bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal stem cells transfer mitochondria to allogeneic Tregs in an HLA-dependent manner improving their immunosuppressive activity
Authors: Piekarska Karolina , Urban-Wójciuk Zuzanna , Kurkowiak Małgorzta , Pelikant-Małecka Iwona , Schumacher Adriana , Sakowska Justyna , Spodnik Jan Henryk , Arcimowicz Łukasz , Zielińska Hanna , Tymoniuk Bogusław , Renkielska Alicja , Siebert Janusz , Słomińska Ewa , Trzonkowski Piotr , Hupp Ted , Marek-Trzonkowska Natalia Maria
Published: February 2022

Cell-based immunotherapies can provide safe and effective treatments for various disorders including autoimmunity, cancer, and excessive proinflammatory events in sepsis or viral infections. However, to achieve this goal there is a need for deeper understanding of mechanisms of the intercellular interactions. Regulatory T cells (Tregs) are a lymphocyte subset that maintain peripheral tolerance, whilst mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitor cells. Despite coming from different origins, Tregs and MSCs share immunoregulatory properties that have been tested in clinical trials. Here we demonstrate how direct and indirect contact with allogenic MSCs improves Tregs’ potential for accumulation of immunosuppressive adenosine and suppression of conventional T cell proliferation, making them more potent therapeutic tools. Our results also demonstrate that direct communication between Tregs and MSCs is based on transfer of active mitochondria and fragments of plasma membrane from MSCs to Tregs, an event that is HLA-dependent and associates with HLA-C and HLA-DRB1 eplet mismatch load between Treg and MSC donors.
A deep-learning system bridging molecule structure and biomedical text with comprehension comparable to human professionals
Authors: Zeng Zheni , Yao Yuan , Liu Zhiyuan , Sun Maosong
Published: February 2022

To accelerate biomedical research process, deep-learning systems are developed to automatically acquire knowledge about molecule entities by reading large-scale biomedical data. Inspired by humans that learn deep molecule knowledge from versatile reading on both molecule structure and biomedical text information, we propose a knowledgeable machine reading system that bridges both types of information in a unified deep-learning framework for comprehensive biomedical research assistance. We solve the problem that existing machine reading models can only process different types of data separately, and thus achieve a comprehensive and thorough understanding of molecule entities. By grasping meta-knowledge in an unsupervised fashion within and across different information sources, our system can facilitate various real-world biomedical applications, including molecular property prediction, biomedical relation extraction and so on. Experimental results show that our system even surpasses human professionals in the capability of molecular property comprehension, and also reveal its promising potential in facilitating automatic drug discovery and documentation in the future.
Structural insights into the Venus flytrap mechanosensitive ion channel Flycatcher1
Authors: Jojoa-Cruz Sebastian , Saotome Kei , Tsui Che Chun Alex , Lee Wen-Hsin , Sansom Mark S. P. , Murthy Swetha E. , Patapoutian Ardem , Ward Andrew B.
Published: February 2022

Flycatcher1 (FLYC1), a MscS homolog, has recently been identified as a candidate mechanosensitive (MS) ion channel involved in Venus flytrap prey recognition. FLYC1 is a larger protein and its sequence diverges from previously studied MscS homologs, suggesting it has unique structural features that contribute to its function. Here, we characterize FLYC1 by cryo-electron microscopy, molecular dynamics simulations, and electrophysiology. Akin to bacterial MscS and plant MSL1 channels, we find that FLYC1 central core includes side portals in the cytoplasmic cage that regulate ion preference and conduction, by identifying critical residues that modulate channel conductance. Topologically unique cytoplasmic flanking regions can adopt ‘up’ or ‘down’ conformations, making the channel asymmetric. Disruption of an up conformation-specific interaction severely delays channel deactivation by 40-fold likely due to stabilization of the channel open state. Our results illustrate novel structural features and likely conformational transitions that regulate mechano-gating of FLYC1.
Dynamic FMR1 granule phase switch instructed by m6A modification contributes to maternal RNA decay
Authors: Zhang Guoqiang , Xu Yongru , Wang Xiaona , Zhu Yuanxiang , Wang Liangliang , Zhang Wenxin , Wang Yiru , Gao Yajie , Wu Xuna , Cheng Ying , Sun Qinmiao , Chen Dahua
Published: February 2022

Maternal RNA degradation is critical for embryogenesis and is tightly controlled by maternal RNA-binding proteins. Fragile X mental-retardation protein (FMR1) binds target mRNAs to form ribonucleoprotein (RNP) complexes/granules that control various biological processes, including early embryogenesis. However, how FMR1 recognizes target mRNAs and how FMR1-RNP granule assembly/disassembly regulates FMR1-associated mRNAs remain elusive. Here we show that Drosophila FMR1 preferentially binds mRNAs containing m6A-marked “AGACU” motif with high affinity to contributes to maternal RNA degradation. The high-affinity binding largely depends on a hydrophobic network within FMR1 KH2 domain. Importantly, this binding greatly induces FMR1 granule condensation to efficiently recruit unmodified mRNAs. The degradation of maternal mRNAs then causes granule de-condensation, allowing normal embryogenesis. Our findings reveal that sequence-specific mRNAs instruct FMR1-RNP granules to undergo a dynamic phase-switch, thus contributes to maternal mRNA decay. This mechanism may represent a general principle that regulated RNP-granules control RNA processing and normal development.
Toward scalable fabrication of electrochemical paper sensor without surface functionalization
Authors: Wang Cheng , Wu Rui , Ling Hao , Zhao Zhiling , Han Wenjia , Shi Xiaowen , Payne Gregory F. , Wang Xiaohui
Published: February 2022

Paper-based electrochemical sensors provide the opportunity for low-cost, portable and environmentally friendly single-use chemical analysis and there are various reports of surface-functionalized paper electrodes. Here we report a composite paper electrode that is fabricated through designed papermaking using cellulose, carbon fibers (CF), and graphene oxide (GO). The composite paper has well-controlled structure, stable, and repeatable properties, and offers the electrocatalytic activities for sensitive and selective chemical detection. We demonstrate that this CF/GO/cellulose composite paper can be reduced electrochemically using relatively mild conditions and this GO reduction confers electrocatalytic properties to the composite paper. Finally, we demonstrate that this composite paper offers sensing performance (sensitivity and selectivity) comparable to, or better than, paper-based sensors prepared by small-batch surface-modification (e.g., printing) methods. We envision this coupling of industrialized papermaking technologies with interfacial engineering and electrochemical reduction can provide a platform for single-use and portable chemical detection for a wide range of applications.
Increase in Arctic coastal erosion and its sensitivity to warming in the twenty-first century
Authors: Nielsen David Marcolino , Pieper Patrick , Barkhordarian Armineh , Overduin Paul , Ilyina Tatiana , Brovkin Victor , Baehr Johanna , Dobrynin Mikhail
Published: February 2022

Arctic coastal erosion damages infrastructure, threatens coastal communities and releases organic carbon from permafrost. However, the magnitude, timing and sensitivity of coastal erosion increase to global warming remain unknown. Here we project the Arctic-mean erosion rate to increase and very likely exceed its historical range of variability before the end of the century in a wide range of emission scenarios. The sensitivity of erosion to warming roughly doubles, reaching 0.4–0.8 m yr−1 °C−1 and 2.3–4.2 TgC yr−1 °C−1 by the end of the century. We develop a simplified semi-empirical model to produce twenty-first-century pan-Arctic coastal erosion rate projections. Our results will inform policymakers on coastal conservation and socioeconomic planning, and organic carbon flux projections lay out the path for future work to investigate the impact of Arctic coastal erosion on the changing Arctic Ocean, its role as a global carbon sink, and the permafrost–carbon feedback.
The hypertriglyceridemic waist phenotype is associated with fatty liver and glycometabolic profiles in overweight and obese adults: a cross-sectional study
Authors: Zhou Meiling , Li Feifei , Tang Haokai , Wu Si , Meng Li , Dong Yanhui , Wang Fei , Quach Binh , Yang Yide , Ma Jun , Baker Julien Steven
Published: February 2022

The present study aimed to distinguish different hypertriglyceridemic waist phenotypes and relevant risks of developing fatty liver and abnormal glycometabolic profiles in overweight/obese adults. A total of 1221 Chinese adults with mean (standard deviation [SD]) age of 37 (9) years, 37.3% males and 62.7% females, body mass index (BMI) of 29.0 (4.0) kg/m2, triglyceride (TG) 2.04 (1.45) mmol/L, and waist circumference (WC) 95.8 (10.7) cm were included and classified into four phenotypes: normal TG & normal WC (N-N); normal TG & high WC (N-WC); high TG & normal WC (TG-N); high TG & high WC (TG-WC). Participants in TG-WC group had the highest BMI, WC, blood pressure (BP), insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL), and fatty liver. Participants within N-WC group had a significantly higher risk of fatty liver (adjusted OR 3.50 [95% CI 2.05–5.97]), as well as TG-N (adjusted OR 2.59 [95% CI 1.61–4.16]) and TG-WC (adjusted OR 4.12 [95% CI 2.28–7.46]). The risk of elevated HOMA-IR was significantly higher in TG-N (adjusted OR 2.16 [95% CI 1.33–3.50]) and TG-WC (adjusted OR 2.04 [95% CI 1.22–3.40]). The risk of elevated HbA1c was significantly higher in the TG-WC (adjusted OR 2.79 [95% CI 1.47–5.31]). Hypertriglyceridemic waist phenotype can be a potential and cost-effective method to identify individuals with a high risk of fatty liver and glycometabolic disorders.
Targeted deletion of the RNA-binding protein Caprin1 leads to progressive hearing loss and impairs recovery from noise exposure in mice
Authors: Nolan Lisa S. , Chen Jing , Gonçalves Ana-Cláudia , Bullen Anwen , Towers Emily R. , Steel Karen P. , Dawson Sally J. , Gale Jonathan E.
Published: February 2022

Cell cycle associated protein 1 (Caprin1) is an RNA-binding protein that can regulate the cellular post-transcriptional response to stress. It is a component of both stress granules and neuronal RNA granules and is implicated in neurodegenerative disease, synaptic plasticity and long-term memory formation. Our previous work suggested that Caprin1 also plays a role in the response of the cochlea to stress. Here, targeted inner ear-deletion of Caprin1 in mice leads to an early onset, progressive hearing loss. Auditory brainstem responses from Caprin1-deficient mice show reduced thresholds, with a significant reduction in wave-I amplitudes compared to wildtype. Whilst hair cell structure and numbers were normal, the inner hair cell-spiral ganglion neuron (IHC-SGN) synapse revealed abnormally large post-synaptic GluA2 receptor puncta, a defect consistent with the observed wave-I reduction. Unlike wildtype mice, mild-noise-induced hearing threshold shifts in Caprin1-deficient mice did not recover. Oxidative stress triggered TIA-1/HuR-positive stress granule formation in ex-vivo cochlear explants from Caprin1-deficient mice, showing that stress granules could still be induced. Taken together, these findings suggest that Caprin1 plays a key role in maintenance of auditory function, where it regulates the normal status of the IHC-SGN synapse.
Stochastic dynamics of a few sodium atoms in presence of a cold potassium cloud
Authors: Bhatt Rohit Prasad , Kilinc Jan , Höcker Lilo , Jendrzejewski Fred
Published: February 2022

Single particle resolution is a requirement for numerous experimental protocols that emulate the dynamics of small systems in a bath. Here, we accurately resolve through atom counting the stochastic dynamics of a few sodium atoms in presence of a cold potassium cloud. This capability enables us to rule out the effect of inter-species interaction on sodium atom number dynamics, at very low atomic densities present in these experiments. We study the noise sources for sodium and potassium in a common framework. Thereby, we assign the detection limits to 4.3 atoms for potassium and 0.2 atoms (corresponding to 96% fidelity) for sodium. This opens possibilities for future experiments with a few atoms immersed in a quantum degenerate gas.
Bodily ownership of an independent supernumerary limb: an exploratory study
Authors: Umezawa Kohei , Suzuki Yuta , Ganesh Gowrishankar , Miyawaki Yoichi
Published: February 2022

Can our brain perceive a sense of ownership towards an independent supernumerary limb; one that can be moved independently of any other limb and provides its own independent movement feedback? Following the rubber-hand illusion experiment, a plethora of studies have shown that the human representation of “self” is very plastic. But previous studies have almost exclusively investigated ownership towards “substitute” artificial limbs, which are controlled by the movements of a real limb and/or limbs from which non-visual sensory feedback is provided on an existing limb. Here, to investigate whether the human brain can own an independent artificial limb, we first developed a novel independent robotic “sixth finger.” We allowed participants to train using the finger and examined whether it induced changes in the body representation using behavioral as well as cognitive measures. Our results suggest that unlike a substitute artificial limb (like in the rubber hand experiment), it is more difficult for humans to perceive a sense of ownership towards an independent limb. However, ownership does seem possible, as we observed clear tendencies of changes in the body representation that correlated with the cognitive reports of the sense of ownership. Our results provide the first evidence to show that an independent supernumerary limb can be embodied by humans.
Optimization, purification and characterization of laccase from Ganoderma leucocontextum along with its phylogenetic relationship
Authors: Umar Aisha , Ahmed Shakil
Published: February 2022

The aim of this work to study an efficient laccase producing fungus Ganoderma leucocontextum, which was identified by ITS regions of DNA and phylogenetic tree was constructed. This study showed the laccase first-time from G. leucocontextum by using medium containing guaiacol. The growth cultural (pH, temperature, incubation days, rpm) and nutritional (carbon and nitrogen sources) conditions were optimized, which enhanced the enzyme production up to 4.5-folds. Laccase production increased 855 U/L at 40 °C. The pH 5.0 was suitable for laccase secretion (2517 U/L) on the 7th day of incubation at 100 rpm (698.3 U/L). Glucose and sucrose were good carbon source to enhance the laccase synthesis. The 10 g/L beef (4671 U/L) and yeast extract (5776 U/L) were the best nitrogen source for laccase secretion from G. leucocontextum. The laccase was purified from the 80% ammonium sulphate precipitations of protein identified by nucleotides sequence. The molecular weight (65.0 kDa) of purified laccase was identified through SDS and native PAGE entitled as Glacc110. The Glacc110 was characterized under different parameters. It retained > 90% of its activity for 16 min incubation at 60 °C in acidic medium (pH 4.0). This enzyme exerted its optimal activity at pH 3.0 and temperature 70 °C with guaiacol substrate. The catalytic parameters Km and Vmax was 1.658 (mM) and 2.452 (mM/min), respectively. The thermo stability of the laccase produced by submerged fermentation of G. leucocontextum has potential for industrial and biotechnology applications. The results remarked the G. leucocontextum is a good source for laccase production.
Development of a code-free machine learning model for the classification of cataract surgery phases
Authors: Touma Samir , Antaki Fares , Duval Renaud
Published: February 2022

This study assessed the performance of automated machine learning (AutoML) in classifying cataract surgery phases from surgical videos. Two ophthalmology trainees without coding experience designed a deep learning model in Google Cloud AutoML Video Classification for the classification of 10 different cataract surgery phases. We used two open-access publicly available datasets (total of 122 surgeries) for model training, validation and testing. External validation was performed on 10 surgeries issued from another dataset. The AutoML model demonstrated excellent discriminating performance, even outperforming bespoke deep learning models handcrafter by experts. The area under the precision-recall curve was 0.855. At the 0.5 confidence threshold cut-off, the overall performance metrics were as follows: sensitivity (81.0%), recall (77.1%), accuracy (96.0%) and F1 score (0.79). The per-segment metrics varied across the surgical phases: precision 66.7–100%, recall 46.2–100% and specificity 94.1–100%. Hydrodissection and phacoemulsification were the most accurately predicted phases (100 and 92.31% correct predictions, respectively). During external validation, the average precision was 54.2% (0.00–90.0%), the recall was 61.1% (0.00–100%) and specificity was 96.2% (91.0–99.0%). In conclusion, a code-free AutoML model can accurately classify cataract surgery phases from videos with an accuracy comparable or better than models developed by experts.
A proficient approach to forecast COVID-19 spread via optimized dynamic machine learning models
Authors: Alali Yasminah , Harrou Fouzi , Sun Ying
Published: February 2022

This study aims to develop an assumption-free data-driven model to accurately forecast COVID-19 spread. Towards this end, we firstly employed Bayesian optimization to tune the Gaussian process regression (GPR) hyperparameters to develop an efficient GPR-based model for forecasting the recovered and confirmed COVID-19 cases in two highly impacted countries, India and Brazil. However, machine learning models do not consider the time dependency in the COVID-19 data series. Here, dynamic information has been taken into account to alleviate this limitation by introducing lagged measurements in constructing the investigated machine learning models. Additionally, we assessed the contribution of the incorporated features to the COVID-19 prediction using the Random Forest algorithm. Results reveal that significant improvement can be obtained using the proposed dynamic machine learning models. In addition, the results highlighted the superior performance of the dynamic GPR compared to the other models (i.e., Support vector regression, Boosted trees, Bagged trees, Decision tree, Random Forest, and XGBoost) by achieving an averaged mean absolute percentage error of around 0.1%. Finally, we provided the confidence level of the predicted results based on the dynamic GPR model and showed that the predictions are within the 95% confidence interval. This study presents a promising shallow and simple approach for predicting COVID-19 spread.
Lab-on-chip microscope platform for electro-manipulation of a dense microtubules network
Authors: Havelka Daniel , Zhernov Ilia , Teplan Michal , Lánský Zdeněk , Chafai Djamel Eddine , Cifra Michal
Published: February 2022

Pulsed electric field (PEF) technology is promising for the manipulation of biomolecular components and has potential applications in biomedicine and bionanotechnology. Microtubules, nanoscopic tubular structures self-assembled from protein tubulin, serve as important components in basic cellular processes as well as in engineered biomolecular nanosystems. Recent studies in cell-based models have demonstrated that PEF affects the cytoskeleton, including microtubules. However, the direct effects of PEF on microtubules are not clear. In this work, we developed a lab-on-a-chip platform integrated with a total internal reflection fluorescence microscope system to elucidate the PEF effects on a microtubules network mimicking the cell-like density of microtubules. The designed platform enables the delivery of short (microsecond-scale), high-field-strength ($$\le$$
≤
 25 kV/cm) electric pulses far from the electrode/electrolyte interface. We showed that microsecond PEF is capable of overcoming the non-covalent microtubule bonding force to the substrate and translocating the microtubules. This microsecond PEF effect combined with macromolecular crowding led to aggregation of microtubules. Our results expand the toolbox of bioelectronics technologies and electromagnetic tools for the manipulation of biomolecular nanoscopic systems and contribute to the understanding of microsecond PEF effects on a microtubule cytoskeleton.
North to south gradient and local waves of influenza in Chile
Authors: Garcia-Calavaro Christian , Harrison Lee H. , Pokutnaya Darya , Mair Christina F. , Brooks Maria M. , van Panhuis Wilbert
Published: February 2022

Influenza seasonality is caused by complex interactions between environmental factors, viral mutations, population crowding, and human travel. To date, no studies have estimated the seasonality and latitudinal patterns of seasonal influenza in Chile. We obtained influenza-like illness (ILI) surveillance data from 29 Chilean public health networks to evaluate seasonality using wavelet analysis. We assessed the relationship between the start, peak, and latitude of the ILI epidemics using linear and piecewise regression. To estimate the presence of incoming and outgoing traveling waves (timing vs distance) between networks and to assess the association with population size, we used linear and logistic regression. We found a north to south gradient of influenza and traveling waves that were present in the central, densely populated region of Chile. Our findings suggest that larger populations in central Chile drive seasonal influenza epidemics.
Angularly quantized spin rotations in hexagonal LuMnO3
Authors: Kim Seung , Nam Jiyeon , Xu Xianghan , Cheong Sang-Wook , Yang In-Sang
Published: February 2022

Optical control of the spin degree of freedom is often desired in application of the spin technology. Here we report spin-rotational excitations observed through inelastic light scattering of the hexagonal LuMnO3 in the antiferromagnetically (AFM) ordered state. We propose a model based on the spin–spin interaction Hamiltonian associated with the spin rotation of the Mn ions, and find that the spin rotations are angularly quantized by 60°, 120°, and 180°. Angular quantization is considered to be a consequence of the symmetry of the triangular lattice of the Mn-ion plane in the hexagonal LuMnO3. These angularly-quantized spin excitations may be pictured as isolated flat bubbles in the sea of the ground state, which may lead to high-density information storage if applied to spin devices. Optically pumped and detected spin-excitation bubbles would bring about the advanced technology of optical control of the spin degree of freedom in multiferroic materials.
Using citizen science to test for acoustic niche partitioning in frogs
Authors: Allen-Ankins Slade , Schwarzkopf Lin
Published: February 2022

The acoustic niche hypothesis proposes that to avoid interference with breeding signals, vocal species should evolve to partition acoustic space, minimising similarity with co-occurring signals. Tests of the acoustic niche hypothesis are typically conducted using a single assemblage, with mixed outcomes, but if the process is evolutionarily important, a pattern of reduced acoustic competition should emerge, on average, over many communities. Using a continental-scale dataset derived from audio recordings collected by citizen scientists, we show that frogs do partition acoustic space. Differences in calls were predominately caused by differences in spectral, rather than temporal, features. Specifically, the 90% frequency bandwidths of observed frog assemblages overlapped less than expected, and there was greater distance between dominant frequencies than expected. To our knowledge, this study is the first to use null models to test for acoustic niche partitioning over a large geographic scale.
Differential maturation and chaperone dependence of the paralogous protein kinases DYRK1A and DYRK1B
Authors: Papenfuss Marco , Lützow Svenja , Wilms Gerrit , Babendreyer Aaron , Flaßhoff Maren , Kunick Conrad , Becker Walter
Published: February 2022

The HSP90/CDC37 chaperone system not only assists the maturation of many protein kinases but also maintains their structural integrity after folding. The interaction of mature kinases with the HSP90/CDC37 complex is governed by the conformational stability of the catalytic domain, while the initial folding of the protein kinase domain is mechanistically less well characterized. DYRK1A (Dual-specificity tyrosine (Y)-phosphorylation Regulated protein Kinase 1A) and DYRK1B are closely related protein kinases with discordant HSP90 client status. DYRK kinases stoichiometrically autophosphorylate on a tyrosine residue immediately after folding, which served us as a traceable marker of successful maturation. In the present study, we used bacterial expression systems to compare the capacity of autonomous maturation of DYRK1A and DYRK1B in the absence of eukaryotic cofactors or chaperones. Under these conditions, autophosphorylation of human DYRK1B was severely compromised when compared with DYRK1A or DYRK1B orthologs from zebrafish and Xenopus. Maturation of human DYRK1B could be restored by bacterial expression at lower temperatures, suggesting that folding was not absolutely dependent on eukaryotic chaperones. The differential folding properties of DYRK1A and DYRK1B were largely due to divergent sequences of the C-terminal lobes of the catalytic domain. Furthermore, the mature kinase domain of DYRK1B featured lower thermal stability than that of DYRK1A when exposed to heat challenge in vitro or in living cells. In summary, our study enhances the mechanistic understanding of the differential thermodynamic properties of two closely related protein kinases during initial folding and as mature kinases.
Obsessive–compulsive personality disorder in rapid eye movement sleep behavior disorder
Authors: Luca Antonina , Cicero Calogero Edoardo , Giuliano Loretta , Sgroi Riccardo , Vancheri Edoardo , Terravecchia Claudio , Squillaci Raffaele , Rascunà Cristina , Donzuso Giulia , Mostile Giovanni , Sciacca Giorgia , Zappia Mario , Nicoletti Alessandra
Published: February 2022

Rapid eye movement sleep behavior disorder (RBD) is a common prodromic non-motor symptom of Parkinson’s disease (PD). Only few studies have evaluated the personality of RBD patients with conflicting results. Aim of the study was to evaluate the frequency of Personality Disorders (PeDs)in RBD. RBD patients, PD patients and healthy controls (HC) were enrolled. All the enrolled subjects underwent a full neurological examination. Motor symptoms were evaluated with the UPDRS-Motor Examination. PeDs were assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). Twenty-nine RBD patients [14 men (48.3%); mean age 55.6 ± 11.1], 30 PD patients [17 men (56.7%); mean age 65.7 ± 10.7] and 30 HC [12 men (40%); mean age 65.7 ± 5.4] were enrolled in the study. PD patients had a disease duration of 4.5 ± 4.6 and presented a mean UPDRS-ME score of 26.7 ± 9.4. The most frequent PeDs was the Obsessive–Compulsive one (OCPeD); OCPeD was significantly more frequent in RBD (55.2%) patients than HC (13.3%;p-value < 0.001). No significant differences were found comparing the frequency of OCPeD in RBD patients to that in PD. In the present study, the prevalence of OCPeD in RBD patients was close to that reported in PD patients. Our data could suggest the existence of a common disease-specific RBD-PD personality profile.
Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice
Authors: Ota Hidetaka , Kodama Ayuto
Published: February 2022

Senolytics are a class of drugs that selectively remove senescent cells. Dasatinib and quercetin have been discovered, and their combination has shown various anti-ageing effects. The SAMP10 mouse strain is a model of brain ageing. Here, we investigated the effect of combination on frailty characteristics in SAMP10. By comparing SAMP10 with SAMR1 mice as normal ageing controls, we investigated some frailty characteristics. Frailty was assessed at 18–38 weeks of age with a clinical frailty index. Motor and cognitive function of these mice were evaluated using behavioral experiments. SAMP10 mice were divided into vehicle and combination, and these functions and histological changes in the brain hippocampus were investigated. Finally, the in vitro effects of combination on oxidative stress-induced senescent muscle and neuronal cells were investigated. As a result, we found that frailty index was higher in SAMP10 than SAMR1. Motor and cognitive function were worse in SAMP10 than SAMR1. Furthermore, combination therapy improved frailty, motor and cognitive function, and the senescent phenotype of the hippocampus compared with vehicle in SAMP10. In summary, SAMP10 showed more marked frailty characteristics than SAMR1, and dasatinib and quercetin attenuated them in SAMP10. From our results, senolytic therapy might contribute protective effects against frailty.
Spin-glass transition in the spin–orbit-entangled Jeff = 0 Mott insulating double-perovskite ruthenate
Authors: Yatsuzuka Hayato , Haraguchi Yuya , Matsuo Akira , Kindo Koichi , Katori Hiroko Aruga
Published: February 2022

We have successfully synthesized new Ru4+ double perovskite oxides SrLaInRuO6 and SrLaGaRuO6, which are expected to be a spin–orbit coupled Jeff = 0 Mott insulating ground state. Their magnetic susceptibility is much significant than that expected for a single Ru4+ ion for which exchange coupling with other ions is negligible. Their isothermal magnetization process suggests that there are about 20 percent isolated spins. These origins would be the Ru3+/Ru5+ magnetic defects, while the regular Ru4+ sites remain nonmagnetic. Moreover, SrLaGaRuO6 shows a spin-glass-like magnetic transition at low temperatures, probably caused by isolated spins. The observed spin-glass can be interpreted by the analogy of a dilute magnetic alloy, which can be seen as a precursor to the mobile Jeff = 1 exciton as a dispersive mode as predicted.
Pre-infection plasma cytokines and chemokines as predictors of HIV disease progression
Authors: Ngcobo Samukelisiwe , Molatlhegi Refilwe P. , Osman Farzana , Ngcapu Sinaye , Samsunder Natasha , Garrett Nigel J. , Abdool Karim Salim S. , Abdool Karim Quarraisha , McKinnon Lyle R. , Sivro Aida
Published: February 2022

Previous studies have highlighted the role of pre-infection systemic inflammation on HIV acquisition risk, but the extent to which it predicts disease progression outcomes is less studied. Here we examined the relationship between pre-infection plasma cytokine expression and the rate of HIV disease progression in South African women who seroconverted during the CAPRISA 004 tenofovir gel trial. Bio-Plex 200 system was used to measure the expression of 47 cytokines/chemokines in 69 seroconvertors from the CAPRISA 004 trial. Cox proportional hazards regression analyses were used to measure associations between cytokine expression and CD4 decline prior to antiretroviral therapy initiation. Linear regression models were used to assess whether pre-infection cytokine expression were predictors of disease progression outcomes including peak and set-point viral load and CD4:CD8 ratio at less and greater than180 days post infection. Several cytokines were associated with increased peak HIV viral load (including IL-16, SCGFβ, MCP-3, IL-12p40, SCF, IFNα2 and IL-2). The strongest association with peak viral load was observed for SCGFβ, which was also inversely associated with lowest CD4:CD8 ratio < 180 days post infection and faster CD4 decline below 500 cells/µl (adjusted HR 4.537, 95% CI 1.475–13.954;p = 0.008) in multivariable analysis adjusting for age, study site, contraception, baseline HSV-2 status and trial arm allocation. Our results show that pre-infection systemic immune responses could play a role in HIV disease progression, especially in the early stages of infection.
Visual learning in a virtual reality environment upregulates immediate early gene expression in the mushroom bodies of honey bees
Authors: Geng Haiyang , Lafon Gregory , Avarguès-Weber Aurore , Buatois Alexis , Massou Isabelle , Giurfa Martin
Published: February 2022

Free-flying bees learn efficiently to solve numerous visual tasks. Yet, the neural underpinnings of this capacity remain unexplored. We used a 3D virtual reality (VR) environment to study visual learning and determine if it leads to changes in immediate early gene (IEG) expression in specific areas of the bee brain. We focused on kakusei, Hr38 and Egr1, three IEGs that have been related to bee foraging and orientation, and compared their relative expression in the calyces of the mushroom bodies, the optic lobes and the rest of the brain after color discrimination learning. Bees learned to discriminate virtual stimuli displaying different colors and retained the information learned. Successful learners exhibited Egr1 upregulation only in the calyces of the mushroom bodies, thus uncovering a privileged involvement of these brain regions in associative color learning and the usefulness of Egr1 as a marker of neural activity induced by this phenomenon.
Sensitizer-enhanced two-photon patterning of biomolecules in photoinstructive hydrogels
Authors: Krüger Heike , Asido Marvin , Wachtveitl Josef , Tampé Robert , Wieneke Ralph
Published: February 2022

Photoresponsive hydrogels can be employed to coordinate the organization of proteins in three dimensions (3D) and thus to spatiotemporally control their physiochemical properties by light. However, reversible and user-defined tethering of proteins and protein complexes to biomaterials pose a considerable challenge as this is a cumbersome process, which, in many cases, does not support the precise localization of biomolecules in the z direction. Here, we report on the 3D patterning of proteins with polyhistidine tags based on in-situ two-photon lithography. By exploiting a two-photon activatable multivalent chelator head, we established the protein mounting of hydrogels with micrometer precision. In the presence of photosensitizers, a substantially enhanced two-photon activation of the developed tool inside hydrogels was detected, enabling the user-defined 3D protein immobilization in hydrogels with high specificity, micrometer-scale precision, and under mild light doses. Our protein-binding strategy allows the patterning of a wide variety of proteins and offers the possibility to dynamically modify the biofunctional properties of materials at defined subvolumes in 3D.
Observations and modeling of symmetric instability in the ocean interior in the Northwestern Equatorial Pacific
Authors: Zhou Hui , Dewar William , Yang Wenlong , Liu Hengchang , Chen Xu , Li Rui , Liu Chenglong , Gopalakrishnan Ganesh
Published: February 2022

Symmetric instability is a mechanism that can transfer geostrophic kinetic energy to overturning and dissipation. To date, symmetric instability has only been recognized to occur at the ocean surface or near topographic boundary layers. Analyses of direct microstructure measurements reveal enhanced dissipation caused by symmetric instability in the northwestern equatorial Pacific thermocline, which provides the first observational evidence of subsurface symmetric instability away from boundaries. Enhanced subsurface cross-equatorial exchange provides the negative potential vorticity needed to drive the symmetric instability, which is well reproduced by numerical modeling. These results suggest a new route to energy dissipation for large scale currents, and hence a new ocean turbulent mixing process in the ocean interior. Given the importance of vertical mixing in the evolution of equatorial thermocline, models may need to account for this mechanism to produce more reliable climate projections.
A human cell atlas of the pressure-induced hypertrophic heart
Authors: Nicin Luka , Schroeter Sam Michael , Glaser Simone Franziska , Schulze-Brüning Ralf , Pham Minh-Duc , Hille Susanne S. , Yekelchyk Michail , Kattih Badder , Abplanalp Wesley Tyler , Tombor Lukas , Müller Oliver J. , Braun Thomas , Meder Benjamin , Reich Christoph , Arsalan Mani , Holubec Tomas , Walther Thomas , Emrich Fabian , Krishnan Jaya , Zeiher Andreas M. , John David , Dimmeler Stefanie
Published: February 2022

Pathological cardiac hypertrophy is a leading cause of heart failure, but knowledge of the full repertoire of cardiac cells and their gene expression profiles in the human hypertrophic heart is missing. Here, by using large-scale single-nucleus transcriptomics, we present the transcriptional response of human cardiomyocytes to pressure overload caused by aortic valve stenosis and describe major alterations in cardiac cellular crosstalk. Hypertrophied cardiomyocytes had reduced input from endothelial cells and fibroblasts. Genes encoding Eph receptor tyrosine kinases, particularly EPHB1, were significantly downregulated in cardiomyocytes of the hypertrophied heart. Consequently, EPHB1 activation by its ligand ephrin (EFN)B2, which is mainly expressed by endothelial cells, was reduced. EFNB2 inhibited cardiomyocyte hypertrophy in vitro, while silencing its expression in endothelial cells induced hypertrophy in co-cultured cardiomyocytes. Our human cell atlas of the hypertrophied heart highlights the importance of intercellular crosstalk in disease pathogenesis and provides a valuable resource.
Aerobic photolysis of methylcobalamin: unraveling the photoreaction mechanism
Authors: Ghosh Arghya Pratim , Lodowski Piotr , Kozlowski Pawel M.
Published: February 2022

The photo-reactivity of cobalamins (Cbls) is influenced by the nature of axial ligands and the cofactor's environment.
Intramolecular charge transfer of a push–pull chromophore with restricted internal rotation of an electron donor
Authors: Lee Sebok , Jen Myungsam , Lee Gisang , Jang Taehyung , Pang Yoonsoo
Published: February 2022

A push–pull chromophore LD688 with hindered internal rotation of the dimethylamino group occurs via twisting of the julolidine moiety with intramolecular charge transfer.
Enhancement of p-xylene selectivity in the reaction between 2,5-dimethylfuran and ethanol over an ammonium fluoride-modified ZSM-5 zeolite
Authors: Zhao Rongrong , Li Shikun , Bi Lixin , Fu Qiang , Tan Hongzi , Wang Ming , Cui Hongyou
Published: February 2022

A renewable synthesis of p-xylene (PX) via 2,5-dimethylfuran (2,5-DMF) and ethanol was achieved on a hierarchical MFI zeolite, which shows excellent performances with PX selectivity of 78% and yield of 55%.
Catalytic cracking of CH3Cl on copper-based phases
Authors: Blaser Eugénie , Rosier Cécile , Huet Michel , Geantet Christophe , Loridant Stéphane
Published: February 2022

CuCl and Cu are active phases for CH3Cl cracking, a side reaction of the methylchlorosilanes direct synthesis. In the presence of black carbon simulating coke, CuCl is reduced leading to Cu, inactive for the direct synthesis, and chlorinated coke.
Phenolate-bonded bis(μ-oxido)-bis-copper(iii) intermediates: hydroxylation and dehalogenation reactivities
Authors: Kang Peng , Lin Bo-Lin , Large Tao A. G. , Ainsworth Jasper , Wasinger Erik C. , Stack T. Daniel P.
Published: February 2022

A Cu(iii) intermediate, ADBPD, effects novel dehalogenation–hydroxylations of exogenous phenolates; it is best formulated as containing 2 phenolates/Cu2O2 core.
Effects of two polysaccharides from Lepidium meyenii (maca) on intestinal immunity and inflammation in vitro
Authors: Chen Wenbo , Zhu Xiaolu , Wang Lei , Xin Xuan , Zhang Mengmeng
Published: February 2022

Effects of maca polysaccharides on intestinal immunity and intestinal inflammation.
Phycocyanin ameliorates mouse colitisviaphycocyanobilin-dependent antioxidant and anti-inflammatory protection of the intestinal epithelial barrier
Authors: Guo Wei , Zeng Mingyong , Zhu Suqin , Li Shiyang , Qian Yilin , Wu Haohao
Published: February 2022

Phycocyanobilin is responsible for the gut protection by phycocyanin in DSS-induced C57BL/6 mice due to its antioxidant and anti-inflammatory effects.
Screening and identification of a novel antidiabetic peptide from collagen hydrolysates of Chinese giant salamander skin: network pharmacology, inhibition kinetics and protection of IR-HepG2 cells
Authors: Zhou Ming , Ren Guoyan , Zhang Bin , Ma Fuli , Fan Jinling , Qiu Zhijun
Published: February 2022

A new antidiabetic peptide was screened from the collagen hydrolysates of Andrias davidianus skin by the network pharmacology method, and its glucose-lowering activity was detected by α-glycosidase inhibition assay and cell assay.
Oil bodies extracted from high-oil soybeans (Glycine max) exhibited higher oxidative and physical stability than oil bodies from high-protein soybeans
Authors: Zhou Xuan , Zhao Jiale , Zhao Xu , Sun Rongbo , Sun Chuanqiang , Hou Dongdong , Zhang Xuewei , Jiang Lianzhou , Hou Juncai , Jiang Zhanmei
Published: February 2022

This study investigated the composition, antioxidant capacity, oxidative stability and physical stability of soybean oil body emulsions recovered from three high-protein and three high-oil genotype soybeans.
Adhesion properties of cell surface proteins in Lactobacillus strains in the GIT environment
Authors: Yu Yixing , Zong Manli , Lao Lifeng , Wen Jianzhu , Pan Daodong , Wu Zhen
Published: February 2022

Surface molecules of the Lactobacillus strains are related to the adhesion property and this property are enhanced upon the external environmental stress, such as temperature, pH, sub-strength and ion concentration through the Quorum sensing effect.
Photophysical, electrochemical properties and flexible organic solar cell application of 7,7-bis(1-cyclopropyl carbonyl piperazino)-8,8 dicyanoquinodimethane
Authors: Syed Anwarhussaini , H Renuka , Mohitkar Anuradha , Pallepogu Raghavaiah , Challa Mahadev Sai Karthik , Goel Sanket , Jayanty Subbalakshmi
Published: February 2022

7,7-Bis(1-cyclopropylcarbonylpiperazino)-8,8-dicyanoquinodimethane, a novel thermally stable fluorophore manifested PCE of 2.26%; ∼10 folds improvement than the plain standalone device, finding its suitability in flexible optoelectronic applications.
Mechanical strain, thermal and pressure effects on the absorption edge of an organic charge-transfer polymer for flexible photovoltaics and sensors
Authors: Ratajczyk Paulina , Katrusiak Andrzej , Bogdanowicz Krzysztof A. , Przybył Wojciech , Krysiak Piotr , Kwak Anna , Iwan Agnieszka
Published: February 2022

A highly stretchable elastic organic charge-transfer polymer displays improved photovoltaic characteristics under high pressure.
Magnetic nanocarriers adorned on graphene: promising contrast-enhancing agents with state-of-the-art performance in magnetic resonance imaging (MRI) and theranostics
Authors: Gulati Shikha , Mansi  , Vijayan Sneha , Kumar Sanjay , Agarwal Varnika , Harikumar Bharath , Varma Rajender S.
Published: February 2022

Graphene-decorated magnetic nanocarriers applied as contrast agents to enhance MR images.
Non-steroidal anti-inflammatory drugs: recent advances in the use of synthetic COX-2 inhibitors
Authors: Ahmadi Mohsen , Bekeschus Sander , Weltmann Klaus-Dieter , von Woedtke Thomas , Wende Kristian
Published: February 2022

Overview of the structure and function of recent synthetic COX-2 inhibitors and the mechanism of action inside the active-site cavity.
Armeniaspirol analogues with more potent Gram-positive antibiotic activity show enhanced inhibition of the ATP-dependent proteases ClpXP and ClpYQ
Authors: Darnowski Michael G. , Lanosky Taylor D. , Labana Puneet , Brazeau-Henrie Jordan T. , Calvert Nicholas D. , Dornan Mark H. , Natola Claudia , Paquette André R. , Shuhendler Adam J. , Boddy Christopher N.
Published: February 2022

Antibiotics with fundamentally new mechanisms of action such as the armeniaspirols, which target the ATP-dependent proteases ClpXP and ClpYQ, must be developed to combat antimicrobial resistance.
Structural topologies involving energetically significant antiparallel π-stacking and unconventional N(nitrile)⋯π(fumarate) contacts in dinuclear Zn(ii) and polymeric Mn(ii) compounds: antiproliferative evaluation and theoretical studies
Authors: Sharma Pranay , Baishya Trishnajyoti , Gomila Rosa M. , Frontera Antonio , Barcelo-Oliver Miquel , Verma Akalesh K. , Das Jumi , Bhattacharyya Manjit K.
Published: February 2022

Anticancer activities considering cell viability, apoptosis and molecular docking have been explored in dinuclear Zn(ii) and polymeric Mn(ii) compounds involving energetically significant unconventional N(nitrile)⋯π(fum) contacts.
Efficient synthesis of an apremilast precursor and chiral β-hydroxy sulfones via ketoreductase-catalyzed asymmetric reduction
Authors: Guo Jiyang , Gao Xiao , Qian Dong , Wang Huibin , Jia Xian , Zhang Wenhe , Qin Bin , You Song
Published: February 2022

The synthesis of an apremilast precursor and chiral β-hydroxy sulfones catalyzed by ketoreductase with high efficiency and enantioselectivity is reported.
A multi-functional chromone-modified polyethylene obtained by metal-free C–H activation
Authors: Zhang Yongjie , Li Xiaopei , Zhu Wenqin , Liu Pibo , Ren Juntao , Chen Shangtao , Hu Yanming , Zhou Guangyuan
Published: February 2022

A chromone-modified polyethylene possessing intriguing antioxidative, fluorescence, and compatibility properties was facilely synthesized by a radical-mediated C–H activation method.
Ionic liquid surfactant-derived carbon micro/nanostructures toward application of supercapacitors
Authors: Li Weizheng , Gao Qiang , Shen Ming , Li Bingyu , Ren Chuanli , Yang Jun
Published: February 2022

Microequilibrium transformation of micelles and vesicles assembled by ionic liquid surfactants enables the precise structural design and controlled synthesis of carbon micro/nanospheres, which can be used for high-performance supercapacitor electrodes.
How the substrate affects amination reaction kinetics of nitrochlorobenzene
Authors: Lan Zhou , Lu Yangcheng
Published: February 2022

The reaction rate of the amination is affected by its electron-withdrawing group, however, there is currently a lack of quantitative research on the reaction rate of different substrates in experiments and simulations.
Fluorine-induced diastereodivergence discovered in an equally rare enantioselective syn-aza-Henry reaction
Authors: Bing Jade A. , Schley Nathan D. , Johnston Jeffrey N.
Published: February 2022

A comparison of enantioselective aza-Henry reactions with both non-fluorinated and α-fluoro nitroalkanes reveals an unusual reversal of diastereoselection favoring the rare syn-aza-Henry product as a result of fluorine-based diastereodivergence.
Controlling the lifetime of cucurbit[8]uril based self-abolishing nanozymes
Authors: Das Saurav , Das Tanushree , Das Priyam , Das Debapratim
Published: February 2022

Self-inhibitory feedback regulated transient assembly of a CB[8] based nanozyme is reported whose lifetime can be manipulated in multiple ways, ranging from minutes to hours.
Electrochemical oxidative N–H/P–H cross-coupling with H2 evolution towards the synthesis of tertiary phosphines
Authors: Yuan Yong , Liu Xue , Hu Jingcheng , Wang Pengjie , Wang Shengchun , Alhumade Hesham , Lei Aiwen
Published: February 2022

A facile and novel electrochemical oxidative N–H/P–H cross-coupling method for obtaining tertiary phosphines(iii) was developed.
Chemical lattice strain in nonstoichiometric oxides: an overview
Authors: Tsvetkov Dmitry S. , Sereda Vladimir V. , Malyshkin Dmitry A. , Ivanov Ivan L. , Zuev Andrey Yu.
Published: February 2022

This article reviews the state of the art – from the experimental and computational data available to the models, origins and possible uses – in the field of chemical strain of oxide materials (primarily those for elevated-temperature applications).