bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic diversity ofJatropha curcascollections from different islands in Indonesia
Authors: Anggraeni Tantri Dyah Ayu , Satyawan Dani , Kang Yang Jae , Ha Jungmin , Kim Moon Young , Chitikineni Annapurna , Varshney Rajeev K. , Lee Suk-Ha
Published: March 2018

Jatropha curcasL. is a potential bioenergy crop but has a lack of improved cultivars with high yields and oil content. Therefore, increasing our understanding ofJ. curcasgermplasm is important for designing breeding strategies. This study was performed to investigate the genetic diversity and population structure of IndonesianJ. curcaspopulations from six different islands. To construct a reference, wede novoassembled the scaffolds (N50 = 355.5 kb) using 182 Gb Illumina HiSeq sequencing data from ThaiJ. curcasvariety Chai Nat. Genetic diversity analysis among 52 IndonesianJ. curcasaccessions was conducted based on yield traits and single nucleotide polymorphism (SNP) markers detected by mapping genotyping-by-sequencing reads from Indonesian population to Chai Nat scaffolds. Strong variation in yield traits was detected among accessions. UsingJ. integerrimaas an outgroup, 13,916 SNPs were detected. AmongJ. curcasaccessions, including accessions from other countries (Thailand, the Philippines and China), 856 SNPs were detected, but only 297 SNPs were detected among IndonesianJ. curcaspopulations, representing low genetic diversity. Through phylogenetic and structural analysis, the populations were clustered into two major groups. Group one consists of populations from Bangka and Sulawesi in the northern part of Indonesia, which are located at a distance of 1572.59 km. Group two contains populations from islands in the southern part: Java, Lombok-Sumbawa, Flores and Timor. These results indicate that introduction of diverseJ. curcasgermplasms is necessary for the improvement of the genetic variation in the Indonesian collections.
Longitudinal slotted waveguide array feed networks
Authors: Soleiman Meiguni J. , Keshavarz Haddad S. , Hosseinbeig A.
Published: March 2018

In this paper, two new feed network designs for single layer and double layer slotted waveguide array antennas are presented. A microstrip to substrate integrated waveguide transition is applied to the single layer antenna. The aperture coupling mechanism is used in order to find the optimum feed network for double-layer structure and to obtain stable radiation characteristics over the frequency band. The prototypes of the proposed antennas have been fabricated and tested. The measured results were compared very well with the simulation results obtained from CST microwave studio and showed low side lobe level at the center frequency of 11.5 GHz for the low-profile 4-channel slotted waveguide arrays.
Multitasking: Gewinn oder „Zeitfalle“? – Eine Übersicht zum medialen Multitasking bei Kindern und Jugendlichen
Authors: Frölich Jan , Lehmkuhl Gerd
Published: March 2018

Zusammenfassung. Fragestellung: Die Entwicklung moderner digitaler Medien, insbesondere des Smartphones, hat zu einer grundlegenden Änderung des Kommunikations- und Freizeitverhaltens von Jugendlichen geführt. Verbunden mit den technischen Möglichkeiten sind häufig Multitaskingprozesse, d. h. die parallele Nutzung mehrerer Medien nebeneinander oder mit nichtmedialen Aktivitäten wie Lernen und Arbeiten. Methodik: Untersucht werden bidirektionale Beziehungen zwischen Multitasking und kognitiven Prozessen, Auswirkungen auf die Qualität von Lernprozessen als auch mögliche negative Folgen für die psychosoziale Entwicklung. Methodik: Der vorliegende Übersichtsartikel beruht auf einer Medlinerecherche, in die vorliegende Studien und Übersichtsarbeiten im Zusammenhang mit der Nutzung digitaler Medien im Jugendlichen- und Erwachsenenalter seit 2000 eingingen. Ergebnisse: Multitasking ist involviert in spezifische neuropsychologische Verarbeitungsprozesse, vor allem des Frontalkortex und des Corpus striatum. Bis zu einer von objektiven wie individuellen neuropsychologischen Verarbeitungskapazitäten abhängigen Grenze führt Multitasking nicht zwingend zu einer Verminderung der Qualität von Arbeitsleistung. Bei objektiver wie individueller Überbeanspruchung kann es, vor allem bei jungen Kindern, zu vermehrtem Stresserleben kommen mit negativen Auswirkungen auf die psychische Gesundheit. Schlussfolgerung: Vorläufig kann festgestellt werden, dass v. a. neue Problemkonstellationen mit hohem kognitiven Anspruch ohne Multitaskingbedingungen bearbeitet werden sollten. Eine Vielzahl weiterer Studien ist notwendig im Hinblick auf eine Verbindung von Multitasking zu spezifischen Störungsbildern, insbesondere zu Suchterkrankungen und Aufmerksamkeitsstörungen (ADHS), aber auch bezüglich des Einsatzes im schulpädagogischen Bereich.
Die NEP-Skala – hinter den (deutschen) Kulissen des Umweltbewusstseins
Authors: Schleyer-Lindenmann Alexandra , Ittner Heidi , Dauvier Bruno , Piolat Michel
Published: March 2018

Zusammenfassung. Angesichts existentieller Umweltprobleme ist eine valide Messung von Umweltbewusstsein und -einstellungen nach wie vor ein zentrales Anliegen umwelt- und sozialpsychologischer Forschung. Es überrascht daher, dass für das seit Jahrzehnten international und disziplinübergreifend meistgenutzte Instrument, die New Ecological Paradigm Scale (NEP-Skala) von Dunlap, Van Liere, Mertig & Jones (2000) , bislang keine psychometrisch differenziert betrachtete deutsche Fassung vorliegt. Dabei wird die theoretische und empirische Verwendung der Originalskala durchaus kritisch diskutiert. Diese Lücke will der vorliegende Beitrag schließen: Es wird eine deutschsprachige Übersetzung der NEP-Skala vorgestellt, für die anhand einer universitären Stichprobe (N = 573) erste empirische Validitätshinweise vorgelegt werden. Dabei ergibt sich ein Faktormodell zweiter Ordnung mit 4 korrelierten Faktoren erster Ordnung, das theoretisch differenziert betrachtet wird. Eine Schmid-Leiman-Lösung weist auf die Möglichkeit einer verkürzten Skala hin, die direkt das höher angesiedelte Konstrukt „Umweltbewusstsein“ messen könnte. Die Ergebnisse unterstreichen die Notwendigkeit, stets die Dimensionalität der Skala methodisch angemessen zu überprüfen als auch, 20 Jahre nach der letzten Überarbeitung, inhaltliche Erweiterungen anzustoßen.
Brain-specific functional relationship networks inform autism spectrum disorder gene prediction
Authors: Duda Marlena , Zhang Hongjiu , Li Hong-Dong , Wall Dennis P. , Burmeister Margit , Guan Yuanfang
Published: March 2018

Autism spectrum disorder (ASD) is a neuropsychiatric disorder with strong evidence of genetic contribution, and increased research efforts have resulted in an ever-growing list of ASD candidate genes. However, only a fraction of the hundreds of nominated ASD-related genes have identified de novo or transmitted loss of function (LOF) mutations that can be directly attributed to the disorder. For this reason, a means of prioritizing candidate genes for ASD would help filter out false-positive results and allow researchers to focus on genes that are more likely to be causative. Here we constructed a machine learning model by leveraging a brain-specific functional relationship network (FRN) of genes to produce a genome-wide ranking of ASD risk genes. We rigorously validated our gene ranking using results from two independent sequencing experiments, together representing over 5000 simplex and multiplex ASD families. Finally, through functional enrichment analysis on our highly prioritized candidate gene network, we identified a small number of pathways that are key in early neural development, providing further support for their potential role in ASD.
Intrinsic functional connectivity predicts remission on antidepressants: a randomized controlled trial to identify clinically applicable imaging biomarkers
Authors: Goldstein-Piekarski Andrea N. , Staveland Brooke R. , Ball Tali M. , Yesavage Jerome , Korgaonkar Mayuresh S. , Williams Leanne M.
Published: March 2018

Default mode network (DMN) dysfunction (particularly within the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC)) has been implicated in major depressive disorder (MDD); however, its contribution to treatment outcome has not been clearly established. Here we tested the role of DMN functional connectivity as a general and differential biomarker for predicting treatment outcomes in a large, unmedicated adult sample with MDD. Seventy-five MDD outpatients completed fMRI scans before and 8 weeks after randomization to escitalopram, sertraline, or venlafaxine-XR. A whole-brain voxel-wise t-test identified profiles of pretreatment intrinsic functional connectivity that distinguished patients who were subsequently classified as remitters or non-remitters at follow-up. Connectivity was seeded in the PCC, an important node of the DMN. We further characterized differences between remitters, non-remitters, and 31 healthy controls and characterized changes pretreatment to posttreatment. Remitters were distinguished from non-remitters by relatively intact connectivity between the PCC and ACC/mPFC, not distinguishable from healthy controls, while non-remitters showed relative hypo-connectivity. In validation analyses, we demonstrate that PCC–ACC/mPFC connectivity predicts remission status with >80% cross-validated accuracy. In analyses testing whether intrinsic connectivity differentially relates to outcomes for a specific type of antidepressant, interaction models did not survive the corrected threshold. Our findings demonstrate that the overall capacity to remit on commonly used antidepressants may depend on intact organization of intrinsic functional connectivity between PCC and ACC/mPFC prior to treatment. The findings highlight the potential utility of functional scans for advancing a more precise approach to tailoring antidepressant treatment choices.
Astrocytic JWA deletion exacerbates dopaminergic neurodegeneration by decreasing glutamate transporters in mice
Authors: Wang Rihua , Zhao Xue , Xu Jin , Wen Yifan , Li Aiping , Lu Ming , Zhou Jianwei
Published: March 2018

Abstract

Astrocytic JWA exerts neuroprotective roles by alleviating oxidative stress and inhibiting inflammation. However, the molecular mechanisms of how astrocytic JWA is involved in dopaminergic neurodegeneration in Parkinson’s disease (PD) remain largely unknown. In this study, we found that astrocyte-specific JWA knockout mice (JWA CKO) exacerbated dopamine (DA) neuronal loss and motor dysfunction, and reduced the levels of DA and its metabolites in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model. Astrocytic JWA deficiency repressed expression of excitatory amino-acid transporter 2 (GLT-1) and glutamate uptake both in vivo and in vitro. Further, the regulation of GLT-1 expression was involved in JWA-triggered activation of the MAPK and PI3K signaling pathways. JWA-increased GLT-1 expression was abolished by inhibitors of MEK and PI3K. Silencing CREB also abrogated JWA-increased GLT-1 expression and glutamate uptake. Additionally, JWA deficiency activated glial fibrillary acidic protein (GFAP), and increased the expression of STAT3. Similarly to the MPTP model, paraquat (PQ) exposure produced PD-like phenotypes in JWA CKO mice. Taken together, our findings provide novel insights into astrocytic JWA function in the pathogenesis of neurotoxin mouse models of PD.
Statistical ensembles without typicality
Authors: Boes Paul , Wilming Henrik , Eisert Jens , Gallego Rodrigo
Published: March 2018

Maximum-entropy ensembles are key primitives in statistical mechanics. Several approaches have been developed in order to justify the use of these ensembles in statistical descriptions. However, there is still no full consensus on the precise reasoning justifying the use of such ensembles. In this work, we provide an approach to derive maximum-entropy ensembles, taking a strictly operational perspective. We investigate the set of possible transitions that a system can undergo together with an environment, when one only has partial information about the system and its environment. The set of these transitions encodes thermodynamic laws and limitations on thermodynamic tasks as particular cases. Our main result is that the possible transitions are exactly those that are possible if both system and environment are assigned the maximum-entropy state compatible with the partial information. This justifies the overwhelming success of such ensembles and provides a derivation independent of typicality or information-theoretic measures.
Insc:LGN tetramers promote asymmetric divisions of mammary stem cells
Authors: Culurgioni Simone , Mari Sara , Bonetti Paola , Gallini Sara , Bonetto Greta , Brennich Martha , Round Adam , Nicassio Francesco , Mapelli Marina
Published: March 2018

Asymmetric cell divisions balance stem cell proliferation and differentiation to sustain tissue morphogenesis and homeostasis. During asymmetric divisions, fate determinants and niche contacts segregate unequally between daughters, but little is known on how this is achieved mechanistically. In Drosophila neuroblasts and murine mammary stem cells, the association of the spindle orientation protein LGN with the stem cell adaptor Inscuteable has been connected to asymmetry. Here we report the crystal structure of Drosophila LGN in complex with the asymmetric domain of Inscuteable, which reveals a tetrameric arrangement of intertwined molecules. We show that Insc:LGN tetramers constitute stable cores of Par3–Insc-LGN-GαiGDP complexes, which cannot be dissociated by NuMA. In mammary stem cells, the asymmetric domain of Insc bound to LGN:GαiGDP suffices to drive asymmetric fate, and reverts aberrant symmetric divisions induced by p53 loss. We suggest a novel role for the Insc-bound pool of LGN acting independently of microtubule motors to promote asymmetric fate specification.
MRN complex-dependent recruitment of ubiquitylated BLM helicase to DSBs negatively regulates DNA repair pathways
Authors: Tripathi Vivek , Agarwal Himanshi , Priya Swati , Batra Harish , Modi Priyanka , Pandey Monica , Saha Dhurjhoti , Raghavan Sathees C. , Sengupta Sagar
Published: March 2018

Mutations in BLM in Bloom Syndrome patients predispose them to multiple types of cancers. Here we report that BLM is recruited in a biphasic manner to annotated DSBs. BLM recruitment is dependent on the presence of NBS1, MRE11 and ATM. While ATM activity is essential for BLM recruitment in early phase, it is dispensable in late phase when MRE11 exonuclease activity and RNF8-mediated ubiquitylation of BLM are the key determinants. Interaction between polyubiquitylated BLM and NBS1 is essential for the helicase to be retained at the DSBs. The helicase activity of BLM is required for the recruitment of HR and c-NHEJ factors onto the chromatin in S- and G1-phase, respectively. During the repair phase, BLM inhibits HR in S-phase and c-NHEJ in G1-phase. Consequently, inhibition of helicase activity of BLM enhances the rate of DNA alterations. Thus BLM utilizes its pro- and anti-repair functions to maintain genome stability.
Ultrafast nonlinear optical response of Dirac fermions in graphene
Authors: Baudisch Matthias , Marini Andrea , Cox Joel D. , Zhu Tony , Silva Francisco , Teichmann Stephan , Massicotte Mathieu , Koppens Frank , Levitov Leonid S. , García de Abajo F. Javier , Biegert Jens
Published: March 2018

The speed of solid-state electronic devices, determined by the temporal dynamics of charge carriers, could potentially reach unprecedented petahertz frequencies through direct manipulation by optical fields, consisting in a million-fold increase from state-of-the-art technology. In graphene, charge carrier manipulation is facilitated by exceptionally strong coupling to optical fields, from which stems an important back-action of photoexcited carriers. Here we investigate the instantaneous response of graphene to ultrafast optical fields, elucidating the role of hot carriers on sub-100 fs timescales. The measured nonlinear response and its dependence on interaction time and field polarization reveal the back-action of hot carriers over timescales commensurate with the optical field. An intuitive picture is given for the carrier trajectories in response to the optical-field polarization state. We note that the peculiar interplay between optical fields and charge carriers in graphene may also apply to surface states in topological insulators with similar Dirac cone dispersion relations.
p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
Authors: Borisova Marina E. , Voigt Andrea , Tollenaere Maxim A. X. , Sahu Sanjeeb Kumar , Juretschke Thomas , Kreim Nastasja , Mailand Niels , Choudhary Chunaram , Bekker-Jensen Simon , Akutsu Masato , Wagner Sebastian A. , Beli Petra
Published: March 2018

Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA-binding proteins as primary substrates and 14-3-3 as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Mechanistically, we show that MK2 phosphorylates the RNA-binding subunit of the NELF complex NELFE on Serine 115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin, which is accompanied by RNA polymerase II elongation.
CDK6 inhibits white to beige fat transition by suppressing RUNX1
Authors: Hou Xiaoli , Zhang Yongzhao , Li Wei , Hu Alexander J. , Luo Chi , Zhou Wenhui , Hu Jamie K. , Daniele Stefano G. , Wang Jinfeng , Sheng Jinghao , Fan Yongsheng , Greenberg Andrew S. , Farmer Stephen R. , Hu Miaofen G.
Published: March 2018

Whereas white adipose tissue depots contribute to the development of metabolic diseases, brown and beige adipose tissue has beneficial metabolic effects. Here we show that CDK6 regulates beige adipocyte formation. We demonstrate that mice lacking the CDK6 protein or its kinase domain (K43M) exhibit significant increases beige cell formation, enhanced energy expenditure, better glucose tolerance, and improved insulin sensitivity, and are more resistant to high-fat diet-induced obesity. Re-expression of CDK6 in Cdk6
−/−
mature or precursor cells, or ablation of RUNX1 in K43M mature or precursor cells, reverses these phenotypes. Furthermore, RUNX1 positively regulates the expression of Ucp-1 and Pgc1α by binding to proximal promoter regions. Our findings indicate that CDK6 kinase activity negatively regulates the conversion of fat-storing cells into fat-burning cells by suppressing RUNX1, and suggest that CDK6 may be a therapeutic target for the treatment of obesity and related metabolic diseases.
Turning microplastics into nanoplastics through digestive fragmentation by Antarctic krill
Authors: Dawson Amanda L. , Kawaguchi So , King Catherine K. , Townsend Kathy A. , King Robert , Huston Wilhelmina M. , Bengtson Nash Susan M.
Published: March 2018

Microplastics (plastics <5 mm diameter) are at the forefront of current environmental pollution research, however, little is known about the degradation of microplastics through ingestion. Here, by exposing Antarctic krill (Euphausia superba) to microplastics under acute static renewal conditions, we present evidence of physical size alteration of microplastics ingested by a planktonic crustacean. Ingested microplastics (31.5 µm) are fragmented into pieces less than 1 µm in diameter. Previous feeding studies have shown spherical microplastics either; pass unaffected through an organism and are excreted, or are sufficiently small for translocation to occur. We identify a new pathway; microplastics are fragmented into sizes small enough to cross physical barriers, or are egested as a mixture of triturated particles. These findings suggest that current laboratory-based feeding studies may be oversimplifying interactions between zooplankton and microplastics but also introduces a new role of Antarctic krill, and potentially other species, in the biogeochemical cycling and fate of plastic.
Author Correction: Metabolic changes in Medaka fish induced by cyanobacterial exposures in mesocosms: an integrative approach combining proteomic and metabolomic analyses
Authors: Sotton Benoît , Paris Alain , Le Manach Séverine , Blond Alain , Lacroix Gérard , Millot Alexis , Duval Charlotte , Huet Hélène , Qiao Qin , Labrut Sophie , Chiappetta Giovanni , Vinh Joelle , Catherine Arnaud , Marie Benjamin
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: Intraskeletal histovariability, allometric growth patterns, and their functional implications in bird-like dinosaurs
Authors: Prondvai Edina , Godefroit Pascal , Adriaens Dominique , Hu Dong-Yu
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
Authors: Mikulska-Ruminska Karolina , Kulik Andrej J. , Benadiba Carine , Bahar Ivet , Dietler Giovanni , Nowak Wieslaw
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria
Authors: Barboza Renato , Lima Flávia Afonso , Reis Aramys Silva , Murillo Oscar Javier , Peixoto Erika Paula Machado , Bandeira Carla Letícia , Fotoran Wesley Luzetti , Sardinha Luis Roberto , Wunderlich Gerhard , Bevilacqua Estela , Lima Maria Regina D’Império , Alvarez José Maria , Costa Fabio Trindade Maranhão , Gonçalves Lígia Antunes , Epiphanio Sabrina , Marinho Claudio Romero Farias
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Small-RNA sequencing identifies dynamic microRNA deregulation during skeletal muscle lineage progression
Authors: Castel David , Baghdadi Meryem B. , Mella Sébastien , Gayraud-Morel Barbara , Marty Virginie , Cavaillé Jérôme , Antoniewski Christophe , Tajbakhsh Shahragim
Published: March 2018

Skeletal muscle satellite cells are quiescent adult resident stem cells that activate, proliferate and differentiate to generate myofibres following injury. They harbour a robust proliferation potential and self-renewing capacity enabling lifelong muscle regeneration. Although several classes of microRNAs were shown to regulate adult myogenesis, systematic examination of stage-specific microRNAs during lineage progression from the quiescent state is lacking. Here we provide a genome-wide assessment of the expression of small RNAs during the quiescence/activation transition and differentiation by RNA-sequencing. We show that the majority of small RNAs present in quiescent, activated and differentiated muscle cells belong to the microRNA class. Furthermore, by comparing expression in distinct cell states, we report a massive and dynamic regulation of microRNAs, both in numbers and amplitude, highlighting their pivotal role in regulation of quiescence, activation and differentiation. We also identify a number of microRNAs with reliable and specific expression in quiescence including several maternally-expressed miRNAs generated at the imprinted Dlk1-Dio3 locus. Unexpectedly, the majority of class-switching miRNAs are associated with the quiescence/activation transition suggesting a poised program that is actively repressed. These data constitute a key resource for functional analyses of miRNAs in skeletal myogenesis, and more broadly, in the regulation of stem cell self-renewal and tissue homeostasis.
Author Correction: Circulating Biomarkers to Identify Responders in Cardiac Cell therapy
Authors: Jokerst Jesse V. , Cauwenberghs Nicholas , Kuznetsova Tatiana , Haddad Francois , Sweeney Timothy , Hou Jiayi , Rosenberg-Hasson Yael , Zhao Eric , Schutt Robert , Bolli Roberto , Traverse Jay H. , Pepine Carl J. , Henry Timothy D. , Schulman Ivonne H. , Moyé Lem , Taylor Doris A. , Yang Phillip C.
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
B49, a BST-2-based peptide, inhibits adhesion and growth of breast cancer cells
Authors: Mahauad-Fernandez Wadie D. , Okeoma Chioma M.
Published: March 2018

Bone marrow stromal antigen 2 (BST-2) also known as Tetherin has been implicated in the growth and progression of many cancers. BST-2 employs its pro-tumor effects through the formation of BST-2:BST-2 dimers which ultimately promotes cell to cell and cell to matrix adhesion, cell motility, survival, and growth. The aim of this study was to evaluate the effect of a novel BST-2-based peptide—B49 on adhesion and growth of breast cancer cells. Homotypic/heterotypic adhesion, three-dimensional spheroid formation, and anchorage-independent growth were used to assess the effect of B49 on cell adhesion and growth. Additionally, we provide evidence of the anti-tumor effect of B49 in a preclinical mouse model of breast cancer. Results show that breast cancer cell adhesion to other cancer cells or components of the tumor microenvironment were inhibited by B49. Most well-known evaluation indexes of cancer cell growth, including spheroid formation, anchorage-independent, and primary tumor growth were significantly inhibited by B49. These data affirm that i) BST-2 plays a key role in mediating breast cancer cell adhesion and growth, and ii) B49 and its analog B49Mod1 significantly inhibits BST-2-mediated cancer cell adhesion and growth. Therefore, B49 and its analogs offer a promising anti-adhesion and therapeutic lead for BST-2-dependent cancers.
Publisher Correction: Acoustic allometry revisited: morphological determinants of fundamental frequency in primate vocal production
Authors: Garcia Maxime , Herbst Christian T. , Bowling Daniel L. , Dunn Jacob C. , Fitch W. Tecumseh
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: Intra-colony disease progression induces fragmentation of coral fluorescent pigments
Authors: Caldwell Jamie M. , Ushijima Blake , Couch Courtney S. , Gates Ruth D.
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Glyco-engineered Long Acting FGF21 Variant with Optimal Pharmaceutical and Pharmacokinetic Properties to Enable Weekly to Twice Monthly Subcutaneous Dosing
Authors: Weng Yan , Ishino Tetsuya , Sievers Annette , Talukdar Saswata , Chabot Jeffrey R. , Tam Amy , Duan Weili , Kerns Kelvin , Sousa Eric , He Tao , Logan Alison , Lee Darwin , Li Dongmei , Zhou Yingjiang , Bernardo Barbara , Joyce Alison , Kavosi Mania , O’Hara Denise M. , Clark Tracey , Guo Jie , Giragossian Craig , Stahl Mark , Calle Roberto A. , Kriz Ron , Somers Will , Lin Laura
Published: March 2018

Pharmacological administration of FGF21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. Here we report the design, optimization, and characterization of a long acting glyco-variant of FGF21. Using a combination of N-glycan engineering for enhanced protease resistance and improved solubility, Fc fusion for further half-life extension, and a single point mutation for improving manufacturability in Chinese Hamster Ovary cells, we created a novel FGF21 analogue, Fc-FGF21[R19V][N171] or PF-06645849, with substantially improved solubility and stability profile that is compatible with subcutaneous (SC) administration. In particular, it showed a low systemic clearance (0.243 mL/hr/kg) and long terminal half-life (~200 hours for intact protein) in cynomolgus monkeys that approaches those of monoclonal antibodies. Furthermore, the superior PK properties translated into robust improvement in glucose tolerance and the effects lasted 14 days post single SC dose in ob/ob mice. PF-06645849 also caused greater body weight loss in DIO mice at lower and less frequent SC doses, compared to previous FGF21 analogue PF-05231023. In summary, the overall PK/PD and pharmaceutical profile of PF-06645849 offers great potential for development as weekly to twice-monthly SC administered therapeutic for chronic treatment of metabolic diseases.
A simple and robust real-time qPCR method for the detection of PIK3CA mutations
Authors: Alvarez-Garcia Virginia , Bartos Clare , Keraite Ieva , Trivedi Urmi , Brennan Paul M. , Kersaudy-Kerhoas Maïwenn , Gharbi Karim , Oikonomidou Olga , Leslie Nicholas R.
Published: March 2018

PIK3CA mutations are seemingly the most common driver mutations in breast cancer with H1047R and E545K being the most common of these, accounting together for around 60% of all PIK3CA mutations and have promising therapeutic implications. Given the low sensitivity and the high cost of current genotyping methods we sought to develop fast, simple and inexpensive assays for PIK3CA H1047R and E545K mutation screening in clinical material. The methods we describe are based on a real-time PCR including a mutation specific primer combined with a non-productive oligonucleotide which inhibits wild-type amplification and a parallel internal control reaction. We demonstrate consistent detection of PIK3CA H1047R mutant DNA in genomic DNA extracted from frozen breast cancer biopsies, FFPE material or cancer cell lines with a detection sensitivity of approximately 5% mutant allele fraction and validate these results using both Sanger sequencing and deep next generation sequencing methods. The detection sensitivity for PIK3CA E545K mutation was approximately 10%. We propose these methods as simple, fast and inexpensive diagnostic tools to determine PIK3CA mutation status.
Intensified summer monsoon and the urbanization of Indus Civilization in northwest India
Authors: Dixit Yama , Hodell David A. , Giesche Alena , Tandon Sampat K. , Gázquez Fernando , Saini Hari S. , Skinner Luke C. , Mujtaba Syed A. I. , Pawar Vikas , Singh Ravindra N. , Petrie Cameron A.
Published: March 2018

Today the desert margins of northwest India are dry and unable to support large populations, but were densely occupied by the populations of the Indus Civilization during the middle to late Holocene. The hydroclimatic conditions under which Indus urbanization took place, which was marked by a period of expanded settlement into the Thar Desert margins, remains poorly understood. We measured the isotopic values (δ18O and δD) of gypsum hydration water in paleolake Karsandi sediments in northern Rajasthan to infer past changes in lake hydrology, which is sensitive to changing amounts of precipitation and evaporation. Our record reveals that relatively wet conditions prevailed at the northern edge of Rajasthan from ~5.1 ± 0.2 ka BP, during the beginning of the agricultural-based Early Harappan phase of the Indus Civilization. Monsoon rainfall intensified further between 5.0 and 4.4 ka BP, during the period when Indus urban centres developed in the western Thar Desert margin and on the plains of Haryana to its north. Drier conditions set in sometime after 4.4 ka BP, and by ~3.9 ka BP an eastward shift of populations had occurred. Our findings provide evidence that climate change was associated with both the expansion and contraction of Indus urbanism along the desert margin in northwest India.
Automated high throughput animal CO1 metabarcode classification
Authors: Porter Teresita M. , Hajibabaei Mehrdad
Published: March 2018

We introduce a method for assigning names to CO1 metabarcode sequences with confidence scores in a rapid, high-throughput manner. We compiled nearly 1 million CO1 barcode sequences appropriate for classifying arthropods and chordates. Compared to our previous Insecta classifier, the current classifier has more than three times the taxonomic coverage, including outgroups, and is based on almost five times as many reference sequences. Unlike other popular rDNA metabarcoding markers, we show that classification performance is similar across the length of the CO1 barcoding region. We show that the RDP classifier can make taxonomic assignments about 19 times faster than the popular top BLAST hit method and reduce the false positive rate from nearly 100% to 34%. This is especially important in large-scale biodiversity and biomonitoring studies where datasets can become very large and the taxonomic assignment problem is not trivial. We also show that reference databases are becoming more representative of current species diversity but that gaps still exist. We suggest that it would benefit the field as a whole if all investigators involved in metabarocoding studies, through collaborations with taxonomic experts, also planned to barcode representatives of their local biota as a part of their projects.
Evaluation of the therapeutic effects of QuickOpt optimization in Chinese patients with chronic heart failure treated by cardiac resynchronization
Authors: Yan Ji , Zhang Shu , Huang Dejia , Xue Xiaolin , Xu Jing , Tao Qianmin , Zhang Weize , Zhang Zheng , Hua Wei , Liang Yanchun , Tang Baopeng , Xu Wei , Xu Geng , Ren Xuejun , Wang Jingfeng , Guo Tao , Jia Shaobin , Dong Yugang , Jiang Hong , Fu Guosheng , Zhu Liguang , Chen Lin , Tian Fuli , Ling Feng , Li Jianmei , Qi Xiaoyong , Hao Yinglu , Wang Yutang , Zheng Liangrong , Pu Xiaoqun , Shen Farong , Li Guangping , Li Hui , Peng Fang
Published: March 2018

In this trial, long-term therapeutic effects and clinical improvements in Chinese chronic heart failure patients optimized by QuickOpt or echocardiography were compared for atrioventricular (AV) and interventricular (VV) delay optimizations after cardiac resynchronization therapy (CRT) with pacing (CRT-P) or with pacing and defibrillator (CRT-D) therapy. One hundred and ninety-six subjects (50%) had dilated cardiomyopathy, 108 (27.6%) had ischemic heart disease and 112 (28.6%) were hypertensive and were randomized into QuickOpt (198) or echocardiographic optimization (control) (194) groups at ≤2-weeks post-implantation. Programmed AV/VV delay was optimized at baseline and at 3 and 6 months. Left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) class, specific activity scale (SAS), and the six-minute walk tests (6MWT) were evaluated by blinded researchers at 12 months. Of the QuickOpt group, LVESV decreased significantly by 24.7% ± 33.9% compared with baseline, while LVESV of Controls decreased by 25.1% ± 36.1% (P = 0.924). NYHA class, SAS and 6MWT also improved similarly in both groups at 12 months. Mortality in both groups was not significantly different (11.0% vs 7.6%, P = 0.289). However, there was a significant difference in the time required for optimization by QuickOpt compared with echocardiography (3.33 ± 3.11 vs 58.79 ± 27.03 minutes, P < 0.000).
Greenhouse gas released from the deep permafrost in the northern Qinghai-Tibetan Plateau
Authors: Mu Cuicui , Li Lili , Wu Xiaodong , Zhang Feng , Jia Lin , Zhao Qian , Zhang Tingjun
Published: March 2018

Deep carbon pool in permafrost regions is an important component of the global terrestrial carbon cycle. However, the greenhouse gas production from deep permafrost soils is not well understood. Here, using soils collected from 5-m deep permafrost cores from meadow and wet meadow on the northern Qinghai-Tibetan Plateau (QTP), we investigated the effects of temperature on CO2and N2O production under aerobic incubations and CH4production under anaerobic incubations. After a 35-day incubation, the CO2,N2O and CH4production at −2 °C to 10 °C were 0.44~2.12 mg C-CO2/g soil C, 0.0027~0.097 mg N-N2O/g soil N, and 0.14~5.88 μg C-CH4/g soil C, respectively. Greenhouse gas production in deep permafrost is related to the C:N ratio and stable isotopes of soil organic carbon (SOC), whereas depth plays a less important role. The temperature sensitivity (Q10) values of the CO2,N2O and CH4production were 1.67–4.15, 3.26–5.60 and 5.22–10.85, without significant differences among different depths. These results indicated that climate warming likely has similar effects on gas production in deep permafrost and surface soils. Our results suggest that greenhouse gas emissions from both the deep permafrost and surface soils to the air will increase under future climate change.
Identification of new abscisic acid receptor agonists using a wheat cell-free based drug screening system
Authors: Nemoto Keiichirou , Kagawa Makiko , Nozawa Akira , Hasegawa Yoshinori , Hayashi Minoru , Imai Kenichiro , Tomii Kentaro , Sawasaki Tatsuya
Published: March 2018

Abscisic acid (ABA) is the main phytohormone involved in abiotic stress response and its adaptation, and is a candidate agrichemical. Consequently, several agonists of ABA have been developed using the yeast two-hybrid system. Here, we describe a novel cell-free-based drug screening approach for the development and validation of ABA receptor agonists. Biochemical validation of this approach between 14 ABA receptors (PYR/PYL/RCARs) and 7 type 2C-A protein phosphatases (PP2CAs) revealed the same interactions as those of previous proteome data, except for nine new interactions. By chemical screening using this approach, we identified two novel ABA receptor agonists, JFA1 (julolidine and fluorine containing ABA receptor activator 1) and JFA2 as its analog. The results of biochemical validation for this approach and biological analysis suggested that JFA1 and JFA2 inhibit seed germination and cotyledon greening of seedlings by activating PYR1 and PYL1, and that JFA2 enhanced drought tolerance without inhibiting root growth by activating not only PYR1 and PYL1 but also PYL5. Thus, our approach was useful for the development of ABA receptor agonists and their validation.
Vector species-specific association between natural Wolbachia infections and avian malaria in black fly populations
Authors: Woodford Luke , Bianco Giovanni , Ivanova Yoana , Dale Maeve , Elmer Kathryn , Rae Fiona , Larcombe Stephen D. , Helm Barbara , Ferguson Heather M. , Baldini Francesco
Published: March 2018

Artificial infection of mosquitoes with the endosymbiont bacteriaWolbachiacan interfere with malaria parasite development. Therefore, the release ofWolbachia-infected mosquitoes has been proposed as a malaria control strategy. However,Wolbachiaeffects on vector competence are only partly understood, as indicated by inconsistent effects on malaria infection reported under laboratory conditions. Studies of naturally-occurringWolbachiainfections in wild vector populations could be useful to identify the ecological and evolutionary conditions under which these endosymbionts can block malaria transmission. Here we demonstrate the occurrence of naturalWolbachiainfections in three species of black fly (genusSimulium), which is a main vector of the avian malaria parasiteLeucocytozoon. Prevalence ofLeucocytozoonwas high (25%), but the nature and magnitude of its association withWolbachiadiffered between black fly species.Wolbachiainfection was positively associated with avian malaria infection inS. cryophilum, negatively associated inS. aureum, and unrelated inS. vernum. These differences suggest thatWolbachiainteracts with the parasite in a vector host species-specific manner. This provides a useful model system for further study of howWolbachiainfluences vector competence. Such knowledge, including the possibility of undesirable positive association, is required to guide endosymbiont based control methods.
Factors associated with prostate specific antigen testing in Australians: Analysis of the New South Wales 45 and Up Study
Authors: Nair-Shalliker Visalini , Bang Albert , Weber Marianne , Goldsbury David E. , Caruana Michael , Emery Jon , Banks Emily , Canfell Karen , O’Connell Dianne L. , Smith David P.
Published: March 2018

Australia has one of the highest incidence rates of prostate cancer (PC) worldwide, due in part to widespread prostate specific antigen (PSA) testing. We aimed to identify factors associated with PSA testing in Australian men without a diagnosis of prostate cancer or prior prostate disease. Participants were men joining the 45 and Up Study in 2006–2009, aged ≥45 years at recruitment. Self-completed questionnaires were linked to cancer registrations, hospitalisations, health services data and deaths. Men with a history of PC, radical prostatectomy or a “monitoring” PSA test for prostate disease were excluded. We identified Medicare reimbursed PSA tests during 2012–2014. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) for the association between having PSA tests and factors of interest. Of the 62,765 eligible men, 51.8% had at least one screening PSA test during 2012–2014. Factors strongly associated with having a PSA test included having 27+ general practitioner consultations (versus 3–9 consultations; OR = 2.00; 95%CI = 1.90–2.11), benign prostatic hyperplasia treatment (versus none; OR = 1.59(95%CI = 1.49–1.70), aged 60–69 years (versus 50–59 years; OR = 1.54; 95%CI = 1.48–1.60). These results emphasise the important role of primary care in decision making about PSA testing.
Estimating wildlife activity curves: comparison of methods and sample size
Authors: Lashley Marcus A. , Cove Michael V. , Chitwood M. Colter , Penido Gabriel , Gardner Beth , DePerno Chris S. , Moorman Chris E.
Published: March 2018

Camera traps and radiotags commonly are used to estimate animal activity curves. However, little empirical evidence has been provided to validate whether they produce similar results. We compared activity curves from two common camera trapping techniques to those from radiotags with four species that varied substantially in size (~1 kg–~50 kg), diet (herbivore, omnivore, carnivore), and mode of activity (diurnal and crepuscular). Also, we sub-sampled photographs of each species with each camera trapping technique to determine the minimum sample size needed to maintain accuracy and precision of estimates. Camera trapping estimated greater activity during feeding times than radiotags in all but the carnivore, likely reflective of the close proximity of foods readily consumed by all species except the carnivore (i.e., corn bait or acorns). However, additional analyses still indicated both camera trapping methods produced relatively high overlap and correlation to radiotags. Regardless of species or camera trapping method, mean overlap increased and overlap error decreased rapidly as sample sizes increased until an asymptote near 100 detections which we therefore recommend as a minimum sample size. Researchers should acknowledge that camera traps and radiotags may estimate the same mode of activity but differ in their estimation of magnitude in activity peaks.
PEG/Dextran Double Layer Influences Fe Ion Release and Colloidal Stability of Iron Oxide Nanoparticles
Authors: Mohammadi M. Rezaa , Malkovskiy Andrey V. , Jothimuthu Preetha , Kim Kwang-Min , Parekh Mansi , Inayathullah Mohammed , Zhuge Yan , Rajadas Jayakumar
Published: March 2018

Despite preliminary confidence on biosafety of polymer coated iron oxide nanoparticles (SPIONs), toxicity concerns have hampered their clinical translation. SPIONs toxicity is known to be due to catalytic activity of their surface and release of toxic Fe ions originating from the core biodegradation, leading to the generation of reactive oxygen species (ROS). Here, we hypothesized that a double-layer polymeric corona comprising of dextran as an interior, and polyethylene glycol (PEG) as an exterior layer better shields the core SPIONs. We found that ROS generation was cell specific and depended on SPIONs concentration, although it was reduced by sufficient PEG immobilization or 100 µM deferoxamine. 24 h following injection, PEGylated samples showed reduction of biodistribution in liver, heterogenous biodistribution profile in spleen, and no influence on NPs blood retention. Sufficient surface masking or administration of deferoxamine could be beneficial strategies in designing and clinical translation of future biomedical SPIONs.
Antimicrobial Photodynamic therapy enhanced by the peptide aurein 1.2
Authors: de Freitas Laura Marise , Lorenzón Esteban Nicolás , Santos-Filho Norival Alves , Zago Lucas Henrique de Paula , Uliana Marciana Pierina , de Oliveira Kleber Thiago , Cilli Eduardo Maffud , Fontana Carla Raquel
Published: March 2018

In the past few years, the World Health Organization has been warning that the post-antibiotic era is an increasingly real threat. The rising and disseminated resistance to antibiotics made mandatory the search for new drugs and/or alternative therapies that are able to eliminate resistant microorganisms and impair the development of new forms of resistance. In this context, antimicrobial photodynamic therapy (aPDT) and helical cationic antimicrobial peptides (AMP) are highlighted for the treatment of localized infections. This study aimed to combine the AMP aurein 1.2 to aPDT using Enterococcus faecalis as a model strain. Our results demonstrate that the combination of aPDT with aurein 1.2 proved to be a feasible alternative capable of completely eliminating E. faecalis employing low concentrations of both PS and AMP, in comparison with the individual therapies. Aurein 1.2 is capable of enhancing the aPDT activity whenever mediated by methylene blue or chlorin-e6, but not by curcumin, revealing a PS-dependent mechanism. The combined treatment was also effective against different strains; noteworthy, it completely eliminated a vancomycin-resistant strain of Enterococcus faecium. Our results suggest that this combined protocol must be exploited for clinical applications in localized infections as an alternative to antibiotics.
A comprehensive sediment dynamics study of a major mud belt system on the inner shelf along an energetic coast
Authors: Liu James T. , Hsu Ray T. , Yang Rick J. , Wang Ya Ping , Wu Hui , Du Xiaoqin , Li Anchun , Chien Steven C. , Lee Jay , Yang Shouye , Zhu Jianrong , Su Chih-Chieh , Chang Yi , Huh Chih-An
Published: March 2018

Globally mud areas on continental shelves are conduits for the dispersal of fluvial-sourced sediment. We address fundamental issues in sediment dynamics focusing on how mud is retained on the seabed on shallow inner shelves and what are the sources of mud. Through a process-based comprehensive study that integrates dynamics, provenance, and sedimentology, here we show that the key mechanism to keep mud on the seabed is the water-column stratification that forms a dynamic barrier in the vertical that restricts the upward mixing of suspended sediment. We studied the 1000 km-long mud belt that extends from the mouth of the Changjiang (Yangtze) River along the coast of Zhejiang and Fujian Provinces of China and ends on the west coast of Taiwan. This mud belt system is dynamically attached to the fluvial sources, of which the Changjiang River is the primary source. Winter is the constructive phase when active deposition takes place of fine-grained sediment carried mainly by the Changjiang plume driven by Zhe-Min Coastal Currents southwestward along the coast.