bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformations and cryo-force spectroscopy of spray-deposited single-strand DNA on gold
Authors: Pawlak Rémy , Vilhena J. G. , Hinaut Antoine , Meier Tobias , Glatzel Thilo , Baratoff Alexis , Gnecco Enrico , Pérez Rubén , Meyer Ernst
Published: February 2019

Cryo-electron microscopy can determine the structure of biological matter in vitrified liquids. However, structure alone is insufficient to understand the function of native and engineered biomolecules. So far, their mechanical properties have mainly been probed at room temperature using tens of pico-newton forces with a resolution limited by thermal fluctuations. Here we combine force spectroscopy and computer simulations in cryogenic conditions to quantify adhesion and intra-molecular properties of spray-deposited single-strand DNA oligomers on Au(111). Sub-nanometer resolution images reveal folding conformations confirmed by simulations. Lifting shows a decay of the measured stiffness with sharp dips every 0.2–0.3 nm associated with the sequential peeling and detachment of single nucleotides. A stiffness of 30–35 N m−1 per stretched repeat unit is deduced in the nano-newton range. This combined study suggests how to better control cryo-force spectroscopy of adsorbed heterogeneous (bio)polymer and to potentially enable single-base recognition in DNA strands only few nanometers long.
Elastic Alfven waves in elastic turbulence
Authors: Varshney Atul , Steinberg Victor
Published: February 2019

Speed of sound waves in gases and liquids are governed by the compressibility of the medium. There exists another type of non-dispersive wave where the wave speed depends on stress instead of elasticity of the medium. A well-known example is the Alfven wave, which propagates through plasma permeated by a magnetic field with the speed determined by magnetic tension. An elastic analogue of Alfven waves has been predicted in a flow of dilute polymer solution where the elastic stress of the stretching polymers determines the elastic wave speed. Here we present quantitative evidence of elastic Alfven waves in elastic turbulence of a viscoelastic creeping flow between two obstacles in channel flow. The key finding in the experimental proof is a nonlinear dependence of the elastic wave speed cel on the Weissenberg number Wi, which deviates from predictions based on a model of linear polymer elasticity.
Intestinal non-canonical NFκB signaling shapes the local and systemic immune response
Authors: Ramakrishnan Sadeesh K. , Zhang Huabing , Ma Xiaoya , Jung Inkyung , Schwartz Andrew J. , Triner Daniel , Devenport Samantha N. , Das Nupur K. , Xue Xiang , Zeng Melody Y. , Hu Yinling , Mortensen Richard M. , Greenson Joel K , Cascalho Marilia , Wobus Christiane E. , Colacino Justin A. , Nunez Gabriel , Rui Liangyou , Shah Yatrik M.
Published: February 2019

Microfold cells (M-cells) are specialized cells of the intestine that sample luminal microbiota and dietary antigens to educate the immune cells of the intestinal lymphoid follicles. The function of M-cells in systemic inflammatory responses are still unclear. Here we show that epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase (NIK) is highly active in intestinal lymphoid follicles, and is required for M-cell maintenance. Intestinal NIK signaling modulates M-cell differentiation and elicits both local and systemic IL-17A and IgA production. Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A. Our work thus defines an important function of non-canonical NFkB and M-cells in immune homeostasis, inflammation and polymicrobial sepsis.
Odd electron wave packets from cycloidal ultrashort laser fields
Authors: Kerbstadt S. , Eickhoff K. , Bayer T. , Wollenhaupt M.
Published: February 2019

Polarization-tailored bichromatic femtosecond laser fields with cycloidal polarization profiles have emerged as a powerful tool for coherent control of quantum processes. We present an optical scheme to create and manipulate three-dimensional free electron wave packets with arbitrary rotational symmetry by combining advanced supercontinuum pulse shaping with high resolution photoelectron tomography. Here we use carrier-envelope phase-stable polarization-tailored bichromatic (3ω:4ω) counter- and corotating femtosecond laser pulses to generate 7-fold rotational symmetric and asymmetric photoelectron momentum distributions by multiphoton ionization of sodium atoms. To elucidate the physical mechanisms, we investigate the interplay between the symmetry properties of the driving field and the resulting electron wave packets by varying the optical field parameters. Our results show that the symmetry properties of electron wave packets are not fully determined by the field symmetry, but completely described by multipath quantum interference of states with different angular momenta.
Enhanced North Pacific deep-ocean stratification by stronger intermediate water formation during Heinrich Stadial 1
Authors: Gong X. , Lembke-Jene L. , Lohmann G. , Knorr G. , Tiedemann R. , Zou J. J. , Shi X. F.
Published: February 2019

The deglacial history of CO2 release from the deep North Pacific remains unresolved. This is due to conflicting indications about subarctic Pacific ventilation changes based on various marine proxies, especially for Heinrich Stadial 1 (HS-1) when a rapid atmospheric CO2 rise occurs. Here, we use a complex Earth System Model to investigate the deglacial North Pacific overturning and its control on ocean stratification. Our results show an enhanced intermediate-to-deep ocean stratification coeval with intensified North Pacific Intermediate Water (NPIW) formation during HS-1, compared to the Last Glacial Maximum. The stronger NPIW formation causes lower salinities and higher temperatures at intermediate depths. By lowering NPIW densities, this enlarges vertical density gradient and thus enhances intermediate-to-deep ocean stratification during HS-1. Physically, this process prevents the North Pacific deep waters from a better communication with the upper oceans, thus prolongs the existing isolation of glacial Pacific abyssal carbons during HS-1.
Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons
Authors: Furigo Isadora C. , Teixeira Pryscila D. S. , de Souza Gabriel O. , Couto Gisele C. L. , Romero Guadalupe García , Perelló Mario , Frazão Renata , Elias Lucila L. , Metzger Martin , List Edward O. , Kopchick John J. , Donato J.
Published: February 2019

Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight loss becomes increasingly difficult with weight regain commonly occurring in most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and GH receptor (GHR) ablation in AgRP cells mitigates highly characteristic hypothalamic and metabolic adaptations induced by weight loss. Thus, the capacity of mice carrying an AgRP-specific GHR ablation to save energy during food deprivation is impaired, leading to increased fat loss. Additionally, administration of a clinically available GHR antagonist (pegvisomant) attenuates the fall of whole-body energy expenditure of food-deprived mice, similarly as seen by leptin treatment. Our findings indicate GH as a starvation signal that alerts the brain about energy deficiency, triggering key adaptive responses to conserve limited fuel stores.
Lithium promoted mesoporous manganese oxide catalyzed oxidation of allyl ethers
Authors: Dutta Biswanath , Clarke Ryan , Raman Sumathy , Shaffer Timothy D. , Achola Laura , Nandi Partha , Suib Steven L.
Published: February 2019

Herein we report the first example of the catalytic aerobic partial oxidation of allyl ether to its acrylate ester derivative. Many partial oxidations often need an expensive oxidant such as peroxides or other species to drive such reactions. In addition, selective generation of esters using porous catalysts has been elusive. This reaction is catalyzed by a Li ion promoted mesoporous manganese oxide (meso-Mn2O3) under mild conditions with no precious metals, a reusable heterogeneous catalyst, and easy isolation. This process is very attractive for the oxidation of allyl ethers. We report on the catalytic activity, selectivity, and scope of the reaction. In the best cases presented, almost complete conversion of allyl ether with near complete chemo-selectivity towards acrylate ester derivatives is observed. Based on results from controlled experiments, we propose a possible reaction mechanism for the case in which N-hydroxyphthalimide (NHPI) is used in combination with trichloroacetonitrile (CCl3CN).
A conserved molecular switch in Class F receptors regulates receptor activation and pathway selection
Authors: Wright Shane C. , Kozielewicz Paweł , Kowalski-Jahn Maria , Petersen Julian , Bowin Carl-Fredrik , Slodkowicz Greg , Marti-Solano Maria , Rodríguez David , Hot Belma , Okashah Najeah , Strakova Katerina , Valnohova Jana , Babu M. Madan , Lambert Nevin A. , Carlsson Jens , Schulte Gunnar
Published: February 2019

Class F receptors are considered valuable therapeutic targets due to their role in human disease, but structural changes accompanying receptor activation remain unexplored. Employing population and cancer genomics data, structural analyses, molecular dynamics simulations, resonance energy transfer-based approaches and mutagenesis, we identify a conserved basic amino acid in TM6 in Class F receptors that acts as a molecular switch to mediate receptor activation. Across all tested Class F receptors (FZD4,5,6,7, SMO), mutation of the molecular switch confers an increased potency of agonists by stabilizing an active conformation as assessed by engineered mini G proteins as conformational sensors. Disruption of the switch abrogates the functional interaction between FZDs and the phosphoprotein Dishevelled, supporting conformational selection as a prerequisite for functional selectivity. Our studies reveal the molecular basis of a common activation mechanism conserved in all Class F receptors, which facilitates assay development and future discovery of Class F receptor-targeting drugs.
Selective electroreduction of carbon dioxide to methanol on copper selenide nanocatalysts
Authors: Yang Dexin , Zhu Qinggong , Chen Chunjun , Liu Huizhen , Liu Zhimin , Zhao Zhijuan , Zhang Xiaoyu , Liu Shoujie , Han Buxing
Published: February 2019

Production of methanol from electrochemical reduction of carbon dioxide is very attractive. However, achieving high Faradaic efficiency with high current density using facile prepared catalysts remains to be a challenge. Herein we report that copper selenide nanocatalysts have outstanding performance for electrochemical reduction of carbon dioxide to methanol, and the current density can be as high as 41.5 mA cm−2 with a Faradaic efficiency of 77.6% at a low overpotential of 285 mV. The copper and selenium in the catalysts cooperate very well for the formation of methanol. The current density is higher than those reported up to date with very high Faradaic efficiency for producing methanol. As far as we know, this is the first work for electrochemical reduction of carbon dioxide using copper selenide as the catalyst.
Functional genomics reveal gene regulatory mechanisms underlying schizophrenia risk
Authors: Huo Yongxia , Li Shiwu , Liu Jiewei , Li Xiaoyan , Luo Xiong-Jian
Published: February 2019

Genome-wide association studies (GWASs) have identified over 180 independent schizophrenia risk loci. Nevertheless, how the risk variants in the reported loci confer schizophrenia susceptibility remains largely unknown. Here we systematically investigate the gene regulatory mechanisms underpinning schizophrenia risk through integrating data from functional genomics (including 30 ChIP-Seq experiments) and position weight matrix (PWM). We identify 132 risk single nucleotide polymorphisms (SNPs) that disrupt transcription factor binding and we find that 97 of the 132 TF binding-disrupting SNPs are associated with gene expression in human brain tissues. We validate the regulatory effect of some TF binding-disrupting SNPs with reporter gene assays (9 SNPs) and allele-specific expression analysis (10 SNPs). Our study reveals gene regulatory mechanisms affected by schizophrenia risk SNPs (including widespread disruption of POLR2A and CTCF binding) and identifies target genes for mechanistic studies and drug development. Our results can be accessed and visualized at SZDB database (http://www.szdb.org/).
Pathways to diagnosis of non-small cell lung cancer: a descriptive cohort study
Authors: Purdie Stuart , Creighton Nicola , White Kahren Maree , Baker Deborah , Ewald Dan , Lee Chee Khoon , Lyon Alison , Man Johnathan , Michail David , Miller Alexis Andrew , Tan Lawrence , Currow David , Young Jane M.
Published: February 2019

Little has been published on the diagnostic and referral pathway for lung cancer in Australia. This study set out to quantify general practitioner (GP) and lung specialist attendance and diagnostic imaging in the lead-up to a diagnosis of non-small cell lung cancer (NSCLC) and identify common pathways to diagnosis in New South Wales (NSW), Australia. We used linked health data for participants of the 45 and Up Study (a NSW population-based cohort study) diagnosed with NSCLC between 2006 and 2012. Our main outcome measures were GP and specialist attendances, X-rays and computed tomography (CT) scans of the chest and lung cancer-related hospital admissions. Among our study cohort (N = 894), 60% (n = 536) had ≥4 GP attendances in the 3 months prior to diagnosis of NSCLC, 56% (n = 505) had GP-ordered imaging (chest X-ray or CT scan), 39% (N = 349) attended a respiratory physician and 11% (N = 102) attended a cardiothoracic surgeon. The two most common pathways to diagnosis, accounting for one in three people, included GP and lung specialist (respiratory physician or cardiothoracic surgeon) involvement. Overall, 25% of people (n = 223) had an emergency hospital admission. For 14% of people (N = 129), an emergency hospital admission was the only event identified on the pathway to diagnosis. We found little effect of remoteness of residence on access to services. This study identified a substantial proportion of people with NSCLC being diagnosed in an emergency setting. Further research is needed to establish whether there were barriers to the timely diagnosis of these cases.
Characterising the correlations of prepare-and-measure quantum networks
Authors: Wang Yukun , Primaatmaja Ignatius William , Lavie Emilien , Varvitsiotis Antonios , Lim Charles Ci Wen
Published: February 2019

Prepare-and-measure (P&M) quantum networks are the basic building blocks of quantum communication and cryptography. These networks crucially rely on non-orthogonal quantum encodings to distribute quantum correlations, thus enabling superior communication rates and information-theoretic security. Here, we present a computational toolbox that can efficiently characterise the set of input–output probability distributions for any discrete-variable P&M quantum network, assuming only the inner-product information of the quantum encodings. Our toolbox is thus highly versatile and can be used to analyse a wide range of quantum network protocols, including those that employ infinite-dimensional quantum code states. To demonstrate the feasibility and efficacy of our toolbox, we use it to solve open problems in multipartite quantum distributed computing and quantum cryptography. Taken together, these findings suggest that our method may have implications for quantum network information theory and the development of new quantum technologies.
Single dose of DPX-rPA, an enhanced-delivery anthrax vaccine formulation, protects against a lethal Bacillus anthracis spore inhalation challenge
Authors: Weir Genevieve M. , MacDonald Lisa D. , Rajagopalan Rajkannan , Sivko Gloria S. , Valderas Michelle W. , Rayner Jonathan , Berger Bradley J. , Sammatur Leeladhar , Stanford Marianne M.
Published: February 2019

Anthrax is a serious biological threat caused by pulmonary exposure to aerosolized spores of Bacillus anthracis. Biothrax® (anthrax vaccine adsorbed (AVA)) is the only Food and Drug Administration-licensed vaccine and requires five administrations over 12 months with annual boosting to maintain pre-exposure prophylaxis. Here we report the evaluation of a single intramuscular injection of recombinant B. anthracis-protective antigen (rPA) formulated in the DPX delivery platform. Immune responses were compared to an alum-based formulation in mice and rabbits. Serological analysis of anti-rPA immunoglobulin G and toxin neutralization activity demonstrated higher responses induced by DPX-rPA when compared to rPA in alum. DPX-rPA was compared to AVA in rabbits and non-human primates (NHPs). In both species, DPX-rPA generated responses after a single immunization, whereas AVA required two immunizations. In rabbits, single injection of DPX-rPA or two injections of AVA conferred 100% protection from anthrax challenge. In NHPs, single-dose DPX-rPA was 100% protective against challenge, whereas one animal in the two-dose AVA group and all saline administered animals succumbed to infection. DPX-rPA was minimally reactogenic in all species tested. These data indicate that DPX-rPA may offer improvement over AVA by reducing the doses needed for protective immune responses and is a promising candidate as a new-generation anthrax vaccine.
Task-irrelevant financial losses inhibit the removal of information from working memory
Authors: Fallon Sean James , Dolfen Nina , Parolo Francesca , Zokaei Nahid , Husain Masud
Published: February 2019

The receipt of financial rewards or penalties - though task-irrelevant - may exert an obligatory effect on manipulating items in working memory (WM) by constraining a forthcoming shift in attention or reinforcing attentional shifts that have previously occurred. Here, we adjudicate between these two hypotheses by varying – after encoding- the order in which task-irrelevant financial outcomes and cues indicating which items need to be retained in memory are presented (so called retrocues). We employed a “what-is-where” design that allowed for the fractionation of WM recall into separate components: identification, precision and binding (between location and identity). Principally, valence-dependent effects were observed only for precision and binding, but only when outcomes were presented before, rather than after, the retrocue. Specifically, task-irrelevant financial losses presented before the retrocue caused a systematic breakdown in binding (misbinding), whereby the features of cued and non-cued memoranda became confused, i.e., the features that made up relevant memoranda were displaced by those of non-cued (irrelevant) items. A control experiment, in which outcomes but no cues were presented, failed to produce the same effects, indicating that the inclusion of retrocues were necessary for generating this effect. These results show that the receipt of financial penalties – even when uncoupled to performance – can prevent irrelevant information from being effectively pruned from WM. These results illustrate the importance of reward-related processing to controlling the contents of WM.
A network biology approach to unraveling inherited axonopathies
Authors: Bis-Brewer Dana M. , Danzi Matt C. , Wuchty Stefan , Züchner Stephan
Published: February 2019

Inherited axonopathies represent a spectrum of disorders unified by the common pathological mechanism of length-dependent axonal degeneration. Progressive axonal degeneration can lead to both Charcot-Marie-Tooth type 2 (CMT2) and Hereditary Spastic Paraplegia (HSP) depending on the affected neurons: peripheral motor and sensory nerves or central nervous system axons of the corticospinal tract and dorsal columns, respectively. Inherited axonopathies display an extreme degree of genetic heterogeneity of Mendelian high-penetrance genes. High locus heterogeneity is potentially advantageous to deciphering disease etiology by providing avenues to explore biological pathways in an unbiased fashion. Here, we investigate ‘gene modules’ in inherited axonopathies through a network-based analysis of the Human Integrated Protein-Protein Interaction rEference (HIPPIE) database. We demonstrate that CMT2 and HSP disease proteins are significantly more connected than randomly expected. We define these connected disease proteins as ‘proto-modules’ and show the topological relationship of these proto-modules by evaluating their overlap through a shortest-path based measurement. In particular, we observe that the CMT2 and HSP proto-modules significantly overlapped, demonstrating a shared genetic etiology. Comparison of both modules with other diseases revealed an overlapping relationship between HSP and hereditary ataxia and between CMT2 + HSP and hereditary ataxia. We then use the DIseAse Module Detection (DIAMOnD) algorithm to expand the proto-modules into comprehensive disease modules. Analysis of disease modules thus obtained reveals an enrichment of ribosomal proteins and pathways likely central to inherited axonopathy pathogenesis, including protein processing in the endoplasmic reticulum, spliceosome, and mRNA processing. Furthermore, we determine pathways specific to each axonopathy by analyzing the difference of the axonopathy modules. CMT2-specific pathways include glycolysis and gluconeogenesis-related processes, while HSP-specific pathways include processes involved in viral infection response. Unbiased characterization of inherited axonopathy disease modules will provide novel candidate disease genes, improve interpretation of candidate genes identified through patient data, and guide therapy development.
Treatment after Progression on Fulvestrant among Metastatic Breast Cancer Patients in Clinical Practice: a Multicenter, Retrospective Study
Authors: Xie Yizhao , Zhao Yannan , Gong Chengcheng , Chen Zhanhong , Zhang Yinbin , Zhao Yanxia , Yuan Peng , Hu Sainan , Li Yi , Hu Xichun , Zhang Jian , Wang Leiping , Wang Biyun
Published: February 2019

Fulvestrant (Ful) is an effective and widely used agent for first- and second-line treatment of hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2−) metastatic breast cancer (MBC). However, there is no evidence of treatment after progression on Ful. Our study aimed to investigate the profile of daily practice regarding therapy after Ful. A consecutive series of 131 HR+, HER2- MBC patients who failed Ful 500 mg as first-line or second-line therapy from June 2014 to June 2017 in 6 institutions were included and analysed. Among 131 patients who failed Ful with similar baseline characteristics, 31 (23.7%) received endocrine therapy (ET), and 100 (76.3%) were treated with chemotherapy (CT). The most frequently applied CT regimen was capecitabine (32%), and the ET regimen was exemestane + everolimus (35.5%). Multivariate analysis showed that patients with bone-only metastasis were associated with lower CT use (OR = 7.97, 95% CI 1.51–41.84, P = 0.01). Among patients who received CT and ET as subsequent treatments, the median progression-free survival (PFS) was 7.5 months (95% CI 6.2–8.8) and 6.0 months (95% CI 4.1–7.9), respectively (p = 0.03). Among patients who were resistant to Ful (PFS < 6 months), the PFS on CT was significantly longer than that on ET (7.1 months vs 3.9 months, p = 0.024, HR = 0.5, 95% CI 0.26–0.97); however, among patients with a PFS ≥6 months on Ful, the efficacy of CT and ET was similar. Additionally, among patients with an older age, bone-only metastasis and ≥3 metastatic sites, no significant difference was observed between the CT and ET groups. Moreover, ET was much more tolerated than CT in terms of the incidence of grade 3/4 toxicities (9.6% vs 27%, P < 0.05). Median overall survival (OS) was not reached. Thus, our findings reveal the pattern of post-Ful treatment in current clinical practice and provide evidence on the efficacy, safety and choice of these treatments.
Diagnosis and characterization of canine distemper virus through sequencing by MinION nanopore technology
Authors: Peserico Alessia , Marcacci Maurilia , Malatesta Daniela , Di Domenico Marco , Pratelli Annamaria , Mangone Iolanda , D’Alterio Nicola , Pizzurro Federica , Cirone Francesco , Zaccaria Guendalina , Cammà Cesare , Lorusso Alessio
Published: February 2019

Prompt identification of the causative pathogen of an infectious disease is essential for the choice of treatment or preventive measures. In this perspective, nucleic acids purified from the brain tissue of a dog succumbed after severe neurological signs were processed with the MinION (Oxford Nanopore Technologies, Oxford UK) sequencing technology. Canine distemper virus (CDV) sequence reads were detected. Subsequently, a specific molecular test and immunohistochemistry were used to confirm the presence of CDV RNA and antigen, respectively, in tissues. This study supports the use of the NGS in veterinary clinical practice with potential advantages in terms of rapidity and broad-range of molecular diagnosis.
Microbial basis of Fusarium wilt suppression by Allium cultivation
Authors: Nishioka Tomoki , Marian Malek , Kobayashi Issei , Kobayashi Yuhko , Yamamoto Kyosuke , Tamaki Hideyuki , Suga Haruhisa , Shimizu Masafumi
Published: February 2019

Crop rotation and intercropping with Allium plants suppresses Fusarium wilt in various crops. However, the mechanisms underlying this phenomenon have not been fully elucidated. This study was designed to assess the role of microorganisms inhabiting Allium rhizospheres and antifungal compounds produced by Allium roots in Fusarium wilt suppression by Allium cultivation. Suppression of cucumber Fusarium wilt and the pathogen multiplication by Allium (Welsh onion and/or onion)-cultivated soils were eliminated by heat treatment at 60 °C, whereas those by Welsh onion-root extract were lost at 40 °C. The addition of antibacterial antibiotics eliminated the suppressive effect of Welsh onion-cultivated soil on pathogen multiplication, suggesting the contribution of antagonistic gram-negative bacteria to the soil suppressiveness. The Illumina MiSeq sequencing of 16S rRNA gene amplicons revealed that genus Flavobacterium was the predominant group that preferentially accumulated in Allium rhizospheres. Flavobacterium species recovered from the rhizosphere soils of these Allium plants suppressed Fusarium wilt on cucumber seedlings. Furthermore, confocal laser scanning microscopy revealed that Flavobacterium isolates inhibited the multiplication of the pathogen in soil. Taken together, we infer that the accumulation of antagonistic Flavobacterium species plays a key role in Fusarium wilt suppression by Allium cultivation.
The transdiagnostic structure of mental effort avoidance
Authors: Patzelt Edward H. , Kool Wouter , Millner Alexander J. , Gershman Samuel J.
Published: February 2019

The law of least mental effort states that, everything else being equal, the brain tries to minimize mental effort expenditure during task performance by avoiding decisions that require greater cognitive demands. Prior studies have shown associations between disruptions in effort expenditure and specific psychiatric illnesses (e.g., schizophrenia and depression) or clinically-related symptoms and traits (e.g., anhedonia and apathy), yet no research has explored this issue transdiagnostically. Specifically, this research has largely focused on a single diagnostic category, symptom, or trait. However, abnormalities in effort expression could be related to several different psychiatrically-relevant constructs that cut across diagnostic boundaries. Therefore, we examined the relationship between avoidance of mental effort and a diverse set of clinically-related symptoms and traits, and transdiagnostic latent factors in a large sample (n = 811). Only lack of perseverance, a dimension of impulsiveness, was associated with increased avoidance of mental effort. In contrast, several constructs were associated with less mental effort avoidance, including positive urgency, distress intolerance, obsessive-compulsive symptoms, disordered eating, and a factor consisting of compulsive behavior and intrusive thoughts. These findings demonstrate that deviations from normative effort expenditure are associated with a number of constructs that are common to several forms of psychiatric illness.
First 3D imaging characterization of Pele’s hair from Kilauea volcano (Hawaii)
Authors: Cannata C. B. , De Rosa R. , Donato P. , Donato S. , Lanzafame G. , Mancini L. , Houghton B. F.
Published: February 2019

In this work the morphologic features of Pele’s hair formed during three different eruptions of Kilauea volcano have been investigated: fountaining from Kilauea Iki’s 1959 Episode 1, weak explosive activity from Halemaumau lava lake and littoral explosions at Waikupanaha (2009). Morphological studies were performed by optical, stereo- and scanning electron microscopy. For the first time 3D image analysis was carried out by synchrotron radiation X-ray computed microtomography, which allowed a high-resolution 3D reconstruction of the internal structure of each Pele’s hair, highlighting several differences in terms of number density, elongation and shape of the vesicles between the samples from the three eruptions. We identified three main parameters determining these differences: initial size of the magma droplet, ejection velocity and magma viscosity. Pele’s hair erupted during the Kilauea Iki’s fountaining shows the highest thickness and the least elongated shape of the vesicles, though it is related to fast ejection of a low viscosity magma. We therefore suggest that the size of magma droplets is the main parameter influencing the morphology and inner textures of the Pele’s hair. The comparison with Pele’s hair of similar eruptions elsewhere demonstrates that there is no univocal correspondence between eruptive style and Pele’s hair texture.
Mint companion plants attract the predatory mite Phytoseiulus persimilis
Authors: Togashi Kazuki , Goto Mifumi , Rim Hojun , Hattori Sayaka , Ozawa Rika , Arimura Gen-ichiro
Published: February 2019

Mint plants could theoretically serve as companion plants (CPs) that attract enemies of herbivores in tritrophic interactions. In order to explore the traits of mint volatiles as attractant cues for enemies of two-spotted spider mites, we performed Y-tube olfactometer assays of predatory mites, Phytoseiulus persimilis and Neoseiulus californicus, towards three mint species, apple mint, candy mint, and spearmint, as odor source. Clean candy mint and spearmint were attractive to P. persimilis, when compared with clean air and undamaged Phaseolus vulgaris plants serving as the target crop. Moreover, clean candy mint plants were even more attractive than volatiles from P. vulgaris plants damaged by spider mites. These predator responses were induced additively by candy mint volatiles plus volatiles from damaged P. vulgaris plants, as shown using both Y-tube olfactometer and open-space assay systems. However, the number of spider mite eggs consumed by P. persimilis on P. vulgaris plants did not differ in the presence compared to the absence of mint volatiles, indicating that mint volatiles affect the attraction but not the appetite of P. persimilis. Together, these findings suggest that the use of candy mint and spearmint as CPs is an ideal platform for spider mite pest management via the attraction of predatory mites.
Metabarcoding reveals that rhizospheric microbiota of Quercus pyrenaica is composed by a relatively small number of bacterial taxa highly abundant
Authors: Lasa Ana V. , Fernández-González Antonio J. , Villadas Pablo J. , Toro Nicolás , Fernández-López Manuel
Published: February 2019

Melojo oak (Quercus pyrenaica Willd.) is a key tree species of Mediterranean forests; however, these forests show an advanced stage of deterioration in the Iberian Peninsula. Plant-associated microorganisms play an essential role improving their host’s fitness, hence, a better understanding of oak rhizospheric microbiome, especially of those active members, could be the first step towards microbiome-based approaches for oak-forest improvement. Here we reported, for the first time, the diversity of total (DNA-based) and potentially active (RNA-based) bacterial communities of different melojo-oak forest formations through pyrosequencing of 16S rRNA gene amplicons. We found that potentially active bacterial communities were as rich and diverse as total bacterial communities, but different in terms of relative abundance patterns in some of the studied areas. Both core microbiomes were dominated by a relatively small percentage of OTUs, most of which showed positive correlation between both libraries. However, the uncoupling between abundance (rDNA) and potential activity (rRNA) for some taxa suggests that the most abundant taxa are not always the most active, and that low-abundance OTUs may have a strong influence on oak’s rhizospheric ecology. Thus, measurement of rRNA:rDNA ratio could be helpful in identifying major players for the development of bacterial bioinoculants.
Malleability of the self: electrophysiological correlates of the enfacement illusion
Authors: Bufalari Ilaria , Sforza Anna Laura , Di Russo Francesco , Mannetti Lucia , Aglioti Salvatore Maria
Published: February 2019

Self-face representation is fundamentally important for self-identity and self-consciousness. Given its role in preserving identity over time, self-face processing is considered as a robust and stable process. Yet, recent studies indicate that simple psychophysics manipulations may change how we process our own face. Specifically, experiencing tactile facial stimulation while seeing similar synchronous stimuli delivered to the face of another individual seen as in a mirror, induces ‘enfacement’ illusion, i.e. the subjective experience of ownership of the other’s face and a bias in attributing to the self, facial features of the other person. Here we recorded visual Event-Related Potentials elicited by the presentation of self, other and morphed faces during a self-other discrimination task performed immediately after participants received synchronous and control asynchronous Interpersonal Multisensory Stimulation (IMS). We found that self-face presentation after synchronous as compared to asynchronous stimulation significantly reduced the late positive potential (LPP; 450–750 ms), a reliable electrophysiological marker of self-identification processes. Additionally, enfacement cancelled out the differences in LPP amplitudes produced by self- and other-face during the control condition. These findings represent the first direct neurophysiological evidence that enfacement may affect self-face processing and pave the way to novel paradigms for exploring defective self-representation and self-other interactions.
Crystalline heterogeneity in single ferroelectric nanocrystals revealed by polarized nonlinear microscopy
Authors: Rendón-Barraza Carolina , Timpu Flavia , Grange Rachel , Brasselet Sophie
Published: February 2019

Ferroelectric nanocrystals have considerable interest for applications in nanophotonics, optical memories and bio-imaging. Their crystalline nature at the nanoscale remains however poorly known, mostly because structural investigation tools on single nanocrystals are lacking. In this work we apply polarization resolved second harmonic generation (P-SHG) imaging on isolated Barium Titanate (BaTiO3) nanocrystals to unravel their crystalline nature, exploiting the sensitivity of polarized SHG to local non-centrosymmetry and nanocrystals surface responses. We evidence crystalline heterogeneities in BaTiO3 nanocrystals manifested by a centrosymmetric shell around the tetragonal core of the crystals, corroborating hypotheses from previous ensemble structural investigations. This study shows that in contrast to bulk materials, nanocrystals exhibit a complex composition, which is seen to be reproducible among nanocrystals. P-SHG appears furthermore as a powerful methodology that reports structural behaviors in nanoscale dielectrics materials, at the individual nanoparticle scale.
Novel findings from 2,838 Adult Brains on Sex Differences in Gray Matter Brain Volume
Authors: Lotze Martin , Domin Martin , Gerlach Florian H. , Gaser Christian , Lueders Eileen , Schmidt Carsten O. , Neumann Nicola
Published: February 2019

There is still disagreement among studies with respect to the magnitude, location, and direction of sex differences of local gray matter volume (GMV) in the human brain. Here, we applied a state-of-the-art technique examining GMV in a well-powered sample (n = 2,838) validating effects in two independent general-population cohorts, age range 21–90 years, measured using the same MRI scanner. More GMV in women than in men was prominent in medial and lateral prefrontal areas, the superior temporal sulcus, the posterior insula, and orbitofrontal cortex. In contrast, more GMV in men than in women was detected in subcortical temporal structures, such as the amygdala, hippocampus, temporal pole, fusiform gyrus, visual primary cortex, and motor areas (premotor cortex, putamen, anterior cerebellum). The findings in this large-scale study may clarify previous inconsistencies and contribute to the understanding of sex-specific differences in cognition and behavior.
School-level electronic cigarette use prevalence and student-level tobacco use intention and behaviours
Authors: Chen Jianjiu , Ho Sai Yin , Leung Lok Tung , Wang Man Ping , Lam Tai Hing
Published: February 2019

Prevalent electronic cigarette (e-cigarette) use in schools may undermine tobacco denormalisation, and thus increase tobacco use in students. We investigated the associations of school-level e-cigarette use prevalence with student-level intention and behaviours related to e-cigarettes, cigarettes, and other tobacco products. In a 2014-15 school-based cross-sectional survey of 41035 secondary school students (grade 7–12; age 11–18 years) in Hong Kong, information was collected on the use of e-cigarettes, cigarettes, and non-cigarette tobacco products (NCTPs), susceptibility to e-cigarette and cigarette use, intention to quit cigarette smoking, and sociodemographic characteristics. The adjusted odds ratio (AOR) of e-cigarette use susceptibility in relation to high (vs low) school-level e-cigarette use prevalence was 1.40 (95% CI 1.05–1.87) in never e-cigarette users. The AORs of cigarette smoking susceptibility in relation to medium and high (vs low) school-level e-cigarette use prevalence were 1.24 (1.01–1.52) and 1.34 (1.02–1.75), respectively, in never cigarette smokers. School-level e-cigarette use prevalence was associated with ever and past 30-day cigarette smoking, but not with intention to quit (in past 30-day cigarette smokers) or past 30-day NCTP use. The findings highlight the importance of strictly banning e-cigarettes in schools, and add to the evidence that prevalent e-cigarette use in adolescents may increase cigarette smoking prevalence.
Integrator is a key component of human telomerase RNA biogenesis
Authors: Rubtsova M. P. , Vasilkova D. P. , Moshareva M. A. , Malyavko A. N. , Meerson M. B. , Zatsepin T. S. , Naraykina Y. V. , Beletsky A. V. , Ravin N. V. , Dontsova O. A.
Published: February 2019

Telomeres are special DNA-protein structures that are located at the ends of linear eukaryotic chromosomes. The telomere length determines the proliferation potential of cells. Telomerase is a key component of the telomere length maintenance system. While telomerase is inactive in the majority of somatic cells, its activity determines the clonogenic potential of stem cells as a resource for tissue and organism regeneration. Reactivation of telomerase occurs during the process of immortalization in the majority of cancer cells. Telomerase is a ribonucleoprotein that contains telomerase reverse transcriptase and telomerase RNA components. The RNA processing mechanism of telomerase involves exosome trimming or degradation of the primary precursor. Recent data provide evidence that the competition between the processing and decay of telomerase RNA may regulate the amount of RNA at the physiological level. We show that termination of human telomerase RNA transcription is dependent on its promoter, which engages with the multisubunit complex Integrator to interact with RNA polymerase II and terminate transcription of the human telomerase RNA gene followed by further processing.
Studies of Multiferroic Palladium Perovskites
Authors: Pradhan Dhiren K. , Mishra Ajay K. , Kumari Shalini , Basu Abhisek , Somayazulu Maddury , Gradauskaite Elzbieta , Smith Rebecca M. , Gardner Jonathan , Turner P. W. , N’Diaye Alpha T. , Holcomb M. B. , Katiyar Ram S. , Zhou Peng , Srinivasan Gopalan , Gregg J. M. , Scott J. F.
Published: February 2019

We have studied the atomic force microscopy (AFM), X-ray Bragg reflections, X-ray absorption spectra (XAS) of the Pd L-edge, Scanning electron microscopey (SEM) and Raman spectra, and direct magnetoelectric tensor of Pd-substituted lead titanate and lead zirconate-titanate. A primary aim is to determine the percentage of Pd+4 and Pd+2 substitutional at the Ti-sites (we find that it is almost fully substitutional). The atomic force microscopy data uniquely reveal a surprise: both threefold vertical (polarized out-of-plane) and fourfold in-plane domain vertices. This is discussed in terms of the general rules for Voronoi patterns (Dirichlet tessellations) in two and three dimensions. At high pressures Raman soft modes are observed, as in pure lead titanate, and X-ray diffraction (XRD) indicates a nearly second-order displacive phase transition. However, two or three transitions are involved: First, there are anomalies in c/a ratio and Raman spectra at low pressures (P = 1 − 2 GPa); and second, the c/a ratio reaches unity at ca. P = 10 GPa, where a monoclinic (Mc) but metrically cubic transition occurs from the ambient tetragonal P4 mm structure in pure PbTiO3; whereas the Raman lines (forbidden in the cubic phase) remain until ca. 17 GPa, where a monoclinic-cubic transition is known in lead titanate.
Neuronal plasticity affects correlation between the size of dendritic spine and its postsynaptic density
Authors: Borczyk Malgorzata , Śliwińska Małgorzata Alicja , Caly Anna , Bernas Tytus , Radwanska Kasia
Published: February 2019

Structural plasticity of dendritic spines is thought to underlie memory formation. Size of a dendritic spine is considered proportional to the size of its postsynaptic density (PSD), number of glutamate receptors and synaptic strength. However, whether this correlation is true for all dendritic spine volumes, and remains stable during synaptic plasticity, is largely unknown. In this study, we take advantage of 3D electron microscopy and reconstruct dendritic spines and cores of PSDs from the stratum radiatum of the area CA1 of organotypic hippocampal slices. We observe that approximately 1/3 of dendritic spines, in a range of medium sizes, fail to reach significant correlation between dendritic spine volume and PSD surface area or PSD-core volume. During NMDA receptor-dependent chemical long-term potentiation (NMDAR-cLTP) dendritic spines and their PSD not only grow, but also PSD area and PSD-core volume to spine volume ratio is increased, and the correlation between the sizes of these two is tightened. Further analysis specified that only spines that contain smooth endoplasmic reticulum (SER) grow during cLTP, while PSD-cores grow irrespectively of the presence of SER in the spine. Dendritic spines with SER also show higher correlation of the volumetric parameters than spines without SER, and this correlation is further increased during cLTP only in the spines that contain SER. Overall, we found that correlation between PSD surface area and spine volume is not consistent across all spine volumes, is modified and tightened during synaptic plasticity and regulated by SER.
Genome wide analysis of W-box element in Arabidopsis thaliana reveals TGAC motif with genes down regulated by heat and salinity
Authors: Dhatterwal Pinky , Basu Samyadeep , Mehrotra Sandhya , Mehrotra Rajesh
Published: February 2019

To design, synthetic promoters leading to stress-specific induction of a transgene, the study of cis-regulatory elements is of great importance. Cis-regulatory elements play a major role in regulating the gene expression spatially and temporally at the transcriptional level. The present work focuses on one of the important cis-regulatory element, W-box having TGAC as a core motif which serves as a binding site for the members of the WRKY transcription factor family. In the present study, we have analyzed the occurrence frequency of TGAC core motifs for varying spacer lengths (ranging from 0 to 30 base pairs) across the Arabidopsis thaliana genome in order to determine the biological and functional significance of these conserved sequences. Further, the available microarray data was used to determine the role of TGAC motif in abiotic stresses namely salinity, osmolarity and heat. It was observed that TGAC motifs with spacer sequences like TGACCCATTTTGAC and TGACCCATGAATTTTGAC had a significant deviation in frequency and were thought to be favored for transcriptional bindings. The microarray data analysis revealed the involvement of TGAC motif mainly with genes down-regulated under abiotic stress conditions. These results were further confirmed by the transient expression studies with promoter-reporter cassettes carrying TGAC and TGAC-ACGT variant motifs with spacer lengths of 5 and 10.
Mechanisms of Antisense Oligonucleotides
Authors: Liu Zhongtian , Corey David R.
Published: February 2019

Antisense oligonucleotides (ASOs) are versatile agents for controlling the translation and splicing of mRNA. ASOs have the potential to control the expression of every gene, providing a versatile platform for the development of therapeutic agents. Unlocking this potential requires understanding the mechanisms of action of ASOs. Most ASOs function by one of two mechanisms. Some recruit RNase H and promote cleavage of an RNA target. Others bind and block RNAs to prevent translation or redirect alternative splicing. Understanding the mechanism is crucial to optimization of function and the design of effective ASOs as experimental tools and therapeutics.
Splicing Modulation for Therapeutics
Authors: Daoutsali Elena , Aartsma-Rus Annemieke
Published: February 2019

For most protein-coding genes, the genetic code is dispersed over a number of exons, which are interspersed by longer non-coding sequences, the introns. Translation of the messenger RNA to protein requires removal of the introns and ligation of the exons, a procedure called precursor mRNA (pre-mRNA) splicing. Soon after the discovery of splicing, it was found that defects in pre-mRNA splicing are a common underlying factor of genetic and acquired diseases. Despite the complexity of splicing, it can be intentionally modulated in different ways. This chapter gives an overview of antisense oligonucleotide-mediated splicing modulation and its progress towards therapeutics. It outlines how this approach can be exploited to restore cryptic splicing, restore open reading frames, establish exon inclusion, alter the ratio of alternatively spliced transcripts and induce the production of less toxic or non-toxic proteins. For each application, specific diseases for which antisense oligonucleotide-mediated splicing modulation has been tested are used to illustrate the approach.