bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible magnetoelectric switching in multiferroic three-dimensional nanocup heterostructure films
Authors: An Hyunji , Hong Hyo Jin , Jo Yong-Ryun , Jung Soon-Gil , Kim Sangmo , Kim Sangwoo , Lee Jongmin , Choi Hojoong , Yoon Hongji , Kim So-Young , Song Jaesun , Jeong Sang Yun , Lee Byoung Hun , Koo Tae-Yeong , Park Tuson , Ko Kyung-Tae , Kim Bongjae , Kim Bong-Joong , Bark Chung Wung , Lee Sanghan
Published: November 2019

Self-assembled nanocomposite films containing ferroelectric and ferromagnetic phases have attracted enormous research interest because they are the most promising candidates for practical multiferroic applications. However, obtaining a genuine magnetoelectric (ME) coupling effect is still challenging in this research area. To substantially improve the ME effect, new heterostructure designs with efficient strain control between two phases are urgently needed. Herein, a novel three-dimensional (3D) nanocup architecture of a heterostructure film is developed. To establish the unique architecture, a heavily Co, Fe-doped ferroelectric Bi3.25La0.75Ti3O12(BLT) target was used during the growth of BLT thin films via pulsed laser deposition. Consequently, 3D nanocup-structured CoFe2O4(CFO) particles formed inside the BLT via spontaneous nucleation and agglomeration. The 3D nanocup BLT-CFO film exhibited magnetically controlled reversible dielectric switching, which is direct evidence of strong ME coupling caused by the efficient interfacial strain coupling and low leakage of the novel nanocup architecture. The obtained results strongly suggest that the 3D nanocup heterostructure film significantly improves the ME coupling effect. In addition, we propose a new paradigm in the architecture design of self-assembled nanocomposite films for diverse multifunctional devices.
Are Asian foods as “fattening” as western-styled fast foods?
Authors: Henry Christiani Jeyakumar , Kaur Bhupinder , Quek Rina Yu Chin
Published: November 2019

In Asia, the consumption of western-styled fast foods is widely perceived as the cause of the rise in obesity and chronic disease. Twenty-five of the most popular local Asian foods were compared for energy, total fat, saturated fat, sodium, and cholesterol with twenty-nine western-styled fast foods. The comparative analysis showed no significant difference in energy (p = 0.150) and total fat (p = 0.346) between the two food categories. These findings suggest that many local Asian foods contribute as much energy and total fat in a single meal as western-styled fast foods. Local Asian foods had greater amounts of sodium (p < 0.001), saturated fat (p = 0.007), and cholesterol (p = 0.009) than western-styled fast foods. The persistent presumption that the consumption of western-styled fast foods is the cause of obesity in Asia needs to be challenged. This observation that local Asian foods are as energy dense as western-styled fast foods, will enable us to redress the necessary strategies to address the Asian diet-health debate.
SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals
Authors: Andres-Alonso Maria , Ammar Mohamed Raafet , Butnaru Ioana , Gomes Guilherme M. , Acuña Sanhueza Gustavo , Raman Rajeev , Yuanxiang PingAn , Borgmeyer Maximilian , Lopez-Rojas Jeffrey , Raza Syed Ahsan , Brice Nicola , Hausrat Torben J. , Macharadze Tamar , Diaz-Gonzalez Silvia , Carlton Mark , Failla Antonio Virgilio , Stork Oliver , Schweizer Michaela , Gundelfinger Eckart D. , Kneussel Matthias , Spilker Christina , Karpova Anna , Kreutz Michael R.
Published: November 2019

Amphisomes are organelles of the autophagy pathway that result from the fusion of autophagosomes with late endosomes. While biogenesis of autophagosomes and late endosomes occurs continuously at axon terminals, non-degradative roles of autophagy at boutons are barely described. Here, we show that in neurons BDNF/TrkB traffick in amphisomes that signal locally at presynaptic boutons during retrograde transport to the soma. This is orchestrated by the Rap GTPase-activating (RapGAP) protein SIPA1L2, which connects TrkB amphisomes to a dynein motor. The autophagosomal protein LC3 regulates RapGAP activity of SIPA1L2 and controls retrograde trafficking and local signaling of TrkB. Following induction of presynaptic plasticity, amphisomes dissociate from dynein at boutons enabling local signaling and promoting transmitter release. Accordingly,sipa1l2knockout mice show impaired BDNF-dependent presynaptic plasticity. Taken together, the data suggest that in hippocampal neurons, TrkB-signaling endosomes are in fact amphisomes that during retrograde transport have local signaling capacity in the context of presynaptic plasticity.
7-Deazaguanine modifications protect phage DNA from host restriction systems
Authors: Hutinet Geoffrey , Kot Witold , Cui Liang , Hillebrand Roman , Balamkundu Seetharamsingh , Gnanakalai Shanmugavel , Neelakandan Ramesh , Carstens Alexander B. , Fa Lui Chuan , Tremblay Denise , Jacobs-Sera Deborah , Sassanfar Mandana , Lee Yan-Jiun , Weigele Peter , Moineau Sylvain , Hatfull Graham F. , Dedon Peter C. , Hansen Lars H. , de Crécy-Lagard Valérie
Published: November 2019

Genome modifications are central components of the continuous arms race between viruses and their hosts. The archaeosine base (G+), which was thought to be found only in archaeal tRNAs, was recently detected in genomic DNA of Enterobacteria phage 9g and was proposed to protect phage DNA from a wide variety of restriction enzymes. In this study, we identify three additional 2′-deoxy-7-deazaguanine modifications, which are all intermediates of the same pathway, in viruses: 2′-deoxy-7-amido-7-deazaguanine (dADG), 2′-deoxy-7-cyano-7-deazaguanine (dPreQ0) and 2′-deoxy-7- aminomethyl-7-deazaguanine (dPreQ1). We identify 180 phages or archaeal viruses that encode at least one of the enzymes of this pathway with an overrepresentation (60%) of viruses potentially infecting pathogenic microbial hosts. Genetic studies with the Escherichia phage CAjan show that DpdA is essential to insert the 7-deazaguanine base in phage genomic DNA and that 2′-deoxy-7-deazaguanine modifications protect phage DNA from host restriction enzymes.
Programmed DNA elimination of germline development genes in songbirds
Authors: Kinsella Cormac M. , Ruiz-Ruano Francisco J. , Dion-Côté Anne-Marie , Charles Alexander J. , Gossmann Toni I. , Cabrero Josefa , Kappei Dennis , Hemmings Nicola , Simons Mirre J. P. , Camacho Juan Pedro M. , Forstmeier Wolfgang , Suh Alexander
Published: November 2019

In some eukaryotes, germline and somatic genomes differ dramatically in their composition. Here we characterise a major germline–soma dissimilarity caused by a germline-restricted chromosome (GRC) in songbirds. We show that the zebra finch GRC contains >115 genes paralogous to single-copy genes on 18 autosomes and the Z chromosome, and is enriched in genes involved in female gonad development. Many genes are likely functional, evidenced by expression in testes and ovaries at the RNA and protein level. Using comparative genomics, we show that genes have been added to the GRC over millions of years of evolution, with embryonic development genes bicc1 and trim71 dating to the ancestor of songbirds and dozens of other genes added very recently. The somatic elimination of this evolutionarily dynamic chromosome in songbirds implies a unique mechanism to minimise genetic conflict between germline and soma, relevant to antagonistic pleiotropy, an evolutionary process underlying ageing and sexual traits.
Genomic and immune profiling of pre-invasive lung adenocarcinoma
Authors: Chen Haiquan , Carrot-Zhang Jian , Zhao Yue , Hu Haichuan , Freeman Samuel S. , Yu Su , Ha Gavin , Taylor Alison M. , Berger Ashton C. , Westlake Lindsay , Zheng Yuanting , Zhang Jiyang , Ramachandran Aruna , Zheng Qiang , Pan Yunjian , Zheng Difan , Zheng Shanbo , Cheng Chao , Kuang Muyu , Zhou Xiaoyan , Zhang Yang , Li Hang , Ye Ting , Ma Yuan , Gao Zhendong , Tao Xiaoting , Han Han , Shang Jun , Yu Ying , Bao Ding , Huang Yechao , Li Xiangnan , Zhang Yawei , Xiang Jiaqing , Sun Yihua , Li Yuan , Cherniack Andrew D. , Campbell Joshua D. , Shi Leming , Meyerson Matthew
Published: November 2019

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.
DNA origami cryptography for secure communication
Authors: Zhang Yinan , Wang Fei , Chao Jie , Xie Mo , Liu Huajie , Pan Muchen , Kopperger Enzo , Liu Xiaoguo , Li Qian , Shi Jiye , Wang Lihua , Hu Jun , Wang Lianhui , Simmel Friedrich C. , Fan Chunhai
Published: November 2019

Biomolecular cryptography exploiting specific biomolecular interactions for data encryption represents a unique approach for information security. However, constructing protocols based on biomolecular reactions to guarantee confidentiality, integrity and availability (CIA) of information remains a challenge. Here we develop DNA origami cryptography (DOC) that exploits folding of a M13 viral scaffold into nanometer-scale self-assembled braille-like patterns for secure communication, which can create a key with a size of over 700 bits. The intrinsic nanoscale addressability of DNA origami additionally allows for protein binding-based steganography, which further protects message confidentiality in DOC. The integrity of a transmitted message can be ensured by establishing specific linkages between several DNA origamis carrying parts of the message. The versatility of DOC is further demonstrated by transmitting various data formats including text, musical notes and images, supporting its great potential for meeting the rapidly increasing CIA demands of next-generation cryptography.
Response to Olaparib in a Patient with Germline BRCA2 Mutation and Breast Cancer Leptomeningeal Carcinomatosis
Authors: Exman Pedro , Mallery Robert M. , Lin Nancy U. , Parsons Heather A.
Published: November 2019

Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic cancer that disproportionately affects patients with advanced breast cancer. Moreover, those with BRCA1/2-mutated disease more often experience leptomeningeal metastasis. Treatment options for LC are limited and often include significant toxicities. PARP inhibitors offer an important potential treatment for patients with BRCA1/2-mutated breast and ovarian cancers, but clinical studies excluded patients with central nervous system (CNS) metastases, including LC. Efficacy data in this area are therefore limited, although a phase I study of olaparib in glioblastoma did show CNS penetration. Here we report a case of a patient with BRCA2-mutated breast cancer and solitary recurrence in the leptomeninges with ongoing complete response to treatment with the PARP inhibitor olaparib. PARP inhibitors may be an important treatment option for patients with BRCA-mutated disease and LC, and warrant further study.
Low-intensity educational interventions supporting self-management to improve outcomes related to chronic breathlessness: a systematic review
Authors: Raymond Bronwyn , Luckett Tim , Johnson Miriam , Hutchinson Ann , Lovell Melanie , Phillips Jane
Published: November 2019

Chronic breathlessness is debilitating and frightening, often resulting in emergency department presentations with acute-on-chronic breathlessness. Self-management is complex, involving 14 components as identified by the Practical Systematic Review in Self-Management Support (PRISMS). Low-intensity educational interventions that support breathlessness self-management through written/visual educational materials, alongside limited health professional support, are available. Our aim was to describe components of low-intensity educational interventions that support and improve self-management for adults with chronic breathlessness and evaluate their efficacy for improving breathlessness-related outcomes. A systematic review was conducted, including RCTs that compared these interventions with usual care in adults with chronic disease. Synthesis took a narrative approach utilizing the PRISMS taxonomy and Template for Intervention Description and Replication (TIDieR) checklist. Of the 1948 articles identified, 7 met criteria reporting 7 RCTs using 6 interventions. Studies utilized 12 out of 14 PRISMS components, the most frequent being training/rehearsal for psychological strategies. Evidence for effectiveness was inconsistent and attempts to identify beneficial components were confounded by intervention complexity and heterogeneity. The optimal content and delivery of low-intensity educational interventions that support self-management to improve chronic breathlessness-related outcomes in adults cannot be defined from current published literature. Future research should incorporate more detailed, standardized reporting to enable comparison and meta-analysis.
Coherent transfer of quantum information in a silicon double quantum dot using resonant SWAP gates
Authors: Sigillito A. J. , Gullans M. J. , Edge L. F. , Borselli M. , Petta J. R.
Published: November 2019

Spin-based quantum processors in silicon quantum dots offer high-fidelity single and two-qubit operation. Recently multi-qubit devices have been realized; however, many-qubit demonstrations remain elusive, partly due to the limited qubit-to-qubit connectivity. These problems can be overcome by using SWAP gates, which are challenging to implement in devices having large magnetic field gradients. Here we use a primitive SWAP gate to transfer spin eigenstates in 100 ns with a fidelity of $${\bar{F}}_{{\rm{SWAP}}}^{{\rm{(p)}}}=98 \%$$F¯SWAP(p)=98%. By swapping eigenstates we are able to demonstrate a technique for reading out and initializing the state of a double quantum dot without shuttling charges through the quantum dot. We then show that the SWAP gate can transfer arbitrary two-qubit product states in 300 ns with a fidelity of $${\bar{F}}_{{\rm{SWAP}}}^{{\rm{(c)}}}=84 \%$$F¯SWAP(c)=84%. This work sets the stage for many-qubit experiments in silicon quantum dots.
From Point to Filament Defects in Hybrid Nematic Films
Authors: Chiccoli Cesare , Pasini Paolo , Zannoni Claudio , Skačej Gregor , Yoshida Hiroyuki , Hiroshima Taiga , Sunami Kanta , Ouchi Tomohiro , Ozaki Masanori
Published: November 2019

We have studied nematic hybrid films with homeotropic alignment at the top surface and various controlled degrees of in plane ordering, going from a random degenerate organization to a completely uniform alignment along one direction, at the bottom one. We show, by Monte Carlo (MC) computer simulations and experiments on photopatterned films with the bottom support surface fabricated with in-plane order similar to the simulated ones, that the point defects observed in the case of random planar orientations at the bottom tend to arrange along a filament as the surface ordering is sufficiently increased. MC simulations complement the polarized microscopy texture observations allowing to inspect the 3D structure of the defects and examine the role of elastic constants.
Time-domain Formulation of a Multi-layer Plane Circuit Coupled with Lumped-parameter Circuits using Maxwell Equations
Authors: Jinno Souma , Kitora Shuji , Toki Hiroshi , Abe Masayuki
Published: November 2019

We calculate electromagnetic phenomena in the multi-layer plane circuit starting from the Maxwell equations. We present a numerical method of potential and current density in two-dimensional conductors, where their time developments are treated as phenomena of wave propagation. We treat the plane conductors by dividing them into small finite-volume elements, similar to the case of the partial element equivalent circuit method, and the transport equations are then solved by the finite-difference time-domain method. Furthermore, we develop a calculation method for the boundary in a multi-layer plane by applying the method we have used in multi-transmission lines. We formulate the boundary conditions of a multi-layer plane coupled with lumped-parameter circuits and introduce an algorithm to reduce calculation costs that are largely associated with the two-dimensional extension from the multi-transmission-line case. We perform calculations of the wave propagation of potential, current density, and charge density in the time domain for a simple plane circuit. These calculations are presented as supplementary materials of the present paper.
Quantum Neimark-Sacker bifurcation
Authors: Yusipov I. I. , Ivanchenko M. V.
Published: November 2019

Recently, it has been demonstrated that asymptotic states of open quantum system can undergo qualitative changes resembling pitchfork, saddle-node, and period doubling classical bifurcations. Here, making use of the periodically modulated open quantum dimer model, we report and investigate a quantum Neimark-Sacker bifurcation. Its classical counterpart is the birth of a torus (an invariant curve in the Poincaré section) due to instability of a limit cycle (fixed point of the Poincaré map). The quantum system exhibits a transition from unimodal to bagel shaped stroboscopic distributions, as for Husimi representation, as for observables. The spectral properties of Floquet map experience changes reminiscent of the classical case, a pair of complex conjugated eigenvalues approaching a unit circle. Quantum Monte-Carlo wave function unraveling of the Lindblad master equation yields dynamics of single trajectories on “quantumtorus” and allows for quantifying it by rotation number. The bifurcation is sensitive to the number of quantum particles that can also be regarded as a control parameter.
Innovative particle standards and long-lived imaging for 2D and 3D dSTORM
Authors: Provost Angelina , Rousset Corentin , Bourdon Laura , Mezhoud Sarra , Reungoat Emma , Fourneaux Camille , Bresson Timothée , Pauly Marine , Béard Nicolas , Possi-Tchouanlong Laura , Grigorov Boyan , Bouvet Philippe , Diaz Jean-Jacques , Chamot Christophe , Pécheur Eve-Isabelle , Ladavière Catherine , Charreyre Marie-Thérèse , Favier Arnaud , Place Christophe , Monier Karine
Published: November 2019

Direct stochastic optical reconstruction microscopy (dSTORM), developed in the last decade, has revolutionised optical microscopy by enabling scientists to visualise objects beyond the resolution provided by conventional microscopy (200 nm). We developed an innovative method based on blinking particle standards and conditions for long-lived imaging over several weeks. Stable localisation precisions within the 10 nm-range were achieved for single virions and in cellulo 2D imaging of centrosomes, as well as their reliable reconstruction in 3D dSTORM.
Re-designing irrigated intensive cereal systems through bundling precision agronomic innovations for transitioning towards agricultural sustainability in North-West India
Authors: Jat H. S. , Sharma P. C. , Datta Ashim , Choudhary Madhu , Kakraliya S. K. , Yadvinder-Singh  , Sidhu Harminder S. , Gerard B. , Jat M. L.
Published: November 2019

A study was conducted to design productive, profitable, irrigation water¸ nitrogen and energy use efficient intensive cereal systems (rice-wheat; RW and maize-wheat; MW) in North-West India. Bundling of conservation agriculture (CA) with sub-surface drip irrigation termed as CA+ were compared with CA alone and conventional tillage based and flood irrigated RW rotation (farmer’s practice; ScI). In contrast to conventional till RW rotation which consumed 1889 mm ha−1 irrigation water (2-yr mean), CA+ system saved 58.4 and 95.5% irrigation water in RW and MW rotations, respectively. CA+ practices saved 45.8 and 22.7% of irrigation water in rice and maize, respectively compared to CA with flood irrigation. On a system basis, CA+ practices saved 46.7 and 44.7% irrigation water under RW (ScV) and MW (ScVI) systems compared to their respective CA-based systems with flood irrigation (ScIII and ScIV). CA+ in RW system recorded 11.2% higher crop productivity and improved irrigation water productivity by 145% and profitability by 29.2% compared to farmers’ practice. Substitution of rice with maize (MW system; ScVI) recorded 19.7% higher productivity, saved 84.5% of irrigation water and increased net returns by 48.9% compared to farmer’s practice. CA+ RW and MW system improved energy productivity by 75 and 169% and partial factor productivity of N by 44.6 and 49.6%, respectively compared to ScI. The sub-surface drip irrigation system saved the fertilizer N by 20% under CA systems. CA+ in RW and MW systems recorded ~13 and 5% (2-yr mean) higher profitability with 80% subsidy on installing sub-surface drip irrigation system and similar profitability without subsidy scenario compared with their respective flood irrigated CA-based systems.
An exploration of ambigrammatic sequences in narnaviruses
Authors: DeRisi Joseph L. , Huber Greg , Kistler Amy , Retallack Hanna , Wilkinson Michael , Yllanes David
Published: November 2019

Narnaviruses have been described as positive-sense RNA viruses with a remarkably simple genome of ~3 kb, encoding only a highly conserved RNA-dependent RNA polymerase (RdRp). Many narnaviruses, however, are ‘ambigrammatic’ and harbour an additional uninterrupted open reading frame (ORF) covering almost the entire length of the reverse complement strand. No function has been described for this ORF, yet the absence of stops is conserved across diverse narnaviruses, and in every case the codons in the reverse ORF and the RdRp are aligned. The >3 kb ORF overlap on opposite strands, unprecedented among RNA viruses, motivates an exploration of the constraints imposed or alleviated by the codon alignment. Here, we show that only when the codon frames are aligned can all stop codons be eliminated from the reverse strand by synonymous single-nucleotide substitutions in the RdRp gene, suggesting a mechanism for de novo gene creation within a strongly conserved amino-acid sequence. It will be fascinating to explore what implications this coding strategy has for other aspects of narnavirus biology. Beyond narnaviruses, our rapidly expanding catalogue of viral diversity may yet reveal additional examples of this broadly-extensible principle for ambigrammatic-sequence development.
Supreme activity of gramicidin S against resistant, persistent and biofilm cells of staphylococci and enterococci
Authors: Berditsch Marina , Afonin Sergii , Reuster Jennifer , Lux Hannah , Schkolin Kristina , Babii Oleg , Radchenko Dmytro S. , Abdullah Issah , William Nicola , Middel Volker , Strähle Uwe , Nelson Andrew , Valko Klara , Ulrich Anne S.
Published: November 2019

Three promising antibacterial peptides were studied with regard to their ability to inhibit the growth and kill the cells of clinical strains of Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium. The multifunctional gramicidin S (GS) was the most potent, compared to the membranotropic temporin L (TL), being more effective than the innate-defence regulator IDR-1018 (IDR). These activities, compared across 16 strains as minimal bactericidal and minimal inhibitory concentrations (MIC), are independent of bacterial resistance pattern, phenotype variations and/or biofilm-forming potency. For S. aureus strains, complete killing is accomplished by all peptides at 5 × MIC. For E. faecalis strains, only GS exhibits a rapid bactericidal effect at 5 × MIC, while TL and IDR require higher concentrations. The biofilm-preventing activities of all peptides against the six strains with the largest biofilm biomass were compared. GS demonstrates the lowest minimal biofilm inhibiting concentrations, whereas TL and IDR are consistently less effective. In mature biofilms, only GS completely kills the cells of all studied strains. We compare the physicochemical properties, membranolytic activities, model pharmacokinetics and eukaryotic toxicities of the peptides and explain the bactericidal, antipersister and antibiofilm activities of GS by its elevated stability, pronounced cell-penetration ability and effective utilization of multiple modes of antibacterial action.
Whole blood RNA signatures in leprosy patients identify reversal reactions before clinical onset: a prospective, multicenter study
Authors: Tió-Coma Maria , van Hooij Anouk , Bobosha Kidist , van der Ploeg-van Schip Jolien J. , Banu Sayera , Khadge Saraswoti , Thapa Pratibha , Kunwar Chhatra B. , Goulart Isabela M. , Bekele Yonas , Hagge Deanna A. , Moraes Milton O. , Teles Rosane M. B. , Pinheiro Roberta Olmo , van Zwet Erik W. , Goeman Jelle J. , Aseffa Abraham , Haks Mariëlle C. , Ottenhoff Tom H. M. , Modlin Robert L. , Geluk Annemieke
Published: November 2019

Early diagnosis of leprosy is challenging, particularly its inflammatory reactions, the major cause of irreversible neuropathy in leprosy. Current diagnostics cannot identify which patients are at risk of developing reactions. This study assessed blood RNA expression levels as potential biomarkers for leprosy. Prospective cohorts of newly diagnosed leprosy patients, including reactions, and healthy controls were recruited in Bangladesh, Brazil, Ethiopia and Nepal. RNA expression in 1,090 whole blood samples was determined for 103 target genes for innate and adaptive immune profiling by dual color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) followed by cluster analysis. We identified transcriptomic biomarkers associated with leprosy disease, different leprosy phenotypes as well as high exposure toMycobacterium lepraewhich respectively allow improved diagnosis and classification of leprosy patients and detection of infection. Importantly, a transcriptomic signature of risk for reversal reactions consisting of five genes (CCL2, CD8A, IL2, IL15andMARCO) was identified based on cross-sectional comparison of RNA expression. In addition, intra-individual longitudinal analyses of leprosy patients before, during and after treatment of reversal reactions, indicated that several IFN-induced genes increased significantly at onset of reaction whereasIL15decreased. This multi-site study, situated in four leprosy endemic areas, demonstrates the potential of host transcriptomic biomarkers as correlates of risk for leprosy. Importantly, a prospective five-gene signature for reversal reactions could predict reversal reactions at least 2 weeks before onset. Thus, transcriptomic biomarkers provide promise for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.
IFN-α as a time-sensitive biomarker during Oropouche virus infection in early and late seroconverters
Authors: de Oliveira Euzébio , Azevedo Raimunda do Socorro Silva , Coelho-dos-Reis Jordana Grazziela , Antonelli Lis Ribeiro do Valle , Ferreira Milene Silveira , Campi-Azevedo Ana Carolina , Costa-Silva Matheus Fernandes , Martins Lívia Carício , Chiang Jannifer Oliveira , Teixeira-Carvalho Andréa , Martins-Filho Olindo Assis , Vasconcelos Pedro Fernando Costa
Published: November 2019

In the present study, patients with acute OROV fever were classified as early seroconverters (IgM/IgG positive at baseline) or late seroconverters (IgM/IgG negative at baseline) and the timeline kinetics of the production of chemokines and cytokines were assessed at 1–3, 4–7, 8–10 and ≥11 days after patients have reported the first symptoms. Regardless immunoglobulin profile, all OROV fever patients presented higher levels of CXCL8, and IFN-α and lower levels of TNF and IL-10 at baseline as compared to healthy donors (HD). Lower levels of CCL2, CXCL10, and IFN-γ and higher levels of CCL2, CXCL10, IL-6, and IL-17A were detected in early and late seroconverters, respectively, as compared to HD. While early seroconverters presented the increasing levels of CCL2 along the timeline, late seroconverters displayed decreasing levels of CCL2, CXCL10, and IL-6 following days of disease onset. Noteworthy was that IFN-α was revealed as universal biomarker of human OROV fever, while CXCL8 & IL-5 and CXCL10 & IL-17 were consistently observed in early and late seroconverters, respectively. Thus, our results suggest that the production of IFN-α, CXCL10, and IL-17 precede the seroconversion bringing novel insights on the immunological events triggered by the OROV disease.
Glucose lowering by SGLT2-inhibitor empagliflozin accelerates atherosclerosis regression in hyperglycemic STZ-diabetic mice
Authors: Pennig Jan , Scherrer Philipp , Gissler Mark Colin , Anto-Michel Nathaly , Hoppe Natalie , Füner Lisa , Härdtner Carmen , Stachon Peter , Wolf Dennis , Hilgendorf Ingo , Mullick Adam , Bode Christoph , Zirlik Andreas , Goldberg Ira J. , Willecke Florian
Published: November 2019

Diabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression. At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression. These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68+ macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.
Isolation and comparative genomics of Mycobacterium tuberculosis isolates from cattle and their attendants in South India
Authors: Palaniyandi Kannan , Kumar Narender , Veerasamy Maroudam , Kabir Refaya Ahmed , Dolla Chandrakumar , Balaji Subramanyam , Baskaran Dhanaraj , Thiruvengadam Kannan , Rajendran Ananthi , Narayanan Sujatha , Raj Dhinakar , Swaminathan Soumya , Peacock Sharon J.
Published: November 2019

The major human pathogen Mycobacterium tuberculosis is rarely reported to cause disease in other animals. Cases in livestock are thought to occur through contact with infected handlers, but previous studies evaluating putative livestock-human transmission used typing techniques with limited resolution. Here, we undertook cross-sectional surveillance for tuberculosis in 271 livestock handlers and 167 cattle on three farms in Chennai, India and defined the relatedness of cultured isolates using whole genome sequencing. Humans and livestock were screened for active mycobacterial infection, and opportunistic post-mortem examination was performed on comparative intradermal test-positive cattle that died. Four cattle and 6 handlers on two farms were culture-positive for M. tuberculosis; M. bovis was not isolated. All 10 isolates (one from each case) belonged to Lineage 1. Pairwise genome comparisons of single nucleotide polymorphism (SNP) differences ranged from 1 to 600 SNPs, but 3 isolate pairs were less than 5 SNPs different. Two pairs were from handlers and the third pair were from two cattle on the same farm. The minimum pairwise SNP difference between a cattle and human isolate was >250 SNPs. Our study confirms the presence of M. tuberculosis infection in cattle in India, sequencing of which characterised relatedness between human and cattle-derived isolates.
Multi-layered core-sheath fiber membranes for controlled drug release in the local treatment of brain tumor
Authors: Han Daewoo , Serra Riccardo , Gorelick Noah , Fatima Umailla , Eberhart Charles G. , Brem Henry , Tyler Betty , Steckl Andrew J.
Published: November 2019

Interstitial chemotherapy plays a pivotal role in the treatment of glioblastoma multiforme (GBM), an aggressive form of primary brain cancer, by enhancing drug biodistribution to the tumor and avoiding systemic toxicities. The use of new polymer structures that extend the release of cytotoxic agents may therefore increase survival and prevent recurrence. A novel core-sheath fiber loaded with the drug carmustine (BCNU) was evaluated in an in vivo brain tumor model. Three-dimensional discs were formed from coaxially electrospun fiber membranes and in vitro BCNU release kinetics were measured. In vivo survival was assessed following implantation of discs made of compressed core-sheath fibers (NanoMesh) either concurrently with or five days after intracranial implantation of 9L gliosarcoma. Co-implantation of NanoMesh and 9L gliosarcoma resulted in statistically significant long-term survival (>150 days). Empty control NanoMesh confirmed the safety of these novel implants. Similarly, Day 5 studies showed significant median, overall, and long-term survival rates, suggesting optimal control of tumor growth, confirmed with histological and immunohistochemical analyses. Local chemotherapy by means of biodegradable NanoMesh implants is a new treatment paradigm for the treatment for brain tumors. Drug delivery with coaxial core-sheath structures benefits from high drug loading, controlled long-term release kinetics, and slow polymer degradation. This represents a promising evolution for the current treatment of GBM.
HDAC4 and 5 repression of TBX5 is relieved by protein kinase D1
Authors: Ghosh Tushar K. , Aparicio-Sánchez José J. , Buxton Sarah , Brook J. David
Published: November 2019

TBX5 is a T-box family transcription factor that regulates heart and forelimb development in vertebrates and functional deficiencies in this protein result in Holt-Oram syndrome. Recently, we have shown that acetylation of TBX5 potentiates its activity and is important for heart and limb development. Here we report that class II histone deacetylases HDAC4 and HDAC5 associate with TBX5 and repress its role in cardiac gene transcription. Both HDAC4 and HDAC5 deacetylate TBX5, which promotes its relocation to the cytoplasm and HDAC4 antagonizes the physical association and functional cooperation between TBX5 and MEF2C. We also show that protein kinase D1 (PRKD1) relieves the HDAC4/5-mediated repression of TBX5. Thus, this study reveals a novel interaction of HDAC4/5 and PRKD1 in the regulation of TBX5 transcriptional activity.
Surgical-orthodontic treatment for class II asymmetry: outcome and influencing factors
Authors: Chen Yun-Fang , Liao Yu-Fang , Chen Ying-An , Chen Yu-Ray
Published: November 2019

The study aimed to evaluate the treatment outcome of bimaxillary surgery for class II asymmetry and find the influencing factors for residual asymmetry. Cone-beam computed tomographic images of 30 adults who had bimaxillary surgery were acquired, and midline and contour landmarks of soft tissue and teeth were identified to assess treatment changes and outcome of facial asymmetry. The postoperative positional asymmetry of each osteotomy segment was also measured. After surgery, the facial midline asymmetry of the mandible, chin, and lower incisors improved significantly (all p < 0.01). However, the residual chin deviation remained as high as 2.64 ± 1.80 mm, and the influencing factors were residual shift asymmetry of the mandible (p < 0.001), chin (p < 0.001), and ramus (p = 0.001). The facial contour asymmetry was not significantly improved after surgery, and the influencing factors were the initial contour asymmetry (p < 0.001), and the residual ramus roll (p < 0.001) or yaw (p < 0.01) asymmetry. The results showed that bimaxillary surgery significantly improved midline but not contour symmetry. The postoperative midline and contour asymmetry was mainly affected by the residual shift and rotational jaw asymmetry respectively.
Effective Mass of Quasiparticles in Armchair Graphene Nanoribbons
Authors: Fischer Marcelo Macedo , de Sousa Leonardo Evaristo , Luiz e Castro Leonardo , Ribeiro Luiz Antonio , de Sousa Rafael Timóteo , Magela e Silva Geraldo , de Oliveira Neto Pedro Henrique
Published: November 2019

Armchair graphene nanoribbons (AGNRs) may present intrinsic semiconducting bandgaps, being of potential interest in developing new organic-based optoelectronic devices. The induction of a bandgap in AGNRs results from quantum confinement effects, which reduce charge mobility. In this sense, quasiparticles’ effective mass becomes relevant for the understanding of charge transport in these systems. In the present work, we theoretically investigate the drift of different quasiparticle species in AGNRs employing a 2D generalization of the Su-Schrieffer-Heeger Hamiltonian. Remarkably, our findings reveal that the effective mass strongly depends on the nanoribbon width and its value can reach 60 times the mass of one electron for narrow lattices. Such underlying property for quasiparticles, within the framework of gap tuning engineering in AGNRs, impact the design of their electronic devices.
A Novel Approach to Sensorimotor Skill Acquisition Utilizing Sensory Substitution: A Driving Simulation Study
Authors: Ueda Sayako , Sakai Hiroyuki , Kumada Takatsune
Published: November 2019

The aim of this study is to demonstrate the potential of sensory substitution/augmentation (SS/A) techniques for driver assistance systems in a simulated driving environment. Using a group-comparison design, we examined lane-keeping skill acquisition in a driving simulator that can provide information regarding vehicle lateral position by changing the binaural balance of auditory white noise delivered to the driver. Consequently, lane-keeping accuracy was significantly degraded when the lower visual scene (proximal part of the road) was occluded, suggesting it conveyed critical visual information necessary for lane keeping. After 40 minutes of training with auditory cueing of vehicle lateral position, lane-keeping accuracy returned to the baseline (normal driving) level. This indicates that auditory cueing can compensate for the loss of visual information. Taken together, our data suggest that auditory cueing of vehicle lateral position is sufficient for lane-keeping skill acquisition and that SS/A techniques can potentially be used for the development of driver assistance systems, particularly for situations where immediate time-sensitive actions are required in response to rapidly changing sensory information. Although this study is the first to apply SS/A techniques to driver assistance, further studies are however required to establish the generalizability of the findings to real-world settings.
Eye-Hand Span is not an Indicator of but a Strategy for Proficient Sight-Reading in Piano Performance
Authors: Lim Yeoeun , Park Jeong Mi , Rhyu Seung -Yeon , Chung Chun Kee , Kim Youn , Yi Suk Won
Published: November 2019

Eye-hand span, i.e., the distance between a performer’s fixation and execution of a note, has been regarded as a decisive indicator of performers’ competence in sight-reading. However, integrated perspectives regarding the relationship between eye-hand span and sight-reading variables have been less discussed. The present study explored the process of sight-reading in terms of three domains and their interrelations. The domain indicators included musical complexity and playing tempo (musical domain), eye-hand span (cognitive domain), and performance accuracy (behavioural domain). Thirty professional pianists sight-read four musical pieces with two different complexities and playing tempi. We measured the participants’ eye-hand span, evaluated their performance accuracy, and divided the participants into three groups according to their performance accuracy values. Interestingly, we found that the eye-hand span did not change solely based on the performance accuracy. In contrast, the relationship between the eye-hand span and performance accuracy changed according to the difficulty of the sight-reading task. Our results demonstrate that the eye-hand span is not a decisive indicator of sight-reading proficiency but is a strategy that can vary according to the difficulty of sight-reading tasks. Thus, proficient sight-readers are performers who are skilled at adjusting their eye-hand span instead of always maintaining an extended span.
Paper-Based SERS Platform for One-Step Screening of Tetracycline in Milk
Authors: Marques Ana , Veigas Bruno , Araújo Andreia , Pagará Beatriz , Baptista Pedro Viana , Águas Hugo , Martins Rodrigo , Fortunato Elvira
Published: November 2019

Throughout the last decade, the expansion of food testing has been gradually moving towards ordinary high throughput screening methods performed on-site. The demand for point-of-care testing, able to distinguish molecular signatures with high accuracy, sensitivity and specificity has been significantly increasing. This new requirement relies on the on-site detection and monitorization of molecular signatures suitable for the surveillance of food production and processing. The widespread use of antibiotics has contributed to disease control of livestock but has also created problems for the dairy industry and consumers. Its therapeutic and subtherapeutic use has increased the risk of contamination in milk in enough concentrations to cause economic losses to the dairy industry and have a health impact in highly sensitive individuals. This study focuses on the development of a simple Surface-Enhanced Raman Spectroscopy (SERS) method for fast high throughput screening of tetracycline (TET) in milk. For this, we integrate a paper-based low-cost, fully recyclable and highly stable SERS platform, with a minimal sample preparation protocol. A two-microliter sample of milk solutions spiked with TET (from 0.01 to 1000 ppm) is dried on a silver nanoparticle coated cardboard substrate and measured via a Raman spectrophotometer. The SERS substrate showed to be extremely stable with a shelf life of several months. A global spectrum principal component analysis approach was used to test all the detected vibrational modes and their correlation with TET concentration. Peak intensity ratios (455 cm−1/1280 cm−1 and 874 cm−1/1397 cm−1) were found to be correlated with TET concentrations in milk, achieving a sensitivity as low as 0.1 ppm. Results indicate that this SERS method combined with portable Raman spectrometer is a potential tool that can be used on-site for the monitoring of TET residues and other antibiotics.
Evaluation of imputation accuracy using the combination of two high-density panels in Nelore beef cattle
Authors: Bernardes Priscila Arrigucci , Nascimento Guilherme Batista do , Savegnago Rodrigo Pelicioni , Buzanskas Marcos Eli , Watanabe Rafael Nakamura , de Almeida Regitano Luciana Correia , Coutinho Luiz Lehmann , Gondro Cedric , Munari Danísio Prado
Published: November 2019

This study compared imputation from lower-density commercial and customized panels to high-density panels and a combined panel (Illumina and Affymetrix) in Nelore beef cattle. Additionally, linkage disequilibrium and haplotype block conformation were estimated in individual high-density panels and compared with corresponding values in the combined panel after imputation. Overall, 814 animals were genotyped using BovineHD BeadChip (IllumHD), and 93 of these animals were also genotyped using the Axion Genome-Wide BOS 1 Array Plate (AffyHD). In general, customization considering linkage disequilibrium and minor allele frequency had the highest accuracies. The IllumHD panel had higher values of linkage disequilibrium for short distances between SNPs than AffyHD and the combined panel. The combined panel had an increased number of small haplotype blocks. The use of a combined panel is recommended due to its increased density and number of haplotype blocks, which in turn increase the probability of a marker being close to a quantitative trait locus of interest. Considering common SNPs between IllumHD and AffyHD for the customization of a low-density panel increases the imputation accuracy for IllumHD, AffyHD and the combined panel.
Detection of colonic neoplasia in vivo using near-infrared-labeled peptide targeting cMet
Authors: Wu Xiaoli , Zhou Juan , Wang Fa , Meng Xiaoqing , Chen Jing , Chang Tse-Shao , Lee Miki , Li Gaoming , Li Xue , Appelman Henry D. , Kuick Rork , Wang Thomas D.
Published: November 2019

White light colonoscopy is widely used to detect colorectal polyps, but flat and depressed lesions are often missed. Here, we report a molecular imaging strategy to potentially improve diagnostic performance by developing a fluorescently-labeled peptide specific for cMet. This 7mer is conjugated to Cy5.5, a near-infrared (NIR) cyanine dye. Specific binding to cMet was confirmed by cell staining, knockdown, and competition assays. The probe showed high binding affinity (kd = 57 nM) and fast onset (k = 1.6 min) to support topical administration in vivo. A mouse model (CPC;Apc) that develops spontaneous adenomas that overexpress cMet was used to demonstrate feasibility for real time in vivo imaging. This targeting ligand showed significantly higher target-to-background (T/B) ratio for polypoid and non-polypoid lesions by comparison with a scrambled control peptide. Immunofluorescence staining on human colon specimens show significantly greater binding to tubular and sessile serrated adenomas versus hyperplastic polyps and normal mucosa. These results demonstrate a peptide specific for cMet that is promising for endoscopic detection of pre-malignant lesions and guiding of tissue biopsy.
Differential DNA methylation in high-grade serous ovarian cancer (HGSOC) is associated with tumor behavior
Authors: Reyes Henry D. , Devor Eric J. , Warrier Akshaya , Newtson Andreea M. , Mattson Jordan , Wagner Vincent , Duncan Gabrielle N. , Leslie Kimberly K. , Gonzalez-Bosquet Jesus
Published: November 2019

The epigenome offers an additional facet of cancer that can help categorize patients into those at risk of disease, recurrence, or treatment failure. We conducted a retrospective, nested, case-control study of advanced and recurrent high-grade serous ovarian cancer (HGSOC) patients in which we assessed epigenome-wide association using Illumina methylationEPIC arrays to characterize DNA methylation status and RNAseq to evaluate gene expression. Comparing HGSOC tumors with normal fallopian tube tissues we observe global hypomethylation but with skewing towards hypermethylation when interrogating gene promoters. In total, 5,852 gene interrogating probes revealed significantly different methylation. Within HGSOC, 57 probes highlighting 17 genes displayed significant differential DNA methylation between primary and recurrent disease. Between optimal vs suboptimal surgical outcomes 99 probes displayed significantly different methylation but only 29 genes showed an inverse correlation between methylation status and gene expression. Overall, differentially methylated genes point to several pathways including RAS as well as hippo signaling in normal vs primary HGSOC; valine, leucine, and isoleucine degradation and endocytosis in primary vs recurrent HGSOC; and pathways containing immune driver genes in optimal vs suboptimal surgical outcomes. Thus, differential DNA methylation identified numerous genes that could serve as potential biomarkers and/or therapeutic targets in HGSOC.