bluuebunny/crossref_metadata_2025 huggingface dataset:
Measured Canadian oil sands CO2 emissions are higher than estimates made using internationally recommended methods
Authors: Liggio John , Li Shao-Meng , Staebler Ralf M. , Hayden Katherine , Darlington Andrea , Mittermeier Richard L. , O’Brien Jason , McLaren Robert , Wolde Mengistu , Worthy Doug , Vogel Felix
Published: April 2019

The oil and gas (O&G) sector represents a large source of greenhouse gas (GHG) emissions globally. However, estimates of O&G emissions rely upon bottom-up approaches, and are rarely evaluated through atmospheric measurements. Here, we use aircraft measurements over the Canadian oil sands (OS) to derive the first top-down, measurement-based determination of the their annual CO2emissions and intensities. The results indicate that CO2emission intensities for OS facilities are 13–123% larger than those estimated using publically available data. This leads to 64% higher annual GHG emissions from surface mining operations, and 30% higher overall OS GHG emissions (17 Mt) compared to that reported by industry, despite emissions reporting which uses the most up to date and recommended bottom-up approaches. Given the similarity in bottom-up reporting methods across the entire O&G sector, these results suggest that O&G CO2emissions inventory data may be more uncertain than previously considered.
An inner activation gate controls TMEM16F phospholipid scrambling
Authors: Le Trieu , Jia Zhiguang , Le Son C. , Zhang Yang , Chen Jianhan , Yang Huanghe
Published: April 2019

Transmembrane protein 16F (TMEM16F) is an enigmatic Ca2+-activated phospholipid scramblase (CaPLSase) that passively transports phospholipids down their chemical gradients and mediates blood coagulation, bone development and viral infection. Despite recent advances in the structure and function understanding of TMEM16 proteins, how mammalian TMEM16 CaPLSases open and close, or gate their phospholipid permeation pathways remains unclear. Here we identify an inner activation gate, which is established by three hydrophobic residues, F518, Y563 and I612, in the middle of the phospholipid permeation pathway of TMEM16F-CaPLSase. Disrupting the inner gate profoundly alters TMEM16F phospholipid permeation. Lysine substitutions of F518 and Y563 even lead to constitutively active CaPLSases that bypass Ca2+-dependent activation. Strikingly, an analogous lysine mutation to TMEM16F-F518 in TMEM16A (L543K) is sufficient to confer CaPLSase activity to the Ca2+-activated Cl− channel (CaCC). The identification of an inner activation gate can help elucidate the gating and permeation mechanism of TMEM16 CaPLSases and channels.
Spectra stable blue perovskite light-emitting diodes
Authors: Jiang Yuanzhi , Qin Chaochao , Cui Minghuan , He Tingwei , Liu Kaikai , Huang Yanmin , Luo Menghui , Zhang Li , Xu Hongyu , Li Saisai , Wei Junli , Liu Zhiyong , Wang Huanhua , Kim Gi-Hwan , Yuan Mingjian , Chen Jun
Published: April 2019

Device performance and in particular device stability for blue perovskite light-emitting diodes (PeLEDs) remain considerable challenges for the whole community. In this manuscript, we conceive an approach by tuning the ‘A-site’ cation composition of perovskites to develop blue-emitters. We herein report a Rubidium-Cesium alloyed, quasi-two-dimensional perovskite and demonstrate its great potential for pure-blue PeLED applications. Composition engineering and in-situ passivation are conducted to further improve the material’s emission property and stabilities. Consequently, we get a prominent film photoluminescence quantum yield of around 82% under low excitation density. Encouraged by these findings, we finally achieve a spectra-stable blue PeLED with the peak external quantum efficiency of 1.35% and a half-lifetime of 14.5 min, representing the most efficient and stable pure-blue PeLEDs reported so far. The strategy is also demonstrated to be able to generate efficient perovskite blue emitters and PeLEDs in the whole blue spectral region (from 454 to 492 nm).
A 3.8 Å resolution cryo-EM structure of a small protein bound to an imaging scaffold
Authors: Liu Yuxi , Huynh Duc T. , Yeates Todd O.
Published: April 2019

Proteins smaller than about 50 kDa are currently too small to be imaged at high resolution by cryo-electron microscopy (cryo-EM), leaving most protein molecules in the cell beyond the reach of this powerful structural technique. Here we use a designed protein scaffold to bind and symmetrically display 12 copies of a small 26 kDa protein, green fluorescent protein (GFP). We show that the bound cargo protein is held rigidly enough to visualize it at a resolution of 3.8 Å by cryo-EM, where specific structural features of the protein are visible. The designed scaffold is modular and can be modified through modest changes in its amino acid sequence to bind and display diverse proteins for imaging, thus providing a general method to break through the lower size limitation in cryo-EM.
Symbiotic cardiac pacemaker
Authors: Ouyang Han , Liu Zhuo , Li Ning , Shi Bojing , Zou Yang , Xie Feng , Ma Ye , Li Zhe , Li Hu , Zheng Qiang , Qu Xuecheng , Fan Yubo , Wang Zhong Lin , Zhang Hao , Li Zhou
Published: April 2019

Self-powered implantable medical electronic devices that harvest biomechanical energy from cardiac motion, respiratory movement and blood flow are part of a paradigm shift that is on the horizon. Here, we demonstrate a fully implanted symbiotic pacemaker based on an implantable triboelectric nanogenerator, which achieves energy harvesting and storage as well as cardiac pacing on a large-animal scale. The symbiotic pacemaker successfully corrects sinus arrhythmia and prevents deterioration. The open circuit voltage of an implantable triboelectric nanogenerator reaches up to 65.2 V. The energy harvested from each cardiac motion cycle is 0.495 μJ, which is higher than the required endocardial pacing threshold energy (0.377 μJ). Implantable triboelectric nanogenerators for implantable medical devices offer advantages of excellent output performance, high power density, and good durability, and are expected to find application in fields of treatment and diagnosis as in vivo symbiotic bioelectronics.
Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis
Authors: Graham Sarah E. , Nielsen Jonas B. , Zawistowski Matthew , Zhou Wei , Fritsche Lars G. , Gabrielsen Maiken E. , Skogholt Anne Heidi , Surakka Ida , Hornsby Whitney E. , Fermin Damian , Larach Daniel B. , Kheterpal Sachin , Brummett Chad M. , Lee Seunggeun , Kang Hyun Min , Abecasis Goncalo R. , Romundstad Solfrid , Hallan Stein , Sampson Matthew G. , Hveem Kristian , Willer Cristen J.
Published: April 2019

Chronic kidney disease (CKD) is a growing health burden currently affecting 10–15% of adults worldwide. Estimated glomerular filtration rate (eGFR) as a marker of kidney function is commonly used to diagnose CKD. We analyze eGFR data from the Nord-Trøndelag Health Study and Michigan Genomics Initiative and perform a GWAS meta-analysis with public summary statistics, more than doubling the sample size of previous meta-analyses. We identify 147 loci (53 novel) associated with eGFR, including genes involved in transcriptional regulation, kidney development, cellular signaling, metabolism, and solute transport. Additionally, sex-stratified analysis identifies one locus with more significant effects in women than men. Using genetic risk scores constructed from these eGFR meta-analysis results, we show that associated variants are generally predictive of CKD with only modest improvements in detection compared with other known clinical risk factors. Collectively, these results yield additional insight into the genetic factors underlying kidney function and progression to CKD.
Multi-level chirality in liquid crystals formed by achiral molecules
Authors: Salamończyk Mirosław , Vaupotič Nataša , Pociecha Damian , Walker Rebecca , Storey John M. D. , Imrie Corrie T. , Wang Cheng , Zhu Chenhui , Gorecka Ewa
Published: April 2019

Complex materials often exhibit a hierarchical structure with an intriguing mechanism responsible for the ‘propagation’ of order from the molecular to the nano- or micro-scale level. In particular, the chirality of biological molecules such as nucleic acids and amino acids is responsible for the helical structure of DNA and proteins, which in turn leads to the lack of mirror symmetry of macro-bio-objects. To fully understand mechanisms of cross-level order transfer there is an intensive search for simpler artificial structures exhibiting hierarchical arrangement. Here we present complex systems built of achiral molecules that show four levels of structural chirality: layer chirality, helicity of a basic repeating unit, mesoscopic helix and helical filaments. The structures are identified by a combination of hard and soft x-ray diffraction measurements, optical studies and theoretical modelling. Similarly to many biological systems, the studied materials exhibit a coupling between chirality at different levels.
PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation
Authors: Miyakawa Kei , Matsunaga Satoko , Yokoyama Masaru , Nomaguchi Masako , Kimura Yayoi , Nishi Mayuko , Kimura Hirokazu , Sato Hironori , Hirano Hisashi , Tamura Tomohiko , Akari Hirofumi , Miura Tomoyuki , Adachi Akio , Sawasaki Tatsuya , Yamamoto Naoki , Ryo Akihide
Published: April 2019

Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response.
Porous metal-metalloporphyrin gel as catalytic binding pocket for highly efficient synergistic catalysis
Authors: Zhang Weijie , Dynes James J. , Hu Yongfeng , Jiang Pingping , Ma Shengqian
Published: April 2019

Synergistic catalysis occurring in an enzyme pocket shows enhanced performance through supramolecular recognition and flexibility. This study presents an aerogel capable of similar function by fabricating a gel catalyst with hierarchical porosity. Here, the as-prepared Co-MMPG, a Co(II) metal-metalloporphyrin gel, maintains enough conformational flexibility and features a binding pocket formed from the co-facial arrangement of the porphyrin rings, as elucidated through the combined studies of solid-state NMR and X-ray absorption near-edge structure (XANES). The cooperativity between two Co(II) sites within the defined nanospace pocket facilitates the binding of different substrates with a favourable geometry thereby rendering Co-MMPG with excellent performance in the context of synergistic catalysis, especially for the kinetic control stereoselective reactions. Our work thus contributes a different enzyme-mimic design strategy to develop a highly efficient heterogeneous catalyst with high chemo/stereo selectivity.
BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors
Authors: Wang Xiaofeng , Wang Su , Troisi Emma C. , Howard Thomas P. , Haswell Jeffrey R. , Wolf Bennett K. , Hawk William H. , Ramos Pilar , Oberlick Elaine M. , Tzvetkov Evgeni P. , Ross Aaron , Vazquez Francisca , Hahn William C. , Park Peter J. , Roberts Charles W. M.
Published: April 2019

Bromodomain-containing protein 9 (BRD9) is a recently identified subunit of SWI/SNF(BAF) chromatin remodeling complexes, yet its function is poorly understood. Here, using a genome-wide CRISPR-Cas9 screen, we show that BRD9 is a specific vulnerability in pediatric malignant rhabdoid tumors (RTs), which are driven by inactivation of the SMARCB1 subunit of SWI/SNF. We find that BRD9 exists in a unique SWI/SNF sub-complex that lacks SMARCB1, which has been considered a core subunit. While SMARCB1-containing SWI/SNF complexes are bound preferentially at enhancers, we show that BRD9-containing complexes exist at both promoters and enhancers. Mechanistically, we show that SMARCB1 loss causes increased BRD9 incorporation into SWI/SNF thus providing insight into BRD9 vulnerability in RTs. Underlying the dependency, while its bromodomain is dispensable, the DUF3512 domain of BRD9 is essential for SWI/SNF integrity in the absence of SMARCB1. Collectively, our results reveal a BRD9-containing SWI/SNF subcomplex is required for the survival of SMARCB1-mutant RTs.
The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis
Authors: Rispal Jérémie , Baron Lucie , Beaulieu Jean-François , Chevillard-Briet Martine , Trouche Didier , Escaffit Fabrice
Published: April 2019

The Tip60/p400 chromatin-modifying complex, which is involved in the incorporation and post-translational modification of the H2A.Z histone variant, regulates cell proliferation and important signaling pathways, such as Wnt. Here, we study the involvement of H2A.Z in intestinal epithelial homeostasis, which is dependent on the finely-tuned equilibrium between stem cells renewal and differentiation, under the control of such pathway. We use cell models and inducible knock-out mice to study the impact of H2A.Z depletion on intestinal homeostasis. We show that H2A.Z is essential for the proliferation of human cancer and normal intestinal crypt cells and negatively controls the expression of a subset of differentiation markers, in cultured cells and mice. H2A.Z impairs the recruitment of the intestine-specific transcription factor CDX2 to chromatin, is itself a target of the Wnt pathway and thus, acts as an integrator for Wnt signaling in the control of intestinal epithelial cell fate and homeostasis.
The extracellular matrix protects Bacillus subtilis colonies from Pseudomonas invasion and modulates plant co-colonization
Authors: Molina-Santiago Carlos , Pearson John R. , Navarro Yurena , Berlanga-Clavero María Victoria , Caraballo-Rodriguez Andrés Mauricio , Petras Daniel , García-Martín María Luisa , Lamon Gaelle , Haberstein Birgit , Cazorla Francisco M. , de Vicente Antonio , Loquet Antoine , Dorrestein Pieter C. , Romero Diego
Published: April 2019

Bacteria of the genera Pseudomonas and Bacillus can promote plant growth and protect plants from pathogens. However, the interactions between these plant-beneficial bacteria are understudied. Here, we explore the interaction between Bacillus subtilis 3610 and Pseudomonas chlororaphis PCL1606. We show that the extracellular matrix protects B. subtilis colonies from infiltration by P. chlororaphis. The absence of extracellular matrix results in increased fluidity and loss of structure of the B. subtilis colony. The P. chlororaphis type VI secretion system (T6SS) is activated upon contact with B. subtilis cells, and stimulates B. subtilis sporulation. Furthermore, we find that B. subtilis sporulation observed prior to direct contact with P. chlororaphis is mediated by histidine kinases KinA and KinB. Finally, we demonstrate the importance of the extracellular matrix and the T6SS in modulating the coexistence of the two species on melon plant leaves and seeds.
Composite topological nodal lines penetrating the Brillouin zone in orthorhombic AgF2
Authors: Shao Dexi , Wang Huaiqiang , Chen Tong , Lu Pengchao , Gu Qinyan , Sheng Li , Xing Dingyu , Sun Jian
Published: April 2019

It has recently been found that nonsymmorphic symmetries can bring many exotic band crossings. Here, based on symmetry analysis, we predict that materials with time-reversal symmetry in the space group of Pbca (No. 61) possess rich symmetry-enforced band crossings, including nodal surfaces, fourfold degenerate nodal lines and hourglass Dirac loops, which appear in triplets as ensured by the cyclic permutation symmetry. We take Pbca AgF2 as an example in real systems and studied its band structures with ab initio calculations. Specifically, in the absence of spin-orbit coupling (SOC), besides the above-mentioned band degeneracies, this system features a nodal chain and a nodal armillary sphere penetrating the Brillouin zone (BZ). While with SOC, we find a new configuration of the hourglass Dirac loop/chain with the feature traversing the BZ, which originates from the splitting of a Dirac loop confined in the BZ. Furthermore, guided by the bulk-surface correspondence, we calculated the surface states to explore these bulk nodal phenomena. The evolution of these interesting nodal phenomena traversing the BZ under two specific uniaxial strains is also discussed.
Universal quantum control through deep reinforcement learning
Authors: Niu Murphy Yuezhen , Boixo Sergio , Smelyanskiy Vadim N. , Neven Hartmut
Published: April 2019

Emerging reinforcement learning techniques using deep neural networks have shown great promise in control optimization. They harness non-local regularities of noisy control trajectories and facilitate transfer learning between tasks. To leverage these powerful capabilities for quantum control optimization, we propose a new control framework to simultaneously optimize the speed and fidelity of quantum computation against both leakage and stochastic control errors. For a broad family of two-qubit unitary gates that are important for quantum simulation of many-electron systems, we improve the control robustness by adding control noise into training environments for reinforcement learning agents trained with trusted-region-policy-optimization. The agent control solutions demonstrate a two-order-of-magnitude reduction in average-gate-error over baseline stochastic-gradient-descent solutions and up to a one-order-of-magnitude reduction in gate time from optimal gate synthesis counterparts. These significant improvements in both fidelity and runtime are achieved by combining new physical understandings and state-of-the-art machine learning techniques. Our results open a venue for wider applications in quantum simulation, quantum chemistry and quantum supremacy tests using near-term quantum devices.
Measuring holographic entanglement entropy on a quantum simulator
Authors: Li Keren , Han Muxin , Qu Dongxue , Huang Zichang , Long Guilu , Wan Yidun , Lu Dawei , Zeng Bei , Laflamme Raymond
Published: April 2019

Quantum simulation promises to have wide applications in many fields where problems are hard to model with classical computers. Various quantum devices of different platforms have been built to tackle the problems in, say, quantum chemistry, condensed matter physics, and high-energy physics. Here, we report an experiment towards the simulation of quantum gravity by simulating the holographic entanglement entropy. On a six-qubit nuclear magnetic resonance quantum simulator, we demonstrate a key result of Anti-de Sitter/conformal field theory (AdS/CFT) correspondence—the Ryu-Takayanagi formula is demonstrated by measuring the relevant entanglement entropies on the perfect tensor state. The fidelity of our experimentally prepared the six-qubit state is 85.0% via full state tomography and reaches 93.7% if the signal-decay due to decoherence is taken into account. Our experiment serves as the basic module of simulating more complex tensor network states that exploring AdS/CFT correspondence. As the initial experimental attempt to study AdS/CFT via quantum information processing, our work opens up new avenues exploring quantum gravity phenomena on quantum simulators.
Real-space observation of charge ordering in epitaxial La2−xSrxCuO4 films
Authors: Wang Yang , Zhong Yong , Luo Zhiling , Liao Menghan , Wang Ruifeng , Dou Ziyuan , Zhang Qinghua , Zhang Ding , Gu Lin , Song Can-Li , Ma Xu-Cun , Xue Qi-Kun
Published: April 2019

The cuprate superconductors exhibit ubiquitous instabilities toward charge-ordered states. These unusual electronic states break the spatial symmetries of the host crystal, and have been widely appreciated as essential ingredients for constructing a theory for high-temperature superconductivity in cuprates. Here, we report real-space imaging of the doping-dependent charge orders in the epitaxial thin films of a canonical cuprate compound La2–xSrxCuO4 using scanning tunneling microscopy. As the films are moderately doped, we observe a crossover from incommensurate to commensurate (4a0, where a0 is the Cu–O–Cu distance) stripes. Furthermore, at lower and higher doping levels, the charge orders occur in the form of distorted Wigner crystal and grid phase of crossed vertical and horizontal stripes. We discuss how the charge orders are stabilized, and their interplay with superconductivity.
Extended regions of suspected mis-assembly in the rat reference genome
Authors: Ramdas Shweta , Ozel Ayse Bilge , Treutelaar Mary K. , Holl Katie , Mandel Myrna , Woods Leah C. Solberg , Li Jun Z.
Published: April 2019

We performed whole-genome sequencing for eight inbred rat strains commonly used in genetic mapping studies. They are the founders of the NIH heterogeneous stock (HS) outbred colony. We provide their sequences and variant calls to the rat genomics community. When analyzing the variant calls we identified regions with unusually high levels of heterozygosity. These regions are consistent across the eight inbred strains, including Brown Norway, which is the basis of the rat reference genome. These regions show higher read depths than other regions in the genome and contain higher rates of apparent tri-allelic variant sites. The evidence suggests that these regions may correspond to duplicated segments that were incorrectly overlaid as a single segment in the reference genome. We provide masks for these regions of suspected mis-assembly as a resource for the community to flag potentially false interpretations of mapping or functional results.
Atlas of RNA sequencing profiles for normal human tissues
Authors: Suntsova Maria , Gaifullin Nurshat , Allina Daria , Reshetun Alexey , Li Xinmin , Mendeleeva Larisa , Surin Vadim , Sergeeva Anna , Spirin Pavel , Prassolov Vladimir , Morgan Alexander , Garazha Andrew , Sorokin Maxim , Buzdin Anton
Published: April 2019

Comprehensive analysis of molecular pathology requires a collection of reference samples representing normal tissues from healthy donors. For the available limited collections of normal tissues from postmortal donors, there is a problem of data incompatibility, as different datasets generated using different experimental platforms often cannot be merged in a single panel. Here, we constructed and deposited the gene expression database of normal human tissues based on uniformly screened original sequencing data. In total, 142 solid tissue samples representing 20 organs were taken from post-mortal human healthy donors of different age killed in road accidents no later than 36 hours after death. Blood samples were taken from 17 healthy volunteers. We then compared them with the 758 transcriptomic profiles taken from the other databases. We found that overall 463 biosamples showed tissue-specific rather than platform- or database-specific clustering and could be aggregated in a single database termed Oncobox Atlas of Normal Tissue Expression (ANTE). Our data will be useful to all those working with the analysis of human gene expression.
Mice lacking Casp1, Ifngr and Nos2 genes exhibit altered depressive- and anxiety-like behaviour, and gut microbiome composition
Authors: Inserra Antonio , Choo Jocelyn M. , Lewis Martin D. , Rogers Geraint B. , Wong Ma-Li , Licinio Julio
Published: April 2019

Converging evidence supports the involvement of pro-inflammatory pathways and the gut microbiome in major depressive disorder (MDD). Pre-clinical and clinical studies suggest that decreasing pro-inflammatory signaling may provide clinical benefit in MDD. In this study, we used the chronic unpredictable stress (CUS) paradigm to assess whether mice lacking the pro-inflammatory caspase 1, interferon gamma-receptor, and nitric oxide synthase (Casp1, Ifngr, Nos2)−/− present altered depressive- and anxiety-like behaviour at baseline and in response to CUS. In comparison to wild-type (wt) mice, (Casp1, Ifngr, Nos2)−/− mice displayed decreased depressive- and anxiety-like behaviour, and increased hedonic-like behaviour and locomotor activity at baseline, and resistance to developing anhedonic-like behaviour and a heightened emotional state following stress. Plasma levels of ACTH and CORT did not differ between the triple knockout and wt mice following stress. The faecal microbiome of (Casp1, Ifngr, Nos2)−/− mice differed from that of wt mice at baseline and displayed reduced changes in response to chronic stress. Our results demonstrate that simultaneous deficit in multiple pro-inflammatory pathways has antidepressant-like effects at baseline, and confers resilience to stress-induced anhedonic-like behaviour. Moreover, accompanying changes in the gut microbiome composition suggest that CASP1, IFNGR and NOS2 play a role in maintaining microbiome homeostasis.
The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients
Authors: Chang Chia Lin , Huang Shang Yu , Hsu Ya Chiung , Chin Tzu Hsuan , Soong Yung Kuei
Published: April 2019

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, oligo- or anovulation, and/or polycystic ovary. It frequently presents with dyslipidemia and insulin resistance. Recent studies have shown that the white adipose tissue-derived asprosin is elevated in humans with insulin resistance. Because many PCOS patients have a propensity to develop dyslipidemia and/or insulin resistance, asprosin metabolism could be dysregulated in PCOS patients. Accordingly, we investigated serum levels of asprosin, irisin, GIP, androgens, LH, glucose, insulin, and lipids as well as HOMA-IR, QUICKI and ISI Matsuda in a cohort of 444 PCOS patients and 156 controls. Patients were stratified based on metabolic syndrome risk factors (ATPIII [+] and [−] groups), or BMI (overweight and lean groups). The irisin level was significantly correlated with body weight, SBP, DBP, Ferriman–Gallwey score, and levels of TSH, triglycerides, glucose and insulin in the overall population, and was elevated in ATPIII(+) and overweight PCOS patients compared to corresponding controls. By contrast, asprosin levels in PCOS, ATPIII(+), or overweight patients were similar to those of corresponding controls. This finding indicated that the regulation of irisin, but not asprosin, metabolism is abnormal in PCOS patients, and this metabolic characteristic is distinctly different from that of diabetes patients.
Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes
Authors: Repouskou Anastasia , Panagiotidou Emily , Panagopoulou Lydia , Bisting Pernilla Larsdotter , Tuck Astrud R. , Sjödin Marcus O. D. , Lindberg Johan , Bozas Evangelos , Rüegg Joëlle , Gennings Chris , Bornehag Carl-Gustaf , Damdimopoulou Pauliina , Stamatakis Antonios , Kitraki Efthymia
Published: April 2019

The increasing concern for the reproductive toxicity of abundantly used phthalates requires reliable tools for exposure risk assessment to mixtures of chemicals, based on real life human exposure and disorder-associated epidemiological evidence. We herein used a mixture of four phthalate monoesters (33% mono-butyl phthalate, 16% mono-benzyl phthalate, 21% mono-ethyl hexyl phthalate, and 30% mono-isononyl phthalate), detected in 1st trimester urine of 194 pregnant women and identified as bad actors for a shorter anogenital distance (AGD) in their baby boys. Mice were treated with 0, 0.26, 2.6 and 13 mg/kg/d of the mixture, corresponding to 0x, 10x, 100x, 500x levels detected in the pregnant women. Adverse outcomes detected in the reproductive system of the offspring in pre-puberty and adulthood included reduced AGD index and gonadal weight, changes in gonadal histology and altered expression of key regulators of gonadal growth and steroidogenesis. Most aberrations were apparent in both sexes, though more pronounced in males, and exhibited a non-monotonic pattern. The phthalate mixture directly affected expression of steroidogenesis as demonstrated in a relevant in vitro model. The detected adversities at exposures close to the levels detected in pregnant women, raise concern on the existing safety limits for early-life human exposures and emphasizes the need for re-evaluation of the exposure risk.
The Piezo2 ion channel is mechanically activated by low-threshold positive pressure
Authors: Shin Kyung Chul , Park Hyun Ji , Kim Jae Gon , Lee In Hwa , Cho Hawon , Park Chanjae , Sung Tae Sik , Koh Sang Don , Park Sang Woong , Bae Young Min
Published: April 2019

Recent parallel studies clearly indicated that Merkel cells and the mechanosensitive piezo2 ion channel play critical roles in the light-touch somatosensation. Moreover, piezo2 was suggested to be a light-touch sensing ion channel without a role in pain sensing in mammals. However, biophysical characteristics of piezo2, such as single channel conductance and sensitivities to various mechanical stimuli, are unclear, hampering a precise understanding of its role in touch sensation. Here, we describe the biophysical properties of piezo2 in human Merkel cell carcinoma (MCC)-13 cells; piezo2 is a low-threshold, positive pressure-specific, curvature-sensitive, mechanically activated cation channel with a single channel conductance of ~28.6 pS. Application of step indentations under the whole-cell mode of the patch-clamp technique, and positive pressures ≥5 mmHg under the cell-attached mode, activated piezo2 currents in MCC-13 and human embryonic kidney 293 T cells where piezo2 was overexpressed. By contrast, application of a negative pressure failed to activate piezo2 in these cells, whereas both positive and negative pressure activated piezo1 in a similar manner. Our results are the first to demonstrate single channel recordings of piezo2. We anticipate that our findings will be a starting point for a more sophisticated understanding of piezo2 roles in light-touch sensation.
Low-temperature microstructural studies on superconducting CaFe2As2
Authors: Huyan S. , Deng L. Z. , Wu Z. , Zhao K. , Sun J. Y. , Wu L. J. , Zhao Y. Y. , Yuan H. M. , Gooch M. , Lv B. , Zhu Y. , Chen S. , Chu C. W.
Published: April 2019

Undoped CaFe2As2 (Ca122) can be stabilized in two slightly different non-superconducting tetragonal phases, PI and PII, through thermal treatments. Upon proper annealing, superconductivity with a Tc up to 25 K emerges in the samples with an admixture of PI and PII phases. Systematic low-temperature X-ray diffraction studies were conducted on undoped Ca122 samples annealed at 350 °C over different time periods. In addition to the diffraction peaks associated with the single-phase aggregation of PI and PII, a broad intermediate peak that shifts with annealing time was observed in the superconducting samples only. Our simulation of phase distribution suggests that the extra peak is associated with the admixture of PI and PII on the nanometer scale. High-resolution transmission electron microscopy confirms the existence of these nano-scale phase admixtures in the superconducting samples. These experimental results and simulation analyses lend further support for our conclusion that interfacial inducement is the most reasonable explanation for the emergence of superconductivity in undoped Ca122 single crystals.
Preparation of a magnetic reduced-graphene oxide/tea waste composite for high-efficiency sorption of uranium
Authors: Yang Aili , Zhu Yukuan , Li Ping , Huang C. P.
Published: April 2019

The preparation and application of adsorptive materials with low cost and high-efficiency recovery of uranium from nuclear waste is necessary for the development of sustainable, clean energy resources and to avoid nuclear pollution. In this work, the capacity of tea waste and tea waste hybrids as inexpensive sorbents for uranium removal from water solutions was investigated. Composites of graphene oxide (GO) and tea waste (TW) exhibited a promising adsorption performance for uranium from aqueous solutions. The composites GOTW and magnetic rGO/Fe3O4/TW show high adsorption capacities (Qm (TW) = 91.72 mg/g, Qm (GOTW) = 111.61 mg/g and Qm (rGO/Fe3O4/TW) = 104.95 mg/g) and removal rates (~99%) for U(VI). The equilibrium sorption of the adsorbents fitted well to the Langmuir model, and the sorption rate fitted well to a pseudo-second-order kinetic model. The thermodynamic parameters indicated that sorption was spontaneous and favourable. The prepared adsorbents were used for the removal of uranium from real water samples as well. The results revealed that GOTW and rGO/Fe3O4/TW can be used to remediate nuclear industrial effluent as a potential adsorbent.
Novel DNA Biosensor for Direct Determination of Carrageenan
Authors: Hassan Riyadh Abdulmalek , Heng Lee Yook , Tan Ling Ling
Published: April 2019

A novel disposable electrochemical biosensor based on immobilized calf thymus double-stranded DNA (dsDNA) on the carbon-based screen-printed electrode (SPE) is developed for rapid biorecognition of carrageenan by using methylene blue (MB) redox indicator. The biosensor protocol for the detection of carrageenan is based on the concept of competitive binding of positively charged MB to the negatively charged dsDNA and carrageenan. The decrement in the MB cathodic peak current (ipc) signal as a result of the released MB from the immobilized dsDNA, and attracted to the carrageenan can be monitored via differential pulse voltammetry (DPV). The biosensor showed high sensitivity and selectivity to carrageenan at low concentration without interference from other polyanions such as alginate, gum arabic and starch. Calibration of the biosensor with carrageenan exhibited an excellent linear dependence from 1–10 mg L−1 (R2 = 0.98) with a detection limit of 0.08 mg L−1. The DNA-based carrageenan biosensor showed satisfactory reproducibility with 5.6–6.9% (n = 3) relative standard deviations (RSD), and possessing several advantages such as simplicity, fast and direct application to real sample analysis without any prior extensive sample treatments, particularly for seaweeds and food analyses.
Adding a new dimension to investigations of early radiolarian evolution
Authors: Kachovich Sarah , Sheng Jiani , Aitchison Jonathan C.
Published: April 2019

Knowledge of the detailed architecture of the earliest radiolarian microfossils is key to resolving the evolution and systematics of this important group of marine protozoans. Non-destructive methods for observing the complexity within the internal structures of their siliceous skeletons have long eluded paleontologists. By developing methodologies that overcome some limitations of existing micro-computed tomography (micro-CT) we demonstrate a technique with potential to provide new insight into their evolution. Using 3D micro-CT data to generate models for six well-preserved siliceous radiolarian skeletons from the Middle Cambrian Inca Formation in far north Queensland, Australia and the Middle Ordovician Piccadilly Formation, in western Newfoundland, Canada, we can reconstruct phylogenetic relationships amongst some of the earliest radiolarians. Better knowledge of early radiolarian morphologies clarifies the vital function of internal structures and hierarchical diagnosis across a range of taxonomic affiliations.
GATA-type transcription factors play a vital role in radiation sensitivity of Cryptococcus neoformans by regulating the gene expression of specific amino acid permeases
Authors: Cui Wanchang , Li XiangHong , Hull Lisa , Xiao Mang
Published: April 2019

Cryptococcus neoformans is a basidiomycete fungus that is highly resistant to ionizing radiation and has been identified in highly radioactive environments. Transcription factors (TFs) are master regulators of gene expression by binding to specific DNA sequences within promoters of target genes. A library of 322 signature-tagged gene deletion strains for 155 C. neoformans TF genes has been established. Previous phenome-based functional analysis of the C. neoformans TF mutant library identified key TFs important for various phenotypes, such as growth, differentiation, virulence-factor production, and stress responses. Here, utilizing the established TF mutant library, we identified 5 TFs that are important for radiation sensitivity, including SRE1, BZP2, GAT5, GAT6, and HCM1. Interestingly, BZP2, GAT5 and GAT6 all belong to the GATA-type transcription factors. These factors regulate transcription of nitrogen catabolite repression (NCR) sensitive genes when preferred nitrogen sources are absent or limiting. In addition to radiation, we found that specific GATA factors are important for other stressors such as rapamycin, fluconazole, and hydroxyurea treatment. Using real-time PCR method, we studied the expression of GATA down-stream genes after radiation exposure and identified that AAP4, AAP5 and URO1 were differentially expressed in the GAT5 and GAT6 mutants compared to the wild type cells. In summary, our data suggest that GATA TFs are important for radiation sensitivity in C. neoformans by regulating specific downstream AAP genes.
Psychological Sleep Interventions for Migraine and Tension-Type Headache: A Systematic Review and Meta-Analysis
Authors: Sullivan Daniel P. , Martin Paul R. , Boschen Mark J.
Published: April 2019

Disordered sleep, poor sleep quality, and insufficient or excessive sleep duration are known triggers of primary and secondary headaches. Given this, it is plausible that improving sleep will subsequently reduce headache activity. We report a systematic review of the literature, examining studies utilising psychological sleep interventions for the treatment of migraine and tension-type headache. PubMed, EMBASE, CINAHL, PsycINFO, and Cochrane Central were searched, using terms pertaining to psychological sleep interventions and headaches. Meta-analysis was performed for two outcome measures; headache frequency, and headache intensity. 103 studies were retrieved, of which 55 were duplicates. After completing reviews, three studies were retained. An additional eligible study was published after the initial search, and was found via monthly update searches, resulting in a total of four included studies. The effects of psychological sleep interventions (and in one study, combined with drug therapy) significantly reduced headache frequency and headache intensity. Three studies improved various sleep outcomes such as duration, efficiency, and excessive sleepiness. Psychological sleep interventions improve headache frequency and sleep, however there is conflicting evidence for the effect on headache intensity between studies. Limitations include the small number of studies conducted to date. Despite this, the notable improvements in headaches and sleep achieved after psychological sleep interventions indicates further research on this promising topic is warranted.
The Role of Follow-up Evaluation in the Diagnostic Algorithm of Idiopathic Interstitial Pneumonia: A Retrospective Study
Authors: Han Qian , Wang Hong-yu , Zhang Xiao-xian , Wu Lu-lu , Wang Lu-lin , Jiang Ying , Deng Kui-miao , Mao Meng-meng , Chen Rong-chang , Kolb Martin , Luo Qun
Published: April 2019

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.
Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures
Authors: Leeman Kristen T. , Pessina Patrizia , Lee Joo-Hyeon , Kim Carla F.
Published: April 2019

Lung epithelial cell damage and dysfunctional repair play a role in the development of lung disease. Effective repair likely requires the normal functioning of alveolar stem/progenitor cells. For example, we have shown in a mouse model of bronchopulmonary dysplasia (BPD) that mesenchymal stem cells (MSC) protect against hyperoxic lung injury at least in part by increasing the number of Epcam+ Sca-1+ distal lung epithelial cells. These cells are capable of differentiating into both small airway (CCSP+) and alveolar (SPC+) epithelial cells in three-dimensional (3D) organoid cultures. To further understand the interactions between MSC and distal lung epithelial cells, we added MSC to lung progenitor 3D cultures. MSC stimulated Epcam+ Sca-1+ derived organoid formation, increased alveolar differentiation and decreased self-renewal. MSC-conditioned media was sufficient to promote alveolar organoid formation, demonstrating that soluble factors secreted by MSC are likely responsible for the response. This work provides strong evidence of a direct effect of MSC-secreted factors on lung progenitor cell differentiation.
Contrasting latitudinal patterns in phylogenetic diversity between woody and herbaceous communities
Authors: Massante Jhonny C. , Götzenberger Lars , Takkis Krista , Hallikma Tiit , Kaasik Ants , Laanisto Lauri , Hutchings Michael J. , Gerhold Pille
Published: April 2019

Although many studies have shown that species richness decreases from low to high latitudes (the Latitudinal Diversity Gradient), little is known about the relationship between latitude and phylogenetic diversity. Here we examine global latitudinal patterns of phylogenetic diversity using a dataset of 459 woody and 589 herbaceous plant communities. We analysed the relationships between community phylogenetic diversity, latitude, biogeographic realm and vegetation type. Using the most recent global megaphylogeny for seed plants and the standardised effect sizes of the phylogenetic diversity metrics ‘mean pairwise distance’ (SESmpd) and ‘mean nearest taxon distance’ (SESmntd), we found that species were more closely-related at low latitudes in woody communities. In herbaceous communities, species were more closely-related at high latitudes than at intermediate latitudes, and the strength of this effect depended on biogeographic realm and vegetation type. Possible causes of this difference are contrasting patterns of speciation and dispersal. Most woody lineages evolved in the tropics, with many gymnosperms but few angiosperms adapting to high latitudes. In contrast, the recent evolution of herbaceous lineages such as grasses in young habitat types may drive coexistence of closely-related species at high latitudes. Our results show that high species richness commonly observed at low latitudes is not associated with high phylogenetic diversity.
New Approach in Ulcer Prevention and Wound Healing Treatment using Doxycycline and Amoxicillin/LDH Nanocomposites
Authors: El-Ela Fatma I. Abo , Farghali Ahmed A. , Mahmoud Rehab K. , Mohamed Nada A. , Moaty S. A. Abdel
Published: April 2019

Doxycycline (DOX) and amoxicillin (AMOX) are important Broad-spectrum antibiotics used in treating multiple human and animal diseases. For the sake of exploring novel medical applications, both antibiotics were loaded into magnesium aluminium layer double hydroxide (Mg-Al)/LDH nanocomposite through the co-precipitation method. The synthesized materials were characterized by XRD, FT-IR, particle size analysis, FESEM and HRTEM. Acute toxicological studies were conducted using median lethal dose LD50, where a total number of 98 rats (200–150 gm) of both sexes were used. An experimental wound was aseptically incised on the anterior-dorsal side of each rat, while 98% of pure medical ethanol was used for ulcer induction. Acute toxicity, wound closure rate, healing percentages, ulcer index, protective rate and histopathological studies were investigated. Antibiotic Nanocomposites has significantly prevented ulcer formation and improved wound healing process to take shorter time than that of the typical processes, when compared with that of same drugs in microscale systems or commercial standard drugs. These results were confirmed by the histopathological findings. By converting it into the Nanoform, which is extremely important, especially with commonly used antibiotics, novel pharmacological properties were acquired from the antibiotics. The safe uses of DOX/LDH and AMOX/LDH Nanocomposites in this study were approved for biomedical applications.
Author Correction: Physical Activity, Energy Expenditure, and Defense of Body Weight in Melanocortin 4 Receptor-Deficient Male Rats
Authors: Almundarij Tariq I. , Smyers Mark E. , Spriggs Addison , Heemstra Lydia A. , Beltz Lisa , Dyne Eric , Ridenour Caitlyn , Novak Colleen M.
Published: April 2019

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Detection and manipulation of methylation in blood cancer DNA using terahertz radiation
Authors: Cheon Hwayeong , Paik Jin Ho , Choi Moran , Yang Hee-Jin , Son Joo-Hiuk
Published: April 2019

DNA methylation is a pivotal epigenetic modification of DNA that regulates gene expression. Abnormal regulation of gene expression is closely related to carcinogenesis, which is why the assessment of DNA methylation is a key factor in cancer research. Terahertz radiation may play an important role in active demethylation for cancer therapy because the characteristic frequency of the methylated DNA exists in the terahertz region. Here, we present a novel technique for the detection and manipulation of DNA methylation using terahertz radiation in blood cancer cell lines. We observed the degree of DNA methylation in blood cancer at the characteristic resonance of approximately 1.7 THz using terahertz time-domain spectroscopy. The terahertz results were cross-checked with global DNA methylation quantification using an enzyme-linked immunosorbent assay. We also achieved the demethylation of cancer DNA using high-power terahertz radiation at the 1.7-THz resonance. The demethylation degrees ranged from 10% to 70%, depending on the type of cancer cell line. Our results show the detection of DNA methylation based on the terahertz molecular resonance and the manipulation of global DNA methylation using high-power terahertz radiation. Terahertz radiation may have potential applications as an epigenetic inhibitor in cancer treatment, by virtue of its ability to induce DNA demethylation, similarly to decitabine.