bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative emotional reactivity moderates the relations between family cohesion and internalizing and externalizing symptoms in adolescence☆
Authors: Rabinowitz Jill A. , Osigwe Ijeoma , Drabick Deborah A.G. , Reynolds Maureen D.
Published: October 2016

Lower family cohesion is associated with adolescent internalizing and externalizing problems. However, there are likely individual differences in youth's responses to family processes. For example, adolescents higher in negative emotional reactivity, who often exhibit elevated physiological responsivity to context, may be differentially affected by family cohesion. We explored whether youth's negative emotional reactivity moderated the relation between family cohesion and youth's symptoms and tested whether findings were consistent with the diathesis‐stress model or differential susceptibility hypothesis. Participants were 651 adolescents (M = 12.99 ± .95 years old; 72% male) assessed at two time points (Time 1, ages 12–14; Time 2, age 16) in Pittsburgh, PA. At Time 1, mothers reported on family cohesion and youth reported on their negative emotional reactivity. At Time 2, youth reported on their symptoms. Among youth higher in negative emotional reactivity, lower family cohesion predicted higher symptoms than higher family cohesion, consistent with the diathesis‐stress model.
Defining imaging biomarker cut points for brain aging and Alzheimer's disease
Authors: Jack Clifford R. , Wiste Heather J. , Weigand Stephen D. , Therneau Terry M. , Lowe Val J. , Knopman David S. , Gunter Jeffrey L. , Senjem Matthew L. , Jones David T. , Kantarci Kejal , Machulda Mary M. , Mielke Michelle M. , Roberts Rosebud O. , Vemuri Prashanthi , Reyes Denise A. , Petersen Ronald C.
Published: October 2016

Introduction

Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro‐deoxyglucose (FDG) PET, and MRI cortical thickness.

Methods

We examined five methods for determining cut points.

Results

The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age‐matched CN method labeled fewer people abnormal.

Discussion

In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age‐matched CN method.
Can curcumin modulate allergic rhinitis in rats?
Authors: Acar M , Muluk N Bayar , Yigitaslan S , Cengiz B P , Shojaolsadati P , Karimkhani H , Ada S , Berkoz M , Cingi C
Published: October 2016

Objectives:

This study aimed to explore the effects of curcumin on experimental allergic rhinitis in rats.

Methods:

Twenty-eight male Wistar albino rats were randomly divided into four groups: a control group; a group in which allergic rhinitis was induced and no treatment given; a group in which allergic rhinitis was induced followed by treatment with azelastine hydrochloride on days 21–28; and a group in which allergic rhinitis was induced followed by treatment with curcumin on days 21–28. Allergy symptoms and histopathological features of the nasal mucosa were examined.

Results:

The sneezing and nasal congestion scores were higher in the azelastine and curcumin treatment groups than in the control group. Histopathological examination showed focal goblet cell metaplasia on the epithelial surface in the azelastine group. In the curcumin group, there was a decrease in goblet cell metaplasia in the epithelium, decreased inflammatory cell infiltration and vascular proliferation in the lamina propria.

Conclusion:

Curcumin is an effective treatment for experimentally induced allergic rhinitis in rats.
The role of chemokines and their receptors during protist parasite infections
Authors: MENZIES FIONA M. , MACPHAIL DAVID , HENRIQUEZ FIONA L.
Published: October 2016

Protists are a diverse collection of eukaryotic organisms that account for a significant global infection burden. Often, the immune responses mounted against these parasites cause excessive inflammation and therefore pathology in the host. Elucidating the mechanisms of both protective and harmful immune responses is complex, and often relies of the use of animal models. In any immune response, leucocyte trafficking to the site of infection, or inflammation, is paramount, and this involves the production of chemokines, small chemotactic cytokines of approximately 8–10 kDa in size, which bind to specific chemokine receptors to induce leucocyte movement. Herein, the scientific literature investigating the role of chemokines in the propagation of immune responses against key protist infections will be reviewed, focussing onPlasmodiumspecies,Toxoplasma gondii, Leishmaniaspecies andCryptosporidiumspecies. Interestingly, many studies find that chemokines can in fact, promote parasite survival in the host, by drawing in leucocytes for spread and further replication. Recent developments in drug targeting against chemokine receptors highlights the need for further understanding of the role played by these proteins and their receptors in many different diseases.
Contaminations of inner surface of magnesium fluoride windows in the ‘Expose-R’ experiment on the International Space Station
Authors: Skurat V. E.
Published: October 2016

A series of experiments was carried out previously on board of the International Space Station in ‘EXPOSE-R’, a multi-user expose facility, provided by European Space Agency attached to the external surface of the Russian Segment. In one experiment, spores of microorganisms and species of higher plant seeds, in heat-sealed polymer bags were irradiated by solar radiation passed through MgF2windows in a high space vacuum. After sample exposure, it was found that in many cases the inner surfaces of windows were contaminated. Analysis of the contamination revealed the presence of chemical groups CH2, CH3, NH, OH, C═O, Si–CH3(Demetset al.in 2015). Their presence in deposits was explained by photofixation of gaseous precursors – some of the vapours of glues and additives in polymeric materials in the core facility of ‘Expose-R’. Carbon-, oxygen- and silicon-containing groups may be deposited from outer intrinsic atmosphere. This atmosphere is connected with sample compartments and core facility. However, the presence of NH groups on inner surfaces of windows was not expected. This paper shows that the process responsible for carbon-, nitrogen- and oxygen-containing group formation can be a photopolymerization of caprolactam, which is released from the outer Nylon 6 layer of polymer bags under Solar vacuum ultraviolet radiation.
P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy
Authors: Jia Yu-Li , Xu Meng , Dou Chang-Wei , Liu Zhi-Kui , Xue Yu-Mo , Yao Bo-Wen , Ding Ling-Long , Tu Kang-Sheng , Zheng Xin , Liu Qing-Guang
Published: October 2016

Aberrant autophagic processes have been found to have fundamental roles in the pathogenesis of different kinds of tumors, including hepatocellular carcinoma (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), performs its function by acetylating both histone and non-histone proteins. Our previous studies showed that PCAF was downregulated in HCC tissues and its high expression was significantly associated with patient survival after surgery, serving as a prognostic marker. In this study we found that overexpression of PCAF induced autophagy of HCC cells and its knockdown depressed autophagy. As type II programmed cell death, autophagy induced by PCAF-elicited cell death in HCC cells. In vivo experiments confirmed that PCAF-induced autophagy inhibited tumor growth. Subsequent in vitro experiments showed that PCAF promoted autophagy by inhibiting Akt/mTOR signaling pathway. Our findings show that PCAF is a novel modulator of autophagy in HCC, and can serve as an attractive therapeutic strategy of HCC treatment.
Inactivation of Sirt1 in mouse livers protects against endotoxemic liver injury by acetylating and activating NF-κB
Authors: Cui Xiaolan , Chen Qian , Dong Zhen , Xu Longmei , Lu Tianfei , Li Dawei , Zhang Jiangjun , Zhang Ming , Xia Qiang
Published: October 2016

Sirtuin 1 (Sirt1) is a deacetylase that regulates many cellular processes in the liver, and so far its role in endotoxemic liver injury is elusive. So we conditionally inactivate Sirt1 in murine hepatocytes to determine its role in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver damage, which is a well-established experimental model mimicking septic liver injury and fulminant hepatitis. Ablation of Sirt1 shows remarkable protection against GalN/LPS-induced liver injury, which is a result of enhanced NF-κB response because knockdown of RelA/p65 negates the protective effect of Sirt1 knockout. Mechanistically, NF-κB p65 is maintained in a hyperacetylated, DNA-binding competent state in tumor necrosis factor-α (TNF-α)-challenged albumin-Cre+ (AlbCre+) hepatocytes. Transfection of hepatocytes with a recombinant acetylated p65 expression construct replicates the protection afforded by Sirt1 knockout. Transfection of AlbCre+ hepatocytes with a recombinant wild-type Sirt1 construct, rather than a deacetylase-defective one, compromises NF-κB activation and resensitizes hepatocytes to TNF-α-induced apoptosis. Taken together, our results demonstrate that Sirt1 deacetylates p65 and compromises NF-κB activity in hepatocytes when confronted with LPS/TNF-α stimulation, leading to increased susceptibility to endotoxemic injury. These findings identify a possible protein effector to maneuver the hepatic NF-κB signaling pathway under inflammatory circumstances and a feasible way to increase hepatocellular resistance to endotoxin/TNF-α toxicity.
Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes
Authors: de Peralta Mauro S Porcel , Mouguelar Valeria S , Sdrigotti María Antonella , Ishiy Felipe A A , Fanganiello Roberto D , Passos-Bueno Maria R , Coux Gabriela , Calcaterra Nora B
Published: October 2016

Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1+/− mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes’ upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.
Modelling proteins’ hidden conformations to predict antibiotic resistance
Authors: Hart Kathryn M. , Ho Chris M. W. , Dutta Supratik , Gross Michael L. , Bowman Gregory R.
Published: October 2016

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM’s specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models’ prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.
Competitive solvent-molecule interactions govern primary processes of diphenylcarbene in solvent mixtures
Authors: Knorr Johannes , Sokkar Pandian , Schott Sebastian , Costa Paolo , Thiel Walter , Sander Wolfram , Sanchez-Garcia Elsa , Nuernberger Patrick
Published: October 2016

Photochemical reactions in solution often proceed via competing reaction pathways comprising intermediates that capture a solvent molecule. A disclosure of the underlying reaction mechanisms is challenging due to the rapid nature of these processes and the intricate identification of how many solvent molecules are involved. Here combining broadband femtosecond transient absorption and quantum mechanics/molecular mechanics simulations, we show for one of the most reactive species, diphenylcarbene, that the decision-maker is not the nearest solvent molecule but its neighbour. The hydrogen bonding dynamics determine which reaction channels are accessible in binary solvent mixtures at room temperature. In-depth analysis of the amount of nascent intermediates corroborates the importance of a hydrogen-bonded complex with a protic solvent molecule, in striking analogy to complexes found at cryogenic temperatures. Our results show that adjacent solvent molecules take the role of key abettors rather than bystanders for the fate of the reactive intermediate.
Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity
Authors: Kubota Naoto , Kubota Tetsuya , Kajiwara Eiji , Iwamura Tomokatsu , Kumagai Hiroki , Watanabe Taku , Inoue Mariko , Takamoto Iseki , Sasako Takayoshi , Kumagai Katsuyoshi , Kohjima Motoyuki , Nakamuta Makoto , Moroi Masao , Sugi Kaoru , Noda Tetsuo , Terauchi Yasuo , Ueki Kohjiro , Kadowaki Takashi
Published: October 2016

Hepatic insulin signalling involves insulin receptor substrates (Irs) 1/2, and is normally associated with the inhibition of gluconeogenesis and activation of lipogenesis. In diabetes and obesity, insulin no longer suppresses hepatic gluconeogenesis, while continuing to activate lipogenesis, a state referred to as ‘selective insulin resistance’. Here, we show that ‘selective insulin resistance’ is caused by the differential expression of Irs1 and Irs2 in different zones of the liver. We demonstrate that hepatic Irs2-knockout mice develop ‘selective insulin resistance’, whereas mice lacking in Irs1, or both Irs1 and Irs2, develop ‘total insulin resistance’. In obese diabetic mice, Irs1/2-mediated insulin signalling is impaired in the periportal zone, which is the primary site of gluconeogenesis, but enhanced in the perivenous zone, which is the primary site of lipogenesis. While hyperinsulinaemia reduces Irs2 expression in both the periportal and perivenous zones, Irs1 expression, which is predominantly in the perivenous zone, remains mostly unaffected. These data suggest that ‘selective insulin resistance’ is induced by the differential distribution, and alterations of hepatic Irs1 and Irs2 expression.
A high-quality human reference panel reveals the complexity and distribution of genomic structural variants
Authors: Hehir-Kwa Jayne Y. , Marschall Tobias , Kloosterman Wigard P. , Francioli Laurent C. , Baaijens Jasmijn A. , Dijkstra Louis J. , Abdellaoui Abdel , Koval Vyacheslav , Thung Djie Tjwan , Wardenaar René , Renkens Ivo , Coe Bradley P. , Deelen Patrick , de Ligt Joep , Lameijer Eric-Wubbo , van Dijk Freerk , Hormozdiari Fereydoun ,   The Genome of the Netherlands Consortium, Bovenberg Jasper A. , de Craen Anton J. M. , Beekman Marian , Hofman Albert , Willemsen Gonneke , Wolffenbuttel Bruce , Platteel Mathieu , Du Yuanping , Chen Ruoyan , Cao Hongzhi , Cao Rui , Sun Yushen , Cao Jeremy Sujie , Neerincx Pieter B. T. , Dijkstra Martijn , Byelas George , Kanterakis Alexandros , Bot Jan , Vermaat Martijn , Laros Jeroen F. J. , den Dunnen Johan T. , de Knijff Peter , Karssen Lennart C. , van Leeuwen Elisa M. , Amin Najaf , Rivadeneira Fernando , Estrada Karol , Hottenga Jouke-Jan , Kattenberg V. Mathijs , van Enckevort David , Mei Hailiang , Santcroos Mark , van Schaik Barbera D. C. , Handsaker Robert E. , McCarroll Steven A. , Ko Arthur , Sudmant Peter , Nijman Isaac J. , Uitterlinden André G. , van Duijn Cornelia M. , Eichler Evan E. , de Bakker Paul I. W. , Swertz Morris A. , Wijmenga Cisca , van Ommen Gert-Jan B. , Slagboom P. Eline , Boomsma Dorret I. , Schönhuth Alexander , Ye Kai , Guryev Victor
Published: October 2016

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100 bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals.
Genome sequence of the basal haplorrhine primate Tarsius syrichta reveals unusual insertions
Authors: Schmitz Jürgen , Noll Angela , Raabe Carsten A. , Churakov Gennady , Voss Reinhard , Kiefmann Martin , Rozhdestvensky Timofey , Brosius Jürgen , Baertsch Robert , Clawson Hiram , Roos Christian , Zimin Aleksey , Minx Patrick , Montague Michael J. , Wilson Richard K. , Warren Wesley C.
Published: October 2016

Tarsiers are phylogenetically located between the most basal strepsirrhines and the most derived anthropoid primates. While they share morphological features with both groups, they also possess uncommon primate characteristics, rendering their evolutionary history somewhat obscure. To investigate the molecular basis of such attributes, we present here a new genome assembly of the Philippine tarsier (Tarsius syrichta), and provide extended analyses of the genome and detailed history of transposable element insertion events. We describe the silencing ofAlumonomers on the lineage leading to anthropoids, and recognize an unexpected abundance of long terminal repeat-derived and LINE1-mobilized transposed elements (Tarsiusinterspersed elements; TINEs). For the first time in mammals, we identify a complete mitochondrial genome insertion within the nuclear genome, then reveal tarsier-specific, positive gene selection and posit population size changes over time. The genomic resources and analyses presented here will aid efforts to more fully understand the ancient characteristics of primate genomes.
Tuning the catalytic CO hydrogenation to straight- and long-chain aldehydes/alcohols and olefins/paraffins
Authors: Xiang Yizhi , Kruse Norbert
Published: October 2016

The catalytic CO hydrogenation is one of the most versatile large-scale chemical syntheses leading to variable chemical feedstock. While traditionally mainly methanol and long-chain hydrocarbons are produced by CO hydrogenation, here we show that the same reaction can be tuned to produce long-chain n-aldehydes, 1-alcohols and olefins, as well as n-paraffins over potassium-promoted CoMn catalysts. The sum selectivity of aldehydes and alcohols is usually >50 wt% whereof up to ∼97% can be n-aldehydes. While the product slate contains ∼60% n-aldehydes at "Equation missing"/pCO=0.5, a 65/35% slate of paraffins/alcohols is obtained at a ratio of 9. A linear Anderson–Schulz–Flory behaviour, independent of the "Equation missing"/pCO ratio, is found for the sum of C4+ products. We advocate a synergistic interaction between a Mn5O8 oxide and a bulk Co2C phase, promoted by the presence of potassium, to be responsible for the unique product spectra in our studies.
Spatiotemporal control of cell–cell reversible interactions using molecular engineering
Authors: Shi Peng , Ju Enguo , Yan Zhengqing , Gao Nan , Wang Jiasi , Hou Jianwen , Zhang Yan , Ren Jinsong , Qu Xiaogang
Published: October 2016

Manipulation of cell–cell interactions has potential applications in basic research and cell-based therapy. Herein, using a combination of metabolic glycan labelling and bio-orthogonal click reaction, we engineer cell membranes with β-cyclodextrin and subsequently manipulate cell behaviours via photo-responsive host-guest recognition. With this methodology, we demonstrate reversible manipulation of cell assembly and disassembly. The method enables light-controllable reversible assembly of cell–cell adhesion, in contrast with previously reported irreversible effects, in which altered structure could not be reused. We also illustrate the utility of the method by designing a cell-based therapy. Peripheral blood mononuclear cells modified with aptamer are effectively redirected towards target cells, resulting in enhanced cell apoptosis. Our approach allows precise control of reversible cell–cell interactions and we expect that it will promote further developments of cell-based therapy.
The scaffold protein Tks4 is required for the differentiation of mesenchymal stromal cells (MSCs) into adipogenic and osteogenic lineages
Authors: Dülk Metta , Kudlik Gyöngyi , Fekete Anna , Ernszt Dávid , Kvell Krisztián , Pongrácz Judit E. , Merő Balázs L. , Szeder Bálint , Radnai László , Geiszt Miklós , Csécsy Dalma E. , Kovács Tamás , Uher Ferenc , Lányi Árpád , Vas Virag , Buday László
Published: October 2016

The commitment steps of mesenchymal stromal cells (MSCs) to adipogenic and other lineages have been widely studied but not fully understood. Therefore, it is critical to understand which molecules contribute to the conversion of stem cells into differentiated cells. The scaffold protein Tks4 plays a role in podosome formation, EGFR signaling and ROS production. Dysfunction of Tks4 causes a hereditary disease called Frank-ter Haar syndrome with a variety of defects concerning certain mesenchymal tissues (bone, fat and cartilage) throughout embryogenic and postnatal development. In this study, we aimed to analyze how the mutation of Tks4 affects the differentiation potential of multipotent bone marrow MSCs (BM-MSCs). We generated a Tks4 knock-out mouse strain on C57Bl/6 background and characterized BM-MSCs isolated from wild type and Tks4−/− mice to evaluate their differentiation. Tks4−/− BM-MSCs had reduced ability to differentiate into osteogenic and adipogenic lineages compared to wild type. Studying the expression profile of a panel of lipid-regulated genes during adipogenic induction revealed that the expression of adipogenic transcription factors, genes responsible for lipid droplet formation, sterol and fatty acid metabolism was delayed or reduced in Tks4−/− BM-MSCs. Taken together, these results establish a novel function for Tks4 in the regulation of MSC differentiation.
Improved Cryopreservation of Human Umbilical Vein Endothelial Cells: A Systematic Approach
Authors: Sultani A. Billal , Marquez-Curtis Leah A. , Elliott Janet A. W. , McGann Locksley E.
Published: October 2016

Cryopreservation of human umbilical vein endothelial cells (HUVECs) facilitated their commercial availability for use in vascular biology, tissue engineering and drug delivery research; however, the key variables in HUVEC cryopreservation have not been comprehensively studied. HUVECs are typically cryopreserved by cooling at 1 °C/min in the presence of 10% dimethyl sulfoxide (DMSO). We applied interrupted slow cooling (graded freezing) and interrupted rapid cooling with a hold time (two-step freezing) to identify where in the cooling process cryoinjury to HUVECs occurs. We found that linear cooling at 1 °C/min resulted in higher membrane integrities than linear cooling at 0.2 °C/min or nonlinear two-step freezing. DMSO addition procedures and compositions were also investigated. By combining hydroxyethyl starch with DMSO, HUVEC viability after cryopreservation was improved compared to measured viabilities of commercially available cryopreserved HUVECs and viabilities for HUVEC cryopreservation studies reported in the literature. Furthermore, HUVECs cryopreserved using our improved procedure showed high tube forming capability in a post-thaw angiogenesis assay, a standard indicator of endothelial cell function. As well as presenting superior cryopreservation procedures for HUVECs, the methods developed here can serve as a model to optimize the cryopreservation of other cells.
Characterization of maize roothairless6 which encodes a D-type cellulose synthase and controls the switch from bulge formation to tip growth
Authors: Li Li , Hey Stefan , Liu Sanzhen , Liu Qiang , McNinch Colton , Hu Heng-Cheng , Wen Tsui-Jung , Marcon Caroline , Paschold Anja , Bruce Wesley , Schnable Patrick S. , Hochholdinger Frank
Published: October 2016

Root hairs are tubular extensions of the epidermis. Root hairs of the monogenic recessive maize mutant roothairless 6 (rth6) are arrested after bulge formation during the transition to tip growth and display a rough cell surface. BSR-Seq in combination with Seq-walking and subsequent analyses of four independently generated mutant alleles established that rth6 encodes CSLD5 a plasma membrane localized 129 kD D-type cellulose synthase with eight transmembrane domains. Cellulose synthases are required for the biosynthesis of cellulose, the most abundant biopolymer of plant cell walls. Phylogenetic analyses revealed that RTH6 is part of a monocot specific clade of D-type cellulose synthases. D-type cellulose synthases are highly conserved in the plant kingdom with five gene family members in maize and homologs even among early land plants such as the moss Physcomitrella patens or the clubmoss Selaginella moellendorffii. Expression profiling demonstrated that rth6 transcripts are highly enriched in root hairs as compared to all other root tissues. Moreover, in addition to the strong knock down of rth6 expression in young primary roots of the mutant rth6, the gene is also significantly down-regulated in rth3 and rth5 mutants, while it is up-regulated in rth2 mutants, suggesting that these genes interact in cell wall biosynthesis.
Mechanism and comparison of needle-type non-thermal direct and indirect atmospheric pressure plasma jets on the degradation of dyes
Authors: Attri Pankaj , Yusupov Maksudbek , Park Ji Hoon , Lingamdinne Lakshmi Prasanna , Koduru Janardhan Reddy , Shiratani Masaharu , Choi Eun Ha , Bogaerts Annemie
Published: October 2016

Purified water supply for human use, agriculture and industry is the major global priority nowadays. The advanced oxidation process based on atmospheric pressure non-thermal plasma (NTP) has been used for purification of wastewater, although the underlying mechanisms of degradation of organic pollutants are still unknown. In this study we employ two needle-type atmospheric pressure non-thermal plasma jets, i.e., indirect (ID-APPJ) and direct (D-APPJ) jets operating at Ar feed gas, for the treatment of methylene blue, methyl orange and congo red dyes, for two different times (i.e., 20 min and 30 min). Specifically, we study the decolorization/degradation of all three dyes using the above mentioned plasma sources, by means of UV-Vis spectroscopy, HPLC and a density meter. We also employ mass spectroscopy to verify whether only decolorization or also degradation takes place after treatment of the dyes by the NTP jets. Additionally, we analyze the interaction of OH radicals with all three dyes using reactive molecular dynamics simulations, based on the density functional-tight binding method. This investigation represents the first report on the degradation of these three different dyes by two types of NTP setups, analyzed by various methods, and based on both experimental and computational studies.
Correction: Corrigendum: Epigenetic inactivation of the CpG demethylase TET1 as a DNA methylation feedback loop in human cancers
Authors: Li Lili , Li Chen , Mao Haitao , Du Zhenfang , Chan Wai Yee , Murray Paul , Luo Bing , Chan Anthony TC , Mok Tony SK , Chan Francis KL , Ambinder Richard F , Tao Qian
Published: October 2016

Scientific Reports 6: Article number: 26591; published online: 26 May 2016; updated: 06 October 2016. This Article contains errors in Figure 2D where the Hodgkin lymphoma ‘TET1-MSP’ methylated and unmethylated MSP bands are incorrect. The correct Figure 2D appears below as Figure 1.
Nonlinear backbone torsional pair correlations in proteins
Authors: Long Shiyang , Tian Pu
Published: October 2016

Protein allostery requires dynamical structural correlations. Physical origin of which, however, remain elusive despite intensive studies during last two and half decades. Based on analysis of molecular dynamics (MD) simulation trajectories for ten proteins with different sizes and folds, we found that nonlinear backbone torsional pair (BTP) correlations, which are mainly spatially long-ranged and are dominantly executed by loop residues, exist extensively in most analyzed proteins. Examination of torsional motion for correlated BTPs suggested that such nonlinear correlations are mainly associated aharmonic torsional state transitions and in some cases strongly anisotropic local torsional motion of participating torsions and occur on widely different and relatively longer time scales. In contrast, correlations between backbone torsions in stable α helices and β strands are mainly linear and spatially short-ranged and are more likely to associate with harmonic local torsional motion. Further analysis revealed that the direct cause of nonlinear contributions are heterogeneous linear correlations. These findings implicate a general search strategy for novel allosteric modulation sites of protein activities.
Characterization of the DNA dependent activation of human ARTD2/PARP2
Authors: Obaji Ezeogo , Haikarainen Teemu , Lehtiö Lari
Published: October 2016

Human ADP-ribosyltransferase 2 (ARTD2/PARP2) is an enzyme catalyzing a post-translational modification, ADP-ribosylation. It is one of the three DNA dependent ARTDs in the 17 member enzyme family. ADP-ribosylation catalyzed by ARTD2 is involved in the regulation of multiple cellular processes such as control of chromatin remodeling, transcription and DNA repair. Here we used a combination of biochemical and biophysical methods to elucidate the structure and function of ARTD2. The solution structures revealed the binding mode of the ARTD2 monomer and dimer to oligonucleotides that mimic damaged DNA. In the complex, DNA binds between the WGR domain and the catalytic fragment. The binding mode is supported by biophysical data that indicate all domains contribute to DNA binding. Also, our study showed that ARTD2 is preferentially activated by short 5′-phosphorylated DNA oligonucleotides. We demonstrate that the N-terminus functions as a high-affinity DNA-binding module, while the WGR domain contributes to DNA binding specificity and subsequent catalytic activation. Our data further suggest that ARTD2 would function in double strand break repair as a dimeric module, while in single strand break repair it would function as a monomer.
Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology
Authors: Stanika Ruslan , Campiglio Marta , Pinggera Alexandra , Lee Amy , Striessnig Jörg , Flucher Bernhard E. , Obermair Gerald J.
Published: October 2016

Dendritic spines are the postsynaptic compartments of glutamatergic synapses in the brain. Their number and shape are subject to change in synaptic plasticity and neurological disorders including autism spectrum disorders and Parkinson’s disease. The L-type calcium channel CaV1.3 constitutes an important calcium entry pathway implicated in the regulation of spine morphology. Here we investigated the importance of full-length CaV1.3L and two C-terminally truncated splice variants (CaV1.342A and CaV1.343S) and their modulation by densin-180 and shank1b for the morphology of dendritic spines of cultured hippocampal neurons. Live-cell immunofluorescence and super-resolution microscopy of epitope-tagged CaV1.3L revealed its localization at the base-, neck- and head-region of dendritic spines. Expression of the short splice variants or deletion of the C-terminal PDZ-binding motif in CaV1.3L induced aberrant dendritic spine elongation. Similar morphological alterations were induced by co-expression of densin-180 or shank1b with CaV1.3L and correlated with increased CaV1.3 currents and dendritic calcium signals in transfected neurons. Together, our findings suggest a key role of CaV1.3 in regulating dendritic spine structure. Under physiological conditions it may contribute to the structural plasticity of glutamatergic synapses. Conversely, altered regulation of CaV1.3 channels may provide an important mechanism in the development of postsynaptic aberrations associated with neurodegenerative disorders.
Biodiversity loss and turnover in alternative states in the Mediterranean Sea: a case study on meiofauna
Authors: Bianchelli Silvia , Buschi Emanuela , Danovaro Roberto , Pusceddu Antonio
Published: October 2016

In the Mediterranean Sea hard-bottom macroalgal meadows may switch to alternative and less-productive barrens grounds, as a result of sea urchins overgrazing. Meiofauna (and especially nematodes) represent key components of benthic ecosystems, are highly-diversified, sensitive to environmental change and anthropogenic impacts, but, so-far, have been neglected in studies on regime shifts. We report here that sedimentary organic matter contents, meiofaunal taxa richness and community composition, nematode α- and β-biodiversity vary significantly between alternative macroalgal and barren states. The observed differences are consistent in six areas spread across the Mediterranean Sea, irrespective of barren extent. Our results suggest also that the low biodiversity levels in barren states are the result of habitat loss/fragmentation, which is associated also with a lower availability of trophic resources. Furthermore, differences in meiofaunal and nematode abundance, biomass and diversity between macroalgal meadow and barren states persist when the latter is not fully formed, or consists of patches interspersed in macroalgal meadows. Since barren grounds are expanding rapidly along the Mediterranean Sea and meiofauna are a key trophic component in marine ecosystems, we suggest that the extension and persistence of barrens at the expenses of macroalgal meadows could also affect resilience of higher trophic level.
Identification of TLR2/TLR6 signalling lactic acid bacteria for supporting immune regulation
Authors: Ren Chengcheng , Zhang Qiuxiang , de Haan Bart J. , Zhang Hao , Faas Marijke M. , de Vos Paul
Published: October 2016

Although many lactic acid bacteria (LAB) influence the consumer’s immune status it is not completely understood how this is established. Bacteria-host interactions between bacterial cell-wall components and toll-like receptors (TLRs) have been suggested to play an essential role. Here we investigated the interaction between LABs with reported health effects and TLRs. By using cell-lines expressing single or combination of TLRs, we show that LABs can signal via TLR-dependent and independent pathways. The strains only stimulated and did not inhibit TLRs. We found that several strains such as L. plantarum CCFM634, L. plantarum CCFM734, L. fermentum CCFM381, L. acidophilus CCFM137 and S. thermophilus CCFM218 stimulated TLR2/TLR6. TLR2/TLR6 is essential in immune regulatory processes and of interest for prevention of diseases. Specificity of the TLR2/TLR6 stimulation was confirmed with blocking antibodies. Immunomodulatory properties of LABs were also studied by assessing IL-10 and IL-6 secretion patterns in bacteria-stimulated THP1-derived macrophages, which confirmed species and strain specific effects of the LABs. With this study we provide novel insight in LAB specific host-microbe interactions. Our data demonstrates that interactions between pattern recognition receptors such as TLRs is species and strain specific and underpins the importance of selecting specific strains for promoting specific health effects.
P[8] and P[4] Rotavirus Infection Associated with Secretor Phenotypes Among Children in South China
Authors: Zhang Xu-Fu , Long Yan , Tan Ming , Zhang Ting , Huang Qiong , Jiang Xi , Tan Wen-Fang , Li Jian-Dong , Hu Gui-Fang , Tang Shixing , Dai Ying-Chun
Published: October 2016

Rotaviruses are known to recognize human histo-blood group antigens (HBGAs) as a host ligand that is believed to play an important role in rotavirus host susceptibility and host range. In this study, paired fecal and saliva samples collected from children with viral gastroenteritis, as well as paired serum and saliva samples collected from the general population in south China were studied to evaluate potential association between rotavirus infections and human HBGA phenotypes. Rotavirus was detected in 75 (28%) of 266 fecal samples and P[8] rotaviruses were found to be the predominant genotype. The HBGA phenotypes of the rotavirus-infected children were determined through their saliva samples. Secretor statuses were found to correlate with the risk of rotavirus infection and all P[8]/P[4] rotavirus infected children were secretors. Accordingly, recombinant VP8* proteins of the P[8]/P[4] rotaviruses bound saliva samples from secretor individuals. Furthermore, correlation between serum P[8]/P[4]-specific IgG and host Lewis and secretor phenotypes has been found among 206 studied serum samples. Our study supported the association between rotavirus infection and the host HBGA phenotypes, which would help further understanding of rotavirus host range and epidemiology.
Clinical associations of IL-10 and IL-37 in systemic lupus erythematosus
Authors: Godsell Jack , Rudloff Ina , Kandane-Rathnayake Rangi , Hoi Alberta , Nold Marcel F. , Morand Eric F. , Harris James
Published: October 2016

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the development of autoantibodies to nuclear antigens and inflammatory responses mediated by multiple cytokines. Although previous studies have determined clinical associations between SLE and the anti-inflammatory cytokines IL-10 and IL-37, their role in the disease, or their potential as biomarkers, remains unclear. We examined serum levels of IL-10 and IL-37 in a large cohort of SLE patients, with detailed longitudinal clinical data. We demonstrate a statistically significant association of serum IL-10 with disease activity, with higher levels in active compared to inactive disease. High first visit IL-10 was predictive of high subsequent disease activity; patients with IL-10 in highest quartile at first visit were 3.6 times more likely to have active disease in subsequent visits. Serum IL-37 was also higher in SLE patients compared to control, and was strongly associated with Asian ethnicity. However, IL-37 was not statistically significantly associated with disease activity. IL-37 was significantly reduced in patients with organ damage but this association was attenuated in multivariable analysis. The data suggest that IL-10, but not IL-37, may have potential as a biomarker predictive for disease activity in SLE.
Evaluation of A Novel Split-Feeding Anaerobic/Oxic Baffled Reactor (A/OBR) For Foodwaste Anaerobic Digestate: Performance, Modeling and Bacterial Community
Authors: Wang Shaojie , Peng Liyu , Jiang Yixin , Gikas Petros , Zhu Baoning , Su Haijia
Published: October 2016

To enhance the treatment efficiency from an anaerobic digester, a novel six-compartment anaerobic/oxic baffled reactor (A/OBR) was employed. Two kinds of split-feeding A/OBRs R2 and R3, with influent fed in the 1st, 3rd and 5th compartment of the reactor simultaneously at the respective ratios of 6:3:1 and 6:2:2, were compared with the regular-feeding reactor R1 when all influent was fed in the 1st compartment (control). Three aspects, the COD removal, the hydraulic characteristics and the bacterial community, were systematically investigated, compared and evaluated. The results indicated that R2 and R3 had similar tolerance to loading shock, but the R2 had the highest COD removal of 91.6% with a final effluent of 345 mg/L. The mixing patterns in both split-feeding reactors were intermediate between plug-flow and completely-mixed, with dead spaces between 8.17% and 8.35% compared with a 31.9% dead space in R1. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis revealed that the split-feeding strategy provided a higher bacterial diversity and more stable bacterial community than that in the regular-feeding strategy. Further analysis indicated that Firmicutes, Bacteroidetes, and Proteobacteria were the dominant bacteria, among which Firmicutes and Bacteroidetes might be responsible for organic matter degradation and Proteobacteria for nitrification and denitrification.
Normative data for the segmental acquisition of contact heat evoked potentials in cervical dermatomes
Authors: Jutzeler Catherine R. , Rosner Jan , Rinert Janosch , Kramer John L. K. , Curt Armin
Published: October 2016

Contact heat evoked potentials (CHEPs) represent a neurophysiological approach to assess conduction in the spinothalamic tract. The aim of this study was to establish normative values of CHEPs acquired from cervical dermatomes (C4, C6, C8) and examine the potential confounds of age, sex, and height. 101 (49 male) healthy subjects of three different age groups (18–40, 41–60, and 61–80 years) were recruited. Normal (NB, 35–52 °C) followed by increased (IB, 42–52 °C) baseline stimulation protocols were employed to record CHEPs. Multi-variate linear models were used to investigate the effect of age, sex, and height on the CHEPs parameters (i.e., N2 latency, N2P2 amplitude, rating of perceived intensity). Compared to NB, IB stimulation reduced latency jitter within subjects, yielding larger N2P2 amplitudes, and decreased inter-subject N2 latency variability. Age was associated with reduced N2P2 amplitude and prolonged N2 latency. After controlling for height, male subjects had significantly longer N2 latencies than females during IB stimulation. The study provides normative CHEPs data in a large cohort of healthy subjects from segmentally examined cervical dermatomes. Age and sex were identified as important factors contributing to N2 latency and N2P2 amplitude. The normative data will improve the diagnosis of spinal cord pathologies.
High-Throughput Design of Two-Dimensional Electron Gas Systems Based on Polar/Nonpolar Perovskite Oxide Heterostructures
Authors: Yang Kesong , Nazir Safdar , Behtash Maziar , Cheng Jianli
Published: October 2016

The two-dimensional electron gas (2DEG) formed at the interface between two insulating oxides such as LaAlO3 and SrTiO3 (STO) is of fundamental and practical interest because of its novel interfacial conductivity and its promising applications in next-generation nanoelectronic devices. Here we show that a group of combinatorial descriptors that characterize the polar character, lattice mismatch, band gap, and the band alignment between the perovskite-oxide-based band insulators and the STO substrate, can be introduced to realize a high-throughput (HT) design of SrTiO3-based 2DEG systems from perovskite oxide quantum database. Equipped with these combinatorial descriptors, we have carried out a HT screening of all the polar perovskite compounds, uncovering 42 compounds of potential interests. Of these, Al-, Ga-, Sc-, and Ta-based compounds can form a 2DEG with STO, while In-based compounds exhibit a strain-induced strong polarization when deposited on STO substrate. In particular, the Ta-based compounds can form 2DEG with potentially high electron mobility at (TaO2)+/(SrO)0 interface. Our approach, by defining materials descriptors solely based on the bulk materials properties, and by relying on the perovskite-oriented quantum materials repository, opens new avenues for the discovery of perovskite-oxide-based functional interface materials in a HT fashion.
A transgenic approach to control hemipteran insects by expressing insecticidal genes under phloem-specific promoters
Authors: Javaid Shaista , Amin Imran , Jander Georg , Mukhtar Zahid , Saeed Nasir A. , Mansoor Shahid
Published: October 2016

The first generation transgenic crops used strong constitutive promoters for transgene expression. However, tissue-specific expression is desirable for more precise targeting of transgenes. Moreover, piercing/sucking insects, which are generally resistant to insecticidal Bacillus thuringiensis (Bt) proteins, have emerged as a major pests since the introduction of transgenic crops expressing these toxins. Phloem-specific promoters isolated from Banana bunchy top virus (BBTV) were used for the expression of two insecticidal proteins, Hadronyche versuta (Blue Mountains funnel-web spider) neurotoxin (Hvt) and onion leaf lectin, in tobacco (Nicotiana tabacum). Here we demonstrate that transgenic plants expressing Hvt alone or in combination with onion leaf lectin are resistant to Phenacoccus solenopsis (cotton mealybug), Myzus persicae (green peach aphids) and Bemisia tabaci (silver leaf whitefly). The expression of both proteins under different phloem-specific promoters resulted in close to 100% mortality and provided more rapid protection than Hvt alone. Our results suggest the employment of the Hvt and onion leaf lectin transgenic constructs at the commercial level will reduce the use of chemical pesticides for control of hemipteran insect pests.