bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance
Authors: Sun Jie , Yan Wei , Zhang Xing-Nan , Lin Xiao , Li Hui , Gong Yi-Miao , Zhu Xi-Mei , Zheng Yong-Bo , Guo Xiang-Yang , Ma Yun-Dong , Liu Zeng-Yi , Liu Lin , Gao Jia-Hong , Vitiello Michael V. , Chang Su-Hua , Liu Xiao-Guang , Lu Lin
Published: July 2020

Chronic pain and sleep disturbance are highly comorbid disorders, which leads to barriers to treatment and significant healthcare costs. Understanding the underlying genetic and neural mechanisms of the interplay between sleep disturbance and chronic pain is likely to lead to better treatment. In this study, we combined 1206 participants with phenotype data, resting-state functional magnetic resonance imaging (rfMRI) data and genotype data from the Human Connectome Project and two large sample size genome-wide association studies (GWASs) summary data from published studies to identify the genetic and neural bases for the association between pain and sleep disturbance. Pittsburgh sleep quality index (PSQI) score was used for sleep disturbance, pain intensity was measured by Pain Intensity Survey. The result showed chronic pain was significantly correlated with sleep disturbance (r = 0.171, p-value < 0.001). Their genetic correlation was rg = 0.598 using linkage disequilibrium (LD) score regression analysis. Polygenic score (PGS) association analysis showed PGS of chronic pain was significantly associated with sleep and vice versa. Nine shared functional connectivity (FCs) were identified involving prefrontal cortex, temporal cortex, precentral/postcentral cortex, anterior cingulate cortex, fusiform gyrus and hippocampus. All these FCs mediated the effect of sleep disturbance on pain and seven FCs mediated the effect of pain on sleep disturbance. The chronic pain PGS was positively associated with the FC between middle temporal gyrus and hippocampus, which further mediated the effect of chronic pain PGS on PSQI score. Mendelian randomization analysis implied a possible causal relationship from chronic pain to sleep disturbance was stronger than that of sleep disturbance to chronic pain. The results provided genetic and neural evidence for the association between pain and sleep disturbance, which may inform future treatment approaches for comorbid chronic pain states and sleep disturbance.
LINC00266-1/miR-548c-3p/SMAD2 feedback loop stimulates the development of osteosarcoma
Authors: Zheng Shengnai , Wan Li , Ge Dawei , Jiang Fan , Qian Zhanyang , Tang Jian , Yang Jin , Yao Yilun , Yan Junwei , Zhao Lei , Li Haijun , Yang Lei
Published: July 2020

Osteosarcoma (OS) is one of the most common primary bone malignancies and accounts for 3.4% of pediatric tumors. Its 5-year survival is as low as about 20%. Differentially expressed lncRNAs in OS profiling were searched in the downloaded profile of GSE12865. As a result, LINC00266-1 was detected to be upregulated in both GSE12865 and OS tissues we collected. SMAD2 was the downstream target binding to promoter sites of LINC00266-1, displaying a positive regulatory interaction. Knockdown of LINC00266-1 suppressed the proliferative and metastatic abilities, and promoted the apoptosis in OS cells. Besides, knockdown of LINC00266-1 significantly alleviated the growth of OS in vivo. MiR-548c-3p was the sponge miRNA of LINC00266-1, which was able to reverse the regulatory effects of LINC00266-1 on OS cell phenotypes. Moreover, miR-548c-3p bound to the 3′-UTR of SMAD2 and thus downregulated SMAD2. Overexpression of SMAD2 partially reversed the regulatory effects of LINC00266-1 on OS cell phenotypes. Finally, we have identified that LINC00266-1/miR-548c-3p/SMAD2 feedback loop was responsible for stimulating the development of OS.
Ligand recognition by the γδ TCR and discrimination between homeostasis and stress conditions
Authors: Deseke Malte , Prinz Immo
Published: July 2020

T lymphocytes comprise cells expressing either an αβ or a γδ TCR. The riddle how αβ TCRs are triggered by specific peptides presented in the context of MHC was elucidated some time ago. In contrast, the mechanisms that underlie antigen recognition by γδ TCRs are still baffling the scientific community. It is clear that activation of γδ TCRs does not necessarily depend on MHC antigen presentation. To date, diverse and largely host-cell-derived molecules have been identified as cognate antigens for the γδ TCR. However, for most γδ TCRs, the activating ligand is still unknown and many open questions with regard to physiological relevance and generalizable concepts remain. Especially the question of how γδ T cells can distinguish homeostatic from stress conditions via their TCR remains largely unresolved. Recent discoveries in the field might have paved the way towards a better understanding of antigen recognition by the γδ TCR and have made it conceivable to revise the current knowledge and contextualize the new findings.
Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity
Authors: Toubal Amine , Kiaf Badr , Beaudoin Lucie , Cagninacci Lucie , Rhimi Moez , Fruchet Blandine , da Silva Jennifer , Corbett Alexandra J. , Simoni Yannick , Lantz Olivier , Rossjohn Jamie , McCluskey James , Lesnik Philippe , Maguin Emmanuelle , Lehuen Agnès
Published: July 2020

Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders.
Author Correction: G9a regulates breast cancer growth by modulating iron homeostasis through the repression of ferroxidase hephaestin
Authors: Wang Ya-fang , Zhang Jie , Su Yi , Shen Yan-yan , Jiang Dong-xian , Hou Ying-yong , Geng Mei-yu , Ding Jian , Chen Yi
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Protein–ligand binding with the coarse-grained Martini model
Authors: Souza Paulo C. T. , Thallmair Sebastian , Conflitti Paolo , Ramírez-Palacios Carlos , Alessandri Riccardo , Raniolo Stefano , Limongelli Vittorio , Marrink Siewert J.
Published: July 2020

The detailed understanding of the binding of small molecules to proteins is the key for the development of novel drugs or to increase the acceptance of substrates by enzymes. Nowadays, computer-aided design of protein–ligand binding is an important tool to accomplish this task. Current approaches typically rely on high-throughput docking essays or computationally expensive atomistic molecular dynamics simulations. Here, we present an approach to use the recently re-parametrized coarse-grained Martini model to perform unbiased millisecond sampling of protein–ligand interactions of small drug-like molecules. Remarkably, we achieve high accuracy without the need of any a priori knowledge of binding pockets or pathways. Our approach is applied to a range of systems from the well-characterized T4 lysozyme over members of the GPCR family and nuclear receptors to a variety of enzymes. The presented results open the way to high-throughput screening of ligand libraries or protein mutations using the coarse-grained Martini model.
Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin
Authors: Krafcikova Petra , Silhan Jan , Nencka Radim , Boura Evzen
Published: July 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. 2′-O-RNA methyltransferase (MTase) is one of the enzymes of this virus that is a potential target for antiviral therapy as it is crucial for RNA cap formation; an essential process for viral RNA stability. This MTase function is associated with the nsp16 protein, which requires a cofactor, nsp10, for its proper activity. Here we show the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Our structural comparisons reveal low conservation of the MTase catalytic site between Zika and SARS-CoV-2 viruses, but high conservation of the MTase active site between SARS-CoV-2 and SARS-CoV viruses; these data suggest that the preparation of MTase inhibitors targeting several coronaviruses - but not flaviviruses - should be feasible. Together, our data add to important information for structure-based drug discovery.
Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties
Authors: Zhang Weiyi , Zhang Youjun , Qiu Haiji , Guo Yafei , Wan Haoliang , Zhang Xiaoliang , Scossa Federico , Alseekh Saleh , Zhang Qinghua , Wang Pu , Xu Li , Schmidt Maximilian H-W , Jia Xinxin , Li Daili , Zhu Anting , Guo Fei , Chen Wei , Ni Dejiang , Usadel Björn , Fernie Alisdair R. , Wen Weiwei
Published: July 2020

Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3’5’H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds.
Mycobacterium tuberculosis FasR senses long fatty acyl-CoA through a tunnel and a hydrophobic transmission spine
Authors: Lara Julia , Diacovich Lautaro , Trajtenberg Felipe , Larrieux Nicole , Malchiodi Emilio L. , Fernández Marisa M. , Gago Gabriela , Gramajo Hugo , Buschiazzo Alejandro
Published: July 2020

Mycobacterium tuberculosis is a pathogen with a unique cell envelope including very long fatty acids, implicated in bacterial resistance and host immune modulation. FasR is a TetR-like transcriptional activator that plays a central role in sensing mycobacterial long-chain fatty acids and regulating lipid biosynthesis. Here we disclose crystal structures of M. tuberculosis FasR in complex with acyl effector ligands and with DNA, uncovering its molecular sensory and switching mechanisms. A long tunnel traverses the entire effector-binding domain, enabling long fatty acyl effectors to bind. Only when the tunnel is entirely occupied, the protein dimer adopts a rigid configuration with its DNA-binding domains in an open state, leading to DNA dissociation. The protein-folding hydrophobic core connects the two domains, and is completed into a continuous spine when the effector binds. Such a transmission spine is conserved in a large number of TetR-like regulators, offering insight into effector-triggered allosteric functional control.
Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors
Authors: Hosaka Kayoko , Yang Yunlong , Seki Takahiro , Du Qiqiao , Jing Xu , He Xingkang , Wu Jieyu , Zhang Yin , Morikawa Hiromasa , Nakamura Masaki , Scherzer Martin , Sun Xiaoting , Xu Yuanfu , Cheng Tao , Li Xuri , Liu Xialin , Li Qi , Liu Yizhi , Hong An , Chen Yuguo , Cao Yihai
Published: July 2020

FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2+ tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2+ pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2+ tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2+ breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
DNA sequence-dependent activity and base flipping mechanisms of DNMT1 regulate genome-wide DNA methylation
Authors: Adam Sabrina , Anteneh Hiwot , Hornisch Maximilian , Wagner Vincent , Lu Jiuwei , Radde Nicole E. , Bashtrykov Pavel , Song Jikui , Jeltsch Albert
Published: July 2020

DNA methylation maintenance by DNMT1 is an essential process in mammals but molecular mechanisms connecting DNA methylation patterns and enzyme activity remain elusive. Here, we systematically analyzed the specificity of DNMT1, revealing a pronounced influence of the DNA sequences flanking the target CpG site on DNMT1 activity. We determined DNMT1 structures in complex with preferred DNA substrates revealing that DNMT1 employs flanking sequence-dependent base flipping mechanisms, with large structural rearrangements of the DNA correlating with low catalytic activity. Moreover, flanking sequences influence the conformational dynamics of the active site and cofactor binding pocket. Importantly, we show that the flanking sequence preferences of DNMT1 highly correlate with genomic methylation in human and mouse cells, and 5-azacytidine triggered DNA demethylation is more pronounced at CpG sites with flanks disfavored by DNMT1. Overall, our findings uncover the intricate interplay between CpG-flanking sequence, DNMT1-mediated base flipping and the dynamic landscape of DNA methylation.
Understanding coordination reaction for producing stable electrode with various low work functions
Authors: Fukagawa Hirohiko , Suzuki Kazuma , Ito Hirokazu , Inagaki Kaito , Sasaki Tsubasa , Oono Taku , Hasegawa Munehiro , Morii Katsuyuki , Shimizu Takahisa
Published: July 2020

The realisation of a cathode with various work functions (WFs) is required to maximise the potential of organic semiconductors that have various electron affinities. However, the barrier-free contact for electrons could only be achieved by using reactive materials, which significantly reduce the environmental stability of organic devices. We show that a stable electrode with various WFs can be produced by utilising the coordination reaction between several phenanthroline derivatives and the electrode. Although the low WF of the electrode realised by using reactive materials is specific to the material, the WF of the phenanthroline-modified electrode is tunable depending on the amount of electron transfer associated with the coordination reaction. A phenanthroline-modified electrode that has a higher electron injection efficiency than lithium fluoride has been demonstrated. The observation of various WFs induced by the coordination reaction affords strategic perspectives on the development of stable cathodes unique to organic electronics.
Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer
Authors: Aubert Léo , Nandagopal Neethi , Steinhart Zachary , Lavoie Geneviève , Nourreddine Sami , Berman Jacob , Saba-El-Leil Marc K. , Papadopoli David , Lin Sichun , Hart Traver , Macleod Graham , Topisirovic Ivan , Gaboury Louis , Fahrni Christoph J. , Schramek Daniel , Meloche Sylvain , Angers Stephane , Roux Philippe P.
Published: July 2020

Despite its importance in human cancers, including colorectal cancers (CRC), oncogenic KRAS has been extremely challenging to target therapeutically. To identify potential vulnerabilities in KRAS-mutated CRC, we characterize the impact of oncogenic KRAS on the cell surface of intestinal epithelial cells. Here we show that oncogenic KRAS alters the expression of a myriad of cell-surface proteins implicated in diverse biological functions, and identify many potential surface-accessible therapeutic targets. Cell surface-based loss-of-function screens reveal that ATP7A, a copper-exporter upregulated by mutant KRAS, is essential for neoplastic growth. ATP7A is upregulated at the surface of KRAS-mutated CRC, and protects cells from excess copper-ion toxicity. We find that KRAS-mutated cells acquire copper via a non-canonical mechanism involving macropinocytosis, which appears to be required to support their growth. Together, these results indicate that copper bioavailability is a KRAS-selective vulnerability that could be exploited for the treatment of KRAS-mutated neoplasms.
Achieving asymmetry and trapping in diffusion with spatiotemporal metamaterials
Authors: Camacho Miguel , Edwards Brian , Engheta Nader
Published: July 2020

The process of diffusion is central to the ever increasing entropic state of the universe and is fundamental in many branches of science and engineering. Although non-reciprocal metamaterials are well developed for wave systems, the studies of diffusive metamaterials have been limited by their characteristic spatial inversion symmetry and time inversion antisymmetry. Here, we achieve large spatial asymmetric diffusion characteristics inside a metamaterial whose material parameters are space- and time-modulated. Inside such a spatiotemporal metamaterial, diffusion occurs as if the material had an intrinsic flow velocity, whose direction is dictated by the relative phase between the modulations of the conductivity and capacity. This creates dramatic out-of-equilibrium concentrations and depletions, which we demonstrate experimentally for the diffusion of electric charges in a one-dimensional electrical system composed of an array of space-time-modulated variable capacitors and switches. These results may offer exciting possibilities in various fields, including electronics, thermal management, chemical mixing, etc.
The unified myofibrillar matrix for force generation in muscle
Authors: Willingham T. Bradley , Kim Yuho , Lindberg Eric , Bleck Christopher K. E. , Glancy Brian
Published: July 2020

Human movement occurs through contraction of the basic unit of the muscle cell, the sarcomere. Sarcomeres have long been considered to be arranged end-to-end in series along the length of the muscle into tube-like myofibrils with many individual, parallel myofibrils comprising the bulk of the muscle cell volume. Here, we demonstrate that striated muscle cells form a continuous myofibrillar matrix linked together by frequently branching sarcomeres. We find that all muscle cells contain highly connected myofibrillar networks though the frequency of sarcomere branching goes down from early to late postnatal development and is higher in slow-twitch than fast-twitch mature muscles. Moreover, we show that the myofibrillar matrix is united across the entire width of the muscle cell both at birth and in mature muscle. We propose that striated muscle force is generated by a singular, mesh-like myofibrillar network rather than many individual, parallel myofibrils.
Divergent effects of climate change on future groundwater availability in key mid-latitude aquifers
Authors: Wu Wen-Ying , Lo Min-Hui , Wada Yoshihide , Famiglietti James S. , Reager John T. , Yeh Pat J.-F. , Ducharne Agnès , Yang Zong-Liang
Published: July 2020

Groundwater provides critical freshwater supply, particularly in dry regions where surface water availability is limited. Climate change impacts on GWS (groundwater storage) could affect the sustainability of freshwater resources. Here, we used a fully-coupled climate model to investigate GWS changes over seven critical aquifers identified as significantly distressed by satellite observations. We assessed the potential climate-driven impacts on GWS changes throughout the 21st century under the business-as-usual scenario (RCP8.5). Results show that the climate-driven impacts on GWS changes do not necessarily reflect the long-term trend in precipitation; instead, the trend may result from enhancement of evapotranspiration, and reduction in snowmelt, which collectively lead to divergent responses of GWS changes across different aquifers. Finally, we compare the climate-driven and anthropogenic pumping impacts. The reduction in GWS is mainly due to the combined impacts of over-pumping and climate effects; however, the contribution of pumping could easily far exceed the natural replenishment.
Author Correction: Caenorhabditis elegans is a useful model for anthelmintic discovery
Authors: Burns Andrew R. , Luciani Genna M. , Musso Gabriel , Bagg Rachel , Yeo May , Zhang Yuqian , Rajendran Luckshi , Glavin John , Hunter Robert , Redman Elizabeth , Stasiuk Susan , Schertzberg Michael , McQuibban G. Angus , Caffrey Conor R. , Cutler Sean R. , Tyers Mike , Giaever Guri , Nislow Corey , Fraser Andy G. , MacRae Calum A. , Gilleard John , Roy Peter J.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Rapid cost decrease of renewables and storage accelerates the decarbonization of China’s power system
Authors: He Gang , Lin Jiang , Sifuentes Froylan , Liu Xu , Abhyankar Nikit , Phadke Amol
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A New Phylogenomic Approach For Quantifying Horizontal Gene Transfer Trends in Prokaryotes
Authors: Avni Eliran , Snir Sagi
Published: July 2020

It is well established nowadays that among prokaryotes, various families of orthologous genes exhibit conflicting evolutionary history. A prime factor for this conflict is horizontal gene transfer (HGT) - the transfer of genetic material not via vertical descent. Thus, the prevalence of HGT is challenging the meaningfulness of the classical Tree of Life concept. Here we present a comprehensive study of HGT representing the entire prokaryotic world. We mainly rely on a novel analytic approach for analyzing an aggregate of gene histories, by means of the quartet plurality distribution (QPD) that we develop. Through the analysis of real and simulated data, QPD is used to reveal evidence of a barrier against HGT, separating the archaea from the bacteria and making HGT between the two domains, in general, quite rare. In contrast, bacteria’s confined HGT is substantially more frequent than archaea’s. Our approach also reveals that despite intensive HGT, a strong tree-like signal can be extracted, corroborating several previous works. Thus, QPD, which enables one to analytically combine information from an aggregate of gene trees, can be used for understanding patterns and rates of HGT in prokaryotes, as well as for validating or refuting models of horizontal genetic transfers and evolution in general.
Microstructural controls of anticrack nucleation in highly porous brittle solids
Authors: Ritter Jonas , Löwe Henning , Gaume Johan
Published: July 2020

Porous brittle solids have the ability to collapse and fail even under compressive stresses. In fracture mechanics, this singular behavior, often referred to as anticrack, demands for appropriate continuum models to predict the catastrophic failure. To identify universal controls of anticracks, we link the microstructure of a porous solid with its yield surface at the onset of plastic flow. We utilize an assembly method for porous structures, which allows to independently vary microstructural properties (density and coordination number) and perform discrete element simulations under mixed-mode (shear-compression) loading. In rescaled stress coordinates, the concurrent influence of the microstructural properties can be cast into a universal, ellipsoidal form of the yield surface that reveals an associative plastic flow rule, as a common feature of these materials. Our results constitute a constructive approach for continuum modeling of anticrack nucleation and propagation in highly porous brittle, engineering and geo-materials.
Fungus-growing insects host a distinctive microbiota apparently adapted to the fungiculture environment
Authors: Barcoto Mariana O. , Carlos-Shanley Camila , Fan Huan , Ferro Milene , Nagamoto Nilson S. , Bacci Mauricio , Currie Cameron R. , Rodrigues Andre
Published: July 2020

Some lineages of ants, termites, and beetles independently evolved a symbiotic association with lignocellulolytic fungi cultivated for food, in a lifestyle known as fungiculture. Fungus-growing insects’ symbiosis also hosts a bacterial community thought to integrate their physiology. Similarities in taxonomic composition support the microbiota of fungus-growing insects as convergent, despite differences in fungus-rearing by these insects. Here, by comparing fungus-growing insects to several hosts ranging diverse dietary patterns, we investigate whether the microbiota taxonomic and functional profiles are characteristic of the fungiculture environment. Compared to other hosts, the microbiota associated with fungus-growing insects presents a distinctive taxonomic profile, dominated by Gammaproteobacteria at class level and by Pseudomonas at genera level. Even with a functional profile presenting similarities with the gut microbiota of herbivorous and omnivorous hosts, some differentially abundant features codified by the microbiota of fungus-growing insects suggest these communities occupying microhabitats that are characteristic of fungiculture. These features include metabolic pathways involved in lignocellulose breakdown, detoxification of plant secondary metabolites, metabolism of simple sugars, fungal cell wall deconstruction, biofilm formation, antimicrobials biosynthesis, and metabolism of diverse nutrients. Our results suggest that the microbiota could be functionally adapted to the fungiculture environment, codifying metabolic pathways potentially relevant to the fungus-growing insects’ ecosystems functioning.
The effect of NMDA-R antagonist, MK-801, on neuronal mismatch along the rat auditory thalamocortical pathway
Authors: Parras Gloria G. , Valdés-Baizabal Catalina , Harms Lauren , Michie Patricia T. , Malmierca Manuel S.
Published: July 2020

Efficient sensory processing requires that the brain maximize its response to unexpected stimuli, while suppressing responsivity to expected events. Mismatch negativity (MMN) is an auditory event-related potential that occurs when a regular pattern is interrupted by an event that violates the expected properties of the pattern. According to the predictive coding framework there are two mechanisms underlying the MMN: repetition suppression and prediction error. MMN has been found to be reduced in individuals with schizophrenia, an effect believed to be underpinned by glutamate N-methyl-d-aspartate receptor (NMDA-R) dysfunction. In the current study, we aimed to test how the NMDA-R antagonist, MK-801 in the anaesthetized rat, affected repetition suppression and prediction error processes along the auditory thalamocortical pathway. We found that low-dose systemic administration of MK-801 differentially affect thalamocortical responses, namely, increasing thalamic repetition suppression and cortical prediction error. Results demonstrate an enhancement of neuronal mismatch, also confirmed by large scale-responses. Furthermore, MK-801 produces faster and stronger dynamics of adaptation along the thalamocortical hierarchy. Clearly more research is required to understand how NMDA-R antagonism and dosage affects processes contributing to MMN. Nonetheless, because a low dose of an NMDA-R antagonist increased neuronal mismatch, the outcome has implications for schizophrenia treatment.
Listening to pulses of radiation: design of a submersible thermoacoustic sensor
Authors: Barmak Rafael , Cernicchiaro Geraldo
Published: July 2020

Nowadays, various collaborations are creating immense machines to try to track and understand the origin of high-energy cosmic particles (e.g., IceCube, ANTARES, Baikal-GVD, P-ONE). The detection mechanism of these sophisticated experiments relies mainly on an optical signal generated by the passage of charged particles on a dielectric medium (Čerenkov radiation). Unfortunately, the dim light produced by passing particles cannot travel too far until it fades away, creating the necessity to instrument large areas with short spacing between sensors. The range limitation of the optical technique has created a fertile ground for experimenting on the detection of acoustic signals generated by radiation—thermoacoustics. Despite the increased use of the thermoacoustic technique, the instrumentation to capture the faint acoustic signals is still scarce. Therefore, this work has the objective to contribute with information on the critical stages of an affordable submersible thermoacoustic sensor: namely the piezoelectric transducer and the amplifying electronics. We tested the sensor in a $$170\,{\textit{l}}$$170l non-anechoic tank using an infrared ($$\lambda =1064\,\hbox {nm}$$λ=1064nm) Q-switched Nd:YAG laser as a pulsed energy source to create the characteristic signals of the thermoacoustic phenomena. In accordance with the thermoacoustic model, a polarity inversion of the pressure signal was observed when transiting from temperatures below the point of maximum density of water to temperatures above it. Also, the amplitude of the acoustic signal displayed a linear relationship with pulse energies up to $$(51.1 \pm 1.7)\,\hbox {mJ}$$(51.1±1.7)mJ ($$R^2 \sim 0.98$$R2∼0.98). Despite the use of cost-effective parts and simple construction methods, the proposed sensor design is a viable instrument for experimental thermoacoustic investigations on high-energy particles.
Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
Authors: Böhm Anja , Keuper Michaela , Meile Tobias , Zdichavsky Marty , Fritsche Andreas , Häring Hans-Ulrich , de Angelis Martin Hrabě , Staiger Harald , Franko Andras
Published: July 2020

Among obese subjects, metabolically healthy (MHO) and unhealthy obese (MUHO) subjects exist, the latter being characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Insulin resistance and obesity are known to associate with alterations in mitochondrial density, morphology, and function. Therefore, we assessed mitochondrial function in human subcutaneous preadipocytes as well as in differentiated adipocytes derived from well-matched donors. Primary subcutaneous preadipocytes from 4 insulin-resistant (MUHO) versus 4 insulin-sensitive (MHO), non-diabetic, morbidly obese Caucasians (BMI > 40 kg/m2), matched for sex, age, BMI, and percentage of body fat, were differentiated in vitro to adipocytes. Real-time cellular respiration was measured using an XF24 Extracellular Flux Analyzer (Seahorse). Lipolysis was stimulated by forskolin (FSK) treatment. Mitochondrial respiration was fourfold higher in adipocytes versus preadipocytes (p = 1.6*10–9). In adipocytes, a negative correlation of mitochondrial respiration with donors’ insulin sensitivity was shown (p = 0.0008). Correspondingly, in adipocytes of MUHO subjects, an increased basal respiration (p = 0.002), higher proton leak (p = 0.04), elevated ATP production (p = 0.01), increased maximal respiration (p = 0.02), and higher spare respiratory capacity (p = 0.03) were found, compared to MHO. After stimulation with FSK, the differences in ATP production, maximal respiration and spare respiratory capacity were blunted. The differences in mitochondrial respiration between MUHO/MHO were not due to altered mitochondrial content, fuel switch, or lipid metabolism. Thus, despite the insulin resistance of MUHO, we could clearly show an elevated mitochondrial respiration of MUHO adipocytes. We suggest that the higher mitochondrial respiration reflects a compensatory mechanism to cope with insulin resistance and its consequences. Preserving this state of compensation might be an attractive goal for preventing or delaying the transition from insulin resistance to overt diabetes.
Improved collateral flow and reduced damage after remote ischemic perconditioning during distal middle cerebral artery occlusion in aged rats
Authors: Ma Junqiang , Ma Yonglie , Shuaib Ashfaq , Winship Ian R.
Published: July 2020

Circulation through cerebral collaterals can maintain tissue viability until reperfusion is achieved. However, collateral circulation is time limited, and failure of collaterals is accelerated in the aged. Remote ischemic perconditioning (RIPerC), which involves inducing a series of repetitive, transient peripheral cycles of ischemia and reperfusion at a site remote to the brain during cerebral ischemia, may be neuroprotective and can prevent collateral failure in young adult rats. Here, we demonstrate the efficacy of RIPerC to improve blood flow through collaterals in aged (16–18 months of age) Sprague Dawley rats during a distal middle cerebral artery occlusion. Laser speckle contrast imaging and two-photon laser scanning microscopy were used to directly measure flow through collateral connections to ischemic tissue. Consistent with studies in young adult rats, RIPerC enhanced collateral flow by preventing the stroke-induced narrowing of pial arterioles during ischemia. This improved flow was associated with reduced early ischemic damage in RIPerC treated aged rats relative to controls. Thus, RIPerC is an easily administered, non-invasive neuroprotective strategy that can improve penumbral blood flow via collaterals. Enhanced collateral flow supports further investigation as an adjuvant therapy to recanalization therapy and a protective treatment to maintain tissue viability prior to reperfusion.
Sierra Nevada sweep: metagenomic measurements of bioaerosols vertically distributed across the troposphere
Authors: Jaing Crystal , Thissen James , Morrison Michael , Dillon Michael B. , Waters Samantha M. , Graham Garrett T. , Be Nicholas A. , Nicoll Patrick , Verma Sonali , Caro Tristan , Smith David J.
Published: July 2020

To explore how airborne microbial patterns change with height above the Earth’s surface, we flew NASA’s C-20A aircraft on two consecutive days in June 2018 along identical flight paths over the US Sierra Nevada mountain range at four different altitudes ranging from 10,000 ft to 40,000 ft. Bioaerosols were analyzed by metagenomic DNA sequencing and traditional culturing methods to characterize the composition and diversity of atmospheric samples compared to experimental controls. The relative abundance of taxa changed significantly at each altitude sampled, and the diversity profile shifted across the two sampling days, revealing a regional atmospheric microbiome that is dynamically changing. The most proportionally abundant microbial genera wereMycobacteriumandAchromobacterat 10,000 ft;StenotrophomonasandAchromobacterat 20,000 ft;DelftiaandPseudoperonosporaat 30,000 ft; andAlcaligenesandPenicilliumat 40,000 ft. Culture-based detections also identified viableBacillus zhangzhouensis,Bacillus pumilus, andBacillusspp. in the upper troposphere. To estimate bioaerosol dispersal, we developed a human exposure likelihood model (7-day forecast) using general aerosol characteristics and measured meteorological conditions. By coupling metagenomics to a predictive atmospheric model, we aim to set the stage for field campaigns that monitor global bioaerosol emissions and impacts.
Diabetes mellitus is independently associated with adverse clinical outcome in soft tissue sarcoma patients
Authors: Stelzl Adrian , Aziz Faisal , Riedl Jakob M. , Posch Florian , Smolle Maria A. , Stojakovic Tatjana , Terbuch Angelika , Pichler Martin , Bergovec Marko , Leithner Andreas , Liegl-Atzwanger Bernadette , Stotz Michael , Gerger Armin , Sourij Harald , Szkandera Joanna
Published: July 2020

Diabetes mellitus (DM) and hyperglycemia are known predictors of adverse outcome in different tumor entities. The present study investigated the effect of DM and pre-surgery blood glucose levels on cancer specific survival (CSS), overall survival (OS), and disease-free survival (DFS) in non-metastatic soft tissue sarcoma (STS) patients. A total of 475 STS patients who underwent curative resection were included in this retrospective study. CSS, DFS, and OS were assessed using Kaplan–Meier curves. The association between pre-existing DM as well as mean pre-surgery blood glucose levels and all 3 survival endpoints was analyzed using Cox-hazard proportional (for OS and DFS) and competing risk regression models (for CSS). In unadjusted analysis, DM was significantly associated with adverse CSS (sub-hazard ratio [SHR]: 2.14, 95% confidence interval [CI] 1.18–3.90, p = 0.013) and OS (hazard ratio [HR]: 2.05, 95% CI 1.28–3.28) and remained significant after adjusting for established prognostic factors (CSS: adjusted SHR 2.33, 95% CI 1.21–4.49, p = 0.012; OS: adjusted HR 1.96, 95% CI 1.17–3.28, p = 0.010), respectively. There was no significant association of DM with DFS (p = 0.149). The mean pre-surgery glucose levels were not significantly associated with inferior outcome (CSS: p = 0.510, OS: p = 0.382 and DFS: p = 0.786). This study shows, that DM represents a negative prognostic factor for clinical outcome in STS patients after curative resection.
The role of nanoparticle structure and morphology in the dissolution kinetics and nutrient release of nitrate-doped calcium phosphate nanofertilizers
Authors: Carmona Francisco J. , Dal Sasso Gregorio , Bertolotti Federica , Ramírez-Rodríguez Gloria B. , Delgado-López José M. , Pedersen Jan Skov , Masciocchi Norberto , Guagliardi Antonietta
Published: July 2020

Bio-inspired synthetic calcium phosphate (CaP) nanoparticles (NPs), mimicking the mineral component of bone and teeth, are emergent materials for sustainable applications in agriculture. These sparingly soluble salts show self-inhibiting dissolution processes in undersaturated aqueous media, the control at the molecular and nanoscale levels of which is not fully elucidated. Understanding the mechanisms of particle dissolution is highly relevant to the efficient delivery of macronutrients to the plants and crucial for developing a valuable synthesis-by-design approach. It has also implications in bone (de)mineralization processes. Herein, we shed light on the role of size, morphology and crystallinity in the dissolution behaviour of CaP NPs and on their nitrate doping for potential use as (P,N)-nanofertilizers. Spherical fully amorphous NPs and apatite-amorphous nanoplatelets (NPLs) in a core-crown arrangement are studied by combining forefront Small-Angle and Wide-Angle X-ray Total Scattering (SAXS and WAXTS) analyses. Ca2+ ion release rates differ for spherical NPs and NPLs demonstrating that morphology plays an active role in directing the dissolution kinetics. Amorphous NPs manifest a rapid loss of nitrates governed by surface-chemistry. NPLs show much slower release, paralleling that of Ca2+ ions, that supports both detectable nitrate incorporation in the apatite structure and dissolution from the core basal faces.
Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model
Authors: Mangarova Dilyana B. , Brangsch Julia , Mohtashamdolatshahi Azadeh , Kosch Olaf , Paysen Hendrik , Wiekhorst Frank , Klopfleisch Robert , Buchholz Rebecca , Karst Uwe , Taupitz Matthias , Schnorr Jörg , Hamm Bernd , Makowski Marcus R.
Published: July 2020

Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. Inflammation is crucial in the disease progression, having a substantial impact on various determinants in AAAs development. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling the highly sensitive detection of magnetic nanoparticles (MNPs), suitable as surrogate marker for molecular targeting of vascular inflammation. For this study, Apolipoprotein E-deficient-mice underwent surgical implantation of osmotic minipumps with constant Angiotensin II infusion. After 3 and 4 weeks respectively, in-vivo-magnetic resonance imaging (MRI), ex-vivo-MPI and ex-vivo-magnetic particle spectroscopy (MPS) were performed. The results were validated by histological analysis, immunohistology and laser ablation-inductively coupled plasma-mass spectrometry. MR-angiography enabled the visualization of aneurysmal development and dilatation in the experimental group. A close correlation (R = 0.87) with histological area assessment was measured. Ex-vivo-MPS revealed abundant iron deposits in AAA samples and ex-vivo histopathology measurements were in good agreement (R = 0.76). Ex-vivo-MPI and MPS results correlated greatly (R = 0.99). CD68-immunohistology stain and Perls’-Prussian-Blue-stain confirmed the colocalization of macrophages and MNPs. This study demonstrates the feasibility of ex-vivo-MPI for detecting inflammation in AAA. The quantitative ability for mapping MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAA in an experimental setting.
Elevational is the main factor controlling the soil microbial community structure in alpine tundra of the Changbai Mountain
Authors: Tang Mingze , Li Lin , Wang Xiaolong , You Jian , Li Jiangnan , Chen Xia
Published: July 2020

To reveal the self-coordination mechanism of the fragile ecosystem of alpine tundra, we explored the relationship between soil microorganisms and other elements. On the alpine tundra of the Changbai Mountain, different vegetation types, altitudes and soil properties were selected as driving factors of soil microbial community. Soil microbial community, C- and N-cycling functional microbial and fungal biomass were analyzed. Structural equation model was used to study the control of biotic and abiotic factors in rhizosphere soil microbial community. The results showed that the pH value of soil had the strongest direct impact on the diversity and community structure of soil microorganisms, and had significant correlation with most of the C- and N-cycling functional microbial; organic carbon and vegetation also have strongest direct effect on fungal biomass, but all of them were not main factors influence soil microbial community structure, the elevation was the main controlling factor. In addition, the elevation mainly through indirect action affects the soil microbial community by driving distribution of plant species, soil organic carbon and pH value. This finding highlighted that elevation was the main predictor to determine rhizosphere microbial community structure but not vegetation in alpine tundra of Changbai Mountain.
Loss of Rsph9 causes neonatal hydrocephalus with abnormal development of motile cilia in mice
Authors: Zou Wenzheng , Lv Yuqing , Liu Zux iang , Xia Pengyan , Li Hong , Jiao Jianwei
Published: July 2020

Hydrocephalus is a brain disorder triggered by cerebrospinal fluid accumulation in brain cavities. Even though cerebrospinal fluid flow is known to be driven by the orchestrated beating of the bundled motile cilia of ependymal cells, little is known about the mechanism of ciliary motility. RSPH9 is increasingly becoming recognized as a vital component of radial spokes in ciliary “9 + 2” ultrastructure organization. Here, we show that deletion of the Rsph9 gene leads to the development of hydrocephalus in the early postnatal period. However, the neurodevelopment and astrocyte development are normal in embryonic Rsph9−/− mice. The tubular structure of the central aqueduct was comparable in Rsph9−/− mice. Using high-speed video microscopy, we visualized lower beating amplitude and irregular rotation beating pattern of cilia bundles in Rsph9−/− mice compared with that of wild-type mice. And the centriolar patch size was significantly increased in Rsph9−/− cells. TEM results showed that deletion of Rsph9 causes little impact in ciliary axonemal organization but the Rsph9−/− cilia frequently had abnormal ectopic ciliary membrane inclusions. In addition, hydrocephalus in Rsph9−/− mice results in the development of astrogliosis, microgliosis and cerebrovascular abnormalities. Eventually, the ependymal cells sloughed off of the lateral wall. Our results collectively suggested that RSPH9 is essential for ciliary structure and motility of mouse ependymal cilia, and its deletion causes the pathogenesis of hydrocephalus.
Role and modulation of the secondary structure of antimicrobial peptides to improve selectivity
Authors: Liang Yangbin , Zhang Xinshuang , Yuan Yueling , Bao Yan , Xiong Menghua
Published: July 2020

Helix is a two-edged sword for AMPs, and conformational modulation of AMPs can control the balance between antimicrobial activity and toxicity.
Hybridizing clinical translatability with enzyme-free DNA signal amplifiers: recent advances in nucleic acid detection and imaging
Authors: Borum Raina M. , Jokerst Jesse V.
Published: July 2020

Strand amplifying HCR and CHA are adaptable with signalers for novel and clinically translatable nucleic acid sensors and imaging agents.
Metallosupramolecules of pillar[5]-bis-trithiacrown including a mercury(ii) iodide ion-triplet complex
Authors: Shin Mingyeong , Seo Sujin , Park In-Hyeok , Lee Eunji , Habata Yoichi , Lee Shim Sung
Published: July 2020

A combination of pillar[5]-bis-trithiacrown and HgI2 afforded a contact ion-triplet complex in which the host encapsulates the (I−–Hg2+–I−) entity via Hg2+⋯π and C–H⋯I− interactions, reflecting geometrical complementarity.
Correction: Citrate combustion synthesized Al-doped CaCu3Ti4O12 quadruple perovskite: synthesis, characterization and multifunctional properties
Authors: Pal Kamalesh , Dey Arka , Jana Rajkumar , Ray Partha P. , Bera Parthasarathi , Kumar Lalit , Mandal Tapas Kumar , Mohanty Paritosh , Seikh Md. Motin , Gayen Arup
Published: July 2020

Correction for ‘Citrate combustion synthesized Al-doped CaCu3Ti4O12 quadruple perovskite: synthesis, characterization and multifunctional properties’ by Kamalesh Pal et al., Phys. Chem. Chem. Phys., 2020, 22, 3499–3511, DOI: 10.1039/C9CP05005A.
Complementary and selective oxidation of hydrocarbon derivatives by two cytochrome P450 enzymes of the same family
Authors: Sarkar Md. Raihan , Bell Stephen G.
Published: July 2020

The cytochrome P450 enzymes CYP101B1 and CYP101C1, from a Novosphingobium bacterium, can efficiently hydroxylate hydrocarbon derivatives containing a carbonyl moiety. Cyclic ketones (C9 to C15) were oxidised with contrasting yet high selectivity.
Recent highlights and future prospects on mixed-metal MOFs as emerging supercapacitor candidates
Authors: Rajak Richa , Kumar Ravinder , Ansari Shagufi Naz , Saraf Mohit , Mobin Shaikh M.
Published: July 2020

Mixed-metallic metal–organic frameworks (M-MOFs) are prepared through one-pot-synthesis or post-synthetic modification approaches and can be easily transformed into various composites/derivatives which offer promising supercapacitor properties.
Crystallinity after decarboxylation of a metal–carboxylate framework: indestructible porosity for catalysis
Authors: Cheng Shengxian , Tieu Peter , Gao Wenpei , Hu Jieying , Feng Weijin , He Jun , Pan Xiaoqing , Xu Zhengtao
Published: July 2020

Towards 3D graphene: cyclizing the polyalkyne linkers of a Zr(iv)-based coordination network leads to an ordered carbon framework for versatile catalysis.