bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk
Authors: Dima Diana C. , Adams Rachael , Linden Stefanie C. , Baird Alister , Smith Jacqueline , Foley Sonya , Perry Gavin , Routley Bethany C. , Magazzini Lorenzo , Drakesmith Mark , Williams Nigel , Doherty Joanne , van den Bree Marianne B. M. , Owen Michael J. , Hall Jeremy , Linden David E. J. , Singh Krish D.
Published: September 2020

Rare copy number variants associated with increased risk for neurodevelopmental and psychiatric disorders (referred to as ND-CNVs) are characterized by heterogeneous phenotypes thought to share a considerable degree of overlap. Altered neural integration has often been linked to psychopathology and is a candidate marker for potential convergent mechanisms through which ND-CNVs modify risk; however, the rarity of ND-CNVs means that few studies have assessed their neural correlates. Here, we used magnetoencephalography (MEG) to investigate resting-state oscillatory connectivity in a cohort of 42 adults with ND-CNVs, including deletions or duplications at 22q11.2, 15q11.2, 15q13.3, 16p11.2, 17q12, 1q21.1, 3q29, and 2p16.3, and 42 controls. We observed decreased connectivity between occipital, temporal, and parietal areas in participants with ND-CNVs. This pattern was common across genotypes and not exclusively characteristic of 22q11.2 deletions, which were present in a third of our cohort. Furthermore, a data-driven graph theory framework enabled us to successfully distinguish participants with ND-CNVs from unaffected controls using differences in node centrality and network segregation. Together, our results point to alterations in electrophysiological connectivity as a putative common mechanism through which genetic factors confer increased risk for neurodevelopmental and psychiatric disorders.
The type of stress matters: repeated injection and permanent social isolation stress in male mice have a differential effect on anxiety- and depressive-like behaviours, and associated biological alterations
Authors: Du Preez Andrea , Law Thomas , Onorato Diletta , Lim Yau M. , Eiben Paola , Musaelyan Ksenia , Egeland Martin , Hye Abdul , Zunszain Patricia A. , Thuret Sandrine , Pariante Carmine M. , Fernandes Cathy
Published: September 2020

Chronic stress can alter the immune system, adult hippocampal neurogenesis and induce anxiety- and depressive-like behaviour in rodents. However, previous studies have not discriminated between the effect(s) of different types of stress on these behavioural and biological outcomes. We investigated the effect(s) of repeated injection vs. permanent social isolation on behaviour, stress responsivity, immune system functioning and hippocampal neurogenesis, in young adult male mice, and found that the type of stress exposure does indeed matter. Exposure to 6 weeks of repeated injection resulted in an anxiety-like phenotype, decreased systemic inflammation (i.e., reduced plasma levels of TNFα and IL4), increased corticosterone reactivity, increased microglial activation and decreased neuronal differentiation in the dentate gyrus (DG). In contrast, exposure to 6 weeks of permanent social isolation resulted in a depressive-like phenotype, increased plasma levels of TNFα, decreased plasma levels of IL10 and VEGF, decreased corticosterone reactivity, decreased microglial cell density and increased cell density for radial glia, s100β-positive cells and mature neuroblasts—all in the DG. Interestingly, combining the two distinct stress paradigms did not have an additive effect on behavioural and biological outcomes, but resulted in yet a different phenotype, characterized by increased anxiety-like behaviour, decreased plasma levels of IL1β, IL4 and VEGF, and decreased hippocampal neuronal differentiation, without altered neuroinflammation or corticosterone reactivity. These findings demonstrate that different forms of chronic stress can differentially alter both behavioural and biological outcomes in young adult male mice, and that combining multiple stressors may not necessarily cause more severe pathological outcomes.
Polygenic risk for autism spectrum disorder affects left amygdala activity and negative emotion in schizophrenia
Authors: Qin Yue , Kang Jujiao , Jiao Zeyu , Wang Yi , Wang Jiucun , Wang Hongyan , Feng Jianfeng , Jin Li , Wang Fei , Gong Xiaohong
Published: September 2020

Although the diagnoses based on phenomenology have many practical advantages, accumulating evidence shows that schizophrenia and autism spectrum disorder (ASD) share some overlap in genetics and clinical presentation. It remains largely unknown how ASD-associated polygenetic risk contributes to the pathogenesis of schizophrenia. In the present study, we calculated high-resolution ASD polygenic risk scores (ASD PRSs) and selected optimal ten ASD PRS with minimal P values in the association analysis of PRSs, with schizophrenia to assess the effect of ASD PRS on brain neural activity in schizophrenia cases and controls. We found that amplitude of low-frequency fluctuation in left amygdala was positively associated with ASD PRSs in our cohort. Correlation analysis of ASD PRSs with facial emotion recognition test identified the negative correlation of ASD PRSs with negative emotions in schizophrenia cases and controls. Finally, functional enrichment analysis of PRS genes revealed that neural system function and development, as well as signal transduction, were mainly enriched in PRS genes. Our results provide empirical evidence that polygenic risk for ASD contributes to schizophrenia by the intermediate phenotypes of left amygdala function and emotion recognition. It provides a promising strategy to understand the relationship between phenotypes and genotypes shared in mental disorders.
Correction: Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study
Authors: Zhang Peixun , Li Jia , Liu Huixin , Han Na , Ju Jiabao , Kou Yuhui , Chen Lei , Jiang Mengxi , Pan Feng , Zheng Yali , Gao Zhancheng , Jiang Baoguo
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RAB31 marks and controls an ESCRT-independent exosome pathway
Authors: Wei Denghui , Zhan Weixiang , Gao Ying , Huang Liyan , Gong Run , Wang Wen , Zhang Ruhua , Wu Yuanzhong , Gao Song , Kang Tiebang
Published: September 2020

Exosomes are generated within the multivesicular endosomes (MVEs) as intraluminal vesicles (ILVs) and secreted during the fusion of MVEs with the cell membrane. The mechanisms of exosome biogenesis remain poorly explored. Here we identify that RAB31 marks and controls an ESCRT-independent exosome pathway. Active RAB31, phosphorylated by epidermal growth factor receptor (EGFR), engages flotillin proteins in lipid raft microdomains to drive EGFR entry into MVEs to form ILVs, which is independent of the ESCRT (endosomal sorting complex required for transport) machinery. Active RAB31 interacts with the SPFH domain and drives ILV formation via the Flotillin domain of flotillin proteins. Meanwhile, RAB31 recruits GTPase-activating protein TBC1D2B to inactivate RAB7, thereby preventing the fusion of MVEs with lysosomes and enabling the secretion of ILVs as exosomes. These findings establish that RAB31 has dual functions in the biogenesis of exosomes: driving ILVs formation and suppressing MVEs degradation, providing an exquisite framework to better understand exosome biogenesis.
Modulated structure determination and ion transport mechanism of oxide-ion conductor CeNbO4+δ
Authors: Li Jian , Pan Fengjuan , Geng Shipeng , Lin Cong , Palatinus Lukas , Allix Mathieu , Kuang Xiaojun , Lin Jianhua , Sun Junliang
Published: September 2020

CeNbO4+δ, a family of oxygen hyperstoichiometry materials with varying oxygen content (CeNbO4, CeNbO4.08, CeNbO4.25, CeNbO4.33) that shows mixed electronic and oxide ionic conduction, has been known for four decades. However, the oxide ionic transport mechanism has remained unclear due to the unknown atomic structures of CeNbO4.08 and CeNbO4.33. Here, we report the complex (3 + 1)D incommensurately modulated structure of CeNbO4.08, and the supercell structure of CeNbO4.33 from single nanocrystals by using a three-dimensional electron diffraction technique. Two oxide ion migration events are identified in CeNbO4.08 and CeNbO4.25 by molecular dynamics simulations, which was a synergic-cooperation knock-on mechanism involving continuous breaking and reformation of Nb2O9 units. However, the excess oxygen in CeNbO4.33 hardly migrates because of the high concentration and the ordered distribution of the excess oxide ions. The relationship between the structure and oxide ion migration for the whole series of CeNbO4+δ compounds elucidated here provides a direction for the performance optimization of these compounds.
Macroecological laws describe variation and diversity in microbial communities
Authors: Grilli Jacopo
Published: September 2020

How the coexistence of many species is maintained is a fundamental and unresolved question in ecology. Coexistence is a puzzle because we lack a mechanistic understanding of the variation in species presence and abundance. Whether variation in ecological communities is driven by deterministic or random processes is one of the most controversial issues in ecology. Here, I study the variation of species presence and abundance in microbial communities from a macroecological standpoint. I identify three macroecological laws that quantitatively characterize the fluctuation of species abundance across communities and over time. Using these three laws, one can predict species’ presence and absence, diversity, and commonly studied macroecological patterns. I show that a mathematical model based on environmental stochasticity, the stochastic logistic model, quantitatively predicts the three macroecological laws, as well as non-stationary properties of community dynamics.
Optical imaging of single-protein size, charge, mobility, and binding
Authors: Ma Guangzhong , Wan Zijian , Yang Yunze , Zhang Pengfei , Wang Shaopeng , Tao Nongjian
Published: September 2020

Detection and identification of proteins are typically achieved by analyzing protein size, charge, mobility and binding to antibodies, which are critical for biomedical research and disease diagnosis and treatment. Despite the importance, measuring these quantities with one technology and at the single-molecule level has not been possible. Here we tether a protein to a surface with a flexible polymer, drive it into oscillation with an electric field, and image the oscillation with a near field optical imaging method, from which we determine the size, charge, and mobility of the protein. We also measure antibody binding and conformation changes in the protein. The work demonstrates a capability for comprehensive protein analysis and precision protein biomarker detection at the single molecule level.
The scaling laws of edge vs. bulk interlayer conduction in mesoscale twisted graphitic interfaces
Authors: Dutta Debopriya , Oz Annabelle , Hod Oded , Koren Elad
Published: September 2020

The unusual electronic properties of edges in graphene-based systems originate from the pseudospinorial character of their electronic wavefunctions associated with their non-trivial topological structure. This is manifested by the appearance of pronounced zero-energy electronic states localized at the material zigzag edges that are expected to have a significant contribution to the interlayer transport in such systems. In this work, we utilize a unique experimental setup and electronic transport calculations to quantitatively distinguish between edge and bulk transport, showing that their relative contribution strongly depends on the angular stacking configuration and interlayer potential. Furthermore, we find that, despite of the strong localization of edge state around the circumference of the contact, edge transport in incommensurate interfaces can dominate up to contact diameters of the order of 2 μm, even in the presence of edge disorder. The intricate interplay between edge and bulk transport contributions revealed in the present study may have profound consequences on practical applications of nanoscale twisted graphene-based electronics.
Visual mate preference evolution during butterfly speciation is linked to neural processing genes
Authors: Rossi Matteo , Hausmann Alexander E. , Thurman Timothy J. , Montgomery Stephen H. , Papa Riccardo , Jiggins Chris D. , McMillan W. Owen , Merrill Richard M.
Published: September 2020

Many animal species remain separate not because their individuals fail to produce viable hybrids but because they “choose” not to mate. However, we still know very little of the genetic mechanisms underlying changes in these mate preference behaviours.Heliconiusbutterflies display bright warning patterns, which they also use to recognize conspecifics. Here, we couple QTL for divergence in visual preference behaviours with population genomic and gene expression analyses of neural tissue (central brain, optic lobes and ommatidia) across development in two sympatricHeliconiusspecies. Within a region containing 200 genes, we identify five genes that are strongly associated with divergent visual preferences. Three of these have previously been implicated in key components of neural signalling (specifically anionotropic glutamate receptorand tworegucalcins), and overall our candidates suggest shifts in behaviour involve changes in visual integration or processing. This would allow preference evolution without altering perception of the wider environment.
In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia
Authors: Sherif Mohamed A. , Neymotin Samuel A. , Lytton William W.
Published: September 2020

Treatment of schizophrenia has had limited success in treating core cognitive symptoms. The evidence of multi-gene involvement suggests that multi-target therapy may be needed. Meanwhile, the complexity of schizophrenia pathophysiology and psychopathology, coupled with the species-specificity of much of the symptomatology, places limits on analysis via animal models, in vitro assays, and patient assessment. Multiscale computer modeling complements these traditional modes of study. Using a hippocampal CA3 computer model with 1200 neurons, we examined the effects of alterations in NMDAR, HCN (Ih current), and GABAAR on information flow (measured with normalized transfer entropy), and in gamma activity in local field potential (LFP). We found that altering NMDARs, GABAAR, Ih, individually or in combination, modified information flow in an inverted-U shape manner, with information flow reduced at low and high levels of these parameters. Theta-gamma phase-amplitude coupling also had an inverted-U shape relationship with NMDAR augmentation. The strong information flow was associated with an intermediate level of synchrony, seen as an intermediate level of gamma activity in the LFP, and an intermediate level of pyramidal cell excitability. Our results are consistent with the idea that overly low or high gamma power is associated with pathological information flow and information processing. These data suggest the need for careful titration of schizophrenia pharmacotherapy to avoid extremes that alter information flow in different ways. These results also identify gamma power as a potential biomarker for monitoring pathology and multi-target pharmacotherapy.
Strong and robust polarization anisotropy of site- and size-controlled single InGaN/GaN quantum wires
Authors: Yeo Hwan-Seop , Lee Kwanjae , Sim Young Chul , Park Seoung-Hwan , Cho Yong-Hoon
Published: September 2020

Optical polarization is an indispensable component in photonic applications, the orthogonality of which extends the degree of freedom of information, and strongly polarized and highly efficient small-size emitters are essential for compact polarization-based devices. We propose a group III-nitride quantum wire for a highly-efficient, strongly-polarized emitter, the polarization anisotropy of which stems solely from its one-dimensionality. We fabricated a site-selective and size-controlled single quantum wire using the geometrical shape of a three-dimensional structure under a self-limited growth mechanism. We present a strong and robust optical polarization anisotropy at room temperature emerging from a group III-nitride single quantum wire. Based on polarization-resolved spectroscopy and strain-included 6-band k·p calculations, the strong anisotropy is mainly attributed to the anisotropic strain distribution caused by the one-dimensionality, and its robustness to temperature is associated with an asymmetric quantum confinement effect.
Rapid functional traits turnover in boreal dragonfly communities (Odonata)
Authors: Dalzochio Marina Schmidt , Périco Eduardo , Dametto Norton , Sahlén Göran
Published: September 2020

All natural populations show fluctuations in space or time. This is fundamental for the maintenance of biodiversity, as it allows species to coexist. Long-term ecological studies are rare, mainly due to logistics, but studies like the one presented below recognize the dimensionality of temporal change and the ecological processes that lead to shifts in community composition over time. Here, we used three sampling occasions from a dataset spanning 20 years where dragonflies in central Sweden were monitored. Our aim was to investigate how the prevalence of ecological and biological species traits varied over time measured as Community-level Weighted Means of trait values (CWM). Most CWM values varied significantly between years. Most of the traits changed between the second and the last sampling occasion, but not between the two first ones. These changes could be linked to major changes in species abundance. Our work indicates that fundamental shifts in community structure can occur over a short time, providing environmental drivers act on species turnover. In our case, Climate change and pH levels in lakes are most likely the most important factors.
Smectite clay minerals reduce the acute toxicity of quaternary alkylammonium compounds towards potentially pathogenic bacterial taxa present in manure and soil
Authors: Heyde Benjamin Justus , Glaeser Stefanie P. , Bisping Linda , Kirchberg Kristin , Ellinghaus Rüdiger , Siemens Jan , Mulder Ines
Published: September 2020

Quaternary alkylammonium compounds (QAACs) are a group of cationic surfactants which are disinfectants with numerous industrial and agricultural applications and frequently released into the environment. One recent hypothesis is that bacteria present in soil will be protected from acute toxic effects of QAACs in the presence of expandable layer silicates due to interlayer sorption. We therefore studied bacterial growth kinetics with high temporal resolution and determined minimal inhibitory concentrations (MICs) of two QAACs, benzyldimethyldodecylammonium chloride (BAC-C12) and didecyldimethylammonium chlorid (DADMAC-C10), for eight strains of different bacterial taxa (Escherichia coli, Acinetobacter, Enterococcus faecium, Enterococcus faecalis, and Pseudomonas fluorescens) in relation to QAAC sorption to smectite and kaolinite. The MICs of BAC-C12 and DADMAC-C10 were in the absence of smectite and kaolinite in the order of 10 to 30 µg mL−1 and 1.0 to 3.5 µg mL−1 for all strains except the more sensitive Acinetobacter strain. For all tested strains and both tested QAACs, the presence of smectite increased apparent MIC values while kaolinite had no effect on MICs. Sorption curves without bacteria showed that smectite sorbed larger amounts of QAACs than kaolinite. Correcting nominal QAAC concentrations employed in toxicity tests for QAAC sorption using the sorption curves explained well the observed shifts in apparent MICs. Transmission electron microscopy (TEM) demonstrated that the interlayer space of smectite expanded from 13.7 ± 1 Å to 19.9 ± 1.5 Å after addition of BAC-C12. This study provides first evidence that low charge 2:1 expandable layer silicates can play an important role for buffering QAAC toxicity in soils.
Vitamin E is necessary for zebrafish nervous system development
Authors: Head Brian , La Du Jane , Tanguay Robyn L. , Kioussi Chrissa , Traber Maret G.
Published: September 2020

Vitamin E (VitE) deficiency results in embryonic lethality. Knockdown of the gene ttpa encoding for the VitE regulatory protein [α-tocopherol transfer protein (α-TTP)] in zebrafish embryos causes death within 24 h post-fertilization (hpf). To test the hypothesis that VitE, not just α-TTP, is necessary for nervous system development, adult 5D strain zebrafish, fed either VitE sufficient (E+) or deficient (E−) diets, were spawned to obtain E+ and E− embryos, which were subjected to RNA in situ hybridization and RT-qPCR. Ttpa was expressed ubiquitously in embryos up to 12 hpf. Early gastrulation (6 hpf) assessed by goosecoid expression was unaffected by VitE status. By 24 hpf, embryos expressed ttpa in brain ventricle borders, which showed abnormal closure in E− embryos. They also displayed disrupted patterns of paired box 2a (pax2a) and SRY-box transcription factor 10 (sox10) expression in the midbrain-hindbrain boundary, spinal cord and dorsal root ganglia. In E− embryos, the collagen sheath notochord markers (col2a1a and col9a2) appeared bent. Severe developmental errors in E− embryos were characterized by improper nervous system patterning of the usually carefully programmed transcriptional signals. Histological analysis also showed developmental defects in the formation of the fore-, mid- and hindbrain and somites of E− embryos at 24 hpf. Ttpa expression profile was not altered by the VitE status demonstrating that VitE itself, and not ttpa, is required for development of the brain and peripheral nervous system in this vertebrate embryo model.
Metagenomic sequencing of stool samples in Bangladeshi infants: virome association with poliovirus shedding after oral poliovirus vaccination
Authors: Tan Susanna K. , Granados Andrea C. , Bouquet Jerome , Hoy-Schulz Yana Emmy , Green Lauri , Federman Scot , Stryke Doug , Haggerty Thomas D. , Ley Catherine , Yeh Ming-Te , Jannat Kaniz , Maldonado Yvonne A. , Andino Raul , Parsonnet Julie , Chiu Charles Y.
Published: September 2020

The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log10vs. 2.25 log10, p = 0.002), particularly from potential viral pathogens (2.78log10vs. 0.83log10, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p = 0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.
Thermal energy storage and thermal conductivity properties of fatty acid/fatty acid-grafted-CNTs and fatty acid/CNTs as novel composite phase change materials
Authors: Al-Ahmed Amir , Sarı Ahmet , Mazumder Mohammad Abu Jafar , Salhi Billel , Hekimoğlu Gökhan , Al-Sulaiman Fahad A. , Inamuddin
Published: September 2020

In recent year, fatty acids (FAs) are heavily studied for heat storage applications and they have shown promising advantages over other organic phase change materials (PCMs). Among the FAs; capric, palmitic and stearic acids are the most studied PCMs. Several researchers have investigated these FAs and tried to improve their thermal properties, mainly by adding different high conducting fillers, such as graphite, metal foams, CNTs, graphene etc. In most cases, these fillers improved the thermal conductivity and heat transfer property but reduce the heat storage capacity considerably. These composites also lose the mixing uniformity during the charging and discharging process. To overcome these issues, selected FAs were grafted on the functionalized CNT surfaces and used as conductive fillers to prepare FA based composite PCMs. This process significantly contributed to prevent the drastic reduction of the overall heat storage capacity and also showed better dispersion in both solid and liquid state. Thermal cycling test showed the variations in the thermal energy storage values of all composite PCMs, however, within the tolerable grade and they had appreciable phase change stability and good chemical stability even after 2,000 cycles.
How people know their risk preference
Authors: Arslan Ruben C. , Brümmer Martin , Dohmen Thomas , Drewelies Johanna , Hertwig Ralph , Wagner Gert G.
Published: September 2020

People differ in their willingness to take risks. Recent work found that revealed preference tasks (e.g., laboratory lotteries)—a dominant class of measures—are outperformed by survey-based stated preferences, which are more stable and predict real-world risk taking across different domains. How can stated preferences, often criticised as inconsequential “cheap talk,” be more valid and predictive than controlled, incentivized lotteries? In our multimethod study, over 3,000 respondents from population samples answered a single widely used and predictive risk-preference question. Respondents then explained the reasoning behind their answer. They tended to recount diagnostic behaviours and experiences, focusing on voluntary, consequential acts and experiences from which they seemed to infer their risk preference. We found that third-party readers of respondents’ brief memories and explanations reached similar inferences about respondents’ preferences, indicating the intersubjective validity of this information. Our results help unpack the self perception behind stated risk preferences that permits people to draw upon their own understanding of what constitutes diagnostic behaviours and experiences, as revealed in high-stakes situations in the real world.
Prognostic value of long-term gamma-glutamyl transferase variability in individuals with diabetes: a nationwide population-based study
Authors: Lee Da Young , Han Kyungdo , Yu Ji Hee , Park Sanghyun , Seo Ji A , Kim Nam Hoon , Yoo Hye Jin , Kim Sin Gon , Kim Seon Mee , Choi Kyung Mook , Baik Sei Hyun , Park Yong Gyu , Kim Nan Hee
Published: September 2020

We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009–2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03–1.10) and 1.23 (1.20–1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.
Quantitative in vivo bioluminescence imaging of orthotopic patient-derived glioblastoma xenografts
Authors: Koessinger Anna L. , Koessinger Dominik , Stevenson Katrina , Cloix Catherine , Mitchell Louise , Nixon Colin , Gomez-Roman Natividad , Chalmers Anthony J. , Norman Jim C. , Tait Stephen W. G.
Published: September 2020

Despite extensive research, little progress has been made in glioblastoma therapy, owing in part to a lack of adequate preclinical in vivo models to study this disease. To mitigate this, primary patient-derived cell lines, which maintain their specific stem-like phenotypes, have replaced established glioblastoma cell lines. However, due to heterogenous tumour growth inherent in glioblastoma, the use of primary cells for orthotopic in vivo studies often requires large experimental group sizes. Therefore, when using intracranial patient-derived xenograft (PDX) approaches, it is advantageous to deploy imaging techniques to monitor tumour growth and allow stratification of mice. Here we show that stable expression of near-infrared fluorescent protein (iRFP) in patient-derived glioblastoma cells enables rapid, direct non-invasive monitoring of tumour development without compromising tumour stemness or tumorigenicity. Moreover, as this approach does not depend on the use of agents like luciferin, which can cause variability due to changing bioavailability, it can be used for quantitative longitudinal monitoring of tumour growth. Notably, we show that this technique also allows quantitative assessment of tumour burden in highly invasive models spreading throughout the brain. Thus, iRFP transduction of primary patient-derived glioblastoma cells is a reliable, cost- and time-effective way to monitor heterogenous orthotopic PDX growth.
Neurostimulation stabilizes spiking neural networks by disrupting seizure-like oscillatory transitions
Authors: Rich Scott , Hutt Axel , Skinner Frances K. , Valiante Taufik A. , Lefebvre Jérémie
Published: September 2020

An improved understanding of the mechanisms underlying neuromodulatory approaches to mitigate seizure onset is needed to identify clinical targets for the treatment of epilepsy. Using a Wilson–Cowan-motivated network of inhibitory and excitatory populations, we examined the role played by intrinsic and extrinsic stimuli on the network’s predisposition to sudden transitions into oscillatory dynamics, similar to the transition to the seizure state. Our joint computational and mathematical analyses revealed that such stimuli, be they noisy or periodic in nature, exert a stabilizing influence on network responses, disrupting the development of such oscillations. Based on a combination of numerical simulations and mean-field analyses, our results suggest that high variance and/or high frequency stimulation waveforms can prevent multi-stability, a mathematical harbinger of sudden changes in network dynamics. By tuning the neurons’ responses to input, stimuli stabilize network dynamics away from these transitions. Furthermore, our research shows that such stabilization of neural activity occurs through a selective recruitment of inhibitory cells, providing a theoretical undergird for the known key role these cells play in both the healthy and diseased brain. Taken together, these findings provide new vistas on neuromodulatory approaches to stabilize neural microcircuit activity.
Key factors behind autofluorescence changes caused by ablation of cardiac tissue
Authors: Muselimyan Narine , Asfour Huda , Sarvazyan Narine
Published: September 2020

Radiofrequency ablation is a commonly used clinical procedure that destroys arrhythmogenic sources in patients suffering from atrial fibrillation and other types of cardiac arrhythmias. To improve the success of this procedure, new approaches for real-time visualization of ablation sites are being developed. One of these promising methods is hyperspectral imaging, an approach that detects lesions based on changes in the endogenous tissue autofluorescence profile. To facilitate the clinical implementation of this approach, we examined the key variables that can influence ablation-induced spectral changes, including the drop in myocardial NADH levels, the release of lipofuscin-like pigments, and the increase in diffuse reflectance of the cardiac muscle beneath the endocardial layer. Insights from these experiments suggested simpler algorithms that can be used to acquire and post-process the spectral information required to reveal the lesion sites. Our study is relevant to a growing number of multilayered clinical targets to which spectral approaches are being applied.
Synthesis of polypyrrole/nitrogen-doped porous carbon matrix composite as the electrode material for supercapacitors
Authors: Feng Minzhen , Lu Wei , Zhou Yun , Zhen Ranran , He Hongmei , Wang Ya , Li Chunmei
Published: September 2020

Polypyrrole complex nitrogen-doped porous carbon matrix (PPy/N-PCM) was synthesized by a simple two-step method. Firstly, graphene oxide was prepared by the modified Hummers method. Secondly, Polypyrrole was compounded on the graphene oxide substrate, and the carbon matrix with a high specific surface area was obtained through high-temperature carbonization and KOH activation, and polypyrrole was used as a nitrogen source for the final nitrogen-doped composite material. The structure characterization of the carbon matrix and the final composite material shows that the carbon matrix surface has obvious porous structure, and the polypyrrole nanospheres grow uniformly on the porous carbon matrix surface. The electrochemical evaluation show that the prepared PPy/N-PCM has excellent supercapacitor performance, and its specific capacitance can reach 237.5 F g−1. When the current density reaches 10 A g−1, it has good cycle stability (the capacitance retention after 1000 charge and discharge is 88.53% of the initial capacitance value, which is better than pure PPy-60.76% and PPy/rGO-C-71.84%). The excellent capacitance performance, good-looking micro-morphology and simple synthesis method of the PPy/N-PCM provide the possibility for its commercialization.
Cellular uptake of extracellular nucleosomes induces innate immune responses by binding and activating cGMP-AMP synthase (cGAS)
Authors: Wang Huawei , Zang Chuanlong , Ren Mengtian , Shang Mengdi , Wang Zhenghua , Peng Xuemei , Zhang Qiangzhe , Wen Xin , Xi Zhen , Zhou Chuanzheng
Published: September 2020

The nucleosome is the basic structural repeating unit of chromatin. DNA damage and cell apoptosis release nucleosomes into the blood circulatory system, and increased levels of circulating nucleosomes have been observed to be related to inflammation and autoimmune diseases. However, how circulating nucleosomes trigger immune responses has not been fully elucidated. cGAS (cGMP-AMP synthase) is a recently discovered pattern recognition receptor that senses cytoplasmic double-stranded DNA (dsDNA). In this study, we employed in vitro reconstituted nucleosomes to examine whether extracellular nucleosomes can gain access to the cytoplasm of mammalian cells to induce immune responses by activating cGAS. We showed that nucleosomes can be taken up by various mammalian cells. Additionally, we found that in vitro reconstituted mononucleosomes and oligonucleosomes can be recognized by cGAS. Compared to dsDNA, nucleosomes exhibit higher binding affinities to cGAS but considerably lower potency in cGAS activation. Incubation of monocytic cells with reconstituted nucleosomes leads to limited production of type I interferons and proinflammatory cytokines via a cGAS-dependent mechanism. This proof-of-concept study reveals the cGAS-dependent immunogenicity of nucleosomes and highlights the potential roles of circulating nucleosomes in autoimmune diseases, inflammation, and antitumour immunity.
Shift work influences the outcomes of Chlamydia infection and pathogenesis
Authors: Lundy Stephanie R. , Richardson Shakyra , Ramsey Anne , Ellerson Debra , Fengxia Yan , Onyeabor Sunny , Kirlin Ward , Thompson Winston , Black Carolyn M. , DeBruyne Jason P. , Davidson Alec J. , Immergluck Lilly C. , Blas-Machado Uriel , Eko Francis O. , Igietseme Joseph U. , He Qing , Omosun Yusuf O.
Published: September 2020

Shift work, performed by approximately 21 million Americans, is irregular or unusual work schedule hours occurring after 6:00 pm. Shift work has been shown to disrupt circadian rhythms and is associated with several adverse health outcomes and chronic diseases such as cancer, gastrointestinal and psychiatric diseases and disorders. It is unclear if shift work influences the complications associated with certain infectious agents, such as pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility resulting from genital chlamydial infection. We used an Environmental circadian disruption (ECD) model mimicking circadian disruption occurring during shift work, where mice had a 6-h advance in the normal light/dark cycle (LD) every week for a month. Control group mice were housed under normal 12/12 LD cycle. Our hypothesis was that compared to controls, mice that had their circadian rhythms disrupted in this ECD model will have a higherChlamydiaload, more pathology and decreased fertility rate followingChlamydiainfection. Results showed that, compared to controls, mice that had their circadian rhythms disrupted (ECD) had higherChlamydialoads, more tissue alterations or lesions, and lower fertility rate associated with chlamydial infection. Also, infected ECD mice elicited higher proinflammatory cytokines compared to mice under normal 12/12 LD cycle. These results imply that there might be an association between shift work and the increased likelihood of developing more severe disease fromChlamydiainfection.
Quantification of extracellular volume fraction by cardiac computed tomography for noninvasive assessment of myocardial fibrosis in hemodialysis patients
Authors: Yamada Akimasa , Kitagawa Kakuya , Nakamura Satoshi , Takafuji Masafumi , Goto Yoshitaka , Okamoto Ryuji , Dohi Kaoru , Sakuma Hajime
Published: September 2020

Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index (r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.
Enabling precision rehabilitation interventions using wearable sensors and machine learning to track motor recovery
Authors: Adans-Dester Catherine , Hankov Nicolas , O’Brien Anne , Vergara-Diaz Gloria , Black-Schaffer Randie , Zafonte Ross , Dy Jennifer , Lee Sunghoon I. , Bonato Paolo
Published: September 2020

The need to develop patient-specific interventions is apparent when one considers that clinical studies often report satisfactory motor gains only in a portion of participants. This observation provides the foundation for “precision rehabilitation”. Tracking and predicting outcomes defining the recovery trajectory is key in this context. Data collected using wearable sensors provide clinicians with the opportunity to do so with little burden on clinicians and patients. The approach proposed in this paper relies on machine learning-based algorithms to derive clinical score estimates from wearable sensor data collected during functional motor tasks. Sensor-based score estimates showed strong agreement with those generated by clinicians. Score estimates of upper-limb impairment severity and movement quality were marked by a coefficient of determination of 0.86 and 0.79, respectively. The application of the proposed approach to monitoring patients’ responsiveness to rehabilitation is expected to contribute to the development of patient-specific interventions, aiming to maximize motor gains.
Large male proboscis monkeys have larger noses but smaller canines
Authors: Matsuda Ikki , Stark Danica J. , Saldivar Diana A. Ramirez , Tuuga Augustine , Nathan Senthilvel K. S. S. , Goossens Benoit , van Schaik Carel P. , Koda Hiroki
Published: September 2020

The uniquely enlarged noses of male proboscis monkeys are prominent adornments, and a sexually selected male trait. A recent study showed significant correlations among nose, body, and testis sizes and clear associations between nose size and the number of females in a male’s harem. However, to date, the analyses of other common male traits, i.e., canines, are lacking. Whereas male nose size had a positive correlation with body size, we unexpectedly found a negative correlation between body and canine sizes. We explain this by an interaction between sexual and natural selection. Larger noses in males may interfere with the use of canines, thereby reducing their effectiveness as weapons. Additionally, longer canines are opposed by natural selection because the larger gape it imposes upon its bearer reduces foraging efficiency, particularly in folivores. This unique case of decoupling of body and canine size reveals that large canines carry an ecological cost.
Publisher Correction: Discovery of four Noggin genes in lampreys suggests two rounds of ancient genome duplication
Authors: Ermakova Galina V. , Kucheryavyy Alexander V. , Zaraisky Andrey G. , Bayramov Andrey V.
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Recent progress in the direct synthesis of γ-valerolactone from biomass-derived sugars catalyzed by RANEY® Ni–Sn alloy supported on aluminium hydroxide
Authors: Rodiansono  , Astuti Maria Dewi , Mustikasari Kamilia , Husain Sadang , Sutomo
Published: September 2020

Direct synthesis of γ-valerolactone from sugars using RANEY® nickel–tin alloy supported on aluminum hydroxide catalysts under mild reaction conditions produced an outstanding yield up to 74.9%.
Direct C–H bond halogenation and pseudohalogenation of hydrocarbons mediated by high-valent 3d metal-oxo species
Authors: Kannan Neppoliyan , Patil Akshay R. , Sinha Arup
Published: September 2020

This perspective delineates the utility of the high valent 3d-transition metal oxo complexes or species in catalyzing direct C–H halogenation and pseudohalogenation reactions.
Aerobic intramolecular carbon–hydrogen bond oxidation promoted by Cu(i) complexes
Authors: Álvarez María , Molina Francisco , Fructos Manuel R. , Urbano Juan , Álvarez Eleuterio , Sodupe Mariona , Lledós Agustí , Pérez Pedro J.
Published: September 2020

The complex TpMsCu(THF) undergoes the intramolecular oxidation of an alkylic C–H bond with O2, leading to the formation of a trinuclear compound where alkoxy and hydroxyl ligands are bonded to the copper centres.
Effect of Pleurotus agaves mushroom addition on the physicochemical and sensory properties of blue maize tortillas produced with traditional and ecological nixtamalization
Authors: García-Rojas D. A. , Meneses M. E. , Martínez-Carrera D. , Figueroa-Cárdenas J. D. , Sánchez-Medina M. A. , Bonilla-Quintero M. , Petlacalco-Sánchez B. , Martínez-Gutiérrez G. A. , Pérez-Herrera A.
Published: September 2020

Mexican blue corn tortillas with ecological nixtamalization, and enriched with Pleurotus agaves mushrooms, have the best levels of bioactive compounds, mainly β-glucans, also, they maintain acceptable rheological and sensory properties.
Maternal diet with sea urchin gangliosides promotes neurodevelopment of young offspringviaenhancing NGF and BDNF expression
Authors: Wang Xiaoxu , Cong Peixu , Wang Xincen , Liu Yanjun , Wu Lulu , Li He , Xue Changhu , Xu Jie
Published: September 2020

Sea urchin gangliosides are superior to GM1 and sialic acid in promoting neuronal differentiation and synapse function of postnatal 15-day mice, via up-regulating the expressions of BDNF and NGF.
Nelumbo nucifera leaf polyphenol extract and gallic acid inhibit TNF-α-induced vascular smooth muscle cell proliferation and migration involving the regulation of miR-21, miR-143 and miR-145
Authors: Chung Dai-Jung , Wu Yi-Liang , Yang Mon-Yuan , Chan Kuei-Chuan , Lee Huei-Jane , Wang Chau-Jong
Published: September 2020

The NLPE and GA potentially prevent atherosclerosis by inhibiting VSMC migration and proliferation. The mechanisms involve the regulation of the miRNA in PTEN, Ras/extracellularsignal-regulated kinase pathway, and Rho family proteins.
Similar hypoglycemic effects of glucomannan and its enzyme degraded products from Amorphophallus albus on type 2 diabetes mellitus in mice and potential mechanisms
Authors: Wu Cheng-Ying , Zhou Jing , Long Fang , Zhang Wei , Shen Hong , Zhu He , Xu Jin-Di , Li Song-Lin
Published: September 2020

In the present study, the hypoglycemic effects of glucomannan (AGM) and its enzyme-degraded products fromAmorphophallus albuswere investigated.
Aleuritin, a novel dinor-diterpenoid from the twigs ofAleurites moluccanuswith an anti-lymphangiogenic effect
Authors: Chang Fang-Rong , Wang Shih-Wei , Chen Shu-Rong , Lee Ching-Ying , Sheu Jyh-Horng , Cheng Yuan-Bin
Published: September 2020

Two new compounds designated aleuritin (1) and aleuritone (2) with anti-lymphangiogenic activity were isolated from the twigs ofAleurites moluccanus.
Microwave-assisted nucleophilic degradation of organophosphorus pesticides in propylene carbonate
Authors: Millán Daniela , Rojas Mabel , Tapia Ricardo A. , Pavez Paulina
Published: September 2020

Degradation of organophosphorus pesticides was achieved by using microwaves, an ionic liquid and propylene carbonate.
Multiple catalytic sites in MOF-based hybrid catalysts for organic reactions
Authors: Wang Yu , Chen Liyu , Hou Chun-Chao , Wei Yong-Sheng , Xu Qiang
Published: September 2020

Catalysts with multiple functions based on/derived from metal–organic frameworks receive growing attention in hybrid catalysis. This review highlights recent advances in organic reactions by MOF-based catalysts with emphasis on multiple catalytic sites and their synergies.
Photodelivery of β-phenylethylamines
Authors: Lee Sumin , Yi Seung Yeon , You Youngmin
Published: September 2020

Photodelivery of amino neurotransmitters.
Impact of backbone composition on homopolymer dynamics and brush block copolymer self-assembly
Authors: Boyle Bret M. , Collins Joseph L. , Mensch Tara E. , Ryan Matthew D. , Newell Brian S. , Miyake Garret M.
Published: September 2020

Four series of brush block copolymers with near identical side chain compositions but varying backbone structures were synthesized to investigate the effect of backbone structure on the thermal self-assembly to photonic crystals.
An in-depth analysis approach enabling precision single chain nanoparticle design
Authors: Engelke Johanna , Tuten Bryan T. , Schweins Ralf , Komber Hartmut , Barner Leonie , Plüschke Laura , Barner-Kowollik Christopher , Lederer Albena
Published: September 2020

The synthesis of single chain nanoparticles (SCNPs) is a vibrant field in macromolecular science. However, to achieve an in-depth understanding of the nature of intramolecular polymer folding, a step-change in the methodologies for SCNP analysis is required.