bluuebunny/crossref_metadata_2025 huggingface dataset:
The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse
Authors: Sragovich Shlomo , Malishkevich Anna , Piontkewitz Yael , Giladi Eliezer , Touloumi Olga , Lagoudaki Roza , Grigoriadis Nikolaos , Gozes Illana
Published: January 2019

Activity-dependent neuroprotective protein (ADNP), essential for brain formation, was discovered as a leading de novo mutated gene causing the autism-like ADNP syndrome. This syndrome is phenotypically characterized by global developmental delays, intellectual disabilities, speech impediments, and motor dysfunctions. The Adnp haploinsufficient mouse mimics the human ADNP syndrome in terms of synapse density and gene expression patterns, as well as in developmental, motor, and cognitive abilities. Peripheral ADNP was also discovered as a biomarker for Alzheimer’s disease and schizophrenia, with nasal administration of the ADNP snippet peptide NAP (enhancing endogenous ADNP activity) leading to partial cognitive and functional protection at the cellular, animal and clinical settings. Here, a novel formulation for effective delivery of NAP is provided with superior brain penetration capabilities. Also provided are methods for treating pertinent clinical implications such as autism, cognitive impairments, olfactory deficits, and muscle strength using the formulation in the Adnp haploinsufficient mouse. Results showed a dramatically specific increase in brain/body bioavailability with the new formulation, without breaching the blood brain barrier. Additional findings included improvements using daily intranasal treatments with NAP, at the behavioral and brain structural levels, diffusion tensor imaging (DTI), translatable to clinical practice. Significant effects on hippocampal and cerebral cortical expression of the presynaptic Slc17a7 gene encoding vesicular excitatory glutamate transporter 1 (VGLUT1) were observed at the RNA and immunohistochemical levels, explaining the DTI results. These findings tie for the first time a reduction in presynaptic glutamatergic synapses with the autism/Alzheimer’s/schizophrenia-linked ADNP deficiency coupled with amelioration by NAP (CP201).
Abnormal ER quality control of neural GPI-anchored proteins via dysfunction in ER export processing in the frontal cortex of elderly subjects with schizophrenia
Authors: Kim Pitna , Scott Madeline R. , Meador-Woodruff James H.
Published: January 2019

Abnormalities of posttranslational protein modifications (PTMs) have recently been implicated in the pathophysiology of schizophrenia. Glycosylphosphatidylinositols (GPIs) are a class of complex glycolipids, which anchor surface proteins and glycoproteins to the cell membrane. GPI attachment to proteins represents one of the most common PTMs and GPI-associated proteins (GPI-APs) facilitate many cell surface processes, including synapse development and maintenance. Mutations in the GPI processing pathway are associated with intellectual disability, emphasizing the potential role of GPI-APs in cognition and schizophrenia-associated cognitive dysfunction. As initial endoplasmic reticulum (ER)-associated protein processing is essential for GPI-AP function, we measured protein expression of molecules involved in attachment (GPAA1), modification (PGAP1), and ER export (Tmp21) of GPI-APs, in homogenates and in an ER enriched fraction derived from dorsolateral prefrontal cortex (DLPFC) of 15 matched pairs of schizophrenia and comparison subjects. In total homogenate we found a significant decrease in transmembrane protein 21 (Tmp21) and in the ER-enriched fraction we found reduced expression of post-GPI attachment protein (PGAP1). PGAP1 modifies GPI-anchors through inositol deacylation, allowing it to be recognized by Tmp21. Tmp21 is a component of the p24 complex that recognizes GPI-anchored proteins, senses the status of the GPI-anchor, and regulates incorporation into COPII vesicles for export to the Golgi apparatus. Together, these proteins are the molecular mechanisms underlying GPI-AP quality control and ER export. To investigate the potential consequences of a deficit in export and/or quality control, we measured cell membrane-associated expression of known GPI-APs that have been previously implicated in schizophrenia, including GPC1, NCAM, MDGA2, and EPHA1, using Triton X-114 phase separation. Additionally, we tested the sensitivity of those candidate proteins to phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme that cleaves GPI from GPI-APs. While we did not observe a difference in the amount of these GPI-APs in Triton X-114 phase separated membrane fractions, we found decreased NCAM and GPC1 within the PI-PLC sensitive fraction. These findings suggest dysregulation of ER-associated GPI-AP protein processing, with impacts on post-translational modifications of proteins previously implicated in schizophrenia such as NCAM and GPC1. These findings provide evidence for a deficit in ER protein processing pathways in this illness.
Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands
Authors: Haller Florian , Bieg Matthias , Will Rainer , Körner Cindy , Weichenhan Dieter , Bott Alexander , Ishaque Naveed , Lutsik Pavlo , Moskalev Evgeny A. , Mueller Sarina K. , Bähr Marion , Woerner Angelika , Kaiser Birgit , Scherl Claudia , Haderlein Marlen , Kleinheinz Kortine , Fietkau Rainer , Iro Heinrich , Eils Roland , Hartmann Arndt , Plass Christoph , Wiemann Stefan , Agaimy Abbas
Published: January 2019

The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. The secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related phosphoproteins of which some are specifically expressed at high levels in the salivary glands and constitute major components of saliva. Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. We show that NR4A3 is specifically upregulated in AciCCs, and that active chromatin regions and gene expression signatures in AciCCs are highly correlated with the NR4A3 transcription factor binding motif. Overexpression of NR4A3 in mouse salivary gland cells increases expression of known NR4A3 target genes and has a stimulatory functional effect on cell proliferation. We conclude that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC.
Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma
Authors: Wong Kim , van der Weyden Louise , Schott Courtney R. , Foote Alastair , Constantino-Casas Fernando , Smith Sionagh , Dobson Jane M. , Murchison Elizabeth P. , Wu Hong , Yeh Iwei , Fullen Douglas R. , Joseph Nancy , Bastian Boris C. , Patel Rajiv M. , Martincorena Inigo , Robles-Espinoza Carla Daniela , Iyer Vivek , Kuijjer Marieke L. , Arends Mark J. , Brenn Thomas , Harms Paul W. , Wood Geoffrey A. , Adams David J.
Published: January 2019

Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such asNRAS,FAT4, PTPRJ, TP53andPTEN, and pathogenic germline alleles ofBRCA1, BRCA2andTP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identifies several candidate drivers includingMDM2,B2M,KNSTRNandBUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.
Author Correction: Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia
Authors: Vijayakrishnan Jayaram , Studd James , Broderick Peter , Kinnersley Ben , Holroyd Amy , Law Philip J. , Kumar Rajiv , Allan James M. , Harrison Christine J. , Moorman Anthony V. , Vora Ajay , Roman Eve , Rachakonda Sivaramakrishna , Kinsey Sally E. , Sheridan Eamonn , Thompson Pamela D. , Irving Julie A. , Koehler Rolf , Hoffmann Per , Nöthen Markus M. , Heilmann-Heimbach Stefanie , Jöckel Karl-Heinz , Easton Douglas F. , Pharaoh Paul D. P. , Dunning Alison M. , Peto Julian , Canzian Frederico , Swerdlow Anthony , Eeles Rosalind A. , Kote-Jarai Zsofia , Muir Kenneth , Pashayan Nora ,   The PRACTICAL consortium, Henderson Brian E. , Haiman Christopher A. , Benlloch Sara , Schumacher Fredrick R. , Olama Ali Amin Al , Berndt Sonja I. , Conti David V. , Wiklund Fredrik , Chanock Stephen , Stevens Victoria L. , Tangen Catherine M. , Batra Jyotsna , Clements Judith , Gronberg Henrik , Schleutker Johanna , Albanes Demetrius , Weinstein Stephanie , Wolk Alicja , West Catharine , Mucci Lorelei , Cancel-Tassin Géraldine , Koutros Stella , Sorensen Karina Dalsgaard , Maehle Lovise , Neal David E. , Travis Ruth C. , Hamilton Robert J. , Ingles Sue Ann , Rosenstein Barry , Lu Yong-Jie , Giles Graham G. , Kibel Adam S. , Vega Ana , Kogevinas Manolis , Penney Kathryn L. , Park Jong Y. , Stanford Janet L. , Cybulski Cezary , Nordestgaard Børge G. , Brenner Hermann , Maier Christiane , Kim Jeri , John Esther M. , Teixeira Manuel R. , Neuhausen Susan L. , De Ruyck Kim , Razack Azad , Newcomb Lisa F. , Lessel Davor , Kaneva Radka , Usmani Nawaid , Claessens Frank , Townsend Paul A. , Gago-Dominguez Manuela , Roobol Monique J. , Menegaux Florence , Greaves Mel , Zimmerman Martin , Bartram Claus R. , Schrappe Martin , Stanulla Martin , Hemminki Kari , Houlston Richard S.
Published: January 2019

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
Over 56.55% Faradaic efficiency of ambient ammonia synthesis enabled by positively shifting the reaction potential
Authors: Wang Mengfan , Liu Sisi , Qian Tao , Liu Jie , Zhou Jinqiu , Ji Haoqing , Xiong Jie , Zhong Jun , Yan Chenglin
Published: January 2019

Ambient electrochemical N2 reduction is emerging as a highly promising alternative to the Haber–Bosch process but is typically hampered by a high reaction barrier and competing hydrogen evolution, leading to an extremely low Faradaic efficiency. Here, we demonstrate that under ambient conditions, a single-atom catalyst, iron on nitrogen-doped carbon, could positively shift the ammonia synthesis process to an onset potential of 0.193 V, enabling a dramatically enhanced Faradaic efficiency of 56.55%. The only doublet coupling representing 15NH4+ in an isotopic labeling experiment confirms reliable NH3 production data. Molecular dynamics simulations suggest efficient N2 access to the single-atom iron with only a small energy barrier, which benefits preferential N2 adsorption instead of H adsorption via a strong exothermic process, as further confirmed by first-principle calculations. The released energy helps promote the following process and the reaction bottleneck, which is widely considered to be the first hydrogenation step, is successfully overcome.
A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia
Authors: Adhikari Kaustubh , Mendoza-Revilla Javier , Sohail Anood , Fuentes-Guajardo Macarena , Lampert Jodie , Chacón-Duque Juan Camilo , Hurtado Malena , Villegas Valeria , Granja Vanessa , Acuña-Alonzo Victor , Jaramillo Claudia , Arias William , Lozano Rodrigo Barquera , Everardo Paola , Gómez-Valdés Jorge , Villamil-Ramírez Hugo , Silva de Cerqueira Caio C. , Hunemeier Tábita , Ramallo Virginia , Schuler-Faccini Lavinia , Salzano Francisco M. , Gonzalez-José Rolando , Bortolini Maria-Cátira , Canizales-Quinteros Samuel , Gallo Carla , Poletti Giovanni , Bedoya Gabriel , Rothhammer Francisco , Tobin Desmond J. , Fumagalli Matteo , Balding David , Ruiz-Linares Andrés
Published: January 2019

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
Strong-correlation induced high-mobility electrons in Dirac semimetal of perovskite oxide
Authors: Fujioka J. , Yamada R. , Kawamura M. , Sakai S. , Hirayama M. , Arita R. , Okawa T. , Hashizume D. , Hoshino M. , Tokura Y.
Published: January 2019

Electrons in conventional metals become less mobile under the influence of electron correlation. Contrary to this empirical knowledge, we report here that electrons with the highest mobility ever found in known bulk oxide semiconductors emerge in the strong-correlation regime of the Dirac semimetal of perovskite CaIrO3. The transport measurements reveal that the high mobility exceeding 60,000 cm2V−1s−1 originates from the proximity of the Fermi energy to the Dirac node (ΔE < 10 meV). The calculation based on the density functional theory and the dynamical mean field theory reveals that the energy difference becomes smaller as the system approaches the Mott transition, highlighting a crucial role of correlation effects cooperating with the spin-orbit coupling. The correlation-induced self-tuning of Dirac node enables the quantum limit at a modest magnetic field with a giant magnetoresistance, thus providing an ideal platform to study the novel phenomena of correlated Dirac electron.
Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects
Authors: Kliewer A. , Schmiedel F. , Sianati S. , Bailey A. , Bateman J. T. , Levitt E. S. , Williams J. T. , Christie M. J. , Schulz S.
Published: January 2019

Opioid analgesics are powerful pain relievers; however, over time, pain control diminishes as analgesic tolerance develops. The molecular mechanisms initiating tolerance have remained unresolved to date. We have previously shown that desensitization of the μ-opioid receptor and interaction with β-arrestins is controlled by carboxyl-terminal phosphorylation. Here we created knockin mice with a series of serine- and threonine-to-alanine mutations that render the receptor increasingly unable to recruit β-arrestins. Desensitization is inhibited in locus coeruleus neurons of mutant mice. Opioid-induced analgesia is strongly enhanced and analgesic tolerance is greatly diminished. Surprisingly, respiratory depression, constipation, and opioid withdrawal signs are unchanged or exacerbated, indicating that β-arrestin recruitment does not contribute to the severity of opioid side effects and, hence, predicting that G-protein-biased µ-agonists are still likely to elicit severe adverse effects. In conclusion, our findings identify carboxyl-terminal multisite phosphorylation as key step that drives acute μ-opioid receptor desensitization and long-term tolerance.
A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies
Authors: Song Yuanbin , Rongvaux Anthony , Taylor Ashley , Jiang Tingting , Tebaldi Toma , Balasubramanian Kunthavai , Bagale Arun , Terzi Yunus Kasim , Gbyli Rana , Wang Xiaman , Fu Xiaoying , Gao Yimeng , Zhao Jun , Podoltsev Nikolai , Xu Mina , Neparidze Natalia , Wong Ellice , Torres Richard , Bruscia Emanuela M. , Kluger Yuval , Manz Markus G. , Flavell Richard A. , Halene Stephanie
Published: January 2019

Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients’ dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample’s genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.
Penaeid shrimp genome provides insights into benthic adaptation and frequent molting
Authors: Zhang Xiaojun , Yuan Jianbo , Sun Yamin , Li Shihao , Gao Yi , Yu Yang , Liu Chengzhang , Wang Quanchao , Lv Xinjia , Zhang Xiaoxi , Ma Ka Yan , Wang Xiaobo , Lin Wenchao , Wang Long , Zhu Xueli , Zhang Chengsong , Zhang Jiquan , Jin Songjun , Yu Kuijie , Kong Jie , Xu Peng , Chen Jack , Zhang Hongbin , Sorgeloos Patrick , Sagi Amir , Alcivar-Warren Acacia , Liu Zhanjiang , Wang Lei , Ruan Jue , Chu Ka Hou , Liu Bin , Li Fuhua , Xiang Jianhai
Published: January 2019

Crustacea, the subphylum of Arthropoda which dominates the aquatic environment, is of major importance in ecology and fisheries. Here we report the genome sequence of the Pacific white shrimp Litopenaeus vannamei, covering ~1.66 Gb (scaffold N50 605.56 Kb) with 25,596 protein-coding genes and a high proportion of simple sequence repeats (>23.93%). The expansion of genes related to vision and locomotion is probably central to its benthic adaptation. Frequent molting of the shrimp may be explained by an intensified ecdysone signal pathway through gene expansion and positive selection. As an important aquaculture organism, L. vannamei has been subjected to high selection pressure during the past 30 years of breeding, and this has had a considerable impact on its genome. Decoding the L. vannamei genome not only provides an insight into the genetic underpinnings of specific biological processes, but also provides valuable information for enhancing crustacean aquaculture.
Label-free spatio-temporal monitoring of cytosolic mass, osmolarity, and volume in living cells
Authors: Midtvedt Daniel , Olsén Erik , Höök Fredrik , Jeffries Gavin D. M.
Published: January 2019

Microorganisms adapt their biophysical properties in response to changes in their local environment. However, quantifying these changes at the single-cell level has only recently become possible, largely relying on fluorescent labeling strategies. In this work, we utilize yeast (Saccharomyces cerevisiae) to demonstrate label-free quantification of changes in both intracellular osmolarity and macromolecular concentration in response to changes in the local environment. By combining a digital holographic microscope with a millifluidic chip, the temporal response of cellular water flux was successfully isolated from the rate of production of higher molecular weight compounds, in addition to identifying the produced compounds in terms of the product of their refractive index increment $$\left( {\frac{{{{{\mathrm{d}}n}}}}{{{{{\mathrm{d}}c}}}}} \right)$$

d
n

d
c

and molar mass. The ability to identify, quantify and temporally resolve multiple biophysical processes in living cells at the single cell level offers a crucial complement to label-based strategies, suggesting broad applicability in studies of a wide-range of cellular processes.
Quantized angular momentum in topological optical systems
Authors: Silveirinha Mário G.
Published: January 2019

The Chern index characterizes the topological phases of nonreciprocal photonic systems. Unlike in electronics, the photonic Chern number has no clear physical meaning, except that it determines the number of unidirectional edge states supported by an interface with a trivial mirror. Here, we fill in this gap by demonstrating that the photonic Chern number can be understood as the quantum of the light-angular momentum in a photonic insulator cavity. It is proven that for a large cavity, the thermal fluctuation-induced angular momentum is precisely quantized in the band-gaps of the bulk states. The nontrivial expectation of the light angular momentum is due to a circulation of thermal energy in closed orbits. Remarkably, this result can be extended to systems without a topological classification, and in such a case the “quantum” of the angular momentum density is determined by the net number of unidirectional edge states supported by the cavity walls.
Lignin-polysaccharide interactions in plant secondary cell walls revealed by solid-state NMR
Authors: Kang Xue , Kirui Alex , Dickwella Widanage Malitha C. , Mentink-Vigier Frederic , Cosgrove Daniel J. , Wang Tuo
Published: January 2019

Lignin is a complex aromatic biopolymer that strengthens and waterproofs plant secondary cell walls, enabling mechanical stability in trees and long-distance water transport in xylem. Lignin removal is a key step in paper production and biomass conversion to biofuels, motivating efforts to re-engineer lignin biosynthesis. However, the physical nature of lignin’s interactions with wall polysaccharides is not well understood. Here we show that lignin self-aggregates to form highly hydrophobic and dynamically unique nanodomains, with extensive surface contacts to xylan. Solid-state NMR spectroscopy of intact maize stems, supported by dynamic nuclear polarization, reveals that lignin has abundant electrostatic interactions with the polar motifs of xylan. Lignin preferentially binds xylans with 3-fold or distorted 2-fold helical screw conformations, indicative of xylans not closely associated with cellulose. These findings advance our knowledge of the molecular-level organization of lignocellulosic biomass, providing the structural foundation for optimization of post-harvest processing for biofuels and biomaterials.
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation
Authors: Campagne Antoine , Lee Ming-Kang , Zielinski Dina , Michaud Audrey , Le Corre Stéphanie , Dingli Florent , Chen Hong , Shahidian Lara Z. , Vassilev Ivaylo , Servant Nicolas , Loew Damarys , Pasmant Eric , Postel-Vinay Sophie , Wassef Michel , Margueron Raphaël
Published: January 2019

In Drosophila, a complex consisting of Calypso and ASX catalyzes H2A deubiquitination and has been reported to act as part of the Polycomb machinery in transcriptional silencing. The mammalian homologs of these proteins (BAP1 and ASXL1/2/3, respectively), are frequently mutated in various cancer types, yet their precise functions remain unclear. Using an integrative approach based on isogenic cell lines generated with CRISPR/Cas9, we uncover an unanticipated role for BAP1 in gene activation. This function requires the assembly of an enzymatically active BAP1-associated core complex (BAP1.com) containing one of the redundant ASXL proteins. We investigate the mechanism underlying BAP1.com-mediated transcriptional regulation and show that it does not participate in Polycomb-mediated silencing. Instead, our results establish that the function of BAP1.com is to safeguard transcriptionally active genes against silencing by the Polycomb Repressive Complex 1.
A brain-wide functional map of the serotonergic responses to
acute stress and fluoxetine
Authors: Grandjean Joanes , Corcoba Alberto , Kahn Martin C. , Upton A. Louise , Deneris Evan S. , Seifritz Erich , Helmchen Fritjof , Mansuy Isabelle M. , Mann Edward O. , Rudin Markus , Saab Bechara J.
Published: January 2019

Central serotonin (5-HT) orchestrates myriad cognitive processes and
lies at the core of many stress-related psychiatric illnesses. However, the basic
relationship between its brain-wide axonal projections and functional dynamics is
not known. Here we combine optogenetics and fMRI to produce a brain-wide 5-HT evoked
functional map. We find that DRN photostimulation leads to an increase in the
hemodynamic response in the DRN itself, while projection areas predominately exhibit
a reduction of cerebral blood volume mirrored by suppression of cortical delta
oscillations. We find that the regional distribution of post-synaptically expressed
5-HT receptors better correlates with DRN 5-HT functional connectivity than
anatomical projections. Our work suggests that neuroarchitecture is not the primary
determinant of function for the DRN 5-HT. With respect to two 5-HT elevating
stimuli, we find that acute stress leads to circuit-wide blunting of the DRN output,
while the SSRI fluoxetine noticeably enhances DRN functional connectivity. These
data provide fundamental insight into the brain-wide functional dynamics of the 5-HT
projection system.
Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins
Authors: Serradell Marianela C. , Rupil Lucía L. , Martino Román A. , Prucca César G. , Carranza Pedro G. , Saura Alicia , Fernández Elmer A. , Gargantini Pablo R. , Tenaglia Albano H. , Petiti Juan P. , Tonelli Renata R. , Reinoso-Vizcaino Nicolás , Echenique José , Berod Luciana , Piaggio Eliane , Bellier Bertrand , Sparwasser Tim , Klatzmann David , Luján Hugo D.
Published: January 2019

Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host’s intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.
Suppression of magnetic ordering in XXZ-type antiferromagnetic monolayer NiPS3
Authors: Kim Kangwon , Lim Soo Yeon , Lee Jae-Ung , Lee Sungmin , Kim Tae Yun , Park Kisoo , Jeon Gun Sang , Park Cheol-Hwan , Park Je-Geun , Cheong Hyeonsik
Published: January 2019

How a certain ground state of complex physical systems emerges, especially in two-dimensional materials, is a fundamental question in condensed-matter physics. A particularly interesting case is systems belonging to the class of XY Hamiltonian where the magnetic order parameter of conventional nature is unstable in two-dimensional materials leading to a Berezinskii−Kosterlitz−Thouless transition. Here, we report how the XXZ-type antiferromagnetic order of a magnetic van der Waals material, NiPS3, behaves upon reducing the thickness and ultimately becomes unstable in the monolayer limit. Our experimental data are consistent with the findings based on renormalization-group theory that at low temperatures a two-dimensional XXZ system behaves like a two-dimensional XY one, which cannot have a long-range order at finite temperatures. This work provides the experimental examination of the XY magnetism in the atomically thin limit and opens opportunities of exploiting these fundamental theorems of magnetism using magnetic van der Waals materials.
Control of structural flexibility of layered-pillared metal-organic frameworks anchored at surfaces
Authors: Wannapaiboon Suttipong , Schneemann Andreas , Hante Inke , Tu Min , Epp Konstantin , Semrau Anna Lisa , Sternemann Christian , Paulus Michael , Baxter Samuel J. , Kieslich Gregor , Fischer Roland A.
Published: January 2019

Flexible metal-organic frameworks (MOFs) are structurally flexible, porous, crystalline solids that show a structural transition in response to a stimulus. If MOF-based solid-state and microelectronic devices are to be capable of leveraging such structural flexibility, then the integration of MOF thin films into a device configuration is crucial. Here we report the targeted and precise anchoring of Cu-based alkylether-functionalised layered-pillared MOF crystallites onto substrates via stepwise liquid-phase epitaxy. The structural transformation during methanol sorption is monitored by in-situ grazing incidence X-ray diffraction. Interestingly, spatially-controlled anchoring of the flexible MOFs on the surface induces a distinct structural responsiveness which is different from the bulk powder and can be systematically controlled by varying the crystallite characteristics, for instance dimensions and orientation. This fundamental understanding of thin-film flexibility is of paramount importance for the rational design of MOF-based devices utilising the structural flexibility in specific applications such as selective sensors.
Both rare and common genetic variants contribute to autism in the Faroe Islands
Authors: Leblond Claire S , Cliquet Freddy , Carton Coralie , Huguet Guillaume , Mathieu Alexandre , Kergrohen Thomas , Buratti Julien , Lemière Nathalie , Cuisset Laurence , Bienvenu Thierry , Boland Anne , Deleuze Jean-François , Stora Tormodur , Biskupstoe Rannva , Halling Jónrit , Andorsdóttir Guðrið , Billstedt Eva , Gillberg Christopher , Bourgeron Thomas
Published: January 2019

The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism.
Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells
Authors: Siddiqui Sahabjada , Ahmad Rumana , Khan Mohsin Ali , Upadhyay Shivbrat , Husain Ishrat , Srivastava Anand Narain
Published: January 2019

Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosis-inducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide β-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose- and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer.
SERS-based cascade amplification bioassay protocol of miRNA-21 by using sandwich structure with biotin–streptavidin system
Authors: Liang Zhaoheng , Zhou Jun , Petti Lucia , Shao Liyang , Jiang Tao , Qing Yanping , Xie Shusen , Wu Guanyi , Mormile Pasquale
Published: January 2019

An ultrasensitive SERS-based cascade amplification bioassay is proposed that couples SERS technology with cascade amplification of the B–S system.
Ultrasensitive and quantitative detection ofEGFRmutations in plasma samples from patients with non-small-cell lung cancer using a dual PNA clamping-mediated LNA-PNA PCR clamp
Authors: Zhang Shichao , Chen Zhiyao , Huang Chenrong , Ding Cheng , Li Chang , Chen Jun , Zhao Jun , Miao Liyan
Published: January 2019

Our method will provide a labor-saving and cost-saving tool for detecting and quantifying plasma mutations.
Direct and rapid analysis of trace levels steroids in water by thermal desorption atmospheric pressure photoionization mass spectrometry
Authors: Zhao Wan , Liu Chengyuan , Yin Hao , Qi Keke , Xu Minggao , Yang Jiuzhong , Pan Yang
Published: January 2019

A novel TD-APPI technique for steroid analysis at trace levels from a 10 μL water sample without derivatization and chromatographic separation.
1,5-Diaminonaphthalene functionalized carbon nanodots as a novel matrix for the analysis of small molecules by matrix-assisted laser desorption/ionization mass spectrometry
Authors: Zhang Yueying , Gao Dan , Li Shangfu , Wei Weili , Lin Jinshun , Jiang Yuyang
Published: January 2019

1,5-Diaminonaphthalene functionalized carbon nanodots (DAN-CDs) were explored as a matrix for direct detection of small molecules by MALDI-MS in negative-ion mode.
Lanthanide coordination polymer-based biosensor for citrate detection in urine
Authors: Shen Haoshuang , Liu Baoxia , Liu Daosheng , Zhu Xu , Wei Xiuhua , Yu Limin , Shen Qi , Qu Peng , Xu Maotian
Published: January 2019

GMP ligand based LCP sensor for Cit with high sensitivity and selectivity was constructed.
Atomic layer deposition for efficient and stable perovskite solar cells
Authors: Seo Seongrok , Jeong Seonghwa , Park Hyoungmin , Shin Hyunjung , Park Nam-Gyu
Published: January 2019

Extended understandings of perovskite solar cells by recent ALD application studies as well as challenges toward enhancing the efficiency and stability will be addressed.
Morphology, topography, and crystal rotation during surface crystallization of BaO/SrO/ZnO/SiO2 glass
Authors: Kracker Michael , Zscheckel Tilman , Thieme Christian , Thieme Katrin , Höche Thomas , Rüssel Christian
Published: January 2019

The initial stages of surface crystallization of glass with the composition 8BaO·8SrO·34ZnO·50SiO2 (mol%) are studied with respect to crystal orientation and morphology.
Synergistic catalysis of carbon-partitioned LaF3–BaF2 composites for the coupling of CH4 with CHF3 to VDF
Authors: Wang Jinchao , Han Wenfeng , Wang Shucheng , Tang Haodong , Liu Wucan , Li Ying , Lu Chunshan , Zhang Jianjun , Kennedy Eric M. , Li Xiaonian
Published: January 2019

Catalytic coupling of CH4 with potent greenhouse gas CHF3 to vinylidene fluoride (VDF) was investigated over composite catalysts.
A carbazole-functionalized metal–organic framework for efficient detection of antibiotics, pesticides and nitroaromatic compounds
Authors: Xu Ning , Zhang Qinghua , Zhang Guoan
Published: January 2019

A carbazole-functionalized Cd-MOF exhibits highly selective and sensitive fluorescence detection towards antibiotics, pesticides and nitroaromatic compounds.
Effect of substituents on molybdenum triiodide complexes bearing PNP-type pincer ligands toward catalytic nitrogen fixation
Authors: Itabashi Takayuki , Mori Ikki , Arashiba Kazuya , Eizawa Aya , Nakajima Kazunari , Nishibayashi Yoshiaki
Published: January 2019

Molybdenum triiodide complexes bearing phenyl and ferrocenyl substituted PNP-type pincer ligands acted as more effective catalysts toward ammonia production under ambient reaction conditions.
From white to beige adipocytes: therapeutic potential of dietary molecules against obesity and their molecular mechanisms
Authors: Wang Siyu , Pan Min-Hsiung , Hung Wei-Lun , Tung Yen-Chen , Ho Chi-Tang
Published: January 2019

The global incidence of obesity and its complications continue to rise along with a demand for novel therapeutic approaches.
Evaluation of the potential use of a carp (Cyprinus carpio) skin gelatine hydrolysate as an antioxidant component
Authors: Tkaczewska Joanna , Jamróz Ewelina , Kulawik Piotr , Morawska Małgorzata , Szczurowska Katarzyna
Published: January 2019

The carp skin gelatin hydrolysate can be used as a food additive in various food systems, at the same time, improving the antioxidant properties of the food products and increasing the value of the by-products of the fish industry.
Introducing an automated high content confocal imaging approach for Organs-on-Chips
Authors: Peel Samantha , Corrigan Adam M. , Ehrhardt Beate , Jang Kyung-Jin , Caetano-Pinto Pedro , Boeckeler Matthew , Rubins Jonathan E. , Kodella Konstantia , Petropolis Debora B. , Ronxhi Janey , Kulkarni Gauri , Foster Alison J. , Williams Dominic , Hamilton Geraldine A. , Ewart Lorna
Published: January 2019

A novel, automated workflow to capture and analyse confocal images of Organ-Chips allowing detailed assessment of cellular phenotype in situ.
Three-dimensional origami paper-based device for portable immunoassay applications
Authors: Chen Chung-An , Yeh Wen-Shin , Tsai Tsung-Ting , Li Yu-De , Chen Chien-Fu
Published: January 2019

A three-dimensional surface-modified origami-paper-based analytical device for Staphylococcus aureus detection in highly viscous human synovial fluid.
Computational insight into the interaction of oxaliplatin with insulin
Authors: Sciortino Giuseppe , Sánchez-Aparicio José-Emilio , Rodríguez-Guerra Pedregal Jaime , Garribba Eugenio , Maréchal Jean-Didier
Published: January 2019

In an organism, cisplatin and its derivatives are known to interact with proteins besides their principal DNA target. These off-target interactions have major therapeutic consequences including undesired side effects, loss of bioavailability and emergence of resistance. Insulin is one of the prototypical protein targets of platinum drugs as it has been seen to be involved in bioavailability reduction and might also determine resistance in certain cancer lines. However, despite the interest in understanding the nature of the oxaliplatin–insulin adducts, no 3D models have been achieved so far. In this study, we apply our recent computational multiscale protocol optimized for bioinorganic interactions to provide structural insights into these systems. To do so, the initial structures are predicted by blind protein–metalloligand docking calculations optimized to account for a metal-containing species, and then refined using a Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) integrated protocol. The results are consistent with experimental information obtained from fragment analysis, and also provide novel structural information like conformational changes occurring upon binding and potential effects on the biological functions of the protein. This study opens an avenue towards applying similar strategies to a wide ensemble of metallodrug–protein/peptide systems for which no structural data are available.
Nanocellulose films with multiple functional nanoparticles in confined spatial distribution
Authors: Roig-Sanchez Soledad , Jungstedt Erik , Anton-Sales Irene , Malaspina David C. , Faraudo Jordi , Berglund Lars A. , Laromaine Anna , Roig Anna
Published: January 2019

Laminated multifunctional bacterial cellulose nanocomposite with a millefeuille topographic distribution of inorganic nanoparticles.
Favorable manipulation of macrophage/endothelial cell functionality and their cross-talk on silicon-doped titania nanotube arrays
Authors: Bai Long , Liu Yanlian , Zhang Xiangyu , Huang Xiaobo , Yao Xiaohong , Hang Ruiqiang , Tang Bin , Xiao Yin
Published: January 2019

Inflammatory reactions and the functionality of endothelial cells (ECs) on the surfaces of coronary stents are critical in the prevention of in-stent restenosis and subsequent neoatherosclerosis.
Photo-mediated co-loading of highly dispersed MnOx-Pt on g-C3N4 boosts the ambient catalytic oxidation of formaldehyde
Authors: Duan Lianjie , Liu Huan , Muhammad Yaseen , Shi Liyi , Wu Haocheng , Zhang Jianping , Yu Dongqi , Huang Lei
Published: January 2019

Photo-mediated co-loading of Pt and MnOx on g-C3N4 boosts the ambient catalytic oxidation of formaldehyde due to the synergistic effects in the adsorption and activation of oxygen.
Novel tunneled phosphorus-doped WO3 films achieved using ignited red phosphorus for stable and fast switching electrochromic performances
Authors: Bon-Ryul Koo , Kim Kue-Ho , Ahn Hyo-Jin
Published: January 2019

Novel tunneled phosphorus (P)-doped WO3 films developed using ignited red P are a valuable electrochromic material with stable fast-switching performances.
Tunable hysteresis behaviour related to trap filling dependence of surface barrier in an individual CH3NH3PbI3 micro/nanowire
Authors: Hong Zhen , Zhao Jie , Li Shujun , Cheng Baochang , Xiao Yanhe , Lei Shuijin
Published: January 2019

For a single CH3NH3PbI3 micro/nanowire-based two-terminal structure, its hysteresis properties with nonvolatile memory can be accurately modulated by illuminating different sites, and its origin can be clearly identified as the variation of surface barrier related to trap filling.
High photoresponsivity and broadband photodetection with a band-engineered WSe2/SnSe2 heterostructure
Authors: Xue Hui , Dai Yunyun , Kim Wonjae , Wang Yadong , Bai Xueyin , Qi Mei , Halonen Kari , Lipsanen Harri , Sun Zhipei
Published: January 2019

Bandgap engineering with two-dimensional layered materials based heterostructures provides a new method for designing high-performance broadband photodetectors, modulators and lasers.
A generalized strategy for the synthesis of two-dimensional metal oxide nanosheets based on a thermoregulated phase transition
Authors: Zhang Jianmin , Lin Xiaoping , Xue Dongyang , Xu Binbin , Long Deng , Xue Fangfang , Duan Xiaochuan , Ye Weibin , Wang Mingsheng , Li Qiuhong
Published: January 2019

The synthesis of two-dimensional metal oxide nanosheets based on the thermoregulated phase transition of surfactant micelles is demonstrated.
Polyethyleneimine-assisted one-pot synthesis of quasi-fractal plasmonic gold nanocomposites as a photothermal theranostic agent
Authors: Mulens-Arias Vladimir , Nicolás-Boluda Alba , Gehanno Alexandre , Balfourier Alice , Carn Florent , Gazeau Florence
Published: January 2019

Polyethyleneimine-assisted one-pot synthesis of gold nanoparticles that self-arrange into fractal nanoaggregates and demonstrate photo-thermal therapeutic and imaging efficiency.
The expanding spectrum of diketopiperazine natural product biosynthetic pathways containing cyclodipeptide synthases
Authors: Borgman Paul , Lopez Ryan D. , Lane Amy L.
Published: January 2019

Tailoring enzymes decorate diketopiperazines to yield unique structures and biological functions.
Group 4 permethylindenyl complexes for slurry-phase polymerisation of ethylene
Authors: Lamb Jessica V. , Buffet Jean-Charles , Turner Zoë R. , O'Hare Dermot
Published: January 2019

Supported group 4 permethylindenyl based catalysts displayed extremely high ethylene polymerisation activity affording popcorn shaped low molecular weights polyethylenes.
One step DNA amplification of mammalian cells in picoliter microwell arrays
Authors: Liu Wenwen , Li Zhao , Liu Yuanjie , Wei Qingquan , Liu Yong , Ren Lufeng , Wang Chenyu , Yu Yude
Published: January 2019

One-step PCR of a single cell in a picoliter microwell array was developed and applied to detect a target with the sensitivity of a single copy.
Highly selective conversion of guaiacol to tert-butylphenols in supercritical ethanol over a H2WO4 catalyst
Authors: Mai Fuhang , Cui Kai , Wen Zhe , Wu Kai , Yan Fei , Chen Mengmeng , Chen Hong , Li Yongdan
Published: January 2019

H2WO4 is an effective catalyst for the conversion of guaiacol, and the Brønsted acid sites on H2WO4 surface promote a high selectivity of tert-butylphenols.
Electrocatalytic oxygen reduction reaction activity of KOH etched carbon films as metal-free cathodic catalysts for fuel cells
Authors: Suo Ni , Wu Aimin , Huang Hao , Cao Guozhong , Zhang Guifeng
Published: January 2019

The etched graphite catalyst has a higher oxygen reduction activity in KOH solution than the un-etched catalyst.
Dual-response CuS@MnO2 nanoparticles with activatable CT/MR-enhanced in vivo imaging guided photothermal therapy
Authors: Huang Hongbo , Li Ke , Liu Qingzhu , Zhao Yunlei , Xu Huiting , Wu Wenjuan , Sun Kairong , Ni Jianming , Lin Jianguo
Published: January 2019

A stable multifunctional nanoplatform with superior biocompatibility and excellent targeting function was synthesized for MR/CT image guided PTT treatment, for potential application in clinical cancer treatment.
Thermal conductivity and molecular heat transport of nanofluids
Authors: Dolatabadi Nader , Rahmani Ramin , Rahnejat Homer , Garner Colin P.
Published: January 2019

The developed model for thermal conductivity of nanofluids integrates the interfacial Kapitza resistance, the characteristics of the nanolayer, convective diffusion and surface energy with capillary condensation.
Synthesis of AuPd nanoparticle-decorated graphene-coated ZnO nanorod arrays with enhanced photoelectrochemical performance and stability
Authors: Zhang Yuzhi , Zhang Yunlong , Guo Yunfeng , Wu Lingnan , Liu Yangqiao , Song Lixing
Published: January 2019

AuPd nanoparticle-decorated graphene-coated ZnO nanorod (ZNR) array electrodes (ZNR@Gr/AuPd) were synthesized via electrostatic self-assembly followed by solution reduction methods.
Structural growth pattern of neutral and negatively charged yttrium-doped silicon clusters YSin0/− (n=6–20): from linked to encapsulated structures
Authors: Liu Yuming , Yang Jucai , Li Suying , Cheng Lin
Published: January 2019

Superatom YSi20−, with an ideal thermodynamic stability and chemical reactivity, is the most suitable building block for novel optical, optoelectronic photosensitive or catalytic nanomaterials.