bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric Properties of the Brief Resilient Coping Scale in a Sample of Stable Severe Mental Disorder Patients
Authors: Mayordomo Teresa , Rubio-Belmonte César , García-Alandete Joaquín , Aragonés-Barberá Inmaculada
Published: June 2020

The aim of this study was to analyze the psychometric properties of the Brief Resilient Coping Scale (BRCS). 57 stable severe mental disorder patients (42 men, 73.7%, and 15 women, 26.3%), ranging in age between 23 and 64 years, (M = 46.25; SD = 7.52) answered to the BRCS and the World Health Organization Quality of Life Assessment (WHOQOL-BREF). Descriptive analyses, estimations of internal consistency, and confirmatory factor analysis were conducted, and correlations between the BRCS and the WHOQOL-BREF were calculated. The factorial validity of the scale was tested using confirmatory factor analysis, with a single dimension of resilience. The BRCS showed acceptable internal consistency (alpha of .69). Correlations between the BRCS and WHOQOL-BREF were positive, r(PhH-R) = .42, r(PsH-R) = .40, r(SR-R) = .33, r(E-R) = .35, and significant (p < .01). In conclusion, the Spanish adaptation of the BRCS seems to be a reliable and valid measure of resilience in stable severe mental disorder patients.
Nick Martin’s Contribution to GxE Research
Authors: Colodro-Conde Lucía , Couvy-Duchesne Baptiste
Published: June 2020

The study and identification of genotype–environment interactions (GxE) has been a hot topic in the field of human genetics for several decades. Yet the extent to which GxE contributes to human behavior variability, and its mechanisms, remains largely unknown. Nick Martin has contributed important advances to the field of GxE for human behavior, which include methodological developments, novel analyses and reviews. Here, we will first review Nick’s contributions to the GxE research, which started during his PhD and consistently appears in many of his over 1000 publications. Then, we recount a project that led to an article testing the diathesis-stress model for the origins of depression. In this publication, we observed the presence of an interaction between polygenic risk scores for depression (the risk in our ‘genotype’) and stressful life events (the experiences from our ‘environment’), which provided the first empirical support of this model.
Arg-128-Leu target-site mutation in PPO2 evolves in wild poinsettia (Euphorbia heterophylla) with cross-resistance to PPO-inhibiting herbicides
Authors: Mendes Rafael R. , Takano Hudson K. , Adegas Fernando S. , Oliveira Rubem S. , Gaines Todd A. , Dayan Franck E.
Published: June 2020

Wild poinsettia (Euphorbia heterophylla L.) is a troublesome broadleaf weed in grain production areas in South America. Herbicide resistance to multiple sites of action has been documented in this species, including protoporphyrinogen oxidase (PPO) inhibitors. We investigated the physiological and molecular bases for PPO-inhibitor resistance in a E. heterophylla population (RPPO) from Southern Brazil. Whole-plant dose–response experiments revealed a cross-resistance profile to three different chemical groups of PPO inhibitors. Based on dose–response parameters, RPPO was resistant to lactofen (47.7-fold), saflufenacil (8.6-fold), and pyraflufen-ethyl (3.5-fold). Twenty-four hours after lactofen treatment (120 g ha−1) POST, RPPO accumulated 27 times less protoporphyrin than the susceptible population (SPPO). In addition, RPPO generated 5 and 4.5 times less hydrogen peroxide and superoxide than SPPO, respectively. The chloroplast PPO (PPO1) sequences were identical between the two populations, whereas 35 single-nucleotide polymorphisms were found for the mitochondrial PPO (PPO2). Based on protein homology modeling, the Arg-128-Leu (homologous to Arg-98-Leu in common ragweed [Ambrosia artemisiifolia L.] was the only one located near the catalytic site, also in a conserved region of PPO2. The cytochrome P450 monooxygenase inhibitor malathion did not reverse resistance to lactofen in RPPO, and both populations showed similar levels of PPO1 and PPO2 expression, suggesting that metabolic resistance and PPO overexpression are unlikely. This is the first report of an Arg-128-Leu mutation in PPO2 conferring cross-resistance to PPO inhibitors in E. heterophylla.
FFT‐Based Multiband Spectrum Sensing in SIMO In‐band Full‐Duplex Cognitive Radio Networks
Authors:   Tripta, Kumar Abhishek , Saha Seemanti
Published: June 2020

This paper presents fast Fourier transform (FFT)‐based multiband spectrum sensing over multipath Rayleigh frequency selective fading channels in single input multiple output (SIMO) in‐band full‐duplex (FD) cognitive radio (CR) networks (FDCRNs) under residual self‐interference (RSI). In this work, first, multiband energy detection using Neyman Pearson criterion is proposed in FDCRNs under RSI, where the secondary user is equipped with multiple receive antennas to exploit spatial diversity. Next, a two‐dimensional averaging is done to overcome spectrum leakage problem occurring due to FFT operation in orthogonal frequency division multiplexing (OFDM) system. The closed form expressions for average probability of detection and probability of false alarm are derived for SIMO FDCRNs under RSI. Further, RSI cancelation is performed employing noise robust wavelet decomposition‐based least squares scheme and the corresponding simulation studies indicate that the proposed algorithm further improves the detection performance in SIMO FDCRNs.
Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia
Authors: Regen Francesca , Cosma Nicoleta-Carmen , Otto Lisa R. , Clemens Vera , Saksone Lana , Gellrich Janine , Uesekes Berk , Ta Thi Minh Tam , Hahn Eric , Dettling Michael , Heuser Isabella , Hellmann-Regen Julian
Published: June 2020

The atypical antipsychotic clozapine is one of the most potent drugs of its class, yet its precise mechanisms of action remain insufficiently understood. Recent evidence points toward the involvement of endogenous retinoic acid (RA) signaling in the pathophysiology of schizophrenia. Here we investigated whether clozapine may modulate RA-signaling. Effects of clozapine on the catabolism ofall-transRA (at-RA), the biologically most active metabolite of Vitamin A, were assessed in murine and human brain tissue and peripheral blood-derived mononuclear cells (PBMC). In patients with schizophrenia with and without clozapine treatment and matched healthy controls,at-RA serum levels and blood mRNA expression of retinoid-related genes in PBMCs were quantified. Clozapine and its metabolites potently inhibited RA catabolism at clinically relevant concentrations. In PBMC-derived microsomes, we found a large interindividual variability of the sensitivity toward the effects of clozapine. Furthermore,at-RA and retinol serum levels were significantly lower in patients with schizophrenia compared with matched healthy controls. Patients treated with clozapine exhibited significantly higherat-RA serum levels compared with patients treated with other antipsychotics, while retinol levels did not differ between treatment groups. Similarly, in patients without clozapine treatment, mRNA expression of RA-inducible targets CYP26A and STRA6, as well as at-RA/retinol ratio, were significantly reduced. In contrast, clozapine-treated patients did not differ from healthy controls in this regard. Our findings provide the first evidence for altered peripheral retinoid homeostasis in schizophrenia and suggest modulation of RA catabolism as a novel mechanism of action of clozapine, which may be useful in future antipsychotic drug development.
Ecological succession in the vaginal microbiota during pregnancy and birth
Authors: Rasmussen M A , Thorsen J , Dominguez-Bello M G , Blaser M J , Mortensen M S , Brejnrod A D , Shah S A , Hjelmsø M H , Lehtimäki J , Trivedi U , Bisgaard H , Sørensen S J , Stokholm J
Published: June 2020

The mother’s vaginal microbiota represents the first microbes to which a child is exposed when delivered vaginally. However, little is known about the composition and development of the vaginal microbiota during pregnancy and birth. Here, we analyzed the vaginal microbiota of 57 women in pregnancy week 24, 36 and at birth after rupture of membranes but before delivery, and further compared the composition with that of the gut and airways of the 1-week-old child. The vaginal community structure had dramatic changes in bacterial diversity and taxonomic distribution, yet carried an individual-specific signature. The relative abundance of most bacterial taxa increased stepwise from week 24 of pregnancy until birth, with a gradual decline of Lactobacillus. Mother-to-child vertical transfer, as suggested by sharing, was modest, with the strongest transfer being for Clostridiales followed by Lactobacillales and Enterobacteriales. In conclusion, late gestation is associated with an increase in maternal vaginal microbiota diversity, and vaginal bacteria at birth only modestly predict the composition of the neonatal microbiota.
Human Schlafen 5 regulates reversible epithelial and mesenchymal transitions in breast cancer by suppression of ZEB1 transcription
Authors: Wan Guoqing , Zhu Jiang , Gu Xuefeng , Yang Yue , Liu Yihao , Wang Zhizheng , Zhao Yuxia , Wu Hailong , Huang Gang , Lu Changlian
Published: June 2020

Background

Human Schlafen 5 (SLFN5) has been reported to inhibit or promote cell invasion in tumours depending on their origin. However, its role in breast cancer (BRCA) is undetermined.

Methods

Differential expression analyses using The Cancer Genome Atlas (TCGA) data, clinical samples and cell lines were performed. Lentiviral knockdown and overexpression experiments were performed to detect changes in cell morphology, molecular markers and invasion. Chromatin immunoprecipitation-sequencing (ChIP-Seq) and luciferase reporter assays were performed to detect the SLFN5-binding motif.

Results

TCGA, clinical samples and cell lines showed that SLFN5 expression was negatively correlated with BRCA metastasis. SLFN5 knockdown induced epithelial–mesenchymal transition (EMT) and enhanced invasion in BRCA cell lines. However, overexpression triggered mesenchymal–epithelial transition (MET). SLFN5 inhibited the expression of ZEB1 but not ZEB2, SNAI1, SNAI2, TWIST1 or TWIST2. Knockdown and overexpression of ZEB1 indicated that it was a mediator of the SLFN5-governed phenotype and invasion changes. Moreover, SLFN5 inhibited ZEB1 transcription by directly binding to the SLFN5-binding motif on the ZEB1 promoter, but a SLFN5 C-terminal deletion mutant did not.

Conclusion

SLFN5 regulates reversible epithelial and mesenchymal transitions, and inhibits BRCA metastasis by suppression of ZEB1 transcription, suggesting that SLFN5 could be a potential target for BRCA therapy.
mTOR-Myc axis drives acinar-to-dendritic cell transition and the CD4+ T cell immune response in acute pancreatitis
Authors: Xu Dan , Xie Rongli , Xu Zhiwei , Zhao Zhifeng , Ding Min , Chen Wei , Zhang Jun , Mao Enqiang , Chen Erzhen , Chen Ying , Yang Kaige , Zhou Tong , Fei Jian
Published: June 2020

The inflammatory response in acute pancreatitis (AP) is associated with acinar-to-dendritic cell transition. The CD4+ T-cell-mediated adaptive immune response is necessary for pancreatic inflammatory damage. However, the effect of acinar-to-dendritic cell transition on the CD4+ T-cell response and the regulatory mechanism remain undefined. A mouse animal model of AP was established by repeated intraperitoneal injection of CAE. The mTOR inhibitor rapamycin was administered before AP induction. Primary acinar cells were isolated and co-incubated with subsets of differentiated CD4+ T cells. The expression of DC-SIGN was also assessed in pancreatic tissues from human AP patients. We found acinar cells expressed DC-SIGN and displayed the phenotype of dendritic cells (DCs), which promoted the differentiation of naive CD4+ T cells into CD4+/IFN-γ+ Th1 and CD4+/IL-17A+ Th17 cells in pancreatic tissues during AP. DC-SIGN was the target gene of Myc. The mTOR inhibitor rapamycin inhibited AP-induced DC-SIGN expression, CD4+ Th1/Th17 cell differentiation and the pro-inflammatory response via Myc. Acinar cells expressed DC-SIGN in pancreatic tissues of human patients with AP. In conclusion, acinar-to-dendritic cell transition is implicated in the CD4+ T-cell immune response via mTOR-Myc-DC-SIGN axis, which might be an effective target for the prevention of local pancreatic inflammation in AP.
Very sharp diffraction peak in nonglass-forming liquid with the formation of distorted tetraclusters
Authors: Koyama Chihiro , Tahara Shuta , Kohara Shinji , Onodera Yohei , Småbråten Didrik R. , Selbach Sverre M. , Akola Jaakko , Ishikawa Takehiko , Masuno Atsunobu , Mizuno Akitoshi , Okada Junpei T. , Watanabe Yuki , Nakata Yui , Ohara Koji , Tamaru Haruka , Oda Hirohisa , Obayashi Ippei , Hiraoka Yasuyuki , Sakata Osami
Published: June 2020

Understanding the liquid structure provides information that is crucial to uncovering the nature of the glass-liquid transition. We apply an aerodynamic levitation technique and high-energy X-rays to liquid (l)-Er2O3 to discover its structure. The sample densities are measured by electrostatic levitation at the International Space Station. Liquid Er2O3 displays a very sharp diffraction peak (principal peak). Applying a combined reverse Monte Carlo – molecular dynamics approach, the simulations produce an Er–O coordination number of 6.1, which is comparable to that of another nonglass-forming liquid, l-ZrO2. The atomic structure of l-Er2O3 comprises distorted OEr4 tetraclusters in nearly linear arrangements, as manifested by a prominent peak observed at ~180° in the Er–O–Er bond angle distribution. This structural feature gives rise to long periodicity corresponding to the sharp principal peak in the X-ray diffraction data. A persistent homology analysis suggests that l-Er2O3 is homologically similar to the crystalline phase. Moreover, electronic structure calculations show that l-Er2O3 has a modest band gap of 0.6 eV that is significantly reduced from the crystalline phase due to the tetracluster distortions. The estimated viscosity is very low above the melting point for l-ZrO2, and the material can be described as an extremely fragile liquid.
Cephalopod-inspired optical engineering of human cells
Authors: Chatterjee Atrouli , Cerna Sanchez Juana Alejandra , Yamauchi Toyohiko , Taupin Vanessa , Couvrette Justin , Gorodetsky Alon A.
Published: June 2020

Although many animals have evolved intrinsic transparency for the purpose of concealment, the development of dynamic, that is, controllable and reversible, transparency for living human cells and tissues has remained elusive to date. Here, by drawing inspiration from the structures and functionalities of adaptive cephalopod skin cells, we design and engineer human cells that contain reconfigurable protein-based photonic architectures and, as a result, possess tunable transparency-changing and light-scattering capabilities. Our findings may lead to the development of unique biophotonic tools for applications in materials science and bioengineering and may also facilitate an improved understanding of a wide range of biological systems.
Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence
Authors: Toda Haruka , Diaz-Varela Miriam , Segui-Barber Joan , Roobsoong Wanlapa , Baro Barbara , Garcia-Silva Susana , Galiano Alicia , Gualdrón-López Melisa , Almeida Anne C. G. , Brito Marcelo A. M. , de Melo Gisely Cardoso , Aparici-Herraiz Iris , Castro-Cavadía Carlos , Monteiro Wuelton Marcelo , Borràs Eva , Sabidó Eduard , Almeida Igor C. , Chojnacki Jakub , Martinez-Picado Javier , Calvo Maria , Armengol Pilar , Carmona-Fonseca Jaime , Yasnot Maria Fernanda , Lauzurica Ricardo , Marcilla Antonio , Peinado Hector , Galinski Mary R. , Lacerda Marcus V. G. , Sattabongkot Jetsumon , Fernandez-Becerra Carmen , del Portillo Hernando A.
Published: June 2020

Plasmodium vivax is the most widely distributed human malaria parasite. Previous studies have shown that circulating microparticles during P. vivax acute attacks are indirectly associated with severity. Extracellular vesicles (EVs) are therefore major components of circulating plasma holding insights into pathological processes. Here, we demonstrate that plasma-derived EVs from Plasmodium vivax patients (PvEVs) are preferentially uptaken by human spleen fibroblasts (hSFs) as compared to the uptake of EVs from healthy individuals. Moreover, this uptake induces specific upregulation of ICAM-1 associated with the translocation of NF-kB to the nucleus. After this uptake, P. vivax-infected reticulocytes obtained from patients show specific adhesion properties to hSFs, reversed by inhibiting NF-kB translocation to the nucleus. Together, these data provide physiological EV-based insights into the mechanisms of human malaria pathology and support the existence of P. vivax-adherent parasite subpopulations in the microvasculature of the human spleen.
Attosecond science based on high harmonic generation from gases and solids
Authors: Li Jie , Lu Jian , Chew Andrew , Han Seunghwoi , Li Jialin , Wu Yi , Wang He , Ghimire Shambhu , Chang Zenghu
Published: June 2020

Recent progress in high power ultrafast short-wave and mid-wave infrared lasers has enabled gas-phase high harmonic generation (HHG) in the water window and beyond, as well as the demonstration of HHG in condensed matter. In this Perspective, we discuss the recent advancements and future trends in generating and characterizing soft X-ray pulses from gas-phase HHG and extreme ultraviolet (XUV) pulses from solid-state HHG. Then, we discuss their current and potential usage in time-resolved study of electron and nuclear dynamics in atomic, molecular and condensed matters.
Mantle data imply a decline of oxidizable volcanic gases could have triggered the Great Oxidation
Authors: Kadoya Shintaro , Catling David C. , Nicklas Robert W. , Puchtel Igor S. , Anbar Ariel D.
Published: June 2020

Aerobic lifeforms, including humans, thrive because of abundant atmospheric O2, but for much of Earth history O2 levels were low. Even after evidence for oxygenic photosynthesis appeared, the atmosphere remained anoxic for hundreds of millions of years until the ~2.4 Ga Great Oxidation Event. The delay of atmospheric oxygenation and its timing remain poorly understood. Two recent studies reveal that the mantle gradually oxidized from the Archean onwards, leading to speculation that such oxidation enabled atmospheric oxygenation. But whether this mechanism works has not been quantitatively examined. Here, we show that these data imply that reducing Archean volcanic gases could have prevented atmospheric O2 from accumulating until ~2.5 Ga with ≥95% probability. For two decades, mantle oxidation has been dismissed as a key driver of the evolution of O2 and aerobic life. Our findings warrant a reconsideration for Earth and Earth-like exoplanets.
Role of serotonergic dorsal raphe neurons in hypercapnia-induced arousals
Authors: Kaur Satvinder , De Luca Roberto , Khanday Mudasir A. , Bandaru Sathyajit S. , Thomas Renner C. , Broadhurst Rebecca Y. , Venner Anne , Todd William D. , Fuller Patrick M. , Arrigoni Elda , Saper Clifford B.
Published: June 2020

During obstructive sleep apnea, elevation of CO2 during apneas contributes to awakening and restoring airway patency. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) containing calcitonin gene related peptide (PBelCGRP neurons) are critical for causing arousal during hypercapnia. However, others found that genetic deletion of serotonin (5HT) neurons in the brainstem also prevented arousal from hypercapnia. To examine interactions between the two systems, we showed that dorsal raphe (DR) 5HT neurons selectively targeted the PBel. Either genetically directed deletion or acute optogenetic silencing of DRSert neurons dramatically increased the latency of mice to arouse during hypercapnia, as did silencing DRSert terminals in the PBel. This effect was mediated by 5HT2a receptors which are expressed by PBelCGRP neurons. Our results indicate that the serotonergic input from the DR to the PBel via 5HT2a receptors is critical for modulating the sensitivity of the PBelCGRP neurons that cause arousal to rising levels of blood CO2.
The ABCG2 Q141K hyperuricemia and gout associated variant illuminates the physiology of human urate excretion
Authors: Hoque Kazi Mirajul , Dixon Eryn E. , Lewis Raychel M. , Allan Jordyn , Gamble Gregory D. , Phipps-Green Amanda J. , Halperin Kuhns Victoria L. , Horne Anne M. , Stamp Lisa K. , Merriman Tony R. , Dalbeth Nicola , Woodward Owen M.
Published: June 2020

The pathophysiological nature of the common ABCG2 gout and hyperuricemia associated variant Q141K (rs2231142) remains undefined. Here, we use a human interventional cohort study (ACTRN12615001302549) to understand the physiological role of ABCG2 and find that participants with the Q141K ABCG2 variant display elevated serum urate, unaltered FEUA, and significant evidence of reduced extra-renal urate excretion. We explore mechanisms by generating a mouse model of the orthologous Q140K Abcg2 variant and find male mice have significant hyperuricemia and metabolic alterations, but only subtle alterations of renal urate excretion and ABCG2 abundance. By contrast, these mice display a severe defect in ABCG2 abundance and function in the intestinal tract. These results suggest a tissue specific pathobiology of the Q141K variant, support an important role for ABCG2 in urate excretion in both the human kidney and intestinal tract, and provide insight into the importance of intestinal urate excretion for serum urate homeostasis.
Spherical trihedral metallo-borospherenes
Authors: Chen Teng-Teng , Li Wan-Lu , Chen Wei-Jia , Yu Xiao-Hu , Dong Xin-Ran , Li Jun , Wang Lai-Sheng
Published: June 2020

The discovery of borospherenes unveiled the capacity of boron to form fullerene-like cage structures. While fullerenes are known to entrap metal atoms to form endohedral metallofullerenes, few metal atoms have been observed to be part of the fullerene cages. Here we report the observation of a class of remarkable metallo-borospherenes, where metal atoms are integral parts of the cage surface. We have produced La3B18– and Tb3B18– and probed their structures and bonding using photoelectron spectroscopy and theoretical calculations. Global minimum searches revealed that the most stable structures of Ln3B18– are hollow cages with D3h symmetry. The B18-framework in the Ln3B18– cages can be viewed as consisting of two triangular B6 motifs connected by three B2 units, forming three shared B10 rings which are coordinated to the three Ln atoms on the cage surface. These metallo-borospherenes represent a new class of unusual geometry that has not been observed in chemistry heretofore.
Type I interferon sensing unlocks dormant adipocyte inflammatory potential
Authors: Chan Calvin C. , Damen Michelle S. M. A. , Moreno-Fernandez Maria E. , Stankiewicz Traci E. , Cappelletti Monica , Alarcon Pablo C. , Oates Jarren R. , Doll Jessica R. , Mukherjee Rajib , Chen Xiaoting , Karns Rebekah , Weirauch Matthew T. , Helmrath Michael A. , Inge Thomas H. , Divanovic Senad
Published: June 2020

White adipose tissue inflammation, in part via myeloid cell contribution, is central to obesity pathogenesis. Mechanisms regulating adipocyte inflammatory potential and consequent impact of such inflammation in disease pathogenesis remain poorly defined. We show that activation of the type I interferon (IFN)/IFNα receptor (IFNAR) axis amplifies adipocyte inflammatory vigor and uncovers dormant gene expression patterns resembling inflammatory myeloid cells. IFNβ-sensing promotes adipocyte glycolysis, while glycolysis inhibition impeded IFNβ-driven intra-adipocyte inflammation. Obesity-driven induction of the type I IFN axis and activation of adipocyte IFNAR signaling contributes to obesity-associated pathogenesis in mice. Notably, IFNβ effects are conserved in human adipocytes and detection of the type I IFN/IFNAR axis-associated signatures positively correlates with obesity-driven metabolic derangements in humans. Collectively, our findings reveal a capacity for the type I IFN/IFNAR axis to regulate unifying inflammatory features in both myeloid cells and adipocytes and hint at an underappreciated contribution of adipocyte inflammation in disease pathogenesis.
Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms
Authors: Subudhi Amit K. , O’Donnell Aidan J. , Ramaprasad Abhinay , Abkallo Hussein M. , Kaushik Abhinav , Ansari Hifzur R. , Abdel-Haleem Alyaa M. , Ben Rached Fathia , Kaneko Osamu , Culleton Richard , Reece Sarah E. , Pain Arnab
Published: June 2020

Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.
Complex strengthening mechanisms in the NbMoTaW multi-principal element alloy
Authors: Li Xiang-Guo , Chen Chi , Zheng Hui , Zuo Yunxing , Ong Shyue Ping
Published: June 2020

Refractory multi-principal element alloys (MPEAs) have exceptional mechanical properties, including high strength-to-weight ratio and fracture toughness, at high temperatures. Here we elucidate the complex interplay between segregation, short-range order, and strengthening in the NbMoTaW MPEA through atomistic simulations with a highly accurate machine learning interatomic potential. In the single crystal MPEA, we find greatly reduced anisotropy in the critically resolved shear stress between screw and edge dislocations compared to the elemental metals. In the polycrystalline MPEA, we demonstrate that thermodynamically driven Nb segregation to the grain boundaries (GBs) and W enrichment within the grains intensifies the observed short-range order (SRO). The increased GB stability due to Nb enrichment reduces the von Mises strain, resulting in higher strength than a random solid solution MPEA. These results highlight the need to simultaneously tune GB composition and bulk SRO to tailor the mechanical properties of MPEAs.
Author Correction: Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson’s disease
Authors: Pontone Gregory M. , Dissanayaka Nadeeka , Apostolova Liana , Brown Richard G. , Dobkin Roseanne , Dujardin Kathy , Friedman Joseph H. , Leentjens Albert F. G. , Lenze Eric J. , Marsh Laura , Mari Lynda , Monchi Oury , Richard Irene H. , Schrag Anette , Strafella Antonio P. , Vernaleo Beth , Weintraub Daniel , Mari Zoltan
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Resource-efficient digital quantum simulation of d-level systems for photonic, vibrational, and spin-s Hamiltonians
Authors: Sawaya Nicolas P. D. , Menke Tim , Kyaw Thi Ha , Johri Sonika , Aspuru-Guzik Alán , Guerreschi Gian Giacomo
Published: June 2020

Simulation of quantum systems is expected to be one of the most important applications of quantum computing, with much of the theoretical work so far having focused on fermionic and spin-$$\frac{1}{2}$$

1

2

systems. Here, we instead consider encodings of d-level (i.e., qudit) quantum operators into multi-qubit operators, studying resource requirements for approximating operator exponentials by Trotterization. We primarily focus on spin-s and truncated bosonic operators in second quantization, observing desirable properties for approaches based on the Gray code, which to our knowledge has not been used in this context previously. After outlining a methodology for implementing an arbitrary encoding, we investigate the interplay between Hamming distances, sparsity patterns, bosonic truncation, and other properties of local operators. Finally, we obtain resource counts for five common Hamiltonian classes used in physics and chemistry, while modeling the possibility of converting between encodings within a Trotter step. The most efficient encoding choice is heavily dependent on the application and highly sensitive to d, although clear trends are present. These operation count reductions are relevant for running algorithms on near-term quantum hardware because the savings effectively decrease the required circuit depth. Results and procedures outlined in this work may be useful for simulating a broad class of Hamiltonians on qubit-based digital quantum computers.
Large Zeeman splitting induced anomalous Hall effect in ZrTe5
Authors: Sun Zeliang , Cao Zhipeng , Cui Jianhua , Zhu Changsheng , Ma Donghui , Wang Honghui , Zhuo Weizhuang , Cheng Zhaohui , Wang Zhenyu , Wan Xiangang , Chen Xianhui
Published: June 2020

Berry phase effects have significant influences on the electronic properties of condensed matter. In particular, the anomalous Hall conductivity has been recognized as an intrinsic property of the systems with non-zero Berry curvature. Here, we present the anomalous Hall effect observed in the non-magnetic material ZrTe5, which hosts a large Zeeman splitting with Landé g-factor of 26.49. The quantum oscillation analysis reveals non-linear band dispersion near the top of valence band in bulk band structure, and no Weyl node forms with applied magnetic field. The anomalous Hall conductivity reaches 129 Ω−1 cm−1 at 2 K, and shows weak temperature dependence. All these combined with theoretical analysis suggest that the anomalous Hall effect observed in ZrTe5 originates from the non-vanishing Berry curvature induced by combining large Zeeman splitting and strong spin–orbit coupling. Remarkably, the anomalous Hall resistivity reverses its sign from negative to positive at a hydrostatic pressure P = 1.3 GPa, which confirms that the anomalous Hall effect in ZrTe5 is highly related to the band structure-dependent Berry curvature. Our results have verified the anomalous Hall mechanism in ZrTe5 and offer a new platform to study the anomalous Hall effect.
The vaccinia virus based Sementis Copenhagen Vector vaccine against Zika and chikungunya is immunogenic in non-human primates
Authors: Prow Natalie A. , Liu Liang , McCarthy Mary K. , Walters Kevin , Kalkeri Raj , Geiger Jillian , Koide Fusataka , Cooper Tamara H. , Eldi Preethi , Nakayama Eri , Diener Kerrilyn R. , Howley Paul M. , Hayball John D. , Morrison Thomas E. , Suhrbier Andreas
Published: June 2020

The Sementis Copenhagen Vector (SCV) is a new vaccinia virus-derived, multiplication-defective, vaccine technology assessed herein in non-human primates. Indian rhesus macaques (Macaca mulatta) were vaccinated with a multi-pathogen recombinant SCV vaccine encoding the structural polyproteins of both Zika virus (ZIKV) and chikungunya virus (CHIKV). After one vaccination, neutralising antibody responses to ZIKV and four strains of CHIKV, representative of distinct viral genotypes, were generated. A second vaccination resulted in significant boosting of neutralising antibody responses to ZIKV and CHIKV. Following challenge with ZIKV, SCV-ZIKA/CHIK-vaccinated animals showed significant reductions in viremias compared with animals that had received a control SCV vaccine. Two SCV vaccinations also generated neutralising and IgG ELISA antibody responses to vaccinia virus. These results demonstrate effective induction of immunity in non-human primates by a recombinant SCV vaccine and illustrates the utility of SCV as a multi-disease vaccine platform capable of delivering multiple large immunogens.
Two-Step Mechanism of Cyclin B Degradation Initiated by Proteolytic Cleavage with the 26 S Proteasome in Fish
Authors: Tokumoto Toshinobu , Hossain Md. Forhad , Jyoti Md. Maisum Sarwar , Ali Md. Hasan , Hossain Md. Babul , Acharjee Mrityunjoy , Rezanujjaman Md. , Tokumoto Mika
Published: June 2020

To complete meiosis II, cyclin B is degraded in a short period by the inactivation of M-phase promoting factor (MPF). Previously, we showed that the destruction of cyclin B was initiated by the ubiquitin-independent proteolytic activity of the 26 S proteasome through an initial cut in the N-terminus of cyclin (at K57 in the case of goldfish cyclin B). We hypothesized that this cut allows cyclin to be ubiquitinated for further destruction by the ubiquitin-dependent proteolytic pathway, which leads to MPF inactivation. In this study, we aimed to identify the ubiquitination site for further degradation. The destruction of cyclin B point mutants in which lysine residues in a lysine-rich stretch following the cut site of cyclin B had been mutated was analyzed. All the lysine point mutants except K57R (a point mutant in which K57 was substituted with arginine) were susceptible to proteolytic cleavage by the 26 S proteasome. However, the degradation of the K77R and K7677R mutants in Xenopus egg extracts was significantly slower than the degradation of other mutants, and a 42 kDa truncated form of cyclin B was detected during the onset of the degradation of these mutants. The truncated form of recombinant cyclin B, an N-terminal truncated cyclin BΔ57 produced as cut by the 26 S proteasome, was not further cleaved by the 26 S proteasome but rather degraded in Xenopus egg extracts. The injection of the K57R, K77R and K7677R cyclin B proteins stopped cleavage in Xenopus embryos. From the results of a series of experiments, we concluded that cyclin B degradation involves a two-step mechanism initiated by initial ubiquitin-independent cleavage by the 26 S proteasome at lysine 57 followed by its ubiquitin-dependent destruction by the 26 S proteasome following ubiquitination at lysine 77.
Inhibition of LIPG phospholipase activity suppresses tumor formation of human basal-like triple-negative breast cancer
Authors: Lo Pang-Kuo , Yao Yuan , Zhou Qun
Published: June 2020

The endothelial lipase LIPG possesses serine phospholipase activity and is involved in lipoprotein metabolism. Our previous studies have revealed that LIPG overexpression is required for tumor formation and metastasis of human basal-like triple-negative breast cancer (TNBC). We also demonstrated that LIPG differentially regulates TNBC malignancy through its enzymatic and non-enzymatic functions. The present studies were aimed at determining how XEN445, a specific inhibitor targeting LIPG phospholipase activity, impacts on TNBC tumor formation and malignant features. We established a cell-based LIPG enzymatic assay system to measure the inhibitory effect of XEN445 on LIPG phospholipase activity and determine its IC50. We found that XEN445 preferentially inhibited the proliferation of LIPG-expressing TNBC cells but not LIPG-negative luminal breast cancer cells. XEN445 inhibited the self-renewal of cancer stem cells (CSCs) in vitro and TNBC tumor formation in vivo. However, XEN445 had no inhibitory effect on the invasiveness and CSC stemness of TNBC cells. Our studies suggest that targeting both LIPG enzymatic and non-enzymatic functions is an important strategy for the treatment of TNBC.
Deep learning-based hologram generation using a white light source
Authors: Go Taesik , Lee Sangseung , You Donghyun , Lee Sang Joon
Published: June 2020

Digital holographic microscopy enables the recording of sample holograms which contain 3D volumetric information. However, additional optical elements, such as partially or fully coherent light source and a pinhole, are required to induce diffraction and interference. Here, we present a deep neural network based on generative adversarial network (GAN) to perform image transformation from a defocused bright-field (BF) image acquired from a general white light source to a holographic image. Training image pairs of 11,050 for image conversion were gathered by using a hybrid BF and hologram imaging technique. The performance of the trained network was evaluated by comparing generated and ground truth holograms of microspheres and erythrocytes distributed in 3D. Holograms generated from BF images through the trained GAN showed enhanced image contrast with 3–5 times increased signal-to-noise ratio compared to ground truth holograms and provided 3D positional information and light scattering patterns of the samples. The developed GAN-based method is a promising mean for dynamic analysis of microscale objects with providing detailed 3D positional information and monitoring biological samples precisely even though conventional BF microscopic setting is utilized.
Short-Wavelength and Near-Infrared Autofluorescence in Patients with Deficiencies of the Visual Cycle and Phototransduction
Authors: Oh Jin Kyun , Lima de Carvalho Jose Ronaldo , Ryu Joseph , Tsang Stephen H. , Sparrow Janet R.
Published: June 2020

Fundus autofluorescence is a valuable imaging tool in the diagnosis of inherited retinal dystrophies. With the advent of gene therapy and the numerous ongoing clinical trials for inherited retinal degenerations, quantifiable and reliable outcome measurements continually need to be identified. In this retrospective analysis, normalized and non-normalized short-wavelength (SW-AF) and near-infrared (NIR-AF) autofluorescence images of ten patients with mutations in visual cycle (VC) genes and nineteen patients with mutations in phototransduction (PT) genes were analyzed. Normalized SW-AF and NIR-AF images appeared darker in all patients with mutations in the VC as compared to patients with mutations in PT despite the use of significantly higher detector settings for image acquisition in the former group. These findings were corroborated by quantitative analysis of non-normalized SW-AF and NIR-AF images; signal intensities were significantly lower in all patients with mutations in VC genes as compared to those with mutations in PT genes. We conclude that qualitative and quantitative SW-AF and NIR-AF images can serve as biomarkers of deficiencies specific to the VC. Additionally, quantitative autofluorescence may have potential for use as an outcome measurement to detect VC activity in conjunction with future therapies for patients with mutations in the VC.
Baseline and Disease-Induced Transcriptional Profiles in Children with Sickle Cell Disease
Authors: Creary Susan , Shrestha Chandra L. , Kotha Kavitha , Minta Abena , Fitch James , Jaramillo Lisa , Zhang Shuzhong , Pinto Swaroop , Thompson Rohan , Ramilo Octavio , White Peter , Mejias Asuncion , Kopp Benjamin T.
Published: June 2020

Acute chest syndrome (ACS) is a significant cause of morbidity and mortality in sickle cell disease (SCD), but preventive, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) have overlapping features, which causes diagnostic dilemmas. We explored changes in gene expression profiles among patients with SCD hospitalized for VOC and ACS episodes to better understand ACS disease pathogenesis. Whole blood RNA-Seq was performed for 20 samples from children with SCD at baseline and during a hospitalization for either an ACS (n = 10) or a VOC episode (n = 10). Respiratory viruses were identified from nasopharyngeal swabs. Functional gene analyses were performed using modular repertoires, IPA, Gene Ontology, and NetworkAnalyst 3.0. The VOC group had a numerically higher percentage of female, older, and hemoglobin SS participants compared to the ACS group. Viruses were detected in 50% of ACS cases and 20% of VOC cases. We identified 3004 transcripts that were differentially expressed during ACS episodes, and 1802 transcripts during VOC episodes. Top canonical pathways during ACS episodes were related to interferon signaling, neuro-inflammation, pattern recognition receptors, and macrophages. Top canonical pathways in patients with VOC included IL-10 signaling, iNOS signaling, IL-6 signaling, and B cell signaling. Several genes related to antimicrobial function were down-regulated during ACS compared to VOC. Gene enrichment nodal interactions demonstrated significantly altered pathways during ACS and VOC. A complex network of changes in innate and adaptive immune gene expression were identified during both ACS and VOC episodes. These results provide unique insights into changes during acute events in children with SCD.
Motor axonopathies in a mouse model of Duchenne muscular dystrophy
Authors: Dhindsa Justin S. , McCall Angela L. , Strickland Laura M. , Fusco Anna F. , Kahn Amanda F. , ElMallah Mai K.
Published: June 2020

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by deleterious mutations in the DMD gene which encodes the dystrophin protein. Skeletal muscle weakness and eventual muscle degradation due to loss of dystrophin are well-documented pathological hallmarks of DMD. In contrast, the neuropathology of this disease remains understudied despite the emerging evidence of neurological abnormalities induced by dystrophin loss. Using quantitative morphological analysis of nerve sections, we characterize axonopathies in the phrenic and hypoglossal (XII) nerves of mdx mice. We observe dysfunction in these nerves – which innervate the diaphragm and genioglossus respectively – that we propose contributes to respiratory failure, the most common cause of death in DMD. These observations highlight the importance in the further characterization of the neuropathology of DMD. Additionally, these observations underscore the necessity in correcting both the nervous system pathology in addition to skeletal muscle deficits to ameliorate this disease.
New method for intraocular lens power calculation using a rotating Scheimpflug camera in eyes with corneal refractive surgery
Authors: Cho Kyuyeon , Lim Dong Hui , Yoo Young-Sik , Chung Tae-Young
Published: June 2020

To introduce and evaluate a refraction-based method for calculating the correct power of the intraocular lens (IOL) in eyes with corneal refractive surgery and to compare the results here to previously published methods. Retrospective review of medical records was done. Group 1 was used to derive two formulas. From the relevant IOL calculation and postoperative refractive data, the refraction-derived K values (Krd) were calculated using a linear regression analysis. The values obtained with the two formulas were compared to previously published methods in group 2 to validate the results. The following methods were evaluated: Haigis-L, Barrett True-K (no history), Potvin-Hill, BESSt 2, Scheimpflug total corneal refractive power (TCRP) 4 mm (Haigis), Scheimpflug total refractive power (TRP) 4 mm (Haigis), modified Scheimpflug TCRP 4 mm (Haigis), and modified Scheimpflug TRP 4 mm (Haigis). The modified TCRP 4 mm Krd (Haigis) had good outcomes, with 60% and 90% of eyes within ±0.50 D and ±1.00 D of the refractive target, respectively. A new method using modified Scheimpflug total corneal refractive power in the 4.0 mm zone appeared to be an accurate method for determining IOL power in eyes with corneal refractive surgery.
Acquired contractile ability in human endometrial stromal cells by passive loading of cyclic tensile stretch
Authors: Kim Jeonghyun , Ushida Takashi , Montagne Kevin , Hirota Yasushi , Yoshino Osamu , Hiraoka Takehiro , Osuga Yutaka , Furuakwa Katsuko S.
Published: June 2020

The uterus plays an important and unique role during pregnancy and is a dynamic organ subjected to mechanical stimuli. It has been reported that infertility occurs when the peristalsis is prevented, although its mechanisms remain unknown. In this study, we found that mechanical strain mimicking the peristaltic motion of the uterine smooth muscle layer enabled the endometrial stromal cells to acquire contractility. In order to mimic the peristalsis induced by uterine smooth muscle cells, cyclic tensile stretch was applied to human endometrial stromal cells. The results showed that the strained cells exerted greater contractility in three-dimensional collagen gels in the presence of oxytocin, due to up-regulated alpha-smooth muscle actin expression via the cAMP signaling pathway. These in vitro findings underscore the plasticity of the endometrial stromal cell phenotype and suggest the possibility of acquired contractility by these cells in vivo and its potential contribution to uterine contractile activity. This phenomenon may be a typical example of how a tissue passively acquires new contractile functions under mechanical stimulation from a neighboring tissue, enabling it to support the adjacent tissue’s functions.
Reproductive effects of subchronic exposure to acetamiprid in male rats
Authors: Arıcan Emre Yağmur , Gökçeoğlu Kayalı Damla , Ulus Karaca Bahar , Boran Tuğçe , Öztürk Narin , Okyar Alper , Ercan Feriha , Özhan Gül
Published: June 2020

Acetamiprid, a selective agonist of nicotinic acetylcholine recetors, is one of the most widely used neonicotinoids. There is limited data about toxicity of acetamiprid on male reproductive system. Therefore, the study aimed to investigate the reproductive toxic potential of acetamiprid in male rats orally treated with acetamiprid with low (12.5 mg/kg) medium (25 mg/kg) or high dose (35 mg/kg) for 90 days. According to our results, sperm concentration and plasma testosterone levels decreased in dose dependent manner. Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormeone (FSH), luteinizing hormone (LH) levels increased at low and medium dose groups and acetamiprid caused lipid peroxidation and glutathione (GSH) depletion in the testes. Histologic examinations revealed that acetamiprid induced apoptosis in medium and high dose groups and proliferation index dramatically decreased in high dose group. In conclusion, acetamiprid caused toxicity on male reproductive system in the high dose. The mechanism of the toxic effect may be associated with oxidative stress, hormonal disruptions and apoptosis.
Role of Androgen Receptor for Reconsidering the “True” Polycystic Ovarian Morphology in PCOS
Authors: Gao Xue-ying , Liu Yue , Lv Yue , Huang Tao , Lu Gang , Liu Hong-bin , Zhao Shi-gang
Published: June 2020

Purpose: Polycystic ovarian morphology (PCOM) is one of the key features of polycystic ovary syndrome (PCOS). The diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is debated because of the high prevalence of PCOM in the general population. Androgen receptor (AR) is associated with the PCOS phenotype and might as well play a role during folliculogenesis. This study is aimed to investigate the expression of the AR in PCOS granulosa cells (GCs) and its relationship with the PCOM phenotype. Methods: 106 PCOS cases and 63 controls were included from the Center for Reproductive Medicine, Shandong University. The diagnosis of PCOS was following the Rotterdam criteria (2003). Total RNA was extracted from GCs retrieved from ovarian stimulation. The expression of AR was amplified by means of quantitative real-time polymerase chain reaction. Results: The AR expression was significantly decreased in PCOS cases, especially in the tPCOM subgroup (≥20 antral follicles per ovary). Correlation analyses showed that AR expression was significantly correlated with serum FSH levels in controls and non-tPCOM. In the tPCOM subgroup, the AR expression was significantly correlated with serum LH levels. Interestingly, the significance of these correlations gradually disappeared as the threshold of antral follicles increased above 24 for PCOM. Conclusions:AR was differently expressed in PCOS and especially in the tPCOM subtype. The correlation of AR expression with serum FSH and LH might be associated with the number of follicles in PCOM.