bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological use of a novel scaffold, anomeric N,N-diarylamino tetrahydropyran: molecular similarity search, chemocentric target profiling, and experimental evidence
Authors: Venkanna Arramshetti , Kwon Oh Wook , Afzal Sualiha , Jang Cheongyun , Cho Kyo Hee , Yadav Dharmendra K. , Kim Kang , Park Hyeung-geun , Chun Kwang-Hoon , Kim Sun Yeou , Kim Mi-hyun
Published: September 2017

Rational drug design against a determined target (disease, pathway, or protein) is the main strategy in drug discovery. However, regardless of the main strategy, chemists really wonder how to maximize the utility of their new compounds by drug repositioning them as clinical drug candidates in drug discovery. In this study, we started our drug discovery “from curiosity in the chemical structure of a drug scaffold itself” rather than “for a specific target”. As a new drug scaffold, anomeric diarylamino cyclic aminal scaffold 1, was designed by combining two known drug scaffolds (diphenylamine and the most popular cyclic ether, tetrahydropyran/tetrahydrofuran) and synthesized through conventional Brønsted acid catalysis and metal-free α-C(sp3)–H functionalized oxidative cyclization. To identify the utility of the new scaffold 1, it was investigated through 2D and 3D similarity screening and chemocentric target prediction. The predicted proteins were investigated by an experimental assay. The scaffold 1 was reported to have an antineuroinflammatory agent to reduce NO production, and compound 10 concentration-dependently regulated the expression level of IL-6, PGE-2, TNF-α, ER-β, VDR, CTSD, and iNOS, thus exhibiting neuroprotective activity.
Lead-free Single-molecule Switching Material with Electric, Optical, Thermal Triple Controllable Multifunction Based on Perovskite-like Crystal and Flexible Thin Film
Authors: Chen Cheng , Zhang Wan-Ying , Ye Qiong , Fu Da-Wei
Published: September 2017

With the flourishing development of star molecule (CH3NH3)PbI3, organic-inorganic perovskites with multifunction and flexibility have become a worldwide focus. However, the controllable photoelectric switchable material (especially electric, optical, thermal multifunctional switches) still face great challenges, and most of them are ceramic and toxic lead-based series. Herein a lead-free perovskite-like crystal and flexible thin film, ImMC (ImMC = (HIm)6∙[MnCl4∙MnCl6]) (1), with many advantages over inorganic ceramics and lead-based perovskites, performs ideal optical and dielectric duple switching properties simultaneously. The order-disordered HIm (Im = imidazole) cations of α-type occupy two lattice sites corresponding to “Switch-ON/0” and “Switch-OFF/1” states, respectively. Interestingly, the optical and dielectric “ON/OFF or 0/1” switches can be integrated into one single-molecule single/duple channel module with high signal-noise ratio, in which the “ON/OFF” response can be precisely controlled by temperature or/and light wavelength signal to realize automatically multiple switching. In brief, the lead-free multifunctional switch opens up a brand new route and shows the mark of its real genius as a highly desirable material for its advanced applications in highly integrated circuit and ultrahigh-encrypted storage in flexible photoelectric devices.
Bioelectronic measurement and feedback control of molecules in living cells
Authors: Banerjee Areen , Weaver Isaac , Thorsen Todd , Sarpeshkar Rahul
Published: September 2017

We describe an electrochemical measurement technique that enables bioelectronic measurements of reporter proteins in living cells as an alternative to traditional optical fluorescence. Using electronically programmable microfluidics, the measurement is in turn used to control the concentration of an inducer input that regulates production of the protein from a genetic promoter. The resulting bioelectronic and microfluidic negative-feedback loop then serves to regulate the concentration of the protein in the cell. We show measurements wherein a user-programmable set-point precisely alters the protein concentration in the cell with feedback-loop parameters affecting the dynamics of the closed-loop response in a predictable fashion. Our work does not require expensive optical fluorescence measurement techniques that are prone to toxicity in chronic settings, sophisticated time-lapse microscopy, or bulky/expensive chemo-stat instrumentation for dynamic measurement and control of biomolecules in cells. Therefore, it may be useful in creating a: cheap, portable, chronic, dynamic, and precise all-electronic alternative for measurement and control of molecules in living cells.
Self-Heating-Induced Deterioration of Electromechanical Performance in Polymer-Supported Metal Films for Flexible Electronics
Authors: Jang Dong-Won , Lee Jeong-Hwan , Kim Ansoon , Lee Soon-Bok , Hong Seong-Gu
Published: September 2017

The retention of electrical performance under the combined conditions of mechanical strain and an electrical current is essential for flexible electronics. Here, we report that even below the critical current density required for electromigration, the electrical current can significantly deteriorate the electromechanical performance of metal film/polymer substrate systems. This leads to a loss of stretchability, and this effect becomes more severe with increasing strain as well as increasing current. The local increase of electrical resistance in the metal film caused by damage, such as localized deformations, cracks, etc., locally raises the temperature of the test sample via Joule heating. This weakens the deformation resistance of the polymer substrate, accelerating the necking instability, and consequently leading to a rapid loss of electrical conductivity with strain. To minimize such a current-induced deterioration of the polymer-supported metal films, we develop and demonstrate the feasibility of two methods that enhance the deformation resistance of the polymer substrate at elevated temperatures: increasing the thickness of the polymer substrate, and utilizing a polymer substrate with a high glass transition temperature.
EUF1 – a newly identified gene involved in erythritol utilization in Yarrowia lipolytica
Authors: Rzechonek Dorota A. , Neuvéglise Cécile , Devillers Hugo , Rymowicz Waldemar , Mirończuk Aleksandra M.
Published: September 2017

The gene YALI0F01562g was identified as an important factor involved in erythritol catabolism of the unconventional yeast Yarrowia lipolytica. Its putative role was identified for the first time by comparative analysis of four Y. lipolytica strains: A-101.1.31, Wratislavia K1, MK1 and AMM. The presence of a mutation that seriously damaged the gene corresponded to inability of the strain Wratislavia K1 to utilize erythritol. RT-PCR analysis of the strain MK1 demonstrated a significant increase in YALI0F01562g expression during growth on erythritol. Further studies involving deletion and overexpression of the selected gene showed that it is indeed essential for efficient erythritol assimilation. The deletion strain Y. lipolytica AMM∆euf1 was almost unable to grow on erythritol as the sole carbon source. When the strain was applied in the process of erythritol production from glycerol, the amount of erythritol remained constant after reaching the maximal concentration. Analysis of the YALI0F01562g gene sequence revealed the presence of domains characteristic for transcription factors. Therefore we suggest naming the studied gene Erythritol Utilization Factor – EUF1.
Identification and characterization of the novel colonization factor CS30 based on whole genome sequencing in enterotoxigenic Escherichia coli (ETEC)
Authors: von Mentzer Astrid , Tobias Joshua , Wiklund Gudrun , Nordqvist Stefan , Aslett Martin , Dougan Gordon , Sjöling Åsa , Svennerholm Ann-Mari
Published: September 2017

The ability to colonize the small intestine is essential for enterotoxigenic Escherichia coli (ETEC) to cause diarrhea. Although 22 antigenically different colonization factors (CFs) have been identified and characterized in ETEC at least 30% of clinical ETEC isolates lack known CFs. Ninety-four whole genome sequenced “CF negative” isolates were searched for novel CFs using a reverse genetics approach followed by phenotypic analyses. We identified a novel CF, CS30, encoded by a set of seven genes, csmA-G, related to the human CF operon CS18 and the porcine CF operon 987P (F6). CS30 was shown to be thermo-regulated, expressed at 37 °C, but not at 20 °C, by SDS-page and mass spectrometry analyses as well as electron microscopy imaging. Bacteria expressing CS30 were also shown to bind to differentiated human intestinal Caco-2 cells. The genes encoding CS30 were located on a plasmid (E873p3) together with the genes encoding LT and STp. PCR screening of ETEC isolates revealed that 8.6% (n = 13) of “CF negative” (n = 152) and 19.4% (n = 13) of “CF negative” LT + STp (n = 67) expressing isolates analyzed harbored CS30. Hence, we conclude that CS30 is common among “CF negative” LT + STp isolates and is associated with ETEC that cause diarrhea.
Neoproterozoic rifting in the Upper Yangtze Continental Block: Constraints from granites in the Well W117 borehole, South China
Authors: He Deng-Fa , Li Di , Li Chuan-Xin , Li Ying-Qiang , Mei Qing-Hua
Published: September 2017

Well W117 in the Sichuan Basin reveals a suite of ~814 Ma quartz monzonites, unconformably overlain by Sinian clastic and carbonate sediments. The quartz monzonites contain no muscovite and amphibole, and are characterized by high SiO2 (72.26–77.93%), total alkali, and TFe2O3/MgO content, and low P2O5 and CaO abundance, with variable A/CNK ratio (0.93–1.19), classified as metaluminous to weakly aluminous highly fractionated I-type granites. They are preserved in the Neoproterozoic rift and exhibit restricted negative εNd(t) values (−7.0 to −5.2) and variable zircon εHf(t) values (−13.9 to 2.3), suggesting their generation via melting of both ancient and juvenile crustal materials in an extensional setting. Their parent magmas were formed in a low-temperature condition (831–650 °C) and finally emplaced at ca. 9–10 km below the surface, indicating that the intrusion underwent exhumation before the deposition of Sinian sag basin. Such geological processes, together with evidence for Neoproterozoic structures in the surrounding area, support that the Upper Yangtze craton experienced two main phases of rifting from 830–635 Ma. The Well W117 granites and its overlying sediments record a geodynamic evolution from orogenic collapse to continental rifting, and to thermal subsidence, probably related to the Rodinia supercontinent breakup.
Influence of mismatched and bulged nucleotides on SNP-preferential RNase H cleavage of RNA-antisense gapmer heteroduplexes
Authors: Magner Dorota , Biala Ewa , Lisowiec-Wachnicka Jolanta , Kierzek Ryszard
Published: September 2017

This study focused on determining design rules for gapmer-type antisense oligonucleotides (ASOs), that can differentiate cleavability of two SNP variants of RNA in the presence of ribonuclease H based on the mismatch type and position in the heteroduplex. We describe the influence of structural motifs formed by several arrangements of multiple mismatches (various types of mismatches and their position within the ASO/target RNA duplex) on RNase H cleavage selectivity of five different SNP types. The targets were mRNA fragments of APP, SCA3, SNCA and SOD1 genes, carrying C-to-G, G-to-C, G-to-A, A-to-G and C-to-U substitutions. The results show that certain arrangements of mismatches enhance discrimination between wild type and mutant SNP alleles of RNA in vitro as well as in HeLa cells. Among the over 120 gapmers tested, we found two gapmers that caused preferential degradation of the mutant allele APP 692 G and one that led to preferential cleavage of the mutant SNCA 53 A allele, both in vitro and in cells. However, several gapmers promoted selective cleavage of mRNA mutant alleles in in vitro experiments only.
Fasciclin-like arabinogalactan protein gene expression is associated with yield of flour in the milling of wheat
Authors: Nirmal Ravi C. , Furtado Agnelo , Rangan Parimalan , Henry Robert J.
Published: September 2017

A large portion of the global wheat crop is milled to produce flour for use in the production of foods such as bread. Pressure to increase food supplies sustainably can be address directly by reducing post-harvest losses during processes such as flour milling. The recovery of flour in the milling of wheat is genetically determined but difficult to assess in wheat breeding due to the requirement for a large sample. Here we report the discovery that human selection for altered expression of putative cell adhesion proteins is associated with wheats that give high yields of flour on milling. Genes encoding fasciclin-like arabinogalactan proteins are expressed at low levels in high milling wheat genotypes at mid grain development. Thirty worldwide wheat genotypes were grouped into good and poor millers based flour yield obtained from laboratory scale milling of mature seeds. Differentially expressed genes were identified by comparing transcript profiles at 14 and 30 days post anthesis obtained from RNA-seq data of all the genotypes. Direct selection for genotypes with appropriate expression of these genes will greatly accelerate wheat breeding and ensure high recoveries of flour from wheat by resulting in grains that break up more easily on milling.
Polarized super-resolution structural imaging inside amyloid fibrils using Thioflavine T
Authors: Shaban Haitham A. , Valades-Cruz Cesar A. , Savatier Julien , Brasselet Sophie
Published: September 2017

Thioflavin T (ThT) is standardly used as a fluorescent marker to detect aggregation of amyloid fibrils by conventional fluorescence microscopy, including polarization resolved imaging that brings information on the orientational order of the fibrils. These techniques are however diffraction limited and cannot provide fine structural details at the fibrils scales of 10–100 nm, which lie beyond the diffraction limit. In this work, we evaluate the capacity of ThT to photoswitch when bound to insulin amyloids by adjusting the redox properties of its environment. We demonstrate that on-off duty cycles, intensity and photostability of the ThT fluorescence emission under adequate buffer conditions permit stochastic super-resolution imaging with a localization precision close to 20 nm. We show moreover that signal to noise conditions allow polarized orientational imaging of single ThT molecules, which reveals ultra-structure signatures related to protofilaments twisting within amyloid fibrils.
A pathway analysis of genome-wide association study highlights novel type 2 diabetes risk pathways
Authors: Liu Yang , Zhao Jing , Jiang Tao , Yu Mei , Jiang Guohua , Hu Yang
Published: September 2017

Genome-wide association studies (GWAS) have been widely used to identify common type 2 diabetes (T2D) variants. However, the known variants just explain less than 20% of the overall estimated genetic contribution to T2D. Pathway-based methods have been applied into T2D GWAS datasets to investigate the biological mechanisms and reported some novel T2D risk pathways. However, few pathways were shared in these studies. Here, we performed a pathway analysis using the summary results from a large-scale meta-analysis of T2D GWAS to investigate more genetic signals in T2D. Here, we selected PLNK and VEGAS to perform the gene-based test and WebGestalt to perform the pathway-based test. We identified 8 shared KEGG pathways after correction for multiple tests in both methods. We confirm previous findings, and highlight some new T2D risk pathways. We believe that our results may be helpful to study the genetic mechanisms of T2D.
Intrathoracic solitary fibrous tumor – an international multicenter study on clinical outcome and novel circulating biomarkers
Authors: Ghanim Bahil , Hess Sebastian , Bertoglio Pietro , Celik Ali , Bas Aynur , Oberndorfer Felicitas , Melfi Franca , Mussi Alfredo , Klepetko Walter , Pirker Christine , Berger Walter , Harmati Imrich , Farkas Attila , Jan Ankersmit Hendrik , Dome Balazs , Fillinger Janos , Aigner Clemens , Hegedus Balazs , Renyi-Vamos Ferenc , Lang György
Published: September 2017

Intrathoracic solitary fibrous tumor (SFT) is a rare disease. Radical resection is the standard of care. However, estimating prognosis and planning follow-up and treatment strategies remains challenging. Data were retrospectively collected by five international centers to explore outcome and biomarkers for predicting event-free-survival (EFS). 125 histological proven SFT patients (74 female; 59.2%; 104 benign; 83.2%) were analyzed. The one-, three-, five- and ten-year EFS after curative-intent surgery was 98%, 90%, 77% and 67%, respectively. Patients age (≥59 vs. <59 years hazard ratio (HR) 4.23, 95 confidence interval (CI) 1.56–11.47, p = 0.005), tumor-dignity (malignant vs. benign HR 6.98, CI 3.01–16.20, p <0.001), tumor-size (>10 cm vs. ≤10 cm HR 2.53, CI 1.10–5.83, p = 0.030), de Perrot staging (late vs. early HR 3.85, CI 1.65–8.98, p = 0.002) and resection margins (positive vs. negative HR 4.17, CI 1.15–15.17, p = 0,030) were associated with EFS. Furthermore, fibrinogen (elevated vs. normal HR 4.00, CI 1.49–10.72, p = 0.006) and the neutrophil–to-lymphocyte-ratio (NLR > 5 vs. < 5 HR 3.91, CI 1.40–10.89, p = 0.009) were prognostic after univariate analyses. After multivariate analyses tumor-dignity and fibrinogen remained as independent prognosticators. Besides validating the role of age, tumor-dignity, tumor-size, stage and resection margins, we identified for the first time inflammatory markers as prognosticators in SFT.
Biochemical efficacy, molecular docking and inhibitory effect of 2, 3-dimethylmaleic anhydride on insect acetylcholinesterase
Authors: Singh Kabrambam D. , Labala Rajendra K. , Devi Thiyam B. , Singh Ningthoujam I. , Chanu Heisnam D. , Sougrakpam Sonia , Nameirakpam Bunindro S. , Sahoo Dinabandhu , Rajashekar Yallappa
Published: September 2017

Evolution of resistance among insects to action of pesticides has led to the discovery of several insecticides (neonicotinoids and organophosphates) with new targets in insect nervous system. Present study evaluates the mode of inhibition of acetylchlonesterase (AChE), biochemical efficacy, and molecular docking of 2,3-dimethylmaleic anhydride, against Periplaneta americana and Sitophilus oryzae. The knockdown activity of 2,3-dimethylmaleic anhydride was associated with in vivo inhibition of AChE. At KD99 dosage, the 2,3-dimethylmaleic anhydride showed more than 90% inhibition of AChE activity in test insects. A significant impairment in antioxidant system was observed, characterized by alteration in superoxide dismutase and catalase activities along with increase in reduced glutathione levels. Computational docking programs provided insights in to the possible interaction between 2,3-dimethylmaleic anhydride and AChE of P. americana. Our study reveals that 2,3-dimethylmaeic anhydride elicits toxicity in S. oryzae and P. americana primarily by AChE inhibition along with oxidative stress.
Enhancing Cell Proliferation and Osteogenic Differentiation of MC3T3-E1 Pre-osteoblasts by BMP-2 Delivery in Graphene Oxide-Incorporated PLGA/HA Biodegradable Microcarriers
Authors: Fu Chuan , Yang Xiaoyu , Tan Shulian , Song Liangsong
Published: September 2017

Lack of bioactivity has seriously restricted the development of biodegradable implants for bone tissue engineering. Therefore, surface modification of the composite is crucial to improve the osteointegration for bone regeneration. Bone morphogenetic protein-2 (BMP-2), a key factor in inducing osteogenesis and promoting bone regeneration, has been widely used in various clinical therapeutic trials. In this study, BMP-2 was successfully immobilized on graphene oxide-incorporated PLGA/HA (GO-PLGA/HA) biodegradable microcarriers. Our study demonstrated that the graphene oxide (GO) facilitated the simple and highly efficient immobilization of peptides on PLGA/HA microcarriers within 120 min. To further test in vitro, MC3T3-E1 cells were cultured on different microcarriers to observe various cellular activities. It was found that GO and HA significantly enhanced cell adhesion and proliferation. More importantly, the immobilization of BMP-2 onto the GO-PLGA/HA microcarriers resulted in significantly greater osteogenic differentiation of cells in vitro, as indicated by the alkaline phosphate activity test, quantitative real-time polymerase chain reaction analysis, immunofluorescence staining and mineralization on the deposited substrates. Findings from this study revealed that the method to use GO-PLGA/HA microcarriers for immobilizing BMP-2 has a great potential for the enhancement of the osseointegration of bone implants.
Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene
Authors: Cheon Chong Kun , Lim So-Hee , Kim Yoo-Mi , Kim Doyoun , Lee Na-Yoon , Yoon Tae-Sung , Kim Nam-Soon , Kim Eunjoon , Lee Jae-Ran
Published: September 2017

KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance.
Periodic and transient motions of large woodpeckers
Authors: Collins Michael D.
Published: September 2017

Two types of periodic and transient motions of large woodpeckers are considered. A drumming woodpecker may be modeled as a harmonic oscillator with a periodic forcing function. The transient behavior that occurs after the forcing is turned off suggests that the double knocks of Campephilus woodpeckers may be modeled in terms of a harmonic oscillator with an impulsive forcing, and this hypothesis is consistent with audio and video recordings. Wingbeats are another type of periodic and transient motion of large woodpeckers. A model for the flap rate in cruising flight is applied to the Pileated Woodpecker (Dryocopus pileatus) and the Ivory-billed Woodpecker (Campephilus principalis). During a brief transient just after taking off, the wing motion and flap rate of a large woodpecker may not be the same as in cruising flight. These concepts are relevant to videos that contain evidence for the persistence of the Ivory-billed Woodpecker.
DNA barcoding analysis and phylogenetic relationships of tree species in tropical cloud forests
Authors: Kang Yong , Deng Zhiyan , Zang Runguo , Long Wenxing
Published: September 2017

DNA barcoding is a useful tool for species identification and phylogenetic construction. But present studies have far reached a consistent result on the universality of DNA barcoding. We tested the universality of tree species DNA barcodes including rbcL, matK, trnH-psbA and ITS, and examined their abilities of species identification and phylogenetic construction in three tropical cloud forests. Results showed that the success rates of PCR amplification of rbcL, matK, trnH-psbA and ITS were 75.26% ± 3.65%, 57.24% ± 4.42%, 79.28% ± 7.08%, 50.31% ± 6.64%, and the rates of DNA sequencing were 63.84% ± 4.32%, 50.82% ± 4.36%, 72.87% ± 11.37%, 45.15% ± 8.91% respectively, suggesting that both rbcL and trnH-psbA are universal for tree species in the tropical cloud forests. The success rates of species identification of the four fragments were higher than 41.00% (rbcL: 41.50% ± 2.81%, matK: 42.88% ± 2.59%, trnH-psbA: 46.16% ± 5.11% and ITS: 47.20% ± 5.76%), demonstrating that these fragments have potentiality in species identification. When the phylogenetic relationships were built with random fragment combinations, optimal evolutionary tree with high supporting values were established using the combinations of rbcL + matK + trnH-psbA in tropical cloud forests.
Blood-derived macrophages prone to accumulate lysosomal lipids trigger oxLDL-dependent murine hepatic inflammation
Authors: Houben Tom , Oligschlaeger Yvonne , Bitorina Albert V. , Hendrikx Tim , Walenbergh Sofie M. A. , Lenders Marie-Hélène , Gijbels Marion J. J. , Verheyen Fons , Lütjohann Dieter , Hofker Marten H. , Binder Christoph J. , Shiri-Sverdlov Ronit
Published: September 2017

Despite the consistent rise of non-alcoholic steatohepatitis (NASH) worldwide, the mechanisms that govern the inflammatory aspect of this disease remain unknown. Previous research showed an association between hepatic inflammation and lysosomal lipid accumulation in blood-derived hepatic macrophages. Additionally, in vitro findings indicated that lipids, specifically derived from the oxidized low-density lipoprotein (oxLDL) particle, are resistant to removal from lysosomes. On this basis, we investigated whether lysosomal lipid accumulation in blood-derived hepatic macrophages is causally linked to hepatic inflammation and assessed to what extent increasing anti-oxLDL IgM autoantibodies can affect this mechanism. By creating a proof-of-concept mouse model, we demonstrate a causal role for lysosomal lipids in blood-derived hepatic macrophages in mediating hepatic inflammation and initiation of fibrosis. Furthermore, our findings show that increasing anti-oxLDL IgM autoantibody levels reduces inflammation. Hence, therapies aimed at improving lipid-induced lysosomal dysfunction and blocking oxLDL-formation deserve further investigation in the context of NASH.
TM-Aligner: Multiple sequence alignment tool for transmembrane proteins with reduced time and improved accuracy
Authors: Bhat Basharat , Ganai Nazir A. , Andrabi Syed Mudasir , Shah Riaz A. , Singh Ashutosh
Published: September 2017

Membrane proteins plays significant role in living cells. Transmembrane proteins are estimated to constitute approximately 30% of proteins at genomic scale. It has been a difficult task to develop specific alignment tools for transmembrane proteins due to limited number of experimentally validated protein structures. Alignment tools based on homology modeling provide fairly good result by recapitulating 70–80% residues in reference alignment provided all input sequences should have known template structures. However, homology modeling tools took substantial amount of time, thus aligning large numbers of sequences becomes computationally demanding. Here we present TM-Aligner, a new tool for transmembrane protein sequence alignment. TM-Aligner is based on Wu-Manber and dynamic string matching algorithm which has significantly improved its accuracy and speed of multiple sequence alignment. We compared TM-Aligner with prevailing other popular tools and performed benchmarking using three separate reference sets, BaliBASE3.0 reference set7 of alpha-helical transmembrane proteins, structure based alignment of transmembrane proteins from Pfam database and structure alignment from GPCRDB. Benchmarking against reference datasets indicated that TM-Aligner is more advanced method having least turnaround time with significant improvements over the most accurate methods such as PROMALS, MAFFT, TM-Coffee, Kalign, ClustalW, Muscle and PRALINE. TM-Aligner is freely available through http://lms.snu.edu.in/TM-Aligner/.
The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice
Authors: Benito E , Ramachandran B , Schroeder H , Schmidt G , Urbanke H , Burkhardt S , Capece V , Dean C , Fischer A
Published: September 2017

Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer’s disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1—a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT—on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer’s disease. Systemic administration of JQ1 elicited a hippocampal gene expression program that is associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory.
Investigating the genetic underpinnings of early-life irritability
Authors: Riglin L , Eyre O , Cooper M , Collishaw S , Martin J , Langley K , Leibenluft E , Stringaris A , Thapar A K , Maughan B , O'Donovan M C , Thapar A
Published: September 2017

Severe irritability is one of the commonest reasons prompting referral to mental health services. It is frequently seen in neurodevelopmental disorders that manifest early in development, especially attention-deficit/hyperactivity disorder (ADHD). However, irritability can also be conceptualized as a mood problem because of its links with anxiety/depressive disorders; notably DSM-5 currently classifies severe, childhood-onset irritability as a mood disorder. Investigations into the genetic nature of irritability are lacking although twin studies suggest it shares genetic risks with both ADHD and depression. We investigated the genetic underpinnings of irritability using a molecular genetic approach, testing the hypothesis that early irritability (in childhood/adolescence) is associated with genetic risk for ADHD, as indexed by polygenic risk scores (PRS). As a secondary aim we investigated associations between irritability and PRS for major depressive disorder (MDD). Three UK samples were utilized: two longitudinal population-based cohorts with irritability data from childhood (7 years) to adolescence (15–16 years), and one ADHD patient sample (6–18 years). Irritability was defined using parent reports. PRS were derived from large genome-wide association meta-analyses. We observed associations between ADHD PRS and early irritability in our clinical ADHD sample and one of the population samples. This suggests that early irritability traits share genetic risk with ADHD in the general population and are a marker of higher genetic loading in individuals with an ADHD diagnosis. Associations with MDD PRS were not observed. This suggests that early-onset irritability could be conceptualized as a neurodevelopmental difficulty, behaving more like disorders such as ADHD than mood disorders.
Two titanium(iv)-oxo-clusters: synthesis, structures, characterization and recycling catalytic activity in the oxygenation of sulfides
Authors: Wu Rong-Hui , Guo Ming , Yu Ming-Xin , Zhu Long-Guan
Published: September 2017

Two titanium(iv)-oxo-clusters were synthesized and can be used as homogeneous recycling catalysts in the oxygenation of sulfides.
Phosphate and phytate adsorption and precipitation on ferrihydrite surfaces
Authors: Wang Xiaoming , Hu Yongfeng , Tang Yadong , Yang Peng , Feng Xionghan , Xu Wenqian , Zhu Mengqiang
Published: September 2017

Transition of phosphate bidentate-binuclear surface complexation to precipitation with increasing P sorption loading was explored using differential pair distribution function (d-PDF) analysis.
Procyanidins extracted from the litchi pericarp ameliorate atherosclerosis in ApoE knockout mice: their effects on nitric oxide bioavailability and oxidative stress
Authors: Rong Shuang , Hu Xueting , Zhao Siqi , Zhao Yanting , Xiao Xiao , Bao Wei , Liu Liegang
Published: September 2017

Epidemiological studies strongly support the role of procyanidin-rich beverages and fruit in the prevention of cardiovascular diseases.
Biocompatible conjugated polymer nanoparticles for highly efficient photoacoustic imaging of orthotopic brain tumors in the second near-infrared window
Authors: Guo Bing , Sheng Zonghai , Kenry Kenry , Hu Dehong , Lin Xiangwei , Xu Shidang , Liu Chengbo , Zheng Hairong , Liu Bin
Published: September 2017

NIR II conjugated polymer nanoparticles with good biocompatibility, excellent photoacoustic stability and high imaging contrast are formulated, which allows highly efficient imaging of orthotopic brain tumors with a high signal/background ratio and a good penetration depth.
Iron–sulfur cluster biosynthesis and trafficking – impact on human disease conditions
Authors: Wachnowsky C. , Fidai I. , Cowan J. A.
Published: September 2017

Iron–sulfur cluster biogenesis and trafficking enables the function of a number of cellular proteins. As such, mutations or perturbations in these pathways lead to disease states.
Boron nitride nanotubes as a heat sinking and stress-relaxation layer for high performance light-emitting diodes
Authors: Seo Tae Hoon , Lee Gun Hee , Park Ah Hyun , Cho Hyunjin , Kim Jun-Hee , Chandramohan S. , Jeon Seong-Ran , Jang Se Gyu , Kim Myung Jong , Suh Eun-Kyung
Published: September 2017

High density dislocations, large compressive strain, and poor thermal properties are major obstacles for the light emitting diodes (LED) performance.
Structural discontinuity induced surface second harmonic generation in single, thin zinc-blende GaAs nanowires
Authors: Wei Yu-Ming , Yu Ying , Wang Jing , Liu Lin , Ni Hai-Qiao , Niu Zhi-Chuan , Li Jun-Tao , Wang Xue-Hua , Yu Si-Yuan
Published: September 2017

We investigate optical second harmonic generation (SHG) from individual self-catalyzed zinc-blende (ZB) GaAs nanowires (NWs), where the polarimetry strongly depends on the NW diameter.
Compositional tuning in sputter-grown highly-oriented Bi–Te films and their optical and electronic structures
Authors: Saito Yuta , Fons Paul , Makino Kotaro , Mitrofanov Kirill V. , Uesugi Fumihiko , Takeguchi Masaki , Kolobov Alexander V. , Tominaga Junji
Published: September 2017

Controlling the compositions of topological insulating Bi-Te films by sputtering.
Biotemplated synthesis of magnetic filaments
Authors: Bereczk-Tompa Éva , Vonderviszt Ferenc , Horváth Barnabás , Szalai István , Pósfai Mihály
Published: September 2017

With the aim of creating one-dimensional magnetic nanostructures, we genetically engineered flagellar filaments produced by Salmonella bacteria to display iron- or magnetite-binding sites, and used the mutant filaments as templates for both nucleation and attachment of the magnetic iron oxide magnetite.
Contrasting water adhesion strengths of hydrophobic surfaces engraved with hierarchical grooves: lotus leaf and rose petal effects
Authors: Zhang Zhengqing , Ha Man Yeong , Jang Joonkyung
Published: September 2017

Molecular dynamics study on the (de)wetting transition of hierarchical grooves engraved on a superhydrophobic surface.
Engineering a nanotubular mesoporous cobalt phosphide electrocatalyst by the Kirkendall effect towards highly efficient hydrogen evolution reactions
Authors: Miao Yue-E , Li Fei , Zhou Yu , Lai Feili , Lu Hengyi , Liu Tianxi
Published: September 2017

Through a feasible electrospinning strategy, mesoporous cobalt phosphide nanotubes are obtained with a three-dimensional network structure, which exhibit a low onset overpotential of 53 mV with a low Tafel slope of 50 mV dec−1 toward hydrogen evolution reactions.
Control of electrostatic interaction between a molecular beacon aptamer and conjugated polyelectrolyte for detection range-tunable ATP assay
Authors: Jeong J.-E. , Woo H. Y.
Published: September 2017

A new strategy is suggested to fine-tune the detection range by controlling the ionic density of CPEs in the MBA/CPE-based ATP assay.
Yb3+-Concentration dependent upconversion luminescence and temperature sensing behavior in Yb3+/Er3+ codoped Gd2MoO6 nanocrystals prepared by a facile citric-assisted sol–gel method
Authors: Du Peng , Huang Xiaoyong , Yu Jae Su
Published: September 2017

Er3+/Yb3+-Codoped Gd2MoO6 upconversion nanocrystals with high sensor sensitivity and wide operation range were demonstrated for non-contact optical thermometry.
Calcium triggered self-assembly of alginate-graft-POEGMA via RAFT for the encapsulation of lipophillic actives
Authors: Kumar Jatin N. , Pang Victoria Y. T. , Aik Shalen X. L.
Published: September 2017

Self-assembly of alginate into nanoparticles was realized by grafting hydrophilic brushesviaRAFT.
2,3-Dialdehyde nanofibrillated cellulose as a potential material for the treatment of MRSA infection
Authors: Mou Kaiwen , Li Juanjuan , Wang Yunyun , Cha Ruitao , Jiang Xingyu
Published: September 2017

Nanocellulose materials have undergone rapid development in recent years as promising biomedical materials due to their excellent physical and biological properties, in particular their biocompatibility, biodegradability, and low cytotoxicity.
Enhanced antimicrobial effect of berberine in nanogel carriers with cationic surface functionality
Authors: Al-Awady Mohammed J. , Fauchet Adelaide , Greenway Gillian M. , Paunov Vesselin N.
Published: September 2017

We demonstrate a strong enhancement in the antimicrobial and antifungal action of berberine encapsulated in nanogel carriers whose surface is functionalised with a cationic polyelectrolyte. The effect comes from the electrostatic adhesion of the cationic nanocarriers on the cell wall.
Polarisation‐independent UWB frequency selective surface based on 2.5D miniaturised hexagonal ring
Authors: Hua Boyu , He Xiaoxiang , Yang Yang
Published: September 2017

A novel frequency selective surface (FSS) exploiting 2.5D miniaturised hexagonal rings (2.5D MHR) is proposed. It can obtain an ultra‐wide stopband and an improved polarisation‐independent property due to the compact hexagon arrangement of 2.5D MHRs. The −10 dB bandwidth of the proposed FSS is from 1.97 to 8.08 GHz, and the deviation of resonant frequencies at 30° under transverse electric/transverse magnetic polarisations is merely 0.006f0. A prototype of the proposed FSS is fabricated and measured to validate the good consistency between simulations and measurements.
Required SNR improvement for downlink optical communication via channel coding and aperture diversity by utilising PPM
Authors: Şahin Selami
Published: September 2017

In this study, it is aimed to investigate the required signal‐to‐noise ratio (SNR) that provides a sufficient bit error rate (BER) according to the zenith angle between the ground station and satellite when pulse position modulation is utilised. Many parameters such as scintillation index, link distance, wavelength, Rytov variance, Fried's parameter, aperture diameter of the receiver and zenith angle have been considered to achieve realistic results. Due to the restrictions on the system, some parameters are specified as deterministic; the obtained results suggest that the required SNR value changes in a wide range from small to large values of the zenith angle to achieve sufficient BER. Therefore, either SNR adjustment as a function of the zenith angle is provided or the interval of the zenith angles to establish the link is determined previously in order to avoid the high link margin. It is shown that, instead of the second choice, aperture diversity is utilised at the receiver to establish communication even for large zenith angles with a reasonable value of the SNR. Besides aperture diversity, channel coding with error correction codes further improves the performance.
Planetary Radio Interferometry and Doppler Experiment (PRIDE) technique: A test case of the Mars Express Phobos Flyby
Authors: Bocanegra-Bahamón T. M. , Molera Calvés G. , Gurvits L. I. , Duev D. A. , Pogrebenko S. V. , Cimò G. , Dirkx D. , Rosenblatt P.
Published: September 2017

Context. Closed-loop Doppler data obtained by deep space tracking networks, such as the NASA Deep Space Network (DSN) and the ESA tracking station network (Estrack), are routinely used for navigation and science applications. By shadow tracking the spacecraft signal, Earth-based radio telescopes involved in the Planetary Radio Interferometry and Doppler Experiment (PRIDE) can provide open-loop Doppler tracking data only when the dedicated deep space tracking facilities are operating in closed-loop mode.

Aims. We explain the data processing pipeline in detail and discuss the capabilities of the technique and its potential applications in planetary science.

Methods. We provide the formulation of the observed and computed values of the Doppler data in PRIDE tracking of spacecraft and demonstrate the quality of the results using an experiment with the ESA Mars Express spacecraft as a test case.

Results. We find that the Doppler residuals and the corresponding noise budget of the open-loop Doppler detections obtained with the PRIDE stations compare to the closed-loop Doppler detections obtained with dedicated deep space tracking facilities.
A virtual element method for the vibration problem of Kirchhoff plates
Authors: Mora David , Rivera Gonzalo , Velásquez Iván
Published: September 2017

The aim of this paper is to develop a virtual element method (VEM) for the vibration problem of thin plates on polygonal meshes. We consider a variational formulation relying only on the transverse displacement of the plate and propose anH2(Ω) conforming discretization by means of the VEM which is simple in terms of degrees of freedom and coding aspects. Under standard assumptions on the computational domain, we establish that the resulting scheme provides a correct approximation of the spectrum and prove optimal order error estimates for the eigenfunctions and a double order for the eigenvalues. Finally, we report several numerical experiments illustrating the behaviour of the proposed scheme and confirming our theoretical results on different families of meshes. Additional examples of cases not covered by our theory are also presented.
Evolution of a semidiscrete system modeling the scattering of acoustic waves by a piezoelectric solid
Authors: Brown Thomas S. , Sánchez-Vizuet Tonatiuh , Sayas Francisco-Javier
Published: September 2017

We consider a model problem of the scattering of linear acoustic waves in free homogeneous space by an elastic solid. The stress tensor in the solid combines the effect of a linear dependence of strains with the influence of an existing electric field. The system is closed using Gauss’s law for the associated electric displacement. Well-posedness of the system is studied by its reformulation as a first order in space and time differential system with help of an elliptic lifting operator. We then proceed to studying a semidiscrete formulation, corresponding to an abstract Finite Element discretization in the electric and elastic fields, combined with an abstract Boundary Element approximation of a retarded potential representation of the acoustic field. The results obtained with this approach improve estimates obtained with Laplace domain techniques. While numerical experiments illustrating convergence of a fully discrete version of this problem had already been published, we demonstrate some properties of the full model with some simulations for the two dimensional case.
Analysis and optimization of weighted ensemble sampling
Authors: Aristoff David
Published: September 2017

We give a mathematical framework for weighted ensemble (WE) sampling, a binning and resampling technique for efficiently computing probabilities in molecular dynamics. We prove that WE sampling is unbiased in a very general setting that includes adaptive binning. We show that when WE is used for stationary calculations in tandem with a coarse model, the coarse model can be used to optimize the allocation of replicas in the bins.
Metal-Free Mild Synthesis of Novel 1′H-Spiro[Cycloalkyl-1,2′-quinazolin]-4′(3′H)-ones by an Organocatalytic Cascade Reaction
Authors: Ramesh Rathinam , Kalisamy Periyathambi , Malecki Jan , Lalitha Appaswami
Published: September 2017

A concise organocatalytic method for the facile synthesis of some novel 1′H-spiro[cycloalkyl-1,2′-quinazolin]-4′(3′H)-ones via a one-pot, three-component condensation of isatoic anhydride, aryl or aliphatic amines and a cyclic ketone is described.
Summary to the Plant Theory
Authors: Scholten Jan
Published: September 2017

This article is a summary of ‘Introduction to the Plant Theory’ published in LINKS 2/2017. It describes the application of the theory with the use of the Remedy code.
Psyche and Substance: Essays on Homeopathy in the Light of Jungian Psychology
Authors: Yasgur Jay
Published: September 2017

‘Classics from our literature’ is an occasional column devoted to important contributions from our homeopathic ancestors.
Thunbergia Grandiflora
Authors: Ritzer Friedrich , Eberle Hans
Published: September 2017

Thunbergia grandiflora is a remedy for people who suffer after a heavy or even lethal accident or a suicide of a close person. They are feeling guilty not having been aware enough to prevent the tragedy. Two cases and a proving are presented.
Variación del músculo braquial anterior (brachialis). Importancia en el abordaje a elementos nobles del codo
Authors: Bianchi H. F. , Pinoni V.
Published: September 2017

Las variedades musculares tienen importancia para el cirujano cuando pueden dificultar la ubicación de elementos nobles durante un abordaje quirúrgico, o bien ser causa de compresión de los mismos. En nuestra presentación destacamos la relación existente entre fascículos accesorios y prolongaciones aponeuróticas del m. brachialis, con el n. radialis y el paquete vasculonervioso del codo. Es importante tener en cuenta estas diversidades cuando se deban explorar, con distintos fines, elementos nobles, tanto del canal bicipital interno como de la corredera entre el grupo muscular supinoextensor y el m. brachialis.
Erstbehandlung von Patientinnen mit primärem Mammakarzinom: Evidenz, Kontroversen, Konsens
Authors: Untch Michael , Huober Jens , Jackisch Christian , Schneeweiss Andreas , Brucker Sara , Dall Peter , Denkert Carsten , Fasching Peter , Fehm Tanja , Gerber Bernd , Janni Wolfgang , Kühn Thorsten , Lüftner Diana , Möbus Volker , Müller Volkmar , Rody Achim , Sinn Peter , Thill Marc , Thomssen Christoph , Harbeck Nadia , Liedtke Cornelia
Published: September 2017

Seit über 30 Jahren findet regelmäßig (in den letzten 6 Jahren alle 2 Jahre) die internationale St. Gallen-Konsensuskonferenz zur Behandlung von Patientinnen mit primärem Mammakarzinom statt. Die Ergebnisse des internationalen St. Gallen-Konsensus-Panels wurden auch dieses Jahr wieder von einer deutschen Arbeitsgruppe führender Brustkrebsexperten für den Klinikalltag in Deutschland diskutiert. Fünf der Brustkrebsexperten aus Deutschland sind zugleich Mitglieder des diesjährigen St. Gallen-Panels. Der Vergleich der St. Gallen-Empfehlungen mit den jährlich aktualisierten Therapieempfehlungen der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-Mamma 2017) und der aktuell im Jahre 2017 abgestimmten S3-Leitlinie ist sinnvoll. Die Empfehlungen des St. Gallen-Panels stellen ein Meinungsbild von Experten unterschiedlicher Länder und Fachdisziplinen dar, wohingegen S3-Leitlinie und AGO-Empfehlungen evidenzbasiert sind. Die diesjährige 15. St. Gallen-Konsensuskonferenz stand unter dem Motto „Escalating and De-Escalating“, das sich durch alle Therapiebereiche zog, die zur Abstimmung standen. Ziel war es, Patientinnen individuellere Therapieoptionen anzubieten und das Risiko einer Über- bzw. Untertherapie zu vermeiden.