption process, kinetic studies were also conducted. For both adsorbents, the Langmuir and pseudo-second-order models were found to be the best fit to predict isotherm and kinetics of adsorption. Based on the Langmuir model, maximum adsorption capacities of 105.3 and 109.9 mg g−1were obtained for methacrylate-modified FDU-12/poly(methyl methacrylate) and amine-modified FDU-12/Nylon 6,6, respectively.
Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders
Authors: Area-Gomez Estela , Larrea D. , Yun T. , Xu Y. , Hupf J. , Zandkarimi F. , Chan R. B. , Mitsumoto H.
Published: June 2021

Motor neuron disorders (MND) include a group of pathologies that affect upper and/or lower motor neurons. Among them, amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle weakness, with fatal outcomes only in a few years after diagnosis. On the other hand, primary lateral sclerosis (PLS), a more benign form of MND that only affects upper motor neurons, results in life-long progressive motor dysfunction. Although the outcomes are quite different, ALS and PLS present with similar symptoms at disease onset, to the degree that both disorders could be considered part of a continuum. These similarities and the lack of reliable biomarkers often result in delays in accurate diagnosis and/or treatment. In the nervous system, lipids exert a wide variety of functions, including roles in cell structure, synaptic transmission, and multiple metabolic processes. Thus, the study of the absolute and relative concentrations of a subset of lipids in human pathology can shed light into these cellular processes and unravel alterations in one or more pathways. In here, we report the lipid composition of longitudinal plasma samples from ALS and PLS patients initially, and after 2 years following enrollment in a clinical study. Our analysis revealed common aspects of these pathologies suggesting that, from the lipidomics point of view, PLS and ALS behave as part of a continuum of motor neuron disorders.
Drosophila tubulin polymerization promoting protein mutants reveal pathological correlates relevant to human Parkinson’s disease
Authors: Xie Jing , Chen Shuting , Bopassa Jean C. , Banerjee Swati
Published: June 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no known cure. PD is characterized by locomotion deficits, nigrostriatal dopaminergic neuronal loss, mitochondrial dysfunctions and formation of α-Synuclein aggregates. A well-conserved and less understood family of Tubulin Polymerization Promoting Proteins (TPPP) is also implicated in PD and related disorders, where TPPP exists in pathological aggregates in neurons in patient brains. However, there are no in vivo studies on mammalian TPPP to understand the genetics and neuropathology linking TPPP aggregation or neurotoxicity to PD. Recently, we discovered the onlyDrosophilahomolog of human TPPP named Ringmaker (Ringer). Here, we report that adultringermutants display progressive locomotor disabilities, reduced lifespan and neurodegeneration. Importantly, our findings reveal that Ringer is associated with mitochondria andringermutants have mitochondrial structural damage and dysfunctions. Adultringermutants also display progressive loss of dopaminergic neurons. Together, these phenotypes ofringermutants recapitulate some of the salient features of human PD patients, thus allowing us to utilizeringermutants as a fly model relevant to PD, and further explore its genetic and molecular underpinnings to gain insights into the role of human TPPP in PD.
Conveyance of texture signals along a rat whisker
Authors: Oladazimi Maysam , Putelat Thibaut , Szalai Robert , Noda Kentaro , Shimoyama Isao , Champneys Alan , Schwarz Cornelius
Published: June 2021

Neuronal activities underlying a percept are constrained by the physics of sensory signals. In the tactile sense such constraints are frictional stick–slip events, occurring, amongst other vibrotactile features, when tactile sensors are in contact with objects. We reveal new biomechanical phenomena about the transmission of these microNewton forces at the tip of a rat’s whisker, where they occur, to the base where they engage primary afferents. Using high resolution videography and accurate measurement of axial and normal forces at the follicle, we show that the conical and curved rat whisker acts as a sign-converting amplification filter for moment to robustly engage primary afferents. Furthermore, we present a model based on geometrically nonlinear Cosserat rod theory and a friction model that recreates the observed whole-beam whisker dynamics. The model quantifies the relation between kinematics (positions and velocities) and dynamic variables (forces and moments). Thus, only videographic assessment of acceleration is required to estimate forces and moments measured by the primary afferents. Our study highlights how sensory systems deal with complex physical constraints of perceptual targets and sensors.
The effects of camel chymosin and Withania coagulans extract on camel and bovine milk cheeses
Authors: Mbye Mustapha , Mohamed Huda , Raziq Abdul , Kamal-Eldin Afaf
Published: June 2021

Withania coagulans (W. coagulans) extract and camel chymosin have aspartic protease capable of coagulating milk for cheese production. This study investigated the quality of camel and bovine milk cheeses coagulated using Withania extracts, came chymosin, and their mixture in two experiments. In Experiment (1), a factorial design with four factors (W. coagulans, camel chymosin, incubation time, and incubation temperature) was performed. The effect of these factors on cheese’s yield and hardness were assessed. An enzyme concentration corresponding to a 36 µg/L of milk of W. coagulans, 50 IMCU/L of camel chymosin, holding time of 4 h, and incubation temperature of 60 °C provided the optimal textural hardness for both camel and bovine milk cheeses. Seven treatments were analyzed in experiment (2) were analyzed for physicochemical properties, yield, and sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGEitation). The results showed that pure Withania extract exhibited the lower coagulating effect resulting in cheeses with low yield, hardness, fat, protein, and total solids. The SDS-PAGE electropherograms of camel cheese showed several low molecular weight bands as compared to bovine cheese. This phenomenon is due to excessive proteolysis in camel cheese, which we believed is caused by the presence of endogenous enzymes.
Anatomy of an extinction revealed by molecular fossils spanning OAE2
Authors: Forkner R. M. , Dahl J. , Fildani A. , Barbanti S. M. , Yurchenko I. A. , Moldowan J. M.
Published: June 2021

The Cenomanian–Turonian mass extinction (Oceanic Anoxic Event 2-OAE2) was a period of profound ecological change that is recorded in the sedimentary record in many locations around the globe. In this study, we provide a new and detailed account of repetitive changes in water column ecology by analyzing the organic geochemical record preserved within the OAE2 section of the Greenhorn Formation, Western Interior Seaway (WIS) of North America. Results from this study provide evidence that OAE2 in the WIS was the result of the cumulative effect of reoccurring environmental stresses rather than a single massive event. During OAE2, extreme variations in biotic composition occurred erratically over periods of several thousands of years as revealed by molecular fossil (biomarker) abundances and distributions calibrated to sedimentation rates. These cycles of marine productivity decline almost certainly had follow-on effects through the ecosystem and likely contributed to the Cenomanian–Turonian mass extinction. While the causes behind organic productivity cycling are yet unproven, we postulate that they may have been linked to repeated episodes of volcanic activity. Catastrophic volcanism and related CO2 outgassing have been interpreted as main drivers for OAE2, though this study provides new evidence that repetitive, punctuated environmental stresses were also important episodes within the anatomy of OAE2. Following OAE2, these cycles of productivity decline disappeared, and the WIS returned to conditions comparable to pre-OAE2 levels.
Transcriptome analysis insight into ethylene metabolism and pectinase activity of apricot (Prunus armeniaca L.) development and ripening
Authors: Xu Min , Zhou Weiquan , Geng Wenjuan , Zhao Shirong , Pan Yan , Fan Guoquan , Zhang Shikui , Wang Yatong , Liao Kang
Published: June 2021

Ethylene metabolism is very important for climacteric fruit, and apricots are typical climacteric fruit. The activity of pectinase is closely related to fruit firmness, which further affects fruit quality. To better understand ethylene metabolism, pectinase activity and their molecular regulation mechanisms during the development and ripening of apricot fruit, ethylene metabolism, pectinase activity and the “Luntaibaixing” apricot fruit transcriptome were analyzed at different developmental stages. Ethylene metabolic precursors, enzyme activities and ethylene release increased during fruit development and ripening, with significant differences between the ripening stage and other stages (P < 0.05). Fruit firmness decreased significantly from the S1 to S5 stages, and polygalacturonase, pectin methylesterase, and pectin lyase activities were significantly higher in the S5 stage than in other stages. RNA sequencing (RNA-seq) analysis of fruit resulted in the identification of 22,337 unigenes and 6629 differentially expressed genes (DEGs) during development and ripening, of which 20,989 unigenes are annotated in public protein databases. In functional enrichment analysis, DEGs among the three stages were found to be involved in plant hormone signal transduction. Four key genes affecting ethylene metabolism, six key ethylene signal transduction genes and seven genes related to pectinase in apricot fruit were identified by KEGG pathway analysis. By RNA-sequencing, we not only clarified the molecular mechanism of ethylene metabolism during the ripening of "Luntaibaixing" apricot fruit but also provided a theoretical basis for understanding pectin metabolism in apricot fruit.
Bandgap atomistic calculations on hydrogen-passivated GeSi nanocrystals
Authors: Cojocaru Ovidiu , Lepadatu Ana-Maria , Nemnes George Alexandru , Stoica Toma , Ciurea Magdalena Lidia
Published: June 2021

We present a detailed study regarding the bandgap dependence on diameter and composition of spherical Ge-rich GexSi1−x nanocrystals (NCs). For this, we conducted a series of atomistic density functional theory (DFT) calculations on H-passivated NCs of Ge-rich GeSi random alloys, with Ge atomic concentration varied from 50 to 100% and diameters ranging from 1 to 4 nm. As a result of the dominant confinement effect in the DFT computations, a composition invariance of the line shape of the bandgap diameter dependence was found for the entire computation range, the curves being shifted for different Ge concentrations by ΔE(eV) = 0.651(1 − x). The shape of the dependence of NCs bandgap on the diameter is well described by a power function 4.58/d1.25 for 2–4 nm diameter range, while for smaller diameters, there is a tendency to limit the bandgap to a finite value. By H-passivation of the NC surface, the effect of surface states near the band edges is excluded aiming to accurately determine the NC bandgap. The number of H atoms necessary to fully passivate the spherical GexSi1−x NC surface reaches the total number atoms of the Ge + Si core for smallest NCs and still remains about 25% from total number of atoms for bigger NC diameters of 4 nm. The findings are in line with existing theoretical and experimental published data on pure Ge NCs and allow the evaluation of the GeSi NCs behavior required by desired optical sensor applications for which there is a lack of DFT simulation data in literature.
Evaluation of emotional arousal level and depression severity using voice-derived sound pressure change acceleration
Authors: Shinohara Shuji , Toda Hiroyuki , Nakamura Mitsuteru , Omiya Yasuhiro , Higuchi Masakazu , Takano Takeshi , Saito Taku , Tanichi Masaaki , Boku Shuken , Mitsuyoshi Shunji , So Mirai , Yoshino Aihide , Tokuno Shinichi
Published: June 2021

In this research, we propose a new index of emotional arousal level using sound pressure change acceleration, called the emotional arousal level voice index (EALVI), and investigate the relationship between this index and depression severity. First, EALVI values were calculated from various speech recordings in the interactive emotional dyadic motion capture database, and the correlation with the emotional arousal level of each voice was examined. The resulting correlation coefficient was 0.52 (n = 10,039, p < 2.2 × 10−16). We collected a total of 178 datasets comprising 10 speech phrases and the Hamilton Rating Scale for Depression (HAM-D) score of outpatients with major depression at the Ginza Taimei Clinic (GTC) and the National Defense Medical College (NDMC) Hospital. The correlation coefficients between the EALVI and HAM-D scores were − 0.33 (n = 88, p = 1.8 × 10−3) and − 0.43 (n = 90, p = 2.2 × 10−5) at the GTC and NDMC, respectively. Next, the dataset was divided into “no depression” (HAM-D < 8) and “depression” groups (HAM-D ≥ 8) according to the HAM-D score. The number of patients in the “no depression” and “depression” groups were 10 and 78 in the GTC data, and 65 and 25 in the NDMC data, respectively. There was a significant difference in the mean EALVI values between the two groups in both the GTC and NDMC data (p = 8.9 × 10−3, Cliff’s delta = 0.51 and p = 1.6 × 10−3; Cliff’s delta = 0.43, respectively). The area under the curve of the receiver operating characteristic curve when discriminating both groups by EALVI was 0.76 in GTC data and 0.72 in NDMC data. Indirectly, the data suggest that there is some relationship between emotional arousal level and depression severity.
Mechanical strength and hydrostatic testing of VIVO adhesive in sutureless microsurgical anastomoses: an ex vivo study
Authors: Heitzer Marius , Brockhaus Julia , Kniha Kristian , Merkord Felix , Peters Florian , Hölzle Frank , Goloborodko Evgeny , Modabber Ali
Published: June 2021

Conventional anastomoses with interrupted sutures are challenging and inevitably associated with trauma to the vessel walls. The goal of this study was to evaluate a novel alternative adhesive-based suture-free anastomosis technique that uses an intraluminal stent. Overall, 120 porcine coronary vessels were analyzed in an ex vivo model and were examined for their mechanical (n = 20 per cohort) and hydrostatic strength (n = 20 per cohort). Anastomoses were made using the novel VIVO adhesive with an additional intraluminal nitinol stent and was compared to interrupted suture anastomosis and to native vessels. Sutureless anastomoses withstood pressures 299 ± 4.47 [mmHg] comparable to native vessels. They were performed significantly faster 553.8 ± 82.44 [sec] (p ≤ 0.001) and withstood significantly higher pressures (p ≤ 0.001) than sutured anastomoses. We demonstrate that the adhesive-based anastomosis can also resist unphysiologically high longitudinal tensile forces with a mean of 1.33 [N]. Within the limitations of an in vitro study adhesive-based suture-free anastomosis technique has the biomechanical potential to offer a seamless alternative to sutured anastomosis because of its stability, and faster handling. In vivo animal studies are needed to validate outcomes and confirm safety.
Superfluid density and collective modes of fermion superfluid in dice lattice
Authors: Wu Yu-Rong , Zhang Xiao-Fei , Liu Chao-Fei , Liu Wu-Ming , Zhang Yi-Cai
Published: June 2021

The superfluid properties of attractive Hubbard model in dice lattice are investigated. It is found that three superfluid order parameters increase as the interaction increases. When the filling factor falls into the flat band, due to the infinite large density of states, the resultant superfluid order parameters are proportional to interaction strength, which is in striking contrast with the exponentially small counterparts in usual superfluid (or superconductor). When the interaction is weak, and the filling factor is near the bottom of the lowest band (or the top of highest band), the superfluid density is determined by the effective mass of the lowest (or highest) single-particle band. When the interaction is strong and filling factor is small, the superfluid density is inversely proportional to interaction strength, which is related to effective mass of tightly bound pairs. In the strong interaction limit and finite filling, the asymptotic behaviors of superfluid density can be captured by a parabolic function of filling factor. Furthermore, when the filling is in flat band, the superfluid density shows a logarithmic singularity as the interaction approaches zero. In addition, there exist three undamped collective modes for strong interactions. The lowest excitation is gapless phonon, which is characterized by the total density oscillations. The two others are gapped Leggett modes, which correspond relative density fluctuations between sublattices. The collective modes are also reflected in the two-particle spectral functions by sharp peaks. Furthermore, it is found that the two-particle spectral functions satisfy an exact sum-rule, which is directly related to the filling factor (or density of particle). The sum-rule of the spectral functions may be useful to distinguish between the hole-doped and particle-doped superfluid (superconductor) in experiments.
Throttling process of a supersonic cascade studied by high-frequency response pressure and high-speed schlieren
Authors: Wang Ziao , Chang Juntao , Hou Wenxin , Yu Daren
Published: June 2021

In this study, a single-channel supersonic cascade model is investigated experimentally at a freestream Mach number of 2.4 to obtain a better understanding of the flow field evolution during the throttling process. A flap is placed at the channel exit to choke the flow linearly. Measurements include 1-kHz schlieren imaging and 10-kHz simultaneous fast-response wall pressure. Three stages, namely attached flow, separated flow, and oscillatory flow, are identified in the throttling process. The joint time–frequency analysis and wall pressure spectrum contour exhibit the time evolution and spatial distribution of the pressure fluctuation. With the increase in backpressure, the pressure fluctuation in the low-frequency shock oscillation range of 40–400 Hz on the suction surface located in the separated flow gradually enhances. The power spectral, coherence, and phase analyses of the schlieren images describe the dominant oscillation structure and its relationship with other regions. During the separated flow, the pressure change in the subsonic separated region first lead to a change in the state of the separated shear layer, after which the shock waves in the shock train, move. The oscillatory flow is a process wherein the upstream shock wave oscillates, causing the entire downstream channel to fluctuate.
The investigation of the volatile metabolites of lung cancer from the microenvironment of malignant pleural effusion
Authors: Chen Ke-Cheng , Tsai Shih-Wei , Zhang Xiang , Zeng Chian , Yang Hsiao-Yu
Published: June 2021

For malignant pleural effusions, pleural fluid cytology is a diagnostic method, but sensitivity is low. The pleural fluid contains metabolites directly released from cancer cells. The objective of this study was to diagnose lung cancer with malignant pleural effusion using the volatilomic profiling method. We recruited lung cancer patients with malignant pleural effusion and patients with nonmalignant diseases with pleural effusion as controls. We analyzed the headspace air of the pleural effusion by gas chromatography-mass spectrometry. We used partial least squares discriminant analysis (PLS-DA) to identify metabolites and the support vector machine (SVM) to establish the prediction model. We split data into a training set (80%) and a testing set (20%) to validate the accuracy. A total of 68 subjects were included in the final analysis. The PLS-DA showed high discrimination with an R2 of 0.95 and Q2 of 0.58. The accuracy of the SVM in the test set was 0.93 (95% CI 0.66, 0.998), the sensitivity was 83%, the specificity was 100%, and kappa was 0.85, and the area under the receiver operating characteristic curve was 0.96 (95% CI 0.86, 1.00). Volatile metabolites of pleural effusion might be used in patients with cytology-negative pleural effusion to rule out malignancy.
Evaluation of different grafting materials for alveolar cleft repair in the context of orthodontic tooth movement in rats
Authors: Möhlhenrich Stephan Christian , Kniha Kristian , Magnuska Zuzanna , Hermanns-Sachweh Benita , Gremse Felix , Hölzle Frank , Danesh Gholamreza , Modabber Ali
Published: June 2021

To minimize the postoperative risks posed by grafting autologous transplants for cleft repair, efforts are being made to improve grafting materials for use as potential alternatives. The aim of this study was to compare the bone graft quality of different bone substitutes including the gold standard autografts during the healing processes after cleft repair in the context of orthodontic treatment. In 21 Wistar rats, a complete, continuity-interrupting cleft was created. After 4 weeks, cleft repair was performed using autografts from the hips’ ischial tuberosity, human xenografts, or synthetic bone substitutes [beta-tricalcium phosphate (β-TCP)/hydroxyapatite (HA)]. After another 4 weeks, the first molar movement was initiated in the reconstructed jaw for 8 weeks. The bone remodeling was analyzed in vivo using micro-computed tomography (bone mineral density and bone volume fraction) and histology (new bone formation). All the grafting materials were statistically different in bone morphology, which changed during the treatment period. The β-TCP/HA substitute demonstrated less resorption compared to the autologous and xenogeneic/human bone, and the autografts led to a stronger reaction in the surrounding bone. Histologically, the highest level of new bone formation was found in the human xenografts, and the lowest was found in the β-TCP/HA substitute. The differences between the two bone groups and the synthetic materials were statistically significant. Autografts were confirmed to be the gold standard in cleft repair with regard to graft integration. However, parts of the human xenograft seemed comparable to the autografts. Thus, this substitute could perhaps be used as an alternative after additional tissue-engineered modification.
Linear and nonlinear investigations for the adsorption of paracetamol and metformin from water on acid-treated clay
Authors: Elamin Mohamed R. , Abdulkhair Babiker Y. , Algethami Faisal K. , Khezami L.
Published: June 2021

Natural clays are considered a safe, low-cost, and sound sorbent for some pharmaceutical and body care products from water. Metformin (MF) and paracetamol (PA) are of the most consumable drugs worldwide. A portion of natural clay was treated with distilled water, and another part was treated with hydrochloric acid. The water-treated clay (WTC) and the acid-treated clay (ATC) were characterized by scanning electron microscopy-energy dispersive spectroscopy, X-ray diffraction, Fourier transforms infrared spectroscopy, and nitrogen adsorption isotherm. Batch experiments were employed to investigate the influence of contact time and solution parameters on the adsorption of PA and MF on WTC and ATC. 30 min attained the equilibrium for all sorbent-sorbate systems. Both sorbents fitted the pseudo-second-order kinetic model with a preference to the nonlinear fitting, and the mechanism of adsorption partially fitted the liquid-film diffusion model. The PA and MF adsorption on WTC and ATC fitted the Freundlich model in preference to nonlinear fitting. The adsorption of pollutants on both sorbents was spontaneous, exothermic, and physisorption in nature. Even at low concentrations, both WTC and ATC showed efficiency above 80% in removing PA and MF from tab water, groundwater, and Red seawater. These findings nominated natural clay as an alternative to the costly nanomaterials as sorbents for removing pharmaceutical contaminants from water.
Complete plastomes of six species of Wikstroemia (Thymelaeaceae) reveal paraphyly with the monotypic genus Stellera
Authors: He Liefen , Zhang Yonghong , Lee Shiou Yih
Published: June 2021

Wikstroemia (Thymelaeaceae) is a diverse genus that extends from Asia to Australia and has been recorded on the Hawaiian Islands. Despite its medicinal properties and resource utilization in pulp production, genetic studies of the species in this important genus have been neglected. In this study, the plastome sequences of six species of Wikstroemia were sequenced and analysed. The plastomes ranged in size between 172,610 bp (W. micrantha) and 173,697 bp (W. alternifolia) and exhibited a typical genome structure consisting of a pair of inverted repeat (IR) regions separated by a large single-copy (LSC) region and a small single-copy (SSC) region. The six plastomes were similar in the 138 or 139 genes predicted, which consisted of 92 or 93 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The overall GC contents were identical (36.7%). Comparative genomic analyses were conducted with the inclusion of two additional published species of Wikstroemia in which the sequence divergence and expansion of IRs in the plastomes were determined. When compared to the coding sequences (CDSs) of Aquilaria sinensis, five genes, namely, rpl2, rps7, rps18, ycf1 and ycf2, indicated positive selection in W. capitata. The plastome-based phylogenetic analysis inferred that Wikstroemia in its current state is paraphyletic to Stellera chamaejasme, while the ITS-based tree analyses could not properly resolve the phylogenetic relationship between Stellera and Wikstroemia. This finding rekindled interest in the proposal to synonymize Stellera with Wikstroemia, which was previously proposed but rejected due to taxonomic conflicts. Nevertheless, this study provides valuable genomic information to aid in the taxonomic implications and phylogenomic reconstruction of Thymelaeaceae.
Extended JAZ degron sequence for plant hormone binding in jasmonate co-receptor of tomato SlCOI1-SlJAZ
Authors: Saito Rina , Hayashi Kengo , Nomoto Haruna , Nakayama Misuzu , Takaoka Yousuke , Saito Hiroaki , Yamagami Souhei , Muto Toshiya , Ueda Minoru
Published: June 2021

(+)-7-iso-Jasmonoyl-l-isoleucine (JA-Ile) is a lipid-derived phytohormone implicated in plant development, reproduction, and defense in response to pathogens and herbivorous insects. All these effects are instigated by the perception of JA-Ile by the COI1-JAZ co-receptor in the plant body, which in Arabidopsis thaliana is profoundly influenced by the short JAZ degron sequence (V/L)P(Q/I)AR(R/K) of the JAZ protein. Here, we report that SlJAZ-SlCOI1, the COI1-JAZ co-receptor found in the tomato plant, relies on the extended JAZ degron sequence (V/L)P(Q/I)AR(R/K)XSLX instead of the canonical JAZ degron. This finding illuminates our understanding of the mechanism of ligand perception by JA-Ile in this plant, and will inform both efforts to improve it by genetic modification of the SlCOI1-SlJAZ co-receptor, and the development of the synthetic agonists/antagonists.
Biophysical properties of a tau seed
Authors: Hou Zhiqiang , Chen Dailu , Ryder Bryan D. , Joachimiak Lukasz A.
Published: June 2021

Pathogenesis of tauopathies involves conversion of tau monomer into pathological tau conformers that serve as templates to recruit native tau into growing assemblies. Small soluble tau seeds have been proposed to drive pathological tau assembly in vitro, in cells and in vivo. We have previously described the isolation of monomeric pathogenic tau seeds derived from recombinant samples and tauopathy tissues but in-depth biophysical characterization of these species has not been done. Here we describe a chromatographic method to isolate recombinant soluble tau seeds derived from heparin treatment. We used biochemical and biophysical approaches to show that the seeds are predominantly monomeric and have the capacity to nucleate aggregation of inert forms of tau in vitro and in cells. Finally, we used crosslinking mass spectrometry to identify the topological changes in tau as it converts from an inert state to a pathogenic seed. Future studies will reveal the relationship between soluble seeds and structural polymorphs derived from tauopathies to help diagnose and develop therapeutics targeting specific tauopathies.
Identification of natural product modulators of Merkel cell carcinoma cell growth and survival
Authors: Smith Emily A. , Hill Natasha T. , Gelb Tara , Garman Khalid A. , Goncharova Ekaterina I. , Bokesch Heidi R. , Kim Chang-Kwon , Wendt Karen L. , Cichewicz Robert H. , Gustafson Kirk R. , Brownell Isaac , Henrich Curtis J.
Published: June 2021

Merkel cell carcinoma (MCC) is a rare, but aggressive skin cancer the incidence of which has increased significantly in recent years. The majority of MCCs have incorporated Merkel cell polyomavirus (VP-MCC) while the remainder are virus-negative (VN-MCC). Although a variety of therapeutic options have shown promise in treating MCC, there remains a need for additional therapeutics as well as probes for better understanding MCC. A high-throughput screening campaign was used to assess the ability of > 25,000 synthetic and natural product compounds as well as > 20,000 natural product extracts to affect growth and survival of VN-MCC and VP-MCC cell lines. Sixteen active compounds were identified that have mechanisms of action reported in the literature along with a number of compounds with unknown mechanisms. Screening results with pure compounds suggest a range of potential targets for MCC including DNA damage, inhibition of DNA or protein synthesis, reactive oxygen species, and proteasome inhibition as well as NFκB inhibition while also suggesting the importance of zinc and/or copper binding. Many of the active compounds, particularly some of the natural products, have multiple reported targets suggesting that this strategy might be a particularly fruitful approach. Processing of several active natural product extracts resulted in the identification of additional MCC-active compounds. Based on these results, further investigations focused on natural products sources, particularly of fungal origin, are expected to yield further potentially useful modulators of MCC.
Association of depressive disorder with biochemical and anthropometric indices in adult men and women
Authors: Lee Bum Ju
Published: June 2021

Depression is a common psychiatric disorder. Although many risk factors for depression have been reported, the associations of biochemical and anthropometric indices with depressive disorder remain unclear. The objective of this study was to assess whether there are significant associations of depressive disorder with biochemical and obesity indices. This study was based on data from the Korea National Health and Nutrition Examination Survey from 2007 to 2018, and logistic regression was performed to examine the association of depression with biochemical and obesity indices. A total of 33,993 subjects were included in the analyses. Study subjects consisted of 13,178 men in the control group (mean age of 51.12 years), 509 men in the depression group (53.67), 18,279 women in the control group (50.5), and 2027 women in the depression group (55.39). Among men, the depression group was significantly more likely to have a lower height and weight than the control group. Compared to the control group, the depression group was more likely to have higher triglyceride levels and tended to have lower hematocrit and blood urea nitrogen (BUN) levels. Among women, the depression group was more likely to have higher triglyceride, aspartate aminotransferase (AST), BUN, and creatinine levels and lower high-density lipoprotein cholesterol (HDL-C), hematocrit, and red blood cell counts. Several biochemical and anthropometric indices used in this study were associated with depressive disorder, but these associations may differ according to sex.
Parental selection for growth and early-life low stocking density increase the female-to-male ratio in European sea bass
Authors: Geffroy Benjamin , Gesto Manuel , Clota Fréderic , Aerts Johan , Darias Maria J. , Blanc Marie-Odile , Ruelle François , Allal François , Vandeputte Marc
Published: June 2021

In European sea bass (Dicentrarchus labrax), as in many other fish species, temperature is known to influence the sex of individuals, with more males produced at relatively high temperatures. It is however unclear to what extent growth or stress are involved in such a process, since temperature is known to influence both growth rate and cortisol production. Here, we designed an experiment aiming at reducing stress and affecting early growth rate. We exposed larvae and juveniles originating from both captive and wild parents to three different treatments: low stocking density, food supplemented with tryptophan and a control. Low stocking density and tryptophan treatment respectively increased and decreased early growth rate. Each treatment influenced the stress response depending on the developmental stage, although no clear pattern regarding the whole-body cortisol concentration was found. During sex differentiation, fish in the low-density treatment exhibited lower expression of gr1, gr2, mr, and crf in the hypothalamus when compared to the control group. Fish fed tryptophan displayed lower crf in the hypothalamus and higher level of serotonin in the telencephalon compared to controls. Overall, fish kept at low density produced significantly more females than both control and fish fed tryptophan. Parents that have been selected for growth for three generations also produced significantly more females than parents of wild origin. Our findings did not allow to detect a clear effect of stress at the group level and rather point out a key role of early sexually dimorphic growth rate in sex determination.
Identification of novel QTLs for grain fertility and associated traits to decipher poor grain filling of basal spikelets in dense panicle rice
Authors: Sekhar Sudhanshu , Kumar Jitendra , Mohanty Soumya , Mohanty Niharika , Panda Rudraksh Shovan , Das Swagatika , Shaw Birendra Prasad , Behera Lambodar
Published: June 2021

High grain number is positively correlated with grain yield in rice, but it is compromised because of poor filling of basal spikelets in dense panicle bearing numerous spikelets. The phenomenon that turns the basal spikelets of compact panicle sterile in rice is largely unknown. In order to understand the factor(s) that possibly determines such spikelet sterility in compact panicle cultivars, QTLs and candidate genes were identified for spikelet fertility and associated traits like panicle compactness, and ethylene production that significantly influences the grain filling using recombinant inbred lines developed from a cross between indica rice cultivars, PDK Shriram (compact, high spikelet number) and Heera (lax, low spikelet number). Novel QTLs, qSFP1.1, qSFP3.1, and qSFP6.1 for spikelet fertility percentage; qIGS3.2 and qIGS4.1 for panicle compactness; and qETH1.2, qETH3.1, and qETH4.1 for ethylene production were consistently identified in both kharif seasons of 2017 and 2018. The comparative expression analysis of candidate genes like ERF3, AP2-like ethylene-responsive transcription factor, EREBP, GBSS1, E3 ubiquitin-protein ligase GW2, and LRR receptor-like serine/threonine-protein kinase ERL1 associated with identified QTLs revealed their role in poor grain filling of basal spikelets in a dense panicle. These candidate genes thus could be important for improving grain filling in compact-panicle rice cultivars through biotechnological interventions.
Water quality drives the regional patterns of an algal metacommunity in interconnected lakes
Authors: Kim Min Sung , Ahn Seok Hyun , Jeong In Jae , Lee Tae Kwon
Published: June 2021

The metacommunity approach provides insights into how the biological communities are assembled along the environmental variations. The current study presents the importance of water quality on the metacommunity structure of algal communities in six river-connected lakes using long-term (8 years) monitoring datasets. Elements of metacommunity structure were analyzed to evaluate whether water quality structured the metacommunity across biogeographic regions in the riverine ecosystem. The algal community in all lakes was found to exhibit Clementsian or quasi-Clementsian structure properties such as significant turnover, grouped and species sorting indicating that the communities responded to the environmental gradient. Reciprocal averaging clearly classified the lakes into three clusters according to the geographical region in river flow (upstream, midstream, and downstream). The dispersal patterns of algal genera, including Aulacoseira, Cyclotella, Stephanodiscus, and Chlamydomonas across the regions also supported the spatial-based classification results. Although conductivity, chemical oxygen demand, and biological oxygen demand were found to be important variables (loading > |0.5|) of the entire algal community assembly, water temperature was a critical factor in water quality associated with community assembly in each geographical area. These results support the notion that the structure of algal communities is strongly associated with water quality, but the relative importance of variables in structuring algal communities differed by geological regions.
Low-dose aspirin for primary and secondary prevention of cardiovascular events in Denmark 1998–2018
Authors: Christensen Mikkel B. , Jimenez-Solem Espen , Ernst Martin. T. , Schmidt Morten , Pottegård Anton , Grove Erik L.
Published: June 2021

Randomised controlled trials have shown a neutral or even unfavourable risk–benefit balance of aspirin for primary prevention of cardiovascular events. Using Danish nationwide registries, we investigated aspirin use and associated risks during the past two decades (1998–2018). We linked individual patient data on repeated aspirin redemptions with registered hospital ICD-10 diagnoses of atherosclerotic cardiovascular disease and bleedings. The prevalence of aspirin use among 1.1 million Danish adults fluctuated over the 20-year study period peaking in 2008 with 8.5% (5.4% primary prevention) and dropping to 5.1% (3.1% primary prevention) in 2018. Aspirin use showed strong age dependency, and 21% of individuals > 80 years were treated with aspirin for primary prevention in 2018. Medication adding to bleeding risk was used concurrently by 21% of all aspirin users in 2018. The incidence of major bleedings were similar with primary and secondary prevention aspirin use and highest in elderly (2 per 100 patient years among individuals > 80 years in 2018). In conclusion, low-dose aspirin use for primary prevention of cardiovascular events remains prevalent. The widespread use of aspirin, especially among older adults, and substantial concomitant use of medications adding to bleeding risk warrant increased focus on discontinuation of inappropriate aspirin use.
A yeast-optimized single-cell transcriptomics platform elucidates how mycophenolic acid and guanine alter global mRNA levels
Authors: Urbonaite Guste , Lee Jimmy Tsz Hang , Liu Ping , Parada Guillermo E. , Hemberg Martin , Acar Murat
Published: June 2021

Stochastic gene expression leads to inherent variability in expression outcomes even in isogenic single-celled organisms grown in the same environment. The Drop-Seq technology facilitates transcriptomic studies of individual mammalian cells, and it has had transformative effects on the characterization of cell identity and function based on single-cell transcript counts. However, application of this technology to organisms with different cell size and morphology characteristics has been challenging. Here we present yeastDrop-Seq, a yeast-optimized platform for quantifying the number of distinct mRNA molecules in a cell-specific manner in individual yeast cells. Using yeastDrop-Seq, we measured the transcriptomic impact of the lifespan-extending compound mycophenolic acid and its epistatic agent guanine. Each treatment condition had a distinct transcriptomic footprint on isogenic yeast cells as indicated by distinct clustering with clear separations among the different groups. The yeastDrop-Seq platform facilitates transcriptomic profiling of yeast cells for basic science and biotechnology applications.
Structure-based insights into evolution of rhodopsins
Authors: Zabelskii Dmitrii , Dmitrieva Natalia , Volkov Oleksandr , Shevchenko Vitaly , Kovalev Kirill , Balandin Taras , Soloviov Dmytro , Astashkin Roman , Zinovev Egor , Alekseev Alexey , Round Ekaterina , Polovinkin Vitaly , Chizhov Igor , Rogachev Andrey , Okhrimenko Ivan , Borshchevskiy Valentin , Chupin Vladimir , Büldt Georg , Yutin Natalia , Bamberg Ernst , Koonin Eugene , Gordeliy Valentin
Published: June 2021

Rhodopsins, most of which are proton pumps generating transmembrane electrochemical proton gradients, span all three domains of life, are abundant in the biosphere, and could play a crucial role in the early evolution of life on earth. Whereas archaeal and bacterial proton pumps are among the best structurally characterized proteins, rhodopsins from unicellular eukaryotes have not been well characterized. To fill this gap in the current understanding of the proton pumps and to gain insight into the evolution of rhodopsins using a structure-based approach, we performed a structural and functional analysis of the light-driven proton pump LR (Mac) from the pathogenic fungus Leptosphaeria maculans. The first high-resolution structure of fungi rhodopsin and its functional properties reveal the striking similarity of its membrane part to archaeal but not to bacterial rhodopsins. We show that an unusually long N-terminal region stabilizes the protein through direct interaction with its extracellular loop (ECL2). We compare to our knowledge all available structures and sequences of outward light-driven proton pumps and show that eukaryotic and archaeal proton pumps, most likely, share a common ancestor.
Atomic-state-dependent screening model for hot and warm dense plasmas
Authors: Zhou Fuyang , Qu Yizhi , Gao Junwen , Ma Yulong , Wu Yong , Wang Jianguo
Published: June 2021

An ion embedded in warm/hot dense plasmas will greatly alter its microscopic structure and dynamics, as well as the macroscopic radiation transport properties of the plasmas, due to complicated many-body interactions with surrounding particles. Accurate theoretically modeling of such kind of quantum many-body interactions is essential but very challenging. In this work, we propose an atomic-state-dependent screening model for treating the plasmas with a wide range of temperatures and densities, in which the contributions of three-body recombination processes are included. We show that the electron distributions around an ion are strongly correlated with the ionic state studied due to the contributions of three-body recombination processes. The feasibility and validation of the proposed model are demonstrated by reproducing the experimental result of the line-shift of hot-dense plasmas as well as the classical molecular dynamic simulations of moderately coupled ultra-cold neutral plasmas. Our work opens a promising way to treat the screening effect of hot and warm dense plasma, which is a bottleneck of those extensive studies in high-energy-density physics, such as atomic processes in plasma, plasma spectra and radiation transport properties, among others.