bluuebunny/crossref_metadata_2025 huggingface dataset:
Autonomic reinnervation and functional regeneration in autologous transplanted submandibular glands in patients with severe keratoconjunctivitis sicca
Authors: Zhang Xueming , Yang Ningyan , Liu Xiaojing , Su Jiazeng , Cong Xin , Wu Liling , Zhang Yan , Yu Guangyan
Published: April 2018

Autologous submandibular gland (SMG) transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously. This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients’ glands 4–6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.
High orange juice consumption with or in-between three meals a day differently affects energy balance in healthy subjects
Authors: Hägele Franziska A , Büsing Franziska , Nas Alessa , Aschoff Julian , Gnädinger Lena , Schweiggert Ralf , Carle Reinhold , Bosy-Westphal Anja
Published: April 2018

Sugar-containing beverages like orange juice can be a risk factor for obesity and type 2 diabetes although the underlying mechanisms are less clear. We aimed to investigate if intake of orange juice with or in-between meals differently affects energy balance or metabolic risk. Twenty-six healthy adults (24.7 ± 3.2 y; BMI 23.2 ± 3.2 kg/m2) participated in a 4-week cross-over intervention and consumed orange juice (20% of energy requirement) either together with 3 meals/d (WM) or in-between 3 meals/d (BM) at ad libitum energy intake. Basal and postprandial insulin sensitivity (primary outcome), daylong glycaemia, glucose variability and insulin secretion were assessed. Body fat mass was measured by air-displacement plethysmography. After BM-intervention, fat mass increased (+1.0 ± 1.8 kg; p < 0.05) and postprandial insulin sensitivity tended to decrease (ΔMatsudaISI: −0.89 ± 2.3; p = 0.06). By contrast, after WM-intervention fat mass and gamma-glutamyl transferase (GGT) decreased (−0.30 ± 0.65 kg; −2.50 ± 3.94; both p < 0.05), whereas glucose variability was higher (ΔMAGE: +0.45 ± 0.59, p < 0.05). Daylong glycaemia, insulin secretion, changes in basal insulin sensitivity, and triglycerides did not differ between WM- and BM-interventions (all p > 0.05). In young healthy adults, a conventional 3-meal structure with orange juice consumed together with meals had a favorable impact on energy balance, whereas juice consumption in-between meals may contribute to a gain in body fat and adverse metabolic effects.
Longitudinal association between egg consumption and the risk of cardiovascular disease: interaction with type 2 diabetes mellitus
Authors: Jang Jiyoung , Shin Min-Jeong , Kim Oh Yoen , Park Kyong
Published: April 2018

Background/objectives

It remains unclear if high egg consumption has beneficial or adverse effects on cardiometabolic health. The present study prospectively evaluated the longitudinal association between egg-consumption levels and incident cardiovascular disease (CVD) among Korean adults.

Subjects/methods

We conducted a prospective cohort study of 9248 Korean adults aged 40–69 years without CVD or cancer at the baseline from the Korean Genome and Epidemiology Study, Ansung–Ansan cohort, South Korea. The egg intake of the participants was estimated using a validated semiquantitative food frequency questionnaire at the baseline and the second follow-up examination and categorized into quartiles. CVD cases were identified using biennial questionnaires and confirmed through repeated in-depth personal interviews. Hazard ratios (HR) and 95% confidence interval (CI) were analyzed using Cox proportional hazard regression.

Results

During the average follow-up of 7.3 years, 570 cases of CVD were newly diagnosed. After adjusting for multiple confounding variables, egg-intake levels were not associated with CVD incidence (HR: 1.14, 95% CI: 0.87–1.49, P for trend: 0.7). However, the association was modified by type 2 diabetes mellitus (T2DM) status. Egg consumption was significantly associated with an increased risk for incident CVD among participants with T2DM; individuals with the highest egg intake (4.2 ± 0.04 eggs/week) had a 2.8 times higher incidence of CVD (HR: 2.81, 95% CI: 1.25–6.30, P for trend: 0.02) than those with the lowest egg intake (0.1 ± 0.02 eggs/week). However, no association was observed among individuals without T2DM (HR: 1.03, 95% CI: 0.77–1.38, P for trend: 0.8).

Conclusions

Higher egg consumption may increase the risk for CVD in Korean patients with T2DM. Our findings provide a basis for the development of an optimal dietary cholesterol intake guideline for the Korean population.
Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts
Authors: Sun Jun , Ermann Joerg , Niu Ningning , Yan Guang , Yang Yang , Shi Yujiang , Zou Weiguo
Published: April 2018

Multiple regulatory mechanisms control osteoblast differentiation and function to ensure unperturbed skeletal formation and remodeling. In this study we identify histone lysine-specific demethylase 1(LSD1/KDM1A) as a key epigenetic regulator of osteoblast differentiation. Knockdown of LSD1 promoted osteoblast differentiation of human mesenchymal stem cells (hMSCs) in vitro and mice lacking LSD1 in mesenchymal cells displayed increased bone mass secondary to accelerated osteoblast differentiation. Mechanistic in vitro studies revealed that LSD1 epigenetically regulates the expression of WNT7B and BMP2. LSD1 deficiency resulted in increased BMP2 and WNT7B expression in osteoblasts and enhanced bone formation, while downregulation of WNT7B- and BMP2-related signaling using genetic mouse model or small-molecule inhibitors attenuated bone phenotype in vivo. Furthermore, the LSD1 inhibitor tranylcypromine (TCP) could increase bone mass in mice. These data identify LSD1 as a novel regulator of osteoblast activity and suggest LSD1 inhibition as a potential therapeutic target for treatment of osteoporosis.
Activation of AhR with nuclear IKKα regulates cancer stem-like properties in the occurrence of radioresistance
Authors: Yan Bin , Liu Shuang , Shi Ying , Liu Na , Chen Ling , Wang Xiang , Xiao Desheng , Liu Xiaoli , Mao Chao , Jiang Yiqun , Lai Weiwei , Xin Xing , Tang Can-E , Luo Dixian , Tan Tan , Jia Jiantao , Liu Yating , Yang Rui , Huang Jun , Zhou Hu , Cheng Yan , Cao Ya , Yu Weishi , Muegge Kathrin , Tao Yongguang
Published: April 2018

Abstract

Most cancer patients receive radiotherapy in the course of their disease and the occurrence of radioresistance is associated with poor prognosis. The molecular pathways that drive enhanced tumorigenic potential during the development of radioresistance are poorly understood. Here, we demonstrate that aryl hydrocarbon receptor (AhR) plays a vital role in the maintenance of cancer stem-like properties. AhR promotes the cancer stem-like phenotype and drives metastasis by directly targeting the promoters of ‘stemness’ genes, such as the ATP-binding cassette sub-family G member 2 (ABCG2) gene. Moreover, the radioresistant sublines display high levels of oncometabolites including α-ketoglutarate, and treatment of cancer cells with α-ketoglutarate enhances their stem-like properties in an AhR activation-dependent manner. IKKα directly activates stemness-related genes through an interaction with AhR as a bone fide chromatin modifier. Thus, AhR is functionally linked with cancer stem-like properties, and it drives tumorigenesis in the occurrence of radioresistance.
Transient PP2A inhibition alleviates normal tissue stem cell susceptibility to cell death during radiotherapy
Authors: Fabbrizi Maria Rita , Meyer Barbara , Misri Sandeep , Raj Suyash , Zobel Cheri L. , Hallahan Dennis E. , Sharma Girdhar G.
Published: April 2018

Unintended outcomes of cancer therapy include ionizing radiation (IR)-induced stem cell depletion, diminished regenerative capacity, and accelerated aging. Stem cells exhibit attenuated DNA damage response (DDR) and are hypersensitive to IR, as compared to differentiated non-stem cells. We performed genomic discovery research to compare stem cells to differentiated cells, which revealed Phosphoprotein phosphatase 2A (PP2A) as a potential contributor to susceptibility in stem cells. PP2A dephosphorylates pATM, γH2AX, pAkt etc. and is believed to play dual role in regulating DDR and apoptosis. Although studied widely in cancer cells, the role of PP2A in normal stem cell radiosensitivity is unknown. Here we demonstrate that constitutively high expression and radiation induction of PP2A in stem cells plays a role in promoting susceptibility to irradiation. Transient inhibition of PP2A markedly restores DNA repair, inhibits apoptosis, and enhances survival of stem cells, without affecting differentiated non-stem and cancer cells. PP2Ai-mediated stem cell radioprotection was demonstrated in murine embryonic, adult neural, intestinal, and hematopoietic stem cells.
Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis
Authors: Rothberg Janet L. Manias , Maganti Harinad B. , Jrade Hani , Porter Christopher J. , Palidwor Gareth A. , Cafariello Christopher , Battaion Hannah L. , Khan Safwat T. , Perkins Theodore J. , Paulson Robert F. , Ito Caryn Y. , Stanford William L.
Published: April 2018

Polycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 to specific genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. Mtf2
−/−
erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions. The resulting de-repression of transcriptional and signaling networks blocks definitive erythroid development, culminating in Mtf2
−/−
embryos dying by e15.5 due to severe anemia. Gene regulatory network (GRN) analysis demonstrated Mtf2 directly regulates Wnt signaling in erythroblasts, leading to activated canonical Wnt signaling in Mtf2-deficient erythroblasts, while chemical inhibition of canonical Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro. Using a combination of in vitro, in vivo and systems analyses, we demonstrate that Mtf2 is a critical epigenetic regulator of Wnt signaling during erythropoiesis and recast the role of polycomb accessory proteins in a tissue-specific context.
Dkk3 dependent transcriptional regulation controls age related skeletal muscle atrophy
Authors: Yin Jie , Yang Lele , Xie Yangli , Liu Yan , Li Sheng , Yang Wenjun , Xu Bo , Ji Hongbin , Ding Lianghua , Wang Kun , Li Gang , Chen Lin , Hu Ping
Published: April 2018

Age-related muscle atrophy (sarcopenia) is the leading cause for disability in aged population, but the underlying molecular mechanisms are poorly understood. Here we identify a novel role for the secreted glycoprotein Dickkopf 3 (Dkk3) in sarcopenia. Forced expression of Dkk3 in muscles in young mice leads to muscle atrophy. Conversely, reducing its expression in old muscles restores both muscle size and function. Dkk3 induces nuclear import of β-catenin and enhances its interaction with FoxO3, which in turn activates the transcription of E3 ubiquitin ligase Fbxo32 and Trim63, driving muscle atrophy. These findings suggest that Dkk3 may be used as diagnostic marker and as therapeutic target for age-related muscle atrophy, and reveal a distinct transcriptional control of Fbxo32 and Trim63.
Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer
Authors: Murillo-Garzón Virginia , Gorroño-Etxebarria Irantzu , Åkerfelt Malin , Puustinen Mikael Christer , Sistonen Lea , Nees Matthias , Carton James , Waxman Jonathan , Kypta Robert M.
Published: April 2018

Wnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription. FZD8 silencing reduces prostate cancer cell migration, invasion, three-dimensional (3D) organotypic cell growth, expression of EMT-related genes, and TGF-β/Smad-dependent signaling. Mechanistically, FZD8 forms a TGF-β-regulated complex with TGF-β receptors that is mediated by the extracellular domains of FZD8 and TGFBR1. Targeting FZD8 may therefore inhibit aberrant activation of both Wnt and TGF-β signals in prostate cancer.
Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site
Authors: Wahlgren Weixiao Y. , Dunevall Elin , North Rachel A. , Paz Aviv , Scalise Mariafrancesca , Bisignano Paola , Bengtsson-Palme Johan , Goyal Parveen , Claesson Elin , Caing-Carlsson Rhawnie , Andersson Rebecka , Beis Konstantinos , Nilsson Ulf J. , Farewell Anne , Pochini Lorena , Indiveri Cesare , Grabe Michael , Dobson Renwick C. J. , Abramson Jeff , Ramaswamy S. , Friemann Rosmarie
Published: April 2018

Many pathogenic bacteria utilise sialic acids as an energy source or use them as an external coating to evade immune detection. As such, bacteria that colonise sialylated environments deploy specific transporters to mediate import of scavenged sialic acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation of SiaT, a sialic acid transporter from Proteus mirabilis. SiaT is a secondary active transporter of the sodium solute symporter (SSS) family, which use Na+ gradients to drive the uptake of extracellular substrates. SiaT adopts the LeuT-fold and is in an outward-open conformation in complex with the sialic acid N-acetylneuraminic acid and two Na+ ions. One Na+ binds to the conserved Na2 site, while the second Na+ binds to a new position, termed Na3, which is conserved in many SSS family members. Functional and molecular dynamics studies validate the substrate-binding site and demonstrate that both Na+ sites regulate N-acetylneuraminic acid transport.
Sulfenate anions as organocatalysts for benzylic chloromethyl coupling polymerization via C=C bond formation
Authors: Li Minyan , Berritt Simon , Wang Carol , Yang Xiaodong , Liu Yang , Sha Sheng-Chun , Wang Bo , Wang Rui , Gao Xuyu , Li Zhanyong , Fan Xinyuan , Tao Youtian , Walsh Patrick J.
Published: April 2018

Organocatalytic polymerization reactions have a number of advantages over their metal-catalyzed counterparts, including environmental friendliness, ease of catalyst synthesis and storage, and alternative reaction pathways. Here we introduce an organocatalytic polymerization method called benzylic chloromethyl-coupling polymerization (BCCP). BCCP is catalyzed by organocatalysts not previously employed in polymerization processes (sulfenate anions), which are generated from bench-stable sulfoxide precatalysts. The sulfenate anion promotes an umpolung polycondensation via step-growth propagation cycles involving sulfoxide intermediates. BCCP represents an example of an organocatalyst that links monomers by C=C double bond formation and offers transition metal-free access to a wide variety of polymers that cannot be synthesized by traditional precursor routes.
Catalytic condensation for the formation of polycyclic heteroaromatic compounds
Authors: Forberg Daniel , Schwob Tobias , Kempe Rhett
Published: April 2018

The conservation of our global element resources is a challenge of the utmost urgency. Since aliphatic and aromatic alcohols are accessible from abundant indigestible kinds of biomass, first and foremost lignocellulose, the development of novel chemical reactions converting alcohols into important classes of compounds is a particularly attractive carbon conservation and CO2-emission reduction strategy. Herein, we report the catalytic condensation of phenols and aminophenols or aminoalcohols. The overall reaction of this synthesis concept proceeds via three steps: hydrogenation, dehydrogenative condensation and dehydrogenation. Reusable catalysts recently developed in our laboratory mediate these reactions highly efficient. The scope of the concept is exemplarily demonstrated by the synthesis of carbazoles, quinolines and acridines, the structural motifs of which figure prominently in many important natural products, drugs and materials.
Architecture of the U6 snRNP reveals specific recognition of 3′-end processed U6 snRNA
Authors: Montemayor Eric J. , Didychuk Allison L. , Yake Allyson D. , Sidhu Gurnimrat K. , Brow David A. , Butcher Samuel E.
Published: April 2018

The spliceosome removes introns from precursor messenger RNA (pre-mRNA) to produce mature mRNA. Prior to catalysis, spliceosomes are assembled de novo onto pre-mRNA substrates. During this assembly process, U6 small nuclear RNA (snRNA) undergoes extensive structural remodeling. The early stages of this remodeling process are chaperoned by U6 snRNP proteins Prp24 and the Lsm2–8 heteroheptameric ring. We now report a structure of the U6 snRNP from Saccharomyces cerevisiae. The structure reveals protein–protein contacts that position Lsm2–8 in close proximity to the chaperone “active site” of Prp24. The structure also shows how the Lsm2–8 ring specifically recognizes U6 snRNA that has been post-transcriptionally modified at its 3′ end, thereby elucidating the mechanism by which U6 snRNPs selectively recruit 3′ end-processed U6 snRNA into spliceosomes. Additionally, the structure reveals unanticipated homology between the C-terminal regions of Lsm8 and the cytoplasmic Lsm1 protein involved in mRNA decay.
High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics
Authors: Mager Thomas , Lopez de la Morena David , Senn Verena , Schlotte Johannes , D´Errico Anna , Feldbauer Katrin , Wrobel Christian , Jung Sangyong , Bodensiek Kai , Rankovic Vladan , Browne Lorcan , Huet Antoine , Jüttner Josephine , Wood Phillip G. , Letzkus Johannes J. , Moser Tobias , Bamberg Ernst
Published: April 2018

Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. We develop mutants leading to a unifying concept for the construction of various channelrhodopsins with fast closing kinetics. Due to different absorption maxima these channelrhodopsins allow fast neural photoactivation over the whole range of the visible spectrum. We focus our functional analysis on the fast-switching, red light-activated Chrimson variants, because red light has lower light scattering and marginal phototoxicity in tissues. We show paradigmatically for neurons of the cerebral cortex and the auditory nerve that the fast Chrimson mutants enable neural stimulation with firing frequencies of several hundred Hz. They drive spiking at high rates and temporal fidelity with low thresholds for stimulus intensity and duration. Optical cochlear implants restore auditory nerve activity in deaf mice. This demonstrates that the mutants facilitate neuroscience research and future medical applications such as hearing restoration.
Topologically guided tuning of Zr-MOF pore structures for highly selective separation of C6 alkane isomers
Authors: Wang Hao , Dong Xinglong , Lin Junzhong , Teat Simon J. , Jensen Stephanie , Cure Jeremy , Alexandrov Eugeny V. , Xia Qibin , Tan Kui , Wang Qining , Olson David H. , Proserpio Davide M. , Chabal Yves J. , Thonhauser Timo , Sun Junliang , Han Yu , Li Jing
Published: April 2018

As an alternative technology to energy intensive distillations, adsorptive separation by porous solids offers lower energy cost and higher efficiency. Herein we report a topology-directed design and synthesis of a series of Zr-based metal-organic frameworks with optimized pore structure for efficient separation of C6 alkane isomers, a critical step in the petroleum refining process to produce gasoline with high octane rating. Zr6O4(OH)4(bptc)3 adsorbs a large amount of n-hexane but excluding branched isomers. The n-hexane uptake is ~70% higher than that of a benchmark adsorbent, zeolite-5A. A derivative structure, Zr6O4(OH)8(H2O)4(abtc)2, is capable of discriminating all three C6 isomers and yielding a high separation factor for 3-methylpentane over 2,3-dimethylbutane. This property is critical for producing gasoline with further improved quality. Multicomponent breakthrough experiments provide a quantitative measure of the capability of these materials for separation of C6 alkane isomers. A detailed structural analysis reveals the unique topology, connectivity and relationship of these compounds.
Author Correction: Evaluation of Weight Loss Indicators and Laparoscopic One-Anastomosis Gastric Bypass Outcomes
Authors: Carbajo Miguel A. , Jiménez Jose M. , Luque-de-León Enrique , Cao María-José , López María , García Sara , Castro María-José
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
EEG Analytics for Early Detection of Autism Spectrum Disorder: A data-driven approach
Authors: Bosl William J. , Tager-Flusberg Helen , Nelson Charles A.
Published: April 2018

Autism spectrum disorder (ASD) is a complex and heterogeneous disorder, diagnosed on the basis of behavioral symptoms during the second year of life or later. Finding scalable biomarkers for early detection is challenging because of the variability in presentation of the disorder and the need for simple measurements that could be implemented routinely during well-baby checkups. EEG is a relatively easy-to-use, low cost brain measurement tool that is being increasingly explored as a potential clinical tool for monitoring atypical brain development. EEG measurements were collected from 99 infants with an older sibling diagnosed with ASD, and 89 low risk controls, beginning at 3 months of age and continuing until 36 months of age. Nonlinear features were computed from EEG signals and used as input to statistical learning methods. Prediction of the clinical diagnostic outcome of ASD or not ASD was highly accurate when using EEG measurements from as early as 3 months of age. Specificity, sensitivity and PPV were high, exceeding 95% at some ages. Prediction of ADOS calibrated severity scores for all infants in the study using only EEG data taken as early as 3 months of age was strongly correlated with the actual measured scores. This suggests that useful digital biomarkers might be extracted from EEG measurements.
Genome-wide Analysis of Large-scale Longitudinal Outcomes using Penalization —GALLOP algorithm
Authors: Sikorska Karolina , Lesaffre Emmanuel , Groenen Patrick J. F. , Rivadeneira Fernando , Eilers Paul H. C.
Published: April 2018

Genome-wide association studies (GWAS) with longitudinal phenotypes provide opportunities to identify genetic variations associated with changes in human traits over time. Mixed models are used to correct for the correlated nature of longitudinal data. GWA studies are notorious for their computational challenges, which are considerable when mixed models for thousands of individuals are fitted to millions of SNPs. We present a new algorithm that speeds up a genome-wide analysis of longitudinal data by several orders of magnitude. It solves the equivalent penalized least squares problem efficiently, computing variances in an initial step. Factorizations and transformations are used to avoid inversion of large matrices. Because the system of equations is bordered, we can re-use components, which can be precomputed for the mixed model without a SNP. Two SNP effects (main and its interaction with time) are obtained. Our method completes the analysis a thousand times faster than the R package lme4, providing an almost identical solution for the coefficients and p-values. We provide an R implementation of our algorithm.
The extent of wind-mediated dispersal of small metazoans, focusing nematodes
Authors: Ptatscheck Christoph , Gansfort Birgit , Traunspurger Walter
Published: April 2018

Wind-mediated transport is an important mechanism in the dispersal of small metazoans. Yet, concrete dispersal rates have hardly been examined. Here we present the results of an one-year field experiment investigating the composition and dispersal rates of aeroplankton. To gain insights into the dynamics of dispersal at the species level, we focused on nematodes, worldwide the most common metazoan taxon. Among the six taxa collected in this study (nematodes, rotifers, collembolans, tardigrades, mites, and thrips), nematodes had the highest dispersal rates (up to >3000 individuals m−2 in 4 weeks, 27 species identified) and represented >44% of aeroplankton. Only living nematodes, and no propagules, were dispersed. All taxa had a higher dispersal potential in environments linked to the source habitat, evidenced by the much higher deposition of organisms in funnels placed on the ground than on the rooftop of a ten-story building. Nematodes under conditions of high humidity and wind speed had the highest dispersal rates, while increasing temperatures and dryness had a significantly positive impact on the wind drift of mites and thrips. The results indicated that wind dispersal over long distances is possible. The notable organismal input by wind dispersal may contribute to biodiversity and ecosystem functions.
In vivo Dynamic Phase-Contrast X-ray Imaging using a Compact Light Source
Authors: Gradl Regine , Dierolf Martin , Günther Benedikt , Hehn Lorenz , Möller Winfried , Kutschke David , Yang Lin , Donnelley Martin , Murrie Rhiannon , Erl Alexander , Stoeger Tobias , Gleich Bernhard , Achterhold Klaus , Schmid Otmar , Pfeiffer Franz , Morgan Kaye Susannah
Published: April 2018

We describe the first dynamic and the first in vivo X-ray imaging studies successfully performed at a laser-undulator-based compact synchrotron light source. The X-ray properties of this source enable time-sequence propagation-based X-ray phase-contrast imaging. We focus here on non-invasive imaging for respiratory treatment development and physiological understanding. In small animals, we capture the regional delivery of respiratory treatment, and two measures of respiratory health that can reveal the effectiveness of a treatment; lung motion and mucociliary clearance. The results demonstrate the ability of this set-up to perform laboratory-based dynamic imaging, specifically in small animal models, and with the possibility of longitudinal studies.
Exploring intrinsically disordered proteins in Chlamydomonas reinhardtii
Authors: Zhang Yizhi , Launay Hélène , Schramm Antoine , Lebrun Régine , Gontero Brigitte
Published: April 2018

The content of intrinsically disordered protein (IDP) is related to organism complexity, evolution, and regulation. In the Plantae, despite their high complexity, experimental investigation of IDP content is lacking. We identified by mass spectrometry 682 heat-resistant proteins from the green alga, Chlamydomonas reinhardtii. Using a phosphoproteome database, we found that 331 of these proteins are targets of phosphorylation. We analyzed the flexibility propensity of the heat-resistant proteins and their specific features as well as those of predicted IDPs from the same organism. Their mean percentage of disorder was about 20%. Most of the IDPs (~70%) were addressed to other compartments than mitochondrion and chloroplast. Their amino acid composition was biased compared to other classic IDPs. Their molecular functions were diverse; the predominant ones were nucleic acid binding and unfolded protein binding and the less abundant one was catalytic activity. The most represented proteins were ribosomal proteins, proteins associated to flagella, chaperones and histones. We also found CP12, the only experimental IDP from C. reinhardtii that is referenced in disordered protein database. This is the first experimental investigation of IDPs in C. reinhardtii that also combines in silico analysis.
Genomic analysis and immune response in a murine mastitis model of vB_EcoM-UFV13, a potential biocontrol agent for use in dairy cows
Authors: da Silva Duarte Vinícius , Dias Roberto Sousa , Kropinski Andrew M. , Campanaro Stefano , Treu Laura , Siqueira Carolina , Vieira Marcella Silva , da Silva Paes Isabela , Santana Gabriele Rocha , Martins Franciele , Crispim Josicelli Souza , da Silva Xavier André , Ferro Camila Geovana , Vidigal Pedro M. P. , da Silva Cynthia Canêdo , de Paula Sérgio Oliveira
Published: April 2018

Bovine mastitis remains the main cause of economic losses for dairy farmers. Mammary pathogenic Escherichia coli (MPEC) is related to an acute mastitis and its treatment is still based on the use of antibiotics. In the era of antimicrobial resistance (AMR), bacterial viruses (bacteriophages) present as an efficient treatment or prophylactic option. However, this makes it essential that its genetic structure, stability and interaction with the host immune system be thoroughly characterized. The present study analyzed a novel, broad host-range anti-mastitis agent, the T4virus vB_EcoM-UFV13 in genomic terms, and its activity against a MPEC strain in an experimental E. coli-induced mastitis mouse model. 4,975 Single Nucleotide Polymorphisms (SNPs) were assigned between vB_EcoM-UFV13 and E. coli phage T4 genomes with high impact on coding sequences (CDS) (37.60%) for virion proteins. Phylogenetic trees and genome analysis supported a recent infection mix between vB_EcoM-UFV13 and Shigella phage Shfl2. After a viral stability evaluation (e.g pH and temperature), intramammary administration (MOI 10) resulted in a 10-fold reduction in bacterial load. Furthermore, pro-inflammatory cytokines, such as IL-6 and TNF-α, were observed after viral treatment. This work brings the whole characterization and immune response to vB_EcoM-UFV13, a biocontrol candidate for bovine mastitis.
Effect of in-situ aged and fresh biochar on soil hydraulic conditions and microbial C use under drought conditions
Authors: Paetsch Lydia , Mueller Carsten W. , Kögel-Knabner Ingrid , von Lützow Margit , Girardin Cyril , Rumpel Cornelia
Published: April 2018

Biochar (BC) amendments may be suitable to increase the ecosystems resistance to drought due to their positive effects on soil water retention and availability. We investigated the effect of BC in situ ageing on water availability and microbial parameters of a grassland soil. We used soil containing 13C labeled BC and determined its water holding capacity, microbial biomass and activity during a 3 months incubation under optimum and drought conditions. Our incubation experiment comprised three treatments: soil without BC (Control), soil containing aged BC (BCaged) and soil containing fresh BC (BCfresh), under optimum soil water (pF 1.8) and drought conditions (pF 3.5). Under optimum water as well as drought conditions, soils containing BC showed higher soil organic carbon (SOC) mineralization as compared to control soil. Moreover, BC effects on the soil water regime increase upon in situ aging. Native SOC mineralization increased most for soils containing BCaged. The BCaged led to improved C use under drought as compared to the other treatments. We conclude that BC addition to soils can ameliorate their water regime, especially under drought conditions. This beneficial effect of BC increases upon its aging, which also improved native substrate availability.
Volatile diterpene emission by two Mediterranean Cistaceae shrubs
Authors: Yáñez-Serrano A. M. , Fasbender L. , Kreuzwieser J. , Dubbert D. , Haberstroh S. , Lobo-do-Vale R. , Caldeira M. C. , Werner C.
Published: April 2018

Mediterranean vegetation emits a wide range of biogenic volatile organic compounds (BVOCs) among which isoprenoids present quantitatively the most important compound class. Here, we investigated the isoprenoid emission from two Mediterranean Cistaceae shrubs, Halimium halimifolium and Cistus ladanifer, under controlled and natural conditions, respectively. For the first time, diurnal emission patterns of the diterpene kaurene were detected in real-time by Proton-Transfer-Reaction-Time-of-Flight-Mass-Spectrometer. Kaurene emissions were strongly variable among H. halimifolium plants, ranging from 0.01 ± 0.003 to 0.06 ± 0.01 nmol m−2 s−1 in low and high emitting individuals, respectively. They were in the same order of magnitude as monoterpene (0.01 ± 0.01 to 0.11 ± 0.04 nmol m−2 s−1) and sesquiterpene (0.01 ± 0.01 to 0.52 nmol m−2 s−1) emission rates. Comparable range and variability was found for C. ladanifer under natural conditions. Labelling with 13C-pyruvate suggested that emitted kaurene was not derived from de novo biosynthesis. The high kaurene content in leaves, the weak relationship with ecophysiological parameters and the tendency of higher emissions with increasing temperatures in the field indicate an emission from storage pools. This study highlights significant emissions of kaurene from two Mediterranean shrub species, indicating that the release of diterpenes into the atmosphere should probably deserve more attention in the future.
UNG-1 and APN-1 are the major enzymes to efficiently repair 5-hydroxymethyluracil DNA lesions in C. elegans
Authors: Papaluca Arturo , Wagner J. Richard , Saragovi H. Uri , Ramotar Dindial
Published: April 2018

In Caenorhabditis elegans, two DNA glycosylases, UNG-1 and NTH-1, and two AP endonucleases, APN-1 and EXO-3, have been characterized from the base-excision repair (BER) pathway that repairs oxidatively modified DNA bases. UNG-1 removes uracil, while NTH-1 can remove 5-hydroxymethyluracil (5-hmU), an oxidation product of thymine, as well as other lesions. Both APN-1 and EXO-3 can incise AP sites and remove 3′-blocking lesions at DNA single strand breaks, and only APN-1 possesses 3′- to 5′-exonulease and nucleotide incision repair activities. We used C. elegans mutants to study the role of the BER pathway in processing 5-hmU. We observe that ung-1 mutants exhibited a decrease in brood size and lifespan, and an elevated level of germ cell apoptosis when challenged with 5-hmU. These phenotypes were exacerbated by RNAi downregulation of apn-1 in the ung-1 mutant. The nth-1 or exo-3 mutants displayed wild type phenotypes towards 5-hmU. We show that partially purified UNG-1 can act on 5-hmU lesion in vitro. We propose that UNG-1 removes 5-hmU incorporated into the genome and the resulting AP site is cleaved by APN-1 or EXO-3. In the absence of UNG-1, the 5-hmU is removed by NTH-1 creating a genotoxic 3′-blocking lesion that requires the action of APN-1.
Generation and annihilation time of magnetic droplet solitons
Authors: Hang Jinting , Hahn Christian , Statuto Nahuel , Macià Ferran , Kent Andrew D.
Published: April 2018

Magnetic droplet solitons were first predicted to occur in materials with uniaxial magnetic anisotropy due to a long-range attractive interaction between elementary magnetic excitations, magnons. A non-equilibrium magnon population provided by a spin-polarized current in nanocontacts enables their creation and there is now clear experimental evidence for their formation, including direct images obtained with scanning x-ray transmission microscopy. Interest in magnetic droplets is associated with their unique magnetic dynamics that can lead to new types of high frequency nanometer scale oscillators of interest for information processing, including in neuromorphic computing. However, there are no direct measurements of the time required to nucleate droplet solitons or their lifetime–experiments to date only probe their steady-state characteristics, their response to dc spin-currents. Here we determine the timescales for droplet annihilation and generation using current pulses. Annihilation occurs in a few nanoseconds while generation can take several nanoseconds to a microsecond depending on the pulse amplitude. Micromagnetic simulations show that there is an incubation time for droplet generation that depends sensitively on the initial magnetic state of the nanocontact. An understanding of these processes is essential to utilizing the unique characteristics of magnetic droplet solitons oscillators, including their high frequency, tunable and hysteretic response.
Recent climate warming drives ecological change in a remote high-Arctic lake
Authors: Woelders Lineke , Lenaerts Jan T. M. , Hagemans Kimberley , Akkerman Keechy , van Hoof Thomas B. , Hoek Wim Z.
Published: April 2018

The high Arctic is the fastest warming region on Earth, evidenced by extreme near-surface temperature increase in non-summer seasons, recent rapid sea ice decline and permafrost melting since the early 1990’s. Understanding the impact of climate change on the sensitive Arctic ecosystem to climate change has so far been hampered by the lack of time-constrained, high-resolution records and by implicit climate data analyses. Here, we show evidence of sharp growth in freshwater green algae as well as distinct diatom assemblage changes since ~1995, retrieved from a high-Arctic (80 °N) lake sediment record on Barentsøya (Svalbard). The proxy record approaches an annual to biennial resolution. Combining remote sensing and in-situ climate data, we show that this ecological change is concurrent with, and is likely driven by, the atmospheric warming and a sharp decrease in the length of the sea ice covered period in the region, and throughout the Arctic. Moreover, this research demonstrates the value of palaeoclimate records in pristine environments for supporting and extending instrumental records. Our results reinforce and extend observations from other sites that the high Arctic has already undergone rapid ecological changes in response to on-going climate change, and will continue to do so in the future.
Allosteric modulation of the farnesoid X receptor by a small molecule
Authors: Gabler Matthias , Kramer Jan , Schmidt Jurema , Pollinger Julius , Weber Julia , Kaiser Astrid , Löhr Frank , Proschak Ewgenij , Schubert-Zsilavecz Manfred , Merk Daniel
Published: April 2018

The bile acid activated transcription factor farnesoid X receptor (FXR) regulates numerous metabolic processes and is a rising target for the treatment of hepatic and metabolic disorders. FXR agonists have revealed efficacy in treating non-alcoholic steatohepatitis (NASH), diabetes and dyslipidemia. Here we characterize imatinib as first-in-class allosteric FXR modulator and report the development of an optimized descendant that markedly promotes agonist induced FXR activation in a reporter gene assay and FXR target gene expression in HepG2 cells. Differential effects of imatinib on agonist-induced bile salt export protein and small heterodimer partner expression suggest that allosteric FXR modulation could open a new avenue to gene-selective FXR modulators.
Structural Evolution of Hydrothermally Derived Reduced Graphene Oxide
Authors: Huang Hsin-Hui , De Silva K. Kanishka H. , Kumara G. R. A. , Yoshimura Masamichi
Published: April 2018

Hydrothermal reduction is a promising approach for graphene oxide (GO) reduction since it is environmentally friendly, simple, and cost effective. We present a detailed study of structural changes occurring in graphene oxide during the reduction process. The correlations between the interlayer spacing, chemical states, work functions, surface morphology, level of disorders, the number of layers, and processing time are elucidated. The results reveal that GO flakes remain in the early stage of the reduction process and that they are fully reduced after a 4-h hydrothermal treatment. With an increase in the reduction time, the resulting product, i.e., reduced graphene oxide, has a low oxygen content, small interlayer spacing, and crumbled and wrinkled structures. We are convinced that these properties can be tuned to a desired level for various applications.
A randomized, double-blind, placebo-controlled trial on the efficacy of ginger in the prevention of abdominal distention in post cesarean section patients
Authors: Tianthong Wasinee , Phupong Vorapong
Published: April 2018

The objective of the study was to evaluate the efficacy of ginger in the prevention of abdominal distention in post cesarean section patients. A randomized, double-blind, placebo controlled trial was conducted. One hundred and seventy-eight post cesarean section patients were either randomized to the study group receiving oral ginger capsules or to the placebo group receiving oral placebo capsules. The average age of the studied women was 32.3 years. The incidence of postoperative abdominal distention was not different between the ginger and the placebo groups (20.2% vs 29.2%, p = 0.328). The efficacy to relieve abdominal distention was superior in the ginger group than the placebo group (91% vs 65.2%, p < 0.001). With regards to quality of life, the number of patients who had the ability to eat was higher in the ginger group than in the placebo group (59.6% vs 43.8%, p = 0.035). There were no significant differences in time to first flatus, maternal satisfaction, and side effects. Ginger does not decrease the incidence of post cesarean section abdominal distention. But, ginger is more effective than the placebo in relieving the severity of abdominal distention on the fourth day after operation and improving the ability to eat.
Predicting drug resistance related to ABC transporters using unsupervised Consensus Self-Organizing Maps
Authors: Estrada-Tejedor Roger , Ecker Gerhard F.
Published: April 2018

ATP binding cassette (ABC) transporters play a pivotal role in drug elimination, particularly on several types of cancer in which these proteins are overexpressed. Due to their promiscuous ligand recognition, building computational models for substrate classification is quite challenging. This study evaluates the use of modified Self-Organizing Maps (SOM) for predicting drug resistance associated with P-gp, MPR1 and BCRP activity. Herein, we present a novel multi-labelled unsupervised classification model which combines a new clustering algorithm with SOM. It significantly improves the accuracy of substrates classification, catching up with traditional supervised machine learning algorithms. Results can be applied to predict the pharmacological profile of new drug candidates during the drug development process.
Zinc use efficiency is enhanced in wheat through nanofertilization
Authors: Dapkekar Ashwin , Deshpande Paresh , Oak Manoj D. , Paknikar Kishore M. , Rajwade Jyutika M.
Published: April 2018

Ferti-fortification of wheat with zinc, an essential micronutrient is one of the strategies for combating ‘hidden hunger’ in a large proportion of people all over the world. During fertilization, application of large quantities of micronutrients often results in nutrient wastage and subsequent environmental pollution. Here, we report zinc complexed chitosan nanoparticles (Zn-CNP) for ferti-fortification of durum wheat in field-scale experiments. The efficacy of Zn-CNP was assessed vis-à-vis conventionally applied ZnSO4 (0.2%; 400 mgL−1 zinc) in two durum wheat genotypes (MACS 3125, an indigenous high yielding genotype and UC 1114, a genotype containing the Gpc-B1gene). The observed grain zinc enrichment using Zn-CNP nanocarrier (~36%) and conventional ZnSO4 (~50%) were comparable, despite 10 folds less zinc (40 mgL−1) used in the former. Nanofertilizer application increased grain zinc content without affecting grain yield, protein content, spikelets per spike, thousand kernel weight, etc. Grain zinc enrichment observed in the four-year field trials on plots with varying soil zinc content was consistent, proving the utility of Zn-CNP as a novel nanofertilizer which enhanced fertilizer use efficiency. Our work describes a new paradigm in micronutrient fortification, viz. ‘use nanofertilizers at the right place, right time and in right doses’.
Local structure of molten AuGa2 under pressure: Evidence for coordination change and planetary implications
Authors: Kalkan Bora , Godwal Budhiram , Raju Selva Vennila , Jeanloz Raymond
Published: April 2018

In situ x-ray diffraction measurements and inverse Monte Carlo simulations of pair distribution functions were used to characterize the local structure of molten AuGa2 up to 16 GPa and 940 K. Our results document systematic changes in liquid structure due to a combination of bond compression and coordination increase. Empirical potential structure refinement shows the first-neighbor coordination of Ga around Au and of Au around Ga to increase from about 8 to 10 and 4 to 5, respectively between 0 and 16 GPa, and the inferred changes in liquid structure can explain the observed melting-point depression of AuGa2 up to 5 GPa. As intermetallic AuGa2 is an analogue for metallic SiO2 at much higher pressures, our results imply that structural changes documented for non-metallic silicate melts below 100 GPa are followed by additional coordination changes in the metallic state at pressures in the 0.2–1 TPa range achieved inside large planets.
Synthetic Chemistry for Molecular Imprinting
Authors: Huynh Tan-Phat , Le Trung-Anh
Published: April 2018

Synthetic chemistry for molecular imprinting is a necessary ‘jack-of-all-trades’ no matter what application the molecularly imprinted polymers (MIPs) aim for. There is significant interest in developing different types of chemistry for MIPs so that these can be used as selective materials towards analyte sensing. Therefore, this chapter discusses the comprehensive approaches to syntheses of MIPs, including design of functional monomers providing different types of interactions with templates, imprinting and polymerization techniques to form templated MIPs, and template removal. The versatile usage of MIPs as the selectively sensing materials for a broad range of analytes from macro-sized cells, viruses, bacteria, to sub-nano-sized metal ions and organic contaminants is then demonstrated.