bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative efficacy of surgical approaches to disease modification in Parkinson disease
Authors: Rahimpour Shervin , Zhang Su-Chun , Vitek Jerrold L. , Mitchell Kyle T. , Turner Dennis A.
Published: March 2022

Parkinson’s disease (PD) may optimally be treated with a disease-modifying therapy to slow progression. We compare data underlying surgical approaches proposed to impart disease modification in PD: (1) cell transplantation therapy with stem cell-derived dopaminergic neurons to replace damaged cells; (2) clinical trials of growth factors to promote survival of existing dopaminergic neurons; (3) subthalamic nucleus deep brain stimulation early in the course of PD; and (4) abdominal vagotomy to lower risk of potential disease spread from gut to brain. Though targeted to engage potential mechanisms of PD these surgical approaches remain experimental, indicating the difficulty in translating therapeutic concepts into clinical practice. The choice of outcome measures to assess disease modification separate from the symptomatic benefit will be critical to evaluate the effect of the disease-modifying intervention on long-term disease burden, including imaging studies and clinical rating scales, i.e., Unified Parkinson Disease Rating Scale. Therapeutic interventions will require long follow-up times (i.e., 5–10 years) to analyze disease modification compared to symptomatic treatments. The promise of invasive, surgical treatments to achieve disease modification through mechanistic approaches has been constrained by the reality of translating these concepts into effective clinical trials.
Circuit quantization with time-dependent magnetic fields for realistic geometries
Authors: Riwar R.-P. , DiVincenzo D. P.
Published: March 2022

Quantum circuit theory has become a powerful and indispensable tool to predict the dynamics of superconducting circuits. Surprisingly however, the question of how to properly account for a time-dependent driving via external magnetic fields has hardly been addressed so far. Here, we derive a general recipe to construct a low-energy Hamiltonian, taking as input only the circuit geometry and the solution of the external magnetic fields. We find that the interplay of geometry and field distribution leads to a much richer circuit dynamics than commonly anticipated, already in devices as simple as the superconducting quantum interference device (SQUID). These dynamics can be captured by assigning negative, time-dependent or even momentarily singular capacitances to the Josephson junctions. Negative capacitances give rise to a strong enhancement of the qubit relaxation rates, while time-dependent capacitances lead to a finite Berry phase.
Quantum walks of two correlated photons in a 2D synthetic lattice
Authors: Esposito Chiara , Barros Mariana R. , Durán Hernández Andrés , Carvacho Gonzalo , Di Colandrea Francesco , Barboza Raouf , Cardano Filippo , Spagnolo Nicolò , Marrucci Lorenzo , Sciarrino Fabio
Published: March 2022

Quantum walks represent paradigmatic quantum evolutions, enabling powerful applications in the context of topological physics and quantum computation. They have been implemented in diverse photonic architectures, but the realization of two-particle dynamics on a multidimensional lattice has hitherto been limited to continuous-time evolutions. To fully exploit the computational capabilities of quantum interference it is crucial to develop platforms handling multiple photons that propagate across multidimensional lattices. Here, we report a discrete-time quantum walk of two correlated photons in a two-dimensional lattice, synthetically engineered by manipulating a set of optical modes carrying quantized amounts of transverse momentum. Mode-couplings are introduced via the polarization-controlled diffractive action of thin geometric-phase optical elements. The entire platform is compact, efficient, scalable, and represents a versatile tool to simulate quantum evolutions on complex lattices. We expect that it will have a strong impact on diverse fields such as quantum state engineering, topological quantum photonics, and Boson Sampling.
Phase-field simulations of vortex chirality manipulation in ferroelectric thin films
Authors: Liu Di , Wang Jing , Jafri Hasnain Mehdi , Wang Xueyun , Shi Xiaoming , Liang Deshan , Yang Chao , Cheng Xingwang , Huang Houbing
Published: March 2022

The ferroelectric chiral vortex domains are highly desirable for the application of data storage devices with low-energy consumption and high-density integration. However, the controllable switching of vortex chirality remains a challenge in the current ferroelectric community. Utilizing phase-field simulations, we investigate the vortex domain evolution and chirality formation in BiFeO3 thin films. By applying local surface charge or electric field, we demonstrate that the vorticity and the polarity can be manipulated by the initial bi-domain arrangement and the external field with different directions, respectively. By exchanging the domain arrangements, the opposite chirality can be obtained. Importantly, the topological vortex domain is retained after removing the external field. The vortex chirality can be switched reversibly with high reproducibility, which is beneficial to fatigue tolerance of the material in the operation. These results provide theoretical guidance for manipulating the vortex chirality in ferroelectric films.
Adult stress exposure blunts dopamine system hyperresponsivity in a neurodevelopmental rodent model of schizophrenia
Authors: Rincón-Cortés Millie , Grace Anthony A.
Published: March 2022

Stress is a major risk factor for the development of both schizophrenia and depression, and comorbidity between the two is common in schizoaffective disorders. However, the effects of stress exposure (i.e. chronic mild stress-CMS) on depression-related phenotypes in a neurodevelopmental model relevant to schizophrenia (i.e. methylazoxymethanol acetate—MAM) have yet to be explored and could provide insight into shared mechanisms of disease. To this end, we combined the prenatal MAM model with adult CMS exposure and explored the resultant pathophysiology using the social approach test (SAT), immobility in the forced swim test (FST) and amphetamine-induced hyperlocomotion (AIH) as depression- and schizophrenia-related endophenotypes and performed extracellular recordings of ventral tegmental area (VTA) DA neurons. MAM rats exhibited a reduction in social approach and increased VTA DA neuron activity compared to SAL rats or CMS groups. Separate cohorts of MAM animals were subjected to FST and AIH testing (counterbalanced order) or FST only. CMS groups exhibited increased FST immobility. Post-FST, both MAM groups (MAM-CON, MAM-CMS) exhibited blunted locomotor response to amphetamine compared with their SAL counterparts exposed to the same tests. Post-FST, MAM rats exhibited comparable VTA population activity to SAL rats, and CMS groups exhibited attenuated VTA population activity. Apomorphine administration results were consistent with the model suggesting that reductions in VTA DA neuron activity in MAM rats following FST exposure resulted from over-excitation, or depolarization block. These data suggest stress-induced DA downregulation in MAM rats, as FST exposure was sufficient to block the DA hyperresponsivity phenotype.
Heavy metals in leathers, artificial leathers, and textiles in the context of quality and safety of use
Authors: Bielak Elżbieta , Marcinkowska Ewa
Published: March 2022

The article presents research findings on the content of arsenic, cadmium, chromium, copper, lead, and zinc in extracts from leathers, artificial leathers intended for footwear components, and textiles. After extracting the metals using an artificial acidic sweat solution, their contents were quantitatively determined by atomic absorption spectrometry. In the cotton textiles, the metal contents were in accordance with the OEKO-TEX limits, while regarding the artificial leathers, only the acrylic knit fur had a too high chromium content (1.1 mg/kg) as compared with the requirements of theSTANDARD 100 by OEKO-TEXfor products intended for children (< 1.0 mg/kg). The chromium content in lining and upper leather (> 228.0 mg/kg) exceeds the limits for children’s products (< 2.0 mg/kg), but also the less restrictive ones for other products (< 200.0 mg/kg). Regarding the other metals, the leathers met the OEKO-TEX requirements. Approved materials may have elevated heavy metal contents, as demonstrated for chromium. The presence of heavy metals in too large amounts in products is a serious problem due to their allergenic and toxic effect. Therefore, action should be taken aimed at more effective detection and elimination of such products from markets and at reducing the use of chemicals containing harmful metals in manufacturing processes.
Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity
Authors: DeStefanis Rebecca A. , Kratz Jeremy D. , Olson Autumn M. , Sunil Aishwarya , DeZeeuw Alyssa K. , Gillette Amani A. , Sha Gioia C. , Johnson Katherine A. , Pasch Cheri A. , Clipson Linda , Skala Melissa C. , Deming Dustin A.
Published: March 2022

Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardized method to assess therapeutic response and identify subpopulation heterogeneity. There are multiple factors unique to organoid culture that could affect how therapeutic response and MDCO heterogeneity are assessed. Here we describe an analysis of nearly 3500 individual MDCOs where individual organoid morphologic tracking was performed. Change in MDCO diameter was assessed in the presence of control media or targeted therapies. Individual organoid tracking was identified to be more sensitive to treatment response than well-level assessment. The impact of different generations of mice of the same genotype, different regions of the colon, and organoid specific characteristics including baseline size, passage number, plating density, and location within the matrix were examined. Only the starting size of the MDCO altered the subsequent growth. These results were corroborated using ~ 1700 patient-derived cancer organoids (PDCOs) isolated from 19 patients. Here we establish organoid culture parameters for individual organoid morphologic tracking to determine therapeutic response and growth/response heterogeneity for translational studies.
Kinetics of LYVE-1-positive M2-like macrophages in developing and repairing dental pulp in vivo and their pro-angiogenic activity in vitro
Authors: Kieu Thoai Quoc , Tazawa Kento , Kawashima Nobuyuki , Noda Sonoko , Fujii Mayuko , Nara Keisuke , Hashimoto Kentaro , Han Peifeng , Okiji Takashi
Published: March 2022

Tissue-resident macrophages expressing lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) are found in multiple tissues and organs. We aimed to evaluate the dynamics and biological functions of LYVE-1+ macrophages in dental pulp during post-injury tissue remodeling. Immunofluorescence staining of mouse embryos revealed that LYVE-1+ macrophages colonized dental pulp before birth. In mature rat molar dental pulp, LYVE-1+ macrophages were the main subset of macrophages expressing CD163, an M2 marker, and were distributed throughout the tissue. In response to dental pulp injury induced by cavity preparation, LYVE-1+ macrophages quickly disappeared from the affected area of the pulp and gradually repopulated during the wound healing process. RAW264.7 mouse macrophages cultured with a mixture of macrophage colony-stimulating factor, interleukin-4, and dexamethasone increased LYVE-1 expression, whereas lipopolysaccharide-stimulation decreased LYVE-1 expression. Enforced expression of Lyve1 in RAW264.7 cells resulted in increased mRNA expression of matrix metalloproteinase 2 (Mmp2), Mmp9, and vascular endothelial growth factor A (Vegfa). Lyve1-expressing macrophages promoted the migration and tube formation of human umbilical vein endothelial cells. In conclusion, LYVE-1+ tissue-resident M2-like macrophages in dental pulp showed dynamism in response to pulp injury, and possibly play an important role in angiogenesis during wound healing and tissue remodeling.
Estimation of lung cancer deaths attributable to indoor radon exposure in upper northern Thailand
Authors: Somsunun Kawinwut , Prapamontol Tippawan , Pothirat Chaicharn , Liwsrisakun Chalerm , Pongnikorn Donsuk , Fongmoon Duriya , Chantara Somporn , Wongpoomchai Rawiwan , Naksen Warangkana , Autsavapromporn Narongchai , Tokonami Shinji
Published: March 2022

Radon exposure is the second leading cause of lung cancer, after smoking. In upper northern Thailand (UNT), lung cancer incidence was frequently reported by Thailand National Cancer Institute. Besides smoking, radon exposure may also influence the high lung cancer incidence in this region. Indoor radon concentrations were measured in 192 houses in eight provinces of UNT. Indoor radon concentrations ranged from 11 to 405 Bq m−3 and estimated annual effective dose ranged from 0.44 to 12.18 mSv y−1. There were significant differences in indoor radon concentrations between the houses of lung cancer cases and healthy controls (p = 0.033). We estimated that 26% of lung cancer deaths in males and 28% in females were attributable to indoor radon exposure in this region. Other factors influencing indoor radon levels included house characteristics and ventilation. The open window-to-wall ratio was negatively associated with indoor radon levels (B = −0.69, 95% CI −1.37, −0.02) while the bedroom location in the house and building material showed no association. Indoor radon hence induced the fractal proportion of lung cancer deaths in UNT.
Effects of Apolipoprotein E polymorphism on carotid intima-media thickness, incident myocardial infarction and incident stroke
Authors: Pitchika Anitha , Markus Marcello Ricardo Paulista , Schipf Sabine , Teumer Alexander , Van der Auwera Sandra , Nauck Matthias , Dörr Marcus , Felix Stephan , Grabe Hans-Jörgen , Völzke Henry , Ittermann Till
Published: March 2022

The Apolipoprotein E (APOE) gene polymorphism (rs429358 and rs7412) shows a well-established association with lipid profiles, but its effect on cardiovascular disease is still conflicting. Therefore, we examined the association of different APOE alleles with common carotid artery intima-media thickness (CCA-IMT), carotid plaques, incident myocardial infarction (MI) and stroke. We analyzed data from 3327 participants aged 20–79 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 14.5 years. Linear, logistic, and Cox-regression models were used to assess the associations of the APOE polymorphism with CCA-IMT, carotid plaques, incident MI and stroke, respectively. In our study, the APOE E2 allele was associated with lower CCA-IMT at baseline compared to E3 homozygotes (β: − 0.02 [95% CI − 0.04, − 0.004]). Over the follow-up, 244 MI events and 218 stroke events were observed. APOE E2 and E4 allele were not associated with incident MI (E2 HR: 1.06 [95% CI 0.68, 1.66]; E4 HR: 1.03 [95% CI 0.73, 1.45]) and incident stroke (E2 HR: 0.79 [95% CI 0.48, 1.30]; E4 HR: 0.96 [95% CI 0.66, 1.38]) in any of the models adjusting for potential confounders. However, the positive association between CCA-IMT and incident MI was more pronounced in E2 carriers than E3 homozygotes. Thus, our study suggests that while APOE E2 allele may predispose individuals to lower CCA-IMT, E2 carriers may be more prone to MI than E3 homozygotes as the CCA-IMT increases. APOE E4 allele had no effect on CCA-IMT, plaques, MI or stroke.
Investigating expert performance when observing magic effects
Authors: Garcia-Pelegrin Elias , Wilkins Clive , Clayton Nicola S.
Published: March 2022

The use of magic effects to investigate the blind spots in attention and perception and roadblocks in the cognition of the spectator has yielded thought-provoking results elucidating how these techniques operate. However, little is known about the interplay between experience practising magic and being deceived by magic effects. In this study, we performed two common sleight of hand effects and their real transfer counterparts to non-magicians, and to magicians with a diverse range of experience practising magic. Although, as a group, magicians identified the sleights of hand as deceptive actions significantly more than non-magicians; this ability was only evidenced in magicians with more than 5 years in the craft. However, unlike the rest of the participants, experienced magicians had difficulty correctly pinpointing the location of the coin in one of the real transfers presented. We hypothesise that this might be due to the inherent ambiguity of this transfer, in which, contrary to the other real transfer performed, no clear perceptive clue is given about the location of the coin. We suggest that extensive time practising magic might have primed experienced magicians to anticipate foul play when observing ambiguous movements, even when the actions observed are genuine.
Association of choroidal blood flow with autonomic dysfunction in patients with normal tension glaucoma
Authors: Shin Da Young , Hong Kyung Euy , Lee Na Young , Park Chan Kee , Park Hae Young L.
Published: March 2022

There is increasing evidence that autonomic dysfunction is an important factor in the progression of glaucoma. Mechanism of the association between autonomic dysfunction and progression of glaucoma is poorly understood. Since blood circulation is basically regulated by the autonomic nervous system, autonomic dysfunction may contribute to unstable or fluctuating blood pressure. Therefore, It is hypothesized that autonomic dysfunction may contribute to impaired ocular blood flow and lead to glaucoma progression. However, no clinical study yet has evaluated the relationship between ocular blood flow and autonomic nervous function. We enrolled 152 open angle glaucoma patient. Ocular blood flow was assessed by measuring vessel density (VD) using optical coherence tomography angiography, and autonomic nervous function was evaluated with heart-rate variability (HRV) parameters. The low frequency/high frequency (LF/HF) ratio, which is one of the HRV parameters, quantified the degree of sympathovagal balance. This indicator could represent autonomic dysfunction. Higher LF/HF ratio was associated with reduction of the deep parapapillary VD (R =  − 0.243, P = 0.003). Linear regression analysis showed a significant negative association between parapapillary choroidal VD and LF/HF ratio (β =  − 0.249; 95% confidential interval =  − 1.193 to − 0.249; P = 0.002) in multivariate analysis. We demonstarted the association between impaired ocular blood flow (parapapillary choroidal vessel density) and autonomic dysfunction (LF/HF ratio). This study could help understand the role of the autonomic dysfunction in pathophysiology of glaucoma progression.
MicroRNA-mediated post-transcriptional regulation of Pinus pinaster response and resistance to pinewood nematode
Authors: Modesto Inês , Inácio Vera , Van de Peer Yves , Miguel Célia M.
Published: March 2022

Pine wilt disease (PWD), caused by the parasitic nematode Bursaphelenchus xylophilus, or pinewood nematode (PWN), is a serious threat to pine forests in Europe. Pinus pinaster is highly susceptible to the disease and it is currently the most affected European pine species. In this work, we investigated the role of small RNAs (sRNAs) in regulating P. pinaster–PWN interaction in an early stage of infection. After performing an artificial PWN inoculation assay, we have identified 105 plant microRNAs (miRNAs) responsive to PWN. Based on their predicted targets, part of these miRNAs was associated with roles in jasmonate-response pathway, ROS detoxification, and terpenoid biosynthesis. Furthermore, by comparing resistant and susceptible plants, eight miRNAs with putative functions in plant defence and resistance to PWN have been identified. Finally, we explored the possibility of bidirectional trans-kingdom RNA silencing, identifying several P. pinaster genes putatively targeted by PWN miRNAs, which was supported by degradome analysis. Targets for P. pinaster miRNAs were also predicted in PWN, suggesting a role for trans-kingdom miRNA transfer and gene silencing both in PWN parasitism as in P. pinaster resistance to PWD. Our results provide new insights into previously unexplored roles of sRNA post-transcriptional regulation in P. pinaster response and resistance to PWN.
The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ
Authors: Toth Robert , Halmai Miklos , Gyorfy Zsuzsanna , Balint Eva , Unk Ildiko
Published: March 2022

PCNA is a central orchestrator of cellular processes linked to DNA metabolism. It is a binding platform for a plethora of proteins and coordinates and regulates the activity of several pathways. The outer side of PCNA comprises most of the known interacting and regulatory surfaces, whereas the residues at the inner side constitute the sliding surface facing the DNA double helix. Here, by investigating the L154A mutation found at the inner side, we show that the inner surface mediates protein interactions essential for genome stability. It forms part of the binding site of Rad18, a key regulator of DNA damage tolerance, and is required for PCNA sumoylation which prevents unscheduled recombination during replication. In addition, the L154 residue is necessary for stable complex formation between PCNA and the replicative DNA polymerase δ. Hence, its absence increases the mutation burden of yeast cells due to faulty replication. In summary, the essential role of the L154 of PCNA in guarding and maintaining stable replication and promoting DNA damage tolerance reveals a new connection between these processes and assigns a new coordinating function to the central channel of PCNA.
Study on parameter optimization of deep hole cumulative blasting in low permeability coal seams
Authors: Zhao Dan , Shen Zhiyuan , Li Minghao , Liu Baichen , Chen Yinuo , Xie Lina
Published: March 2022

Coal seam gas extraction is an important means of exploiting and utilizing gas resources, as well as a means of preventing coal mine disasters. To improve gas extraction efficiency in high gas and low permeability coal seams while ensuring blasting security, deep hole cumulative blasting parameters were optimized. ANSYS/LS-DYNA software is used to establish a 3-dimensional cumulative blasting model. By comparing and analyzing the blasting stress nephograms, stress time-history curves, and crack expansion curves, the optimal blasthole diameter, charge position, and charge length are obtained. Based on the numerical simulation results, a field test was carried out in the No. 10 coal seam of the Pingdingshan coal mine. The test results show that after cumulative blasting, the gas concentration was increased by an average of 2.25 times, the gas purity was increased by an average of 3.78 times, the permeability coefficient of the coal seam was increased by 21 times, and the effective radius of blasting was up to 7 m. The positive effects of deep hole cumulative blasting parameter optimization on the pressure relief and permeability enhancement of a high gas and low permeability coal seam were determined, which can provide a reference for other similar working faces to implement this technology.
Exploration of a modified stage for pN0 colon cancer patients
Authors: Liu Yunxiao , Zhang Hao , Wang Yuliuming , Zheng Mingyu , Wang Chunlin , Hu Hanqing , Tang Qingchao , Wang Guiyu
Published: March 2022

Exploring a modified stage (mStage) for pN0 colon cancer patients. 39,637 pN0 colon cancer patients were collected from the SEER database (2010–2015) (development cohort) and 455 pN0 colon cancer patients from the Second Affiliated Hospital of Harbin Medical University (2011–2015) (validation cohort). The optimal lymph nodes examined (LNE) stratification for cancer-specific survival (CSS) was obtained by X-tile software in the development cohort. LNE is combined with conventional T stage to form the mStage. The novel N stage was built based on the LNE (N0a: LNE ≥ 26, N0b: LNE = 11–25 and N0c: LNE ≤ 10). The mStage include mStageA (T1N0a, T1N0b, T1N0c and T2N0a), mStageB (T2N0b, T2N0c and T3N0a), mStageC (T3N0b), mStageD (T3N0c, T4aN0a and T4bN0a), mStageE (T4aN0b and T4bN0b) and mStageF (T4aN0c and T4bN0c). Cox regression model showed that mStage was an independent prognostic factor. AUC showed that the predictive accuracy of mStage was better than the conventional T stage for 5-year CSS in the development (0.700 vs. 0.678, P < 0.001) and validation cohort (0.649 vs. 0.603, P = 0.018). The C-index also showed that mStage had a superior model-fitting. Besides, calibration curves for 3-year and 5-year CSS revealed good consistencies between observed and predicted survival rates. For pN0 colon cancer patients, mStage might be superior to conventional T stage in predicting the prognosis.
In vitro characterisation of the MS2 RNA polymerase complex reveals host factors that modulate emesviral replicase activity
Authors: Wagner Alexander , Weise Laura I. , Mutschler Hannes
Published: March 2022

The RNA phage MS2 is one of the most important model organisms in molecular biology and virology. Despite its comprehensive characterisation, the composition of the RNA replication machinery remained obscure. Here, we characterised host proteins required to reconstitute the functional replicase in vitro. By combining a purified replicase sub-complex with elements of an in vitro translation system, we confirmed that the three host factors, EF-Ts, EF-Tu, and ribosomal protein S1, are part of the active replicase holocomplex. Furthermore, we found that the translation initiation factors IF1 and IF3 modulate replicase activity. While IF3 directly competes with the replicase for template binding, IF1 appears to act as an RNA chaperone that facilitates polymerase readthrough. Finally, we demonstrate in vitro formation of RNAs containing minimal motifs required for amplification. Our work sheds light on the MS2 replication machinery and provides a new promising platform for cell-free evolution.
Brain connectivity fingerprinting and behavioural prediction rest on distinct functional systems of the human connectome
Authors: Mantwill Maron , Gell Martin , Krohn Stephan , Finke Carsten
Published: March 2022

The prediction of inter-individual behavioural differences from neuroimaging data is a rapidly evolving field of research focusing on individualised methods to describe human brain organisation on the single-subject level. One method that harnesses such individual signatures is functional connectome fingerprinting, which can reliably identify individuals from large study populations. However, the precise relationship between functional signatures underlying fingerprinting and behavioural prediction remains unclear. Expanding on previous reports, here we systematically investigate the link between discrimination and prediction on different levels of brain network organisation (individual connections, network interactions, topographical organisation, and connection variability). Our analysis revealed a substantial divergence between discriminatory and predictive connectivity signatures on all levels of network organisation. Across different brain parcellations, thresholds, and prediction algorithms, we find discriminatory connections in higher-order multimodal association cortices, while neural correlates of behaviour display more variable distributions. Furthermore, we find the standard deviation of connections between participants to be significantly higher in fingerprinting than in prediction, making inter-individual connection variability a possible separating marker. These results demonstrate that participant identification and behavioural prediction involve highly distinct functional systems of the human connectome. The present study thus calls into question the direct functional relevance of connectome fingerprints.
PowerBacGWAS: a computational pipeline to perform power calculations for bacterial genome-wide association studies
Authors: Coll Francesc , Gouliouris Theodore , Bruchmann Sebastian , Phelan Jody , Raven Kathy E. , Clark Taane G. , Parkhill Julian , Peacock Sharon J.
Published: March 2022

Genome-wide association studies (GWAS) are increasingly being applied to investigate the genetic basis of bacterial traits. However, approaches to perform power calculations for bacterial GWAS are limited. Here we implemented two alternative approaches to conduct power calculations using existing collections of bacterial genomes. First, a sub-sampling approach was undertaken to reduce the allele frequency and effect size of a known and detectable genotype-phenotype relationship by modifying phenotype labels. Second, a phenotype-simulation approach was conducted to simulate phenotypes from existing genetic variants. We implemented both approaches into a computational pipeline (PowerBacGWAS) that supports power calculations for burden testing, pan-genome and variant GWAS; and applied it to collections of Enterococcus faecium, Klebsiella pneumoniae and Mycobacterium tuberculosis. We used this pipeline to determine sample sizes required to detect causal variants of different minor allele frequencies (MAF), effect sizes and phenotype heritability, and studied the effect of homoplasy and population diversity on the power to detect causal variants. ﻿Our pipeline and user documentation are made available and can be applied to other bacterial populations. PowerBacGWAS can be used to determine sample sizes required to find statistically significant associations, or the associations detectable with a given sample size. We recommend to perform power calculations using existing genomes of the bacterial species and population of study.
Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires FcγRIIB and virus-antibody complex with bivalent interaction
Authors: Wang Shuang , Wang Junchao , Yu Xiaojuan , Jiang Wen , Chen Shuo , Wang Rongjuan , Wang Mingzhu , Jiao Shasha , Yang Yingying , Wang Wenbo , Chen Huilin , Chen Ben , Gu Chunying , Liu Chuang , Wang An , Wang Min , Li Gang , Guo Cuicui , Liu Datao , Zhang Jinchao , Zhang Min , Wang Lan , Gui Xun
Published: March 2022

Understanding the underlying molecular mechanisms behind ADE of SARS-CoV-2 is critical for development of safe and effective therapies. Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells. X-ray crystal structure determination and S trimer-binding modeling showed that MW01 and MW05 could bind to RBDs in S trimer with both “up” and “down” states. While, the neutralizing mAb MW07, which has no ADE activity only binds to RBD in S trimer with “up” state. Monovalent MW01 and MW05 completely diminished the ADE activity compared with their bivalent counterparts. Moreover, both macropinocytosis and endocytosis are confirmed involving in ADE of SARS-CoV-2 pseudoviral infection. Blocking endosome transportation and lysosome acidification could inhibit the ADE activity mediated by MW05. Together, our results identified a novel ADE mechanism of SARS-CoV-2 pseudovirus in vitro, FcγRIIB-mediated uptake of SARS-CoV-2/mAb complex with bivalent interaction.
Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation
Authors: Ahn Jinsook , Jeong Soyeon , Kang So-mi , Jo Inseong , Park Bum-Joon , Ha Nam-Chul
Published: March 2022

Lamins are intermediate filaments that form a 3-D meshwork in the periphery of the nuclear envelope. The recent crystal structure of a long fragment of human lamin A/C visualized the tetrameric assembly unit of the central rod domain as a polymerization intermediate. A genetic mutation of S143F caused a phenotype characterized by both progeria and muscular dystrophy. In this study, we determined the crystal structure of the lamin A/C fragment harboring the S143F mutation. The obtained structure revealed the X-shaped interaction between the tetrameric units in the crystals, potentiated by the hydrophobic interactions of the mutated Phe143 residues. Subsequent studies indicated that the X-shaped interaction between the filaments plays a crucial role in disrupting the normal lamin meshwork. Our findings suggest the assembly mechanism of the 3-D meshwork and further provide a molecular framework for understanding the aging process by nuclear deformation.
Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family
Authors: Stogios Peter J. , Bordeleau Emily , Xu Zhiyu , Skarina Tatiana , Evdokimova Elena , Chou Sommer , Diorio-Toth Luke , D’Souza Alaric W. , Patel Sanket , Dantas Gautam , Wright Gerard D. , Savchenko Alexei
Published: March 2022

The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment.
Secretory quality control constrains functional selection-associated protein structure innovation
Authors: Cheng Bin , Lv Jian-Min , Liang Yu-Lin , Zhu Li , Huang Xiao-Ping , Li Hai-Yun , Potempa Lawrence A. , Ji Shang-Rong , Wu Yi
Published: March 2022

Biophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here we show that despite the up to two orders of magnitude differences in levels of C-reactive protein (CRP) in distinct species, the in vivo functions of CRP are paradoxically conserved. Such a pronounced level-function mismatch cannot be explained by activities associated with the conserved native structure, but is coupled to hidden activities associated with the unfolded, activated conformation. This is not the result of selection on structural constraints like foldability and stability, but is achieved by folding determinants-mediated functional selection that keeps a confined carrier structure to pass the stringent eukaryotic quality control on secretion. Further analysis suggests a folding threshold model which may partly explain the mismatch between the vast sequence space and the limited structure space of proteins.
Multiscale reconstruction of various vessels in the intact murine liver lobe
Authors: Zhang Qi , Li Anan , Chen Siqi , Yuan Jing , Jiang Tao , Li Xiangning , Luo Qingming , Feng Zhao , Gong Hui
Published: March 2022

The liver contains a variety of vessels and participates in miscellaneous physiological functions. While past studies generally focused on certain hepatic vessels, we simultaneously obtained all the vessels and cytoarchitectural information of the intact mouse liver lobe at single-cell resolution. Here, taking structural discrepancies of various vessels into account, we reconstruct and visualize the portal vein, hepatic vein, hepatic artery, intrahepatic bile duct, intrahepatic lymph of an intact liver lobe and peribiliary plexus in its selected local areas, providing a technology roadmap for studying the fine hepatic vascular structures and their spatial relationship, which will help research into liver diseases and evaluation of medical efficacies in the future.
The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression
Authors: Guo Xin , Zhang Bo-fang , Zhang Jing , Liu Gen , Hu Qi , Chen Jing
Published: March 2022

Our prior studies have characterized the participation of histone demethylase KDM3A in diabetic vascular remodeling, while its roles in myocardial ischemia/reperfusion (I/R) injury (MIRI) remain to be illustrated. Here we show that KDM3A was significantly downregulated in rat I/R and cellular hypoxia/reoxygenation (H/R) models. Subsequently, gain- and loss-of-function experiments were performed to investigate the effects of KDM3A in the settings of MIRI. KDM3A knockout exacerbated cardiac dysfunction and cardiomyocytes injury both in vivo and in vitro. The deteriorated mitochondrial apoptosis, reactive oxygen species, and inflammation were simultaneously observed. Conversely, KDM3A overexpression developed the ameliorated alternations in MIRI. Mechanistically, the MIRI-alleviating effects of KDM3A were associated with the enhancement of ETS1 expression. ChIP-PCR affirmed that KDM3A bound to the ETS1 promoter and removed dimethylation of histone H3 lysine 9 (H3K9me2), thus promoting ETS1 transcription. Our findings suggest that KDM3A is available for alleviating multi-etiologies of MIRI through the regulation of ETS1.
Southeast Asia must narrow down the yield gap to continue to be a major rice bowl
Authors: Yuan Shen , Stuart Alexander M. , Laborte Alice G. , Rattalino Edreira Juan I. , Dobermann Achim , Kien Le Vu Ngoc , Thúy Lưu Thị , Paothong Kritkamol , Traesang Prachya , Tint Khin Myo , San Su Su , Villafuerte Marcelino Q. , Quicho Emma D. , Pame Anny Ruth P. , Then Rathmuny , Flor Rica Joy , Thon Neak , Agus Fahmuddin , Agustiani Nurwulan , Deng Nanyan , Li Tao , Grassini Patricio
Published: March 2022

Southeast Asia is a major rice-producing region with a high level of internal consumption and accounting for 40% of global rice exports. Limited land resources, climate change and yield stagnation during recent years have once again raised concerns about the capacity of the region to remain as a large net exporter. Here we use a modelling approach to map rice yield gaps and assess production potential and net exports by 2040. We find that the average yield gap represents 48% of the yield potential estimate for the region, but there are substantial differences among countries. Exploitable yield gaps are relatively large in Cambodia, Myanmar, Philippines and Thailand but comparably smaller in Indonesia and Vietnam. Continuation of current yield trends will not allow Indonesia and Philippines to meet their domestic rice demand. In contrast, closing the exploitable yield gap by half would drastically reduce the need for rice imports with an aggregated annual rice surplus of 54 million tons available for export. Our study provides insights for increasing regional production on existing cropland by narrowing existing yield gaps.
Persulfate-based Advanced Oxidation Processes in Other Applications
Authors: Sun Yongjun , Qiu Xiangtao , Shah Kinjal J. , Sun Wenquan
Published: March 2022

The advanced oxidation technology of persulfate is a new type of advanced oxidation technology based on sulfate radicals. It has been a research hotspot in advanced oxidation processes in recent years. It has the advantages of strong oxidation, low cost and high efficiency, being environmentally friendly, safe and stable, with fast reaction speed, and is applied widely. Therefore, it has good development prospects in water treatment fields. This chapter mainly explores the application of persulfate advanced oxidation technology in areas other than sewage treatment, such as deep dewatering of sludge, activated carbon regeneration, contaminated soil remediation, waste gas treatment, metal recovery, and water quality analysis. Analyzing research progress predicts the future applicable areas and development prospects of advanced persulfate oxidation technology, enabling it to be better developed in the future to explore its widespread applications.
Improved osseointegration of strontium-modified titanium implants by regulating angiogenesis and macrophage polarization
Authors: Lu Wei , Zhou Chuan , Ma Yang , Li Jia , Jiang Jimin , Chen Yanqi , Dong Lingqing , He Fuming
Published: March 2022

Strontium (Sr) exerts versatile roles in the regulation of macrophage polarization, angiogenesis and osteogenesis, rendering the therapeutic potential of strontium-modified titanium implants (SLA-Sr) for rapidly vascularized osseointegration.
Molecular dynamics simulations of the initial oxidation process on ferritic Fe–Cr alloy surfaces
Authors: Zhang Yuan-Shuo , Chu Bao-Shuai , Yu Hong-Li , Li Kun , Wang Wei-Hua , Yang Wen
Published: March 2022

Based on the ReaxFF reactive potential, the interaction of O2 molecules with three types of surfaces (100, 110, 111) of ferritic Fe–Cr alloy has been studied by classical molecular dynamics at constant O2 concentrations and temperatures.
Tuning luminescence of the fluorescent molecule 2-(2-hydroxyphenyl)-1H-benzimidazole via zeolitic imidazolate framework-8
Authors: Zhang Yuyi , Zhang Wei , Bian Yajie , Liu Yiting , Zhang Xiaolei , Chen Mengdi , Hu Bingwen , Jin Qingyuan
Published: March 2022

ZIF-8 is regarded as a carrier to capture HPBI and eventually the adsorption of the pore structure would saturate, with altering the luminescent intensity. ZIF-8 may be used to sensitively detect nanoscale molecules via changes in fluorescence.
Dominant dimer emission provides colour stability for red thermally activated delayed fluorescence emitter
Authors: Cardeynaels Tom , Etherington Marc K. , Paredis Simon , Batsanov Andrei S. , Deckers Jasper , Stavrou Kleitos , Vanderzande Dirk , Monkman Andrew P. , Champagne Benoît , Maes Wouter
Published: March 2022

4DTPIPN has a strong tendency for dimer formation, even in dilute film, and possesses a higher colour purity than 4CzIPN but this is traded-off against the photoluminescence quantum yield. (Credit to LeStudio/Shutterstock for the James Bond themed background.)
Monitoring off-resonance signals with SHARPER NMR – the MR-SHARPER experiment
Authors: Davy Matthew , Dickson Claire L. , Wei Ran , Uhrín Dusan , Butts Craig P.
Published: March 2022

We extend the SHARPER NMR method designed to accommodate challenging reaction conditions to monitor simultaneously multiple resonances such as those of a reactant (2,6-difluoro-4-methoxyphenylboronic acid) and product (3,5-difluoroanisole).
Electrocatalytic two-electron oxygen reduction over nitrogen doped hollow carbon nanospheres
Authors: Xu Zhaoquan , Ma Ziyu , Dong Kai , Liang Jie , Zhang Longcheng , Luo Yongsong , Liu Qian , You Jinmao , Feng Zhesheng , Ma Dongwei , Wang Yan , Sun Xuping
Published: March 2022

Hollow carbon nanospheres with abundant mesoporous structure and enhanced N configuration active sites can reduce O2 to H2O2 with an ultrahigh H2O2 yield rate of 7.32 mol gcat.−1 h−1 and a high faradaic efficiency of 96.7% in 0.1 M KOH.
The role of the pre-exponential factor in determining the kinetic selection of polymorphs during solution crystallization of organic compounds
Authors: Verma Vivek , Hodnett Benjamin K.
Published: March 2022

Domain diagram to nucleate metastable or stable form between polymorph pair based on pre-exponential factor values.
Design of robust superamphiphobic surfaces with enlarged area fractions: the considerable role of Laplace pressure in dynamics of contact lines
Authors: Li Yang , He Yuting , Li Jiaoyan , Lu Chunhua , Ge Haixiong , Xu Zhongzi
Published: March 2022

The considerable kinetic role of Laplace pressure in contact angles of superamphobic surfaces can be utilized for robust superamphibic surfaces with an enlarged area fraction via the narrow parallel channel design.
Competition between metal-catalysed electroreduction of dinitrogen, protons, and nitrogen oxides: a DFT perspective
Authors: Carro Pilar , Choi Jaecheol , MacFarlane Douglas R. , Simonov Alexandr N. , Doña-Rodríguez José Miguel , Azofra Luis Miguel
Published: March 2022

Metals are common electrocatalysts for N2-into-NH3 reduction. In protic media, H+ competes with N2 to be reduced into H2. NOx, common air pollutants, are predicted to be more selectively converted into NH3 than N2, and even more than H+ into H2.
Limitations of machine learning models when predicting compounds with completely new chemistries: possible improvements applied to the discovery of new non-fullerene acceptors
Authors: Zhao Zhi-Wen , del Cueto Marcos , Troisi Alessandro
Published: March 2022

We try to determine if machine learning (ML) methods, applied to the discovery of new materials on the basis of existing data sets, have the power to predict new classes of compounds or perform well only when interpolating between known materials.
Zinc germanium nitrides and oxide nitrides: the influence of oxygen on electronic and structural properties
Authors: Breternitz Joachim , Schorr Susan
Published: March 2022

Oxygen alters the properties of semiconducting nitrides, such as ZnGeN2. We study the effect of oxygen incorporation computationally and compare the results to experimental values obtained in the system Zn1+xGe1−x(N1−xOx)2.
Recent trends in computational tools and data-driven modeling for advanced materials
Authors: Singh Varshika , Patra Santanu , Murugan Natarajan Arul , Toncu Dana-Cristina , Tiwari Ashutosh
Published: March 2022

The paradigm of advanced materials has grown exponentially over the last decade, with their new dimensions including digital design, dynamics, and functions.
Research progress on nano-sensitizers for enhancing the effects of radiotherapy
Authors: Zhang Yuan , Han Xiao , Liu Yuan , Wang Shuang , Han Xianlin , Cheng Cui
Published: March 2022

Nano-sensitizers play key roles in tumor radiotherapy in several ways to overcome radioresistance and enhance radioresponse. This review summarizes the recent advances of nano-sensitizers in improving cancer radiotherapy.
Towards three-dimensional nanoarchitectures: highly ordered bi-layer assembly of tailored magnetic nanowire arrays via template-assisted electrodeposition
Authors: Galindo Arturo , Reyes-Rodríguez José Luis , Botez Cristian , Moreno Mario , Ponce Arturo
Published: March 2022

We systematically fabricated a bi-layer assembly of highly ordered arrays of magnetic nanowires with high surface to volume ratios using template assisted electrodeposition. Their morphology and distinct magnetic behavior have been highlighted.
State of the art of ultra-thin gold layers: formation fundamentals and applications
Authors: Liang Suzhe , Schwartzkopf Matthias , Roth Stephan V. , Müller-Buschbaum Peter
Published: March 2022

The insights into the formation of ultra-thin gold layers on solid, soft, and nanostructured substrates, as well as the corresponding applications in optical response, electronic device, and as seed layers are reviewed.
A theoretical study on the proton affinity of sulfur ylides
Authors: Yang Yaxin , Zheng Wenrui , Ren Lufei , Xu Xiaofei
Published: March 2022

The proton affinities of sulfoxide ylides, carbonyl ylides, allyl ylides, benzenyl ylides and heterocyclic ylides with typical substituents were investigated using the SOGGA11-X functional.
Fruity, sticky, stinky, spicy, bitter, addictive, and deadly: evolutionary signatures of metabolic complexity in the Solanaceae
Authors: Fiesel Paul D. , Parks Hannah M. , Last Robert L. , Barry Cornelius S.
Published: March 2022

This review focuses on the biosynthesis and evolution of specialized metabolism in the Solanaceae (Nightshade) family.