bluuebunny/crossref_metadata_2025 huggingface dataset:
The Acceleration of Lunar Ions by Magnetic Forces in the Terrestrial Magnetotail Lobes
Authors: Cao Xin , Halekas Jasper , Poppe Andrew , Chu Feng , Glassmeier Karl‐Heinz
Published: May 2020

In order to study the acceleration of ions originating from the tenuous exosphere and surface of the Moon, we analyzed data from the ElectroStatic Analyzer (ESA) and Flux Gate Magnetometer (FGM) carried by the Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) spacecraft. Previous investigations have modeled the acceleration of lunar ions by the motional electric field of the surrounding plasma. However, in the terrestrial magnetotail, where the lunar ion density can equal or even exceed the ambient plasma density, other forces may play an important role in the tenuous plasma environment. Determining what forces govern lunar ion motion is important in understanding their interaction with the ambient plasma in the unique environment of the magnetotail. Based on a detailed analysis of two individual ARTEMIS observations, we find that magnetic pressure and magnetic tension forces may play an important role in accelerating the lunar ions.
Surface charge of Merkel cell polyomavirus small T antigen determines cell transformation through allosteric FBW7 WD40 domain targeting
Authors: Nwogu Nnenna , Ortiz Luz E. , Kwun Hyun Jin
Published: May 2020

Merkel cell polyomavirus (MCV) small T (sT) is the main oncoprotein in Merkel cell carcinoma (MCC) development. A unique domain of sT, LT stabilization domain (LSD), has been reported to bind and inactivate multiple SCF (Skp1-Cullin-F-box) E3 ligases. These interactions impede the turnover of MCV large T (LT) antigen and cellular oncoproteins such as c-Myc and cyclin E, thereby promoting viral replication and cell transformation. However, it is currently unclear how this LSD region contributes to multiple transforming activities of sT. Structural docking simulation of sT and F-box and WD repeat domain-containing 7 (FBW7) revealed a novel allosteric interaction between sT and FBW7 WD40 domain. This model is supported by experimental evidence confirming that charge engineering in the LSD alters sT-WD40 binding. Specifically, loss of net positive charge in the LSD prevents sT-FBW7 binding by abrogating the electrostatic interaction, thus impeding inhibition of FBW7 by sT. Furthermore, positively charged mutations in the LSD significantly restored the sT function and its ability to transform rodent fibroblast cells. We infer that the surface charge of sT is a major determinant for targeting E3 ligases, which leads to sT-induced cell transformation, an observation that could be used to develop targeted therapeutics for MCC.
Drp1-dependent remodeling of mitochondrial morphology triggered by EBV-LMP1 increases cisplatin resistance
Authors: Xie Longlong , Shi Feng , Li Yueshuo , Li We , Yu Xinfang , Zhao Lin , Zhou Min , Hu Jianmin , Luo Xiangjian , Tang Min , Fan Jia , Zhou Jian , Gao Qiang , Wu Weizhong , Zhang Xin , Liao Weihua , Bode Ann M. , Cao Ya
Published: May 2020

Latent membrane protein 1 (LMP1) is a major Epstein–Barr virus (EBV)-encoded oncoprotein involved in latency infection that regulates mitochondrial functions to facilitate cell survival. Recently, mitochondrial fission has been demonstrated as a crucial mechanism in oncovirus-mediated carcinogenesis. Mitochondrial dynamin-related protein 1 (Drp1)-mediated mitochondrial fission has an impact on the chemoresistance of cancers. However, the mechanism by which oncogenic stress promotes mitochondrial fission, potentially contributing to tumorigenesis, is not entirely understood. The role of Drp1 in the oncogenesis and prognosis of EBV-LMP1-positive nasopharyngeal carcinoma (NPC) was determined in our study. We show that EBV-LMP1 exhibits a new function in remodeling mitochondrial morphology by activating Drp1. A high level of p-Drp1 (Ser616) or a low level of p-Drp1 (Ser637) correlates with poor overall survival and disease-free survival. Furthermore, the protein level of p-Drp1 (Ser616) is related to the clinical stage (TNM stage) of NPC. Targeting Drp1 impairs mitochondrial function and induces cell death in LMP1-positive NPC cells. In addition, EBV-LMP1 regulates Drp1 through two oncogenic signaling axes, AMPK and cyclin B1/Cdk1, which promote cell survival and cisplatin resistance in NPC. Our findings provide novel insight into the role of EBV-LMP1-driven mitochondrial fission in regulating Drp1 phosphorylation at serine 616 and serine 637. Disruption of Drp1 could be a promising therapeutic strategy for LMP1-positive NPC.
Do AKT1, COMT and FAAH influence reports of acute cannabis intoxication experiences in patients with first episode psychosis, controls and young adult cannabis users?
Authors: Hindocha Chandni , Quattrone Diego , Freeman Tom P. , Murray Robin M. , Mondelli Valeria , Breen Gerome , Curtis Charles , Morgan Celia J. A. , Valerie Curran H. , Di Forti Marta
Published: May 2020

Epidemiological and biological evidence support the association between heavy cannabis use and psychosis. However, it is unclear which cannabis users are susceptible to its psychotogenic effect. Therefore, understanding genetic factors contributing to this relationship might prove an important strategy to identify the mechanisms underlying cannabis-associated psychotic experiences. We aimed to determine how variation in AKT1, COMT and FAAH genotypes, and their interaction with three different groups (first episode psychosis (FEP) patients (n = 143), controls (n = 92) and young adult (YA) cannabis usersn = 485)) influenced cannabis experiences, in those who had used cannabis at least once. We investigated the role of AKT1 (rs2494732), COMT Val158Met (rs4680) and FAAH (rs324420) on cannabis experiences by combining data from a large case-control study of FEP patients, with a naturalistic study of YA cannabis users (n = 720). Outcome measures were cannabis-induced psychotic-like experiences (cPLEs) and euphoric experiences (cEEs). We used linear mixed effects models to assess the effects of each genotype and their interaction with group, adjusting for age, sex, ethnicity, age of first cannabis use, years of use and frequency. cPLEs were more frequent in FEP patients than controls and YA cannabis users. cEEs were more prevalent in YA cannabis users than FEP patients or controls. Variation in AKT1, COMT or FAAH was not associated with cPLEs/cEEs. There was no interaction between genotype and group (FEP cases, controls and YA cannabis users) on cPLEs/cEEs. In conclusion, AKT1, COMT or FAAH did not modulate specific psychotomimetic response to cannabis and did not interact with group, contrary to previous research.
Quantitative genetics of wing morphology in the parasitoid wasp Nasonia vitripennis: hosts increase sibling similarity
Authors: Xia Shuwen , Pannebakker Bart A. , Groenen Martien A. M. , Zwaan Bas J. , Bijma Piter
Published: May 2020

The central aim of evolutionary biology is to understand patterns of genetic variation between species and within populations. To quantify the genetic variation underlying intraspecific differences, estimating quantitative genetic parameters of traits is essential. In Pterygota, wing morphology is an important trait affecting flight ability. Moreover, gregarious parasitoids such as Nasonia vitripennis oviposit multiple eggs in the same host, and siblings thus share a common environment during their development. Here we estimate the genetic parameters of wing morphology in the outbred HVRx population of N. vitripennis, using a sire-dam model adapted to haplodiploids and disentangled additive genetic and host effects. The results show that the wing-size traits have low heritability (h2 ~ 0.1), while most wing-shape traits have roughly twice the heritability compared with wing-size traits. However, the estimates increased to h2 ~ 0.6 for wing-size traits when omitting the host effect from the statistical model, while no meaningful increases were observed for wing-shape traits. Overall, host effects contributed to ~50% of the variation in wing-size traits. This indicates that hosts have a large effect on wing-size traits, about fivefold more than genetics. Moreover, bivariate analyses were conducted to derive the genetic relationships among traits. Overall, we demonstrate the evolutionary potential for morphological traits in the N. vitripennis HVRx-outbred population, and report the host effects on wing morphology. Our findings can contribute to a further dissection of the genetics underlying wing morphology in N. vitripennis, with relevance for gregarious parasitoids and possibly other insects as well.
Somatic SF3B1 hotspot mutation in prolactinomas
Authors: Li Chuzhong , Xie Weiyan , Rosenblum Jared S. , Zhou Jianyu , Guo Jing , Miao Yazhou , Shen Yutao , Wang Hongyun , Gong Lei , Li Mingxuan , Zhao Sida , Cheng Sen , Zhu Haibo , Jiang Tao , Ling Shiying , Wang Fei , Zhang Hongwei , Zhang Mingshan , Qu Yanming , Zhang Qi , Li Guilin , Wang Junmei , Ma Jun , Zhuang Zhengping , Zhang Yazhuo
Published: May 2020

The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1R625H) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1R625H mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics.
2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer
Authors: Blomme Arnaud , Ford Catriona A. , Mui Ernest , Patel Rachana , Ntala Chara , Jamieson Lauren E. , Planque Mélanie , McGregor Grace H. , Peixoto Paul , Hervouet Eric , Nixon Colin , Salji Mark , Gaughan Luke , Markert Elke , Repiscak Peter , Sumpton David , Blanco Giovanny Rodriguez , Lilla Sergio , Kamphorst Jurre J. , Graham Duncan , Faulds Karen , MacKay Gillian M. , Fendt Sarah-Maria , Zanivan Sara , Leung Hing Y.
Published: May 2020

Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation of LNCaP cells chronically exposed to multiple AR inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant cells and associated with perturbed glucose and lipid metabolism. To exploit this phenotype, we delineate a subset of proteins consistently associated with ARI resistance and highlight mitochondrial 2,4-dienoyl-CoA reductase (DECR1), an auxiliary enzyme of beta-oxidation, as a clinically relevant biomarker for CRPC. Mechanistically, DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises CRPC cells to ferroptosis. In vivo, DECR1 deletion impairs lipid metabolism and reduces CRPC tumour growth, emphasizing the importance of DECR1 in the development of treatment resistance.
Social-media and newspaper reports reveal large-scale meteorological drivers of floods on Sumatra
Authors: Baranowski Dariusz B. , Flatau Maria K. , Flatau Piotr J. , Karnawati Dwikorita , Barabasz Katarzyna , Labuz Michal , Latos Beata , Schmidt Jerome M. , Paski Jaka A. I. , Marzuki
Published: May 2020

Floods are a major contributor to natural disasters in Sumatra. However, atmospheric conditions leading to floods are not well understood due, among other factors, to the lack of a complete record of floods. Here, the 5 year flood record for Sumatra derived from governmental reports, as well as from crowd-sourcing data, based on Twitter messages and local newspapers’ reports, is created and used to analyze atmospheric phenomena responsible for floods. It is shown, that for the majority of analyzed floods, convectively coupled Kelvin waves, large scale precipitation systems propagating at ∼12 m/s along the equator, play the critical role. While seasonal and intraseasonal variability can also create conditions favorable for flooding, the enhanced precipitation related to Kelvin waves was found in over 90% of flood events. In 30% of these events precipitation anomalies were attributed to Kelvin waves only. These results indicate the potential for increased predictability of flood risk.
nNOS-expressing neurons in the vmPFC transform pPVT-derived chronic pain signals into anxiety behaviors
Authors: Liang Hai-Ying , Chen Zhi-Jin , Xiao Hui , Lin Yu-Hui , Hu Ying-Yi , Chang Lei , Wu Hai-Yin , Wang Peng , Lu Wei , Zhu Dong-Ya , Luo Chun-Xia
Published: May 2020

Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.
Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium
Authors: Goldfarbmuren Katherine C. , Jackson Nathan D. , Sajuthi Satria P. , Dyjack Nathan , Li Katie S. , Rios Cydney L. , Plender Elizabeth G. , Montgomery Michael T. , Everman Jamie L. , Bratcher Preston E. , Vladar Eszter K. , Seibold Max A.
Published: May 2020

Cigarette smoke first interacts with the lung through the cellularly diverse airway epithelium and goes on to drive development of most chronic lung diseases. Here, through single cell RNA-sequencing analysis of the tracheal epithelium from smokers and non-smokers, we generate a comprehensive atlas of epithelial cell types and states, connect these into lineages, and define cell-specific responses to smoking. Our analysis infers multi-state lineages that develop into surface mucus secretory and ciliated cells and then contrasts these to the unique specification of submucosal gland (SMG) cells. Accompanying knockout studies reveal that tuft-like cells are the likely progenitor of both pulmonary neuroendocrine cells and CFTR-rich ionocytes. Our smoking analysis finds that all cell types, including protected stem and SMG populations, are affected by smoking through both pan-epithelial smoking response networks and hundreds of cell-specific response genes, redefining the penetrance and cellular specificity of smoking effects on the human airway epithelium.
DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification
Authors: Lentini Jenna M. , Alsaif Hessa S. , Faqeih Eissa , Alkuraya Fowzan S. , Fu Dragony
Published: May 2020

In mammals, a subset of arginine tRNA isoacceptors are methylated in the anticodon loop by the METTL2 methyltransferase to form the 3-methylcytosine (m3C) modification. However, the mechanism by which METTL2 identifies specific tRNA arginine species for m3C formation as well as the biological role of m3C in mammals is unknown. Here, we show that human METTL2 forms a complex with DALR anticodon binding domain containing 3 (DALRD3) protein to recognize particular arginine tRNAs destined for m3C modification. DALRD3-deficient human cells exhibit nearly complete loss of the m3C modification in tRNA-Arg species. Notably, we identify a homozygous nonsense mutation in the DALRD3 gene that impairs m3C formation in human patients exhibiting developmental delay and early-onset epileptic encephalopathy. These findings uncover an unexpected function for the DALRD3 protein in the targeting of distinct arginine tRNAs for m3C modification and suggest a crucial biological role for DALRD3-dependent tRNA modification in proper neurological development.
Colloidal crystal engineering with metal–organic framework nanoparticles and DNA
Authors: Wang Shunzhi , Park Sarah S. , Buru Cassandra T. , Lin Haixin , Chen Peng-Cheng , Roth Eric W. , Farha Omar K. , Mirkin Chad A.
Published: May 2020

Colloidal crystal engineering with nucleic acid-modified nanoparticles is a powerful way for preparing 3D superlattices, which may be useful in many areas, including catalysis, sensing, and photonics. To date, the building blocks studied have been primarily based upon metals, metal oxides, chalcogenide semiconductors, and proteins. Here, we show that metal–organic framework nanoparticles (MOF NPs) densely functionalized with oligonucleotides can be programmed to crystallize into a diverse set of superlattices with well-defined crystal symmetries and compositions. Electron microscopy and small-angle X-ray scattering characterization confirm the formation of single-component MOF superlattices, binary MOF–Au single crystals, and two-dimensional MOF nanorod assemblies. Importantly, DNA-modified porphyrinic MOF nanorods (PCN-222) were assembled into 2D superlattices and found to be catalytically active for the photooxidation of 2-chloroethyl ethyl sulfide (CEES, a chemical warfare simulant of mustard gas). Taken together, these new materials and methods provide access to colloidal crystals that incorporate particles with the well-established designer properties of MOFs and, therefore, increase the scope of possibilities for colloidal crystal engineering with DNA.
The Ontario Climate Data Portal, a user-friendly portal of Ontario-specific climate projections
Authors: Zhu Huaiping , Liu Jinliang , Zhou Xiaolan , Chen Xiaoyu , Qiu Xin , Bello Richard L. , Deng Ziwang
Published: May 2020

An easily accessible climate data portal,http://yorku.ca/ocdp, was developed and officially launched in 2018 to disseminate a super ensemble of high-resolution regional climate change projections for the province of Ontario, Canada. The spatial resolution is ~10 km × ~10 km and temporal resolution is one day, UTC. The data covers 120 years from 1981 to 2100. This user-friendly portal provides users with thousands of static and interactive maps, decadal variation trend lines, summary tables, reports and terabytes of bias-corrected downscaled data. The data portal was generated with an emphasis on interactive visualization of climate change information for researchers and the public to understand to what extent climate could change locally under different emission scenarios in the future. This paper presents an introduction to the portal structure and functions, the large extent of the datasets available and the data development methodology.
Transformations of superpositions by means of incoherent operations
Authors: Losada Marcelo , Bosyk Gustavo M. , Freytes Hector , Sergioli Giuseppe
Published: May 2020

In this paper we study how the coherence of a superposition of pure states is related with the coherence of its components. We consider two pure initial states and two pure final coherent states, such that the former ones cannot be transformed into the latter ones by means of incoherent transformations. In this situation, we analyze conditions for the existence of superpositions of the initial states that can be transformed into superpositions of the final states. In particular, we consider superpositions formed by quantum states belonging to orthogonal subspaces. By appealing to the majorization theory, we obtain necessary and sufficient conditions for such transformations to be possible. Finally, we provide some examples that illustrate the difference between the obtained conditions and the necessary criterion based on the relative entropy of coherence.
Three-State Majority-vote Model on Scale-Free Networks and the Unitary Relation for Critical Exponents
Authors: Vilela André L. M. , Zubillaga Bernardo J. , Wang Chao , Wang Minggang , Du Ruijin , Stanley H. Eugene
Published: May 2020

We investigate the three-state majority-vote model for opinion dynamics on scale-free and regular networks. In this model, an individual selects an opinion equal to the opinion of the majority of its neighbors with probability 1 − q, and different to it with probability q. The parameter q is called the noise parameter of the model. We build a network of interactions where z neighbors are selected by each added site in the system, a preferential attachment network with degree distribution k−λ, where λ = 3 for a large number of nodes N. In this work, z is called the growth parameter. Using finite-size scaling analysis, we obtain that the critical exponents $$\beta /\bar{\nu }$$
β
/

ν
¯

and $$\gamma /\bar{\nu }$$
γ
/

ν
¯

associated with the magnetization and the susceptibility, respectively. Using Monte Carlo simulations, we calculate the critical noise parameter qc as a function of z for the scale-free networks and obtain the phase diagram of the model. We find that the critical exponents add up to unity when using a special volumetric scaling, regardless of the dimension of the network of interactions. We verify this result by obtaining the critical noise and the critical exponents for the two and three-state majority-vote model on cubic lattice networks.
Human group coordination in a sensorimotor task with neuron-like decision-making
Authors: Schmid Gerrit , Braun Daniel A.
Published: May 2020

The formation of cooperative groups of agents with limited information-processing capabilities to solve complex problems together is a fundamental building principle that cuts through multiple scales in biology from groups of cells to groups of humans. Here, we study an experimental paradigm where a group of humans is joined together to solve a common sensorimotor task that cannot be achieved by a single agent but relies on the cooperation of the group. In particular, each human acts as a neuron-like binary decision-maker that determines in each moment of time whether to be active or not. Inspired by the population vector method for movement decoding, each neuron-like decision-maker is assigned a preferred movement direction that the decision-maker is ignorant about. From the population vector reflecting the group activity, the movement of a cursor is determined, and the task for the group is to steer the cursor into a predefined target. As the preferred movement directions are unknown and players are not allowed to communicate, the group has to learn a control strategy on the fly from the shared visual feedback. Performance is analyzed by learning speed and accuracy, action synchronization, and group coherence. We study four different computational models of the observed behavior, including a perceptron model, a reinforcement learning model, a Bayesian inference model and a Thompson sampling model that efficiently approximates Bayes optimal behavior. The Bayes and especially the Thompson model excel in predicting the human group behavior compared to the other models, suggesting that internal models are crucial for adaptive coordination. We discuss benefits and limitations of our paradigm regarding a better understanding of distributed information processing.
Assessing the effect of current steering on the total electrical energy delivered and ambulation in Parkinson’s disease
Authors: Hui Daphne , Murgai Aditya A. , Gilmore Greydon , Mohideen Shabna I. , Parrent Andrew G. , Jog Mandar S.
Published: May 2020

Vertical current steering (vCS) divides current between multiple contacts, which reduces radial spread to fine-tune the electric field shape and improves neuroanatomical targeting. vCS may improve the variable responsiveness of Parkinsonian gait to conventional deep brain stimulation. We hypothesized that vCS elicits greater improvement in ambulation in Parkinson’s disease patients compared to conventional, single-contact stimulation. vCS was implemented with divisions of 70%/30% and 50%/50% and compared to single-contact stimulation with four therapeutic window amplitudes in current-controlled systems. Walking at a self-selected pace was evaluated in seven levodopa-responsive patients. Integrative measures of gait and stimulation parameters were assessed with the functional ambulation performance (FAP) score and total electrical energy delivered (TEED), respectively. A two-tailed Wilcoxon matched-pairs signed rank test assessed the effect of each stimulation condition on FAP and TEED and compared regression slopes; further, a two-tailed Spearman test identified correlations. vCS significantly lowered the TEED (P < 0.0001); however, FAP scores were not different between conditions (P = 0.786). Compared to single-contact stimulation, vCS elicited higher FAP scores with lower TEED (P = 0.031). FAP and TEED were positively correlated in vCS (P = 2.000 × 10-5, r = 0.397) and single-contact stimulation (P = 0.034, r = 0.205). Therefore, vCS and single-contact stimulation improved ambulation similarly but vCS reduced the TEED and side-effects at higher amplitudes.
Comparison of intradialytic versus home-based exercise programs on physical functioning, physical activity level, adherence, and health-related quality of life: pilot study
Authors: Ortega-Pérez de Villar Lucía , Martínez-Olmos Francisco José , Pérez-Domínguez Francisco de Borja , Benavent-Caballer Vicent , Montañez-Aguilera Francisco Javier , Mercer Tom , Segura-Ortí Eva
Published: May 2020

Intradialytic exercise (ID) programs are effective and safe for hemodialysis (HD) patients to avoid functional deterioration. However, exercise is not routinely undertaken in most HD units, and we do not know if home-based (HB) programs are as effective as ID programs. The purpose of this study was to compare the effects of 16 weeks of ID exercise versus a HB exercise program for HD patients. A total of 46 patients were randomly assigned to the ID group (n = 24) or HB group (n = 22). They completed a 16-week combined exercise program 3 times/week. We measured physical activity level, physical functioning, depression level, and health-related quality of life at baseline and after 16 weeks. A significant time effect was found in both groups for the physical activity level (p = 0.012). There was also a significant group–time interaction effect for the one-leg standing test (OLST) (p = 0.049) and a significant time effect for the Short Physical Performance Battery (p = 0.013), timed up-and-go test (p = 0.005), sit-to-stand-10 (p = 0.027), right and left hand handgrip (p = 0.044, p < 0.001), one-heel left leg raise (p = 0.019), and 6-minute walking (p = 0.006), depression (p = 0.017). HRQoL remained unchanged. There was no difference between the two interventions on the tested outcomes (besides OLST). Both interventions were associated with positive changes of the physical activity levels and physical function.
Comparative analysis of MACROD1, MACROD2 and TARG1 expression, localisation and interactome
Authors: Žaja R. , Aydin G. , Lippok B. E. , Feederle R. , Lüscher B. , Feijs K.L.H.
Published: May 2020

The posttranslational modification ADP-ribosylation is involved in many cellular processes, with distinct roles for poly- and mono(ADP-ribosyl)ation (PAR- and MARylation, respectively). Reversibility of intracellular MARylation was demonstrated with the discovery of MACROD1, MACROD2 and TARG1, three macrodomain-containing enzymes capable of reversing MARylation of proteins and RNA. While the three enzymes have identical activities in vitro, their roles in cells are unclear and published data are partially contradictory, possibly due to a lack of validated reagents. We developed monoclonal antibodies to study these proteins and analysed their tissue distribution and intracellular localisation. MACROD1 is most prevalent in mitochondria of skeletal muscle, MACROD2 localises to nucleo- and cytoplasm and is found so far only in neuroblastoma cells, whereas the more ubiquitously expressed TARG1 is present in nucleoplasm, nucleolus and stress granules. Loss of MACROD1 or loss of TARG1 leads to disruption of mitochondrial or nucleolar morphology, respectively, hinting at their importance for these organelles. To start elucidating the underlying mechanisms, we have mapped their interactomes using BioID. The cellular localisation of interactors supports the mitochondrial, nucleolar and stress granule localisation of MACROD1 and TARG1, respectively. Gene ontology analysis suggests an involvement of MACROD1 and TARG1 in RNA metabolism in their respective compartments. The detailed description of the hydrolases’ expression, localisation and interactome presented here provides a solid basis for future work addressing their physiological function in more detail.
Histopathological lesions and exposure to Plasmodium falciparum infections in the placenta increases the risk of preeclampsia among pregnant women
Authors: Obiri Dorotheah , Erskine Isaac Joe , Oduro Daniel , Kusi Kwadwo Asamoah , Amponsah Jones , Gyan Ben Adu , Adu-Bonsaffoh Kwame , Ofori Michael Fokuo
Published: May 2020

Preeclampsia (PE) is a placental disorder with different phenotypic presentations. In malaria-endemic regions, high incidence of PE is reported, with debilitating foeto-maternal effects, particularly among primigravid women. However, the relationship between placental pathology and Plasmodium falciparum infection in the placenta with PE is underexplored. Placentas from 134 pregnant women were examined after delivery for pathological lesions and placental malaria (PM). They comprised of 69 women without PE (non-PE group) and 65 women diagnosed with PE (PE group). The presence of placental pathology increased the risk of PE, with particular reference to syncytial knots. Placental malaria was 64 (48.1%) and 21 (15.8%) respectively for active and past infections and these proportions were significantly higher in the PE group compared to the non-PE group. Further multivariate analyses showed placental pathology (adjusted (aOR) 3.0, 95% CI = 1.2–7.5), active PM (aOR 6.7, 95% CI = 2.3–19.1), past PM (aOR 12.4, 95% CI = 3.0–51.0) and primigravidity (aOR 6.6, 95% CI 2.4–18.2) to be associated with PE. Our findings suggest that placental histological changes and PM are independent risk factors for PE particularly in primigravida. These findings might improve the management of PE in malaria-endemic regions.
Regulation of Adipocyte Differentiation by METTL4, a 6 mA Methylase
Authors: Zhang Zhenxi , Hou Yingzi , Wang Yao , Gao Tao , Ma Ziyue , Yang Ying , Zhang Pei , Yi Fan , Zhan Jun , Zhang Hongquan , Du Quan
Published: May 2020

As one of the most abundant DNA methylation form in prokaryotes, N6-methyladenine nucleotide (6 mA) was however only recently identified in eukaryotic genomes. To explore the implications of N6-adenine methylation in adipogenesis, genomic N6-adenine methylation was examined across adipocyte differentiation stages of 3T3-L1 cells. When the N6-adenine methylation profiles were analyzed and compared with the levels of gene expression, a positive correlation between the density of promoter 6 mA and gene expression level was uncovered. By means of in vitro methylation and gene knockdown assay, METTL4, a homologue of Drosophila methylase CG14906 and C. elegans methylase DAMT-1, was demonstrated to be a mammalian N6-adenine methylase that functions in adipogenesis. Knockdown of Mettl4 led to altered adipocyte differentiation, shown by defective gene regulation and impaired lipid production. We also found that the effects of N6-adenine methylation on lipid production involved the regulation of INSR signaling pathway, which promotes glucose up-taking and lipid production in the terminal differentiation stage.
Ongoing formation of felsic lower crustal channel by relamination in Zagros collision zone revealed from regional tomography
Authors: Talebi Amir , Koulakov Ivan , Moradi Ali , Rahimi Habib , Gerya Taras
Published: May 2020

Complex interaction of rheologically contrasting layers within the lithosphere during the collision of continental plates leads to active faulting, which represents a serious hazard to the population and infrastructure. One of the collision scenarios presumes the existence of a middle-lower crustal channel composed of subducted silicic upper crustal rocks, which is thought to exist in the Tibetan-Himalayan system. Based on the results of seismic tomography, we argue that a similar mechanism of crustal channeling takes place beneath the Zagros mountain system in southwestern Iran. The 3D seismic velocity model reveals an inverted crustal architecture of the collision zone, in which the low-velocity felsic (granitic and sedimentary) upper crustal rocks of the Arabian plate form a seismically inactive lower crustal channel below the higher-velocity mafic (basaltic) middle-upper crustal layer of the Iranian crust. Based on existing numerical models, we suggest that the formation of the felsic channel is likely governed by separation (delamination) of the weak felsic upper crust of the subducting Arabian lithosphere and its ductile underplating under rheologically stronger upper-middle crust of the Iranian plate.
Effects of thermal annealing on localization and strain in core/multishell GaAs/GaNAs/GaAs nanowires
Authors: Balagula Roman M. , Jansson Mattias , Yukimune Mitsuki , Stehr Jan E. , Ishikawa Fumitaro , Chen Weimin M. , Buyanova Irina A.
Published: May 2020

Core/shell nanowire (NW) heterostructures based on III-V semiconductors and related alloys are attractive for optoelectronic and photonic applications owing to the ability to modify their electronic structure via bandgap and strain engineering. Post-growth thermal annealing of such NWs is often involved during device fabrication and can also be used to improve their optical and transport properties. However, effects of such annealing on alloy disorder and strain in core/shell NWs are not fully understood. In this work we investigate these effects in novel core/shell/shell GaAs/GaNAs/GaAs NWs grown by molecular beam epitaxy on (111) Si substrates. By employing polarization-resolved photoluminescence measurements, we show that annealing (i) improves overall alloy uniformity due to suppressed long-range fluctuations in the N composition; (ii) reduces local strain within N clusters acting as quantum dot emitters; and (iii) leads to partial relaxation of the global strain caused by the lattice mismatch between GaNAs and GaAs. Our results, therefore, underline applicability of such treatment for improving optical quality of NWs from highly-mismatched alloys. They also call for caution when using ex-situ annealing in strain-engineered NW heterostructures.
Facile Synthesis of Porous Polymer Using Biomass Polyphenol Source for Highly Efficient Separation of Cs+ from Aqueous Solution
Authors: Chen Shangqing , Hu Jiayin , Guo Yafei , Deng Tianlong
Published: May 2020

In this work, a series of polyphenol porous polymers were derived from biomass polyphenols via a facile azo-coupling method. The structure and morphologies of the polymer were characterized by BET, TEM, SEM, XRD, TGA and FT-IR techniques. Batch experiments demonstrated their potentialities for adsorptive separation of Cs+ from aqueous solution. Among them, porous polymers prepared with gallic acid as starting material (GAPP) could adsorb Cs+ at wide pH value range effectively, and the optimal adsorption capacity was up to 163.6 mg/g, placing it at top material for Cs+ adsorption. GAPP exhibited significantly high adsorption performance toward Cs+ compared to Na+ and K+, making it possible in selective removal of Cs+ from ground water in presence of co-existing competitive ions. Moreover, the Cs-laden GAPP could be facilely eluted and reused in consecutive adsorption-desorption processes. As a result, we hope this work could provide ideas about the potential utilization of biomass polyphenol in environmental remediation.
Tear Glucose Measurement by Reflectance Spectrum of a Nanoparticle Embedded Contact Lens
Authors: Kim Sooyeon , Jeon Hee-Jae , Park Sijin , Lee Dong Yun , Chung Euiheon
Published: May 2020

Glucose level is a primary indicator in the diagnosis and treatment of diabetes mellitus. According to the correlation between glucose concentration in blood and tears, measuring tear glucose can be an alternative to traditional strips test for blood glucose. Thus, measuring tear glucose levels could provide noninvasive monitoring of blood glucose. As a biocompatible biosensor, a nanoparticle embedded contact lens (NECL) is developed which is composed of glucose oxidase and cerium oxide (III). Using spectroscopy, we found the detectable changes in reflection spectrum of contact lenses with respect to the glucose concentration, and developed correlation curve of the reflection spectrum with known glucose level. Furthermore, we assessed tear glucose level and compared blood glucose level with the diabetic mouse model to evaluate this approach. Our algorithm for regular monitoring of glucose using contact lens biosensor may lead to noninvasive monitoring of tear glucose level. NECL may provide simple and noninvasive glucose monitoring based on the spectral changes in contact lens biosensor.
A facile approach to hydrophilic oxidized fullerenes and their derivatives as cytotoxic agents and supports for nanobiocatalytic systems
Authors: Zygouri Panagiota , Spyrou Konstantinos , Mitsari Efstratia , Barrio María , Macovez Roberto , Patila Michaela , Stamatis Haralambos , Verginadis Ioannis I. , Velalopoulou Anastasia P. , Evangelou Angelos M. , Sideratou Zili , Gournis Dimitrios , Rudolf Petra
Published: May 2020

A facile, environment-friendly, versatile and reproducible approach to the successful oxidation of fullerenes (oxC60) and the formation of highly hydrophilic fullerene derivatives is introduced. This synthesis relies on the widely known Staudenmaier’s method for the oxidation of graphite, to produce both epoxy and hydroxy groups on the surface of fullerenes (C60) and thereby improve the solubility of the fullerene in polar solvents (e.g. water). The presence of epoxy groups allows for further functionalization via nucleophilic substitution reactions to generate new fullerene derivatives, which can potentially lead to a wealth of applications in the areas of medicine, biology, and composite materials. In order to justify the potential of oxidized C60 derivatives for bio-applications, we investigated their cytotoxicity in vitro as well as their utilization as support in biocatalysis applications, taking the immobilization of laccase for the decolorization of synthetic industrial dyes as a trial case.
A new laboratory surrogate (Monocyte Chemotactic Protein-1) for Disease Activity Score28: a favourable indicator for remission in rheumatoid arthritis
Authors: Liou Lieh-bang , Fang Yao-Fan , Tan Chih Feng , Lai Jenn-Haung , Jang Shr-shian , Tsai Ping-Han , Yeh Ting-chih
Published: May 2020

This prospective one-year follow-up study was conducted from 835 visits in 178 rheumatoid arthritis (RA) patients. Tender-/swollen-joint count, Health Assessment Questionnaire Disability Index (HAQ-DI), Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI) and DAS28-monocyte chemotactic protein-1 (DAS28-MCP-1) scores were obtained every 3 months. Radiographs of hands and feet were acquired at baseline and one year. We evaluated the correlation and accuracy of activity scores in predicting remission, HAQ-DI changes and radiographic changes. DAS28-MCP-1 correlated strongly with DAS28-ESR, DAS28-CRP and SDAI scores (0.830, 0.899 and 0.931, respectively, with all P < 0.001). Score changes of DAS28-MCP-1 were comparable to those of DAS28-ESR, DAS28-CRP and SDAI in predicting changes in HAQ-DI and bone erosion. DAS28-MCP-1 (<2.2) was better than DAS28-ESR (<2.6) in indicating modified American Rheumatism Association remission and 2011 American College of Rheumatology/European League Against Rheumatism remission (75.61% vs. 36.99% and 81.71% vs. 49.13%, respectively) with odds ratios of 5.28 and 4.62 (both P < 0.001), respectively. We compared DAS28-MCP-1 with SDAI (≦3.3) in indicating remission with odds ratios of 2.63 (P = 0.002) and 0.98, respectively (and DAS28-MCP-1 with DAS28-CRP < 2.5: 1.33 and 0.92). Therefore, DAS28-MCP-1 is useful as an alternative in assessing RA activity.
The Punatsangchhu-I dam landslide illuminated by InSAR multitemporal analyses
Authors: Dini Benedetta , Manconi Andrea , Loew Simon , Chophel Jamyang
Published: May 2020

We use multitemporal analyses based on Synthetic Aperture Radar differential interferometry (DInSAR) to study the slope adjacent to the large Punatsangchhu-I hydropower plant, a concrete gravity dam under construction in Bhutan since 2009. Several slope failures affected the site since 2013, probably as a consequence of toe undercutting of a previously unrecognised active landslide. Our results indicate that downslope displacement, likely related to the natural instability, was already visible in 2007 on various sectors of the entire valley flank. Moreover, the area with active displacements impinging on the dam site has continuously increased in size since 2007 and into 2018, even though stabilization measures have been implemented since 2013. Stabilisation measures currently only focus on a small portion of the slope, however, the unstable area is larger than previously evaluated. Highly damaged rock is present across many areas of the entire valley flank, indicating that the volumes involved may be orders of magnitude higher than the area on which stabilisation efforts have been concentrated after the 2013 failure. The results highlight that satellite-based DInSAR could be systematically used to support decision making processes in the different phases of a complex hydropower project, from the feasibility study, to the dam site selection and construction phase.
Exosomal miR-21 promotes proliferation, invasion and therapy resistance of colon adenocarcinoma cells through its target PDCD4
Authors: Sun Li-Hua , Tian Dan , Yang Ze-Cheng , Li Jin-Long
Published: May 2020

Exosomes contain cell-specific collections of bioactive materials including proteins, lipids, and RNAs that are transported to recipient cells to exert their impacts. MicroRNAs (miRNAs) can function as tumor suppressor or oncogenic genes and miR-21 is one of the most frequently up-regulated miRNAs in solid tumors including colon cancer. The aim of this study was to investigate the role of miR-21, secreted from exosomes, in proliferation and invasion of colon cancer, along with the mechanistic details. We used a variety of biochemical techniques including ultracentrifugation-based exosome purification, electron transmission microscopy, western blot and RT-qPCR to detect the expression levels of miR-21 in exosomes purified from culture media of human colonic adenocarcinoma cell lines. We then performed functional and mechanistic studies using three colon cancer cell lines HT29, T84 and LS174 as well as the normal colon epithelial cells CRL1831. miR-21 target PDCD4 was investigated for its role in mediating miR-21 effects. Expression of miR-21 was significantly up-regulated in exosomes of colon cancer cells, compared to the normal human colon epithelial cells. Treatment of colon cancer cells with isolated exosomes or miR-21 led to an increased expression of genes involved in cell proliferation, invasion and extracellular matrix formation. miR-21 targets PDCD4, TPM1 and PTEN were down-regulated by exosomes and silencing of PDCD4 mimicked miR-21 functional effects, even the induced resistance against 5-FU. Our study suggests that targeted inhibition of exosomes, particularly those carrying miR-21, may represent a novel approach for treatment of colorectal cancer.
City structure shapes directional resettlement flows in Australia
Authors: Slavko Bohdan , Glavatskiy Kirill , Prokopenko Mikhail
Published: May 2020

Modern urban science views differences in attractiveness of residential suburbs as the main driver of resettlement within a city. In particular, certain suburbs may attract residents due to lower commute costs, and this is believed to lead to compactification of a city, with highly populated central business district and sprawled suburbia. In this paper we assess residential resettlement patterns in Australian capital cities by analyzing the 2011 and 2016 Australian Census data. Rather than explicitly defining a residential attractiveness of each suburb in subjective terms, we introduce and calibrate a model which quantifies the intra-city migration flows in terms of the attractiveness potentials (and their differences), inferring these from the data. We discover that, despite the existence of well-known static agglomeration patterns favouring central districts over the suburbia, the dynamic flows that shape the intra-city migration over the last decade reveal the preference directed away from the central districts with a high density of jobs and population, towards the less populated suburbs on the periphery. Furthermore, we discover that the relocation distance of such resettlement flows plays a vital role, and explains a significant part of the variation in migration flows: the resettlement flow markedly decreases with the relocation distance. Finally, we propose a conjecture that these directional resettlement flows are explained by the cities’ structure, with monocentric cities exhibiting outward flows with much higher reluctance to long-distance relocation. This conjecture is verified across the major Australian capitals: both monocentric (Sydney, Melbourne, Brisbane, Adelaide, Perth, Hobart) and polycentric (Darwin and Canberra).