bluuebunny/crossref_metadata_2025 huggingface dataset:
Putative link between Polo-like kinases (PLKs) and Toll-like receptor (TLR) signaling in transformed and primary human immune cells
Authors: El Maadidi Souhayla , Weber Alexander N. R. , Motshwene Precious , Schüssler Jan Moritz , Backes Daniel , Dickhöfer Sabine , Wang Hui , Liu Xiao , Garcia Magno Delmiro , Taumer Christoph , Soufi Boumediene , Wolz Olaf-Oliver , Klimosch Sascha N. , Franz-Wachtel Mirita , Macek Boris , Gay Nicholas J.
Published: September 2019

Toll-like receptors (TLRs) are important sentinels of bacterial and viral infection and thus fulfil a critical sensory role in innate immunity. Polo-like kinases (PLKs), a five membered family of Ser/Thr protein kinases, have long been studied for their role in mitosis and thus represent attractive therapeutic targets in cancer therapy. Recently, PLKs were implicated in TLR signaling in mice but the role of PLKs in TLR signaling in untransformed primary immune cells has not been addressed, even though PLK inhibitors are in clinical trials. We here identified several phospho-serine and phospho-threonine residues in the known TLR pathway kinases, Interleukin-1 receptor-associated kinase (IRAK) 2 and IRAK4. These sites lie in canonical polo-box motifs (PBM), sequence motifs known to direct recruitment of PLKs to client proteins. Interestingly, PLK1 was phosphorylated and PLK 2 and 3 mRNA induced upon TLR stimulation in primary immune cells, respectively. In whole blood, PLK inhibition disparately affected TLR mediated cytokine responses in a donor- and inhibitor-dependent fashion. Collectively, PLKs may thus potentially interface with TLR signaling in humans. We propose that temporary PLK inhibitor-mediated blockade of TLR-signaling in certain patients receiving such inhibitors during cancer treatment may cause adverse effects such as an increased risk of infections due to a then compromised ability of the TLR recognition system to sense and initiate cytokine responses to invading microbes.
Alternative classifications of neurons based on physiological properties and synaptic responses, a computational study
Authors: Hernáth Ferenc , Schlett Katalin , Szücs Attila
Published: September 2019

One of the central goals of today’s neuroscience is to achieve the conceivably most accurate classification of neuron types in the mammalian brain. As part of this research effort, electrophysiologists commonly utilize current clamp techniques to gain a detailed characterization of the neurons’ physiological properties. While this approach has been useful, it is not well understood whether neurons that share physiological properties of a particular phenotype would also operate consistently under the action of natural synaptic inputs. We approached this problem by simulating a biophysically diverse population of model neurons based on 3 generic phenotypes. We exposed the model neurons to two types of stimulation to investigate their voltage responses under conventional current step protocols and under simulated synaptic bombardment. We extracted standard physiological parameters from the voltage responses elicited by current step stimulation and spike arrival times descriptive of the model’s firing behavior under synaptic inputs. The biophysical phenotypes could be reliably identified using classification based on the ‘static’ physiological properties, but not the interspike interval-based parameters. However, the model neurons associated with the biophysically different phenotypes retained cell type specific features in the fine structure of their spike responses that allowed their accurate classification.
Characterization of SMG7 14-3-3-like domain reveals phosphoserine binding-independent regulation of p53 and UPF1
Authors: Cowen Lauren E. , Luo Hongwei , Tang Yi
Published: September 2019

The 14-3-3-related protein SMG7 plays critical roles in regulation of DNA damage response and nonsense-mediated mRNA decay (NMD). Like 14-3-3, SMG7 engages phosphoserine-dependent protein interactions; however, the precise role of phosphorylation-mediated SMG7 binding remains unknown. Here, we show that DNA damage-induced SMG7-p53 binding requires phosphorylated Ser15 on p53, and that substitution of the conserved lysine residue K66 in the SMG7 14-3-3-like domain with the glutamic acid (E) abolishes interactions with its client proteins p53 and UPF1. Unexpectedly, loss of phosphoserine-dependent SMG7 binding does not significantly affect p53 stabilization/activation, and p53-dependent cell growth arrest or apoptosis upon DNA damage. Also surprisingly, cells expressing the SMG7 K66E-knockin mutant retain fully functional UPF1-mediated NMD. These findings are highly unusual, given that phosphorylation-mediated 14-3-3 binding has essential roles in numerous cellular signaling pathways. Thus, our studies suggest that 14-3-3-like proteins such as SMG7 likely function using additional distinct regulatory mechanisms besides phosphoserine-mediated protein interactions.
Reduction of bias in the evaluation of fractional anisotropy and mean diffusivity in magnetic resonance diffusion tensor imaging using region-of-interest methodology
Authors: Seo Youngseob , Rollins Nancy K. , Wang Zhiyue J.
Published: September 2019

Accurate quantification of fractional anisotropy (FA) and mean diffusivity (MD) in MR diffusion tensor imaging (DTI) requires adequate signal-to-noise ratio (SNR) especially in low FA areas of the brain, which necessitates clinically impractical long image acquisition times. We explored a SNR enhancement strategy using region-of-interest (ROI)-based diffusion tensor for quantification. DTI scans from a healthy male were acquired 15 times and combined into sets with different number of signal averages (NSA = 1–4, 15) at one 1.5-T Philips and three 3-T (Philips, Siemens and GE) scanners. Equivalence test was performed to determine NSA thresholds for bias-free FA and MD quantifications by comparison with reference values derived from images with NSA = 15. We examined brain areas with low FA values including caudate nucleus, globus pallidus, putamen, superior temporal gyrus, and substructures within thalamus (lateral dorsal, ventral anterior and posterior nuclei), where bias-free FA is difficult to obtain using a conventional approach. Our results showed that bias-free FA can be obtained with NSA = 2 or 3 in some cases using ROI-based analysis. ROI-based analysis allows reliable FA and MD quantifications in various brain structures previously difficult to study with clinically feasible data acquisition schemes.
Better grip force control by attending to the controlled object: Evidence for direct force estimation from visual motion
Authors: Takamuku Shinya , Gomi Hiroaki
Published: September 2019

Estimating forces acting between our hand and objects is essential for dexterous motor control. An earlier study suggested that vision contributes to the estimation by demonstrating changes in grip force pattern caused by delayed visual feedback. However, two possible vision-based force estimation processes, one based on hand position and another based on object motion, were both able to explain the effect. Here, to test each process, we examined how visual feedback of hand and object each contribute to grip force control during moving an object (mass) connected to the grip by a damped-spring. Although force applied to the hand could be estimated from its displacement, we did not find any improvements by the hand feedback. In contrast, we found that visual feedback of object motion significantly improved the synchrony between grip and load forces. Furthermore, when both feedback sources were provided, the improvement was observed only when participants were instructed to direct their attention to the object. Our results suggest that visual feedback of object motion contributes to estimation of dynamic forces involved in our actions by means of inverse dynamics computation, i.e., the estimation of force from motion, and that visual attention directed towards the object facilitates this effect.
High Impact Exercise Improves Bone Microstructure and Strength in Growing Rats
Authors: Mustafy Tanvir , Londono Irène , Moldovan Florina , Villemure Isabelle
Published: September 2019

Physical activity is beneficial for skeletal development. However, impact sports during adolescence, leading to bone growth retardation and/or bone quality improvement, remains unexplained. This study investigated the effects of in vivo low (LI), medium (MI), and high (HI) impact loadings applied during puberty on bone growth, morphometry and biomechanics using a rat model. 4-week old rats (n = 30) were divided into control, sham, LI, MI, and HI groups. The impact was applied on the right tibiae, 5 days/week for 8 weeks mimicking walking (450 µε), uphill running (850 µε) and jumping (1250 µε) conditions. Trabecular and cortical parameters were determined by micro-CT, bone growth rate by calcein labeling and toluidine blue staining followed by histomorphometry. Bio-mechanical properties were evaluated from bending tests. HI group reduced rat body weight and food consumption compared to shams. Bone growth rate also decreased in MI and HI groups despite developing thicker hypertrophic and proliferative zone heights. HI group showed significant increment in bone mineral density, trabecular thickness, cortical and total surface area. Ultimate load and stiffness were also increased in MI and HI groups. We conclude that impact loading during adolescence reduces bone growth moderately but improves bone quality and biomechanics at the end of the growing period.
Profiles of volatile indole emitted by Escherichia coli based on CDI-MS
Authors: Zhong Qiaoshi , Cheng Feng , Liang Juchao , Wang Xiaozhong , Chen Yanhui , Fang Xueyao , Hu Longhua , Hang Yaping
Published: September 2019

Escherichia coli is an important pathogen of nosocomial infection in clinical research, Thus, exploring new methods for the rapid detection of this pathogen is urgent. We reported the early release of molecular volatile indole vapour of E. coli cultures and blood cultures analyzed by direct atmospheric corona discharge ionization mass spectrometry (CDI-MS). The concentration of indole in E. coli cultures remarkably increases during the early log and lag phases of bacterial growth, thereby enabling early detection. Technical replicates were cultivated for 3 days for reference diagnosis using current conventional bacteraemia detection. A reference MS screen of common microbes from other genera confirmed that the peaks at m/z 116 signal corresponded to indole were specifically present in E. coli. Our results indicated that volatile indole based on CDI-MS without the need for any sample pretreatment is highly suitable for the reliable and cost-efficient differentiation of E. coli, especially for bacteraemia in humans.
Dissociation between cortical and spinal excitability of the antagonist muscle during combined motor imagery and action observation
Authors: Aoyama Toshiyuki , Kaneko Fuminari , Ohashi Yukari , Kohno Yutaka
Published: September 2019

Inhibitory neural control of antagonist muscle is one of the fundamental neural mechanism of coordinated human limb movement. Previous studies have revealed that motor execution (ME) and motor imagery (MI) share many common neural substrates; however, whether inhibitory neural activity occurs during MI remains unknown. In addition, recent studies have demonstrated that a combined MI and action observation (MI + AO) produces strong neurophysiological changes compared with MI or AO alone. Therefore, we investigated inhibitory changes in cortical and spinal excitability of the antagonist muscle during MI + AO and ME. Single-pulse transcranial magnetic stimulation (TMS) experiments revealed that corticospinal excitability of the antagonist muscle was decreased during MI + AO. Conversely, F-wave experiments showed that F-wave persistence of the antagonist muscle increased. Paired-pulse TMS experiment also demonstrated that short-interval intracortical inhibition (SICI) did not contribute to this inhibition. Therefore, cortical mediated inhibition, except for SICI, may be related to this inhibition. Conversely, such clear inhibition of the antagonist muscle was not observed during ME, presumably owing to the effects of muscle contraction to decelerate the movements and/or sensory input accompanying the joint movements. These findings provide important insights into the neurophysiological differences between MI + AO and ME.
Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling
Authors: Passariello Margherita , D’Alise Anna Morena , Esposito Annachiara , Vetrei Cinzia , Froechlich Guendalina , Scarselli Elisa , Nicosia Alfredo , De Lorenzo Claudia
Published: September 2019

The novel antibody-based immunotherapy in oncology exploits the activation of immune system mediated by immunomodulatory antibodies specific for immune checkpoints. Among them, the programmed death ligand-1 (PD-L1) is of particular interest as it is expressed not only on T-cells, but also on other immune cells and on a large variety of cancer cells, such as breast cancer cells, considering its high expression in both ErbB2-positive and Triple Negative Breast Cancers. We demonstrate here that PD-L1_1, a novel anti-PD-L1 T -cell stimulating antibody, inhibits PD-L1-tumor cell growth also by affecting the intracellular MAPK pathway and by activating caspase 3. Similar in vitro results were obtained for the first time here also with the clinically validated anti-PD-L1 mAb Atezolizumab and in vivo with another validated anti-mouse anti-PD-L1 mAb. Moreover, we found that two high affinity variants of PD-L1_1 inhibited tumor cell viability more efficiently than the parental PD-L1_1 by affecting the same MAPK pathways with a more potent effect. Altogether, these results shed light on the role of PD-L1 in cancer cells and suggest that PD-L1_1 and its high affinity variants could become powerful antitumor weapons to be used alone or in combination with other drugs such as the anti-ErbB2 cAb already successfully tested in in vitro combinatorial treatments.
Comparative metabolomics of MCF-7 breast cancer cells using different extraction solvents assessed by mass spectroscopy
Authors: Semreen Mohammad H. , Alniss Hasan Y. , Grgic Stefan R. , El-Awady Raafat A. , Almehdi Ahmed H. , Mousa Muath K. , Hamoudi Rifat A.
Published: September 2019

Metabolic profiling of cancer cells can play a vital role in revealing the molecular bases of cancer development and progression. In this study, gas chromatography coupled with mass spectrometry (GC-MS) was employed for the determination of signatures found in ER+/PR+ breast cancer cells derived from MCF-7 using different extraction solvents including: A, formic acid in water; B, ammonium hydroxide in water; C, ethyl acetate; D, methanol: water (1:1, v/v); and E, acetonitrile: water (1:1, v/v). The greatest extraction rate and diversity of metabolites occurs with extraction solvents A and E. Extraction solvent D showed moderate extraction efficiency, whereas extraction solvent B and C showed inferior metabolite diversity. Metabolite set enrichment analysis (MSEA) results showed energy production pathways to be key in MCF-7 cell lines. This study showed that mass spectrometry could identify key metabolites associated with cancers. The highest enriched pathways were related to energy production as well as Warburg effect pathways, which may shed light on how energy metabolism has been hijacked to encourage tumour progression and eventually metastasis in breast cancer.
Association between Galectin-3 levels within central and peripheral venous blood, and adverse left ventricular remodelling after first acute myocardial infarction
Authors: Andrejic Olivera M. , Vucic Rada M. , Pavlovic Milan , McClements Lana , Stokanovic Dragana , Jevtovic–Stoimenov Tatjana , Nikolic Valentina N.
Published: September 2019

Our study investigates association between Galectin-3 levels and adverse left ventricular remodelling (LVR) at six months. Fifty-seven patients following first acute myocardial infarction (AMI) were enrolled in this study and blood samples collected on day 1 from the femoral vein and artery, the right atrium near the coronary sinus and the aortic root, and on day 30, from the cubital vein. Patients with LVESV ≥20% at six months, were included in the LVR group. On day 1, Galectin-3 plasma levels in the femoral vein (10.34 ng/ml ± 3.81 vs 8.22 ng/ml ± 2.34, p = 0.01), and near coronary sinus (10.7 ng/ml ± 3.97 vs 8.41 ng/ml ± 2.56, p = 0.007) were higher in the LVR group. Positive correlations between Galectin-3 levels from aortic root and coronary sinus, aortic root and femoral vein, and coronary sinus and femoral vein, were observed in both groups. On day 30, Galectin-3 concentration in the cubital vein was an independent risk factor of LVR six months post-AMI, demonstrating 1.5-fold increased risk. Day-30 Galectin-3 also showed positive correlations with echocardiography parameters indicative of diastolic and systolic dysfunction. Determining Galectin-3 plasma concentration on day 30 following AMI could have beneficial prognostic value in predicting LVR.
Three-dimensional cellular automaton simulation of coupled hydrogen porosity and microstructure during solidification of ternary aluminum alloys
Authors: Gu Cheng , Lu Yan , Ridgeway Colin D. , Cinkilic Emre , Luo Alan A.
Published: September 2019

Hydrogen-induced porosity formed during solidification of aluminum-based alloys has been a major issue adversely affecting the performance of solidification products such as castings, welds or additively manufactured components. A three-dimensional cellular automaton model was developed, for the first time, to predict the formation and evolution of hydrogen porosity coupled with grain growth during solidification of a ternary Al-7wt.%Si-0.3wt.%Mg alloy. The simulation results fully describe the concurrent nucleation and evolution of both alloy grains and hydrogen porosity, yielding the morphology of multiple grains as well as the porosity size and distribution. This model, successfully validated by X-ray micro-tomographic measurements and optical microscopy of a wedge die casting, provides a critical tool for minimizing/controlling porosity formation in solidification products.
Proteomic Investigations of Autism Brain Identify Known and Novel Pathogenetic Processes
Authors: Abraham Joseph R. , Szoko Nicholas , Barnard John , Rubin Robert A. , Schlatzer Daniela , Lundberg Kathleen , Li Xiaolin , Natowicz Marvin R.
Published: September 2019

Autism Spectrum Disorder (ASD) is a set of heterogeneous neurodevelopmental conditions defined by impairments in social communication and restricted, repetitive behaviors, interests or activities. Only a minority of ASD cases are determined to have a definitive etiology and the pathogenesis of most ASD is poorly understood. We hypothesized that a global analysis of the proteomes of human ASD vs. control brain, heretofore not done, would provide important data with which to better understand the underlying neurobiology of autism. In this study, we characterized the proteomes of two brain regions, Brodmann area 19 (BA19) and posterior inferior cerebellum (CB), from carefully selected idiopathic ASD cases and matched controls using label-free HPLC-tandem mass spectrometry. The data revealed marked differences between ASD and control brain proteomes for both brain regions. Unlike earlier transcriptomic analyses using frontal and temporal cortex, however, our proteomic analysis did not support ASD attenuating regional gene expression differences. Bioinformatic analyses of the differentially expressed proteins between cases and controls highlighted canonical pathways involving glutamate receptor signaling and glutathione-mediated detoxification in both BA19 and CB; other pathways such as Sertoli cell signaling and fatty acid oxidation were specifically enriched in BA19 or CB, respectively. Network analysis of both regions of ASD brain showed up-regulation of multiple pre- and post-synaptic membrane or scaffolding proteins including glutamatergic ion channels and related proteins, up-regulation of proteins involved in intracellular calcium signaling, and down-regulation of neurofilament proteins, with DLG4 and MAPT as major hub proteins in BA19 and CB protein interaction networks, respectively. Upstream regulator analysis suggests neurodegeneration-associated proteins drive the differential protein expression for ASD in both BA19 and CB. Overall, the proteomic data provide support for shared dysregulated pathways and upstream regulators for two brain regions in human ASD brain, suggesting a common ASD pathophysiology that has distinctive regional expression.
The central role of peripheral nodes in directed network dynamics
Authors: Wright Edgar A. P. , Yoon Sooyeon , Ferreira António L. , Mendes José F. F. , Goltsev Alexander V.
Published: September 2019

Many social, technological, and biological systems with asymmetric interactions display a variety of collective phenomena, such as opinion formation and synchronization. This has motivated much research on the dynamical impact of local and mesoscopic structure in directed networks. However, the unique constraints imposed by the global organization of directed networks remain largely undiscussed. Here, we control the global organization of directed Erdős–Rényi networks, and study its impact on the emergence of synchronization and ferromagnetic ordering, using Kuramoto and Ising dynamics. In doing so, we demonstrate that source nodes – peripheral nodes without incoming links – can disrupt or entirely suppress the emergence of collective states in directed networks. This effect is imposed by the bow-tie organization of directed networks, where a large connected core does not uniquely ensure the emergence of collective states, as it does for undirected networks.
Prevalence and Risk Factors of Thyroid Dysfunction in Older Adults in the Community
Authors: Diab Nermin , Daya Natalie R. , Juraschek Stephen P. , Martin Seth S. , McEvoy John W. , Schultheiß Ulla T. , Köttgen Anna , Selvin Elizabeth
Published: September 2019

Prevalence estimates and evidence informing treatment targets for thyroid dysfunction largely come from studies of middle-aged adults. We conducted a cross-sectional analysis to determine the prevalence of thyroid dysfunction and risk factors for abnormal thyroid tests in participants aged ≥65 in the Atherosclerosis Risk in Communities (ARIC) study (N = 5,392). We measured serum concentrations of triiodothyronine (T3), free thyroxine (FT4), thyroid peroxidase antibody (Anti-TPO), and thyroid stimulating hormone (TSH). In this population (58% women, 22% black), 17% reported medication use for thyroid dysfunction. Among those not on treatment, the prevalence of overt and subclinical hypothyroidism was 0.82% and 6.06%, respectively. Overt and subclinical hyperthyroidism affected 0.26% and 0.78%, respectively. Multivariable adjusted TSH, FT4 and T3 levels were 25%, 1.3% and 3.9% lower in blacks compared to whites, respectively. Men were less likely to be anti-TPO positive compared to women (p < 0.001). Former and never smoking were associated with lower T3 and FT4 levels compared to current smoking. The prevalence of thyroid dysfunction in older adults is nearly 25%. Multiple illnesses can interact to contribute to declines in health. Additional attention to thyroid dysfunction and screening in this age group is recommended.
A multi-omics analysis of the grapevine pathogen Lasiodiplodia theobromae reveals that temperature affects the expression of virulence- and pathogenicity-related genes
Authors: Félix Carina , Meneses Rodrigo , Gonçalves Micael F. M. , Tilleman Laurentijn , Duarte Ana S. , Jorrín-Novo Jesus V. , Van de Peer Yves , Deforce Dieter , Van Nieuwerburgh Filip , Esteves Ana C. , Alves Artur
Published: September 2019

Lasiodiplodia theobromae (Botryosphaeriaceae, Ascomycota) is a plant pathogen and human opportunist whose pathogenicity is modulated by temperature. The molecular effects of temperature on L. theobromae are mostly unknown, so we used a multi-omics approach to understand how temperature affects the molecular mechanisms of pathogenicity. The genome of L. theobromae LA-SOL3 was sequenced (Illumina MiSeq) and annotated. Furthermore, the transcriptome (Illumina TruSeq) and proteome (Orbitrap LC-MS/MS) of LA-SOL3 grown at 25 °C and 37 °C were analysed. Proteins related to pathogenicity (plant cell wall degradation, toxin synthesis, mitogen-activated kinases pathway and proteins involved in the velvet complex) were more abundant when the fungus grew at 25 °C. At 37 °C, proteins related to pathogenicity were less abundant than at 25 °C, while proteins related to cell wall organisation were more abundant. On the other hand, virulence factors involved in human pathogenesis, such as the SSD1 virulence protein, were expressed only at 37 °C. Taken together, our results showed that this species presents a typical phytopathogenic molecular profile that is compatible with a hemibiotrophic lifestyle. We showed that L. theobromae is equipped with the pathogenesis toolbox that enables it to infect not only plants but also animals.
Enamel peptides reveal the sex of the Late Antique ‘Lovers of Modena’
Authors: Lugli Federico , Di Rocco Giulia , Vazzana Antonino , Genovese Filippo , Pinetti Diego , Cilli Elisabetta , Carile Maria Cristina , Silvestrini Sara , Gabanini Gaia , Arrighi Simona , Buti Laura , Bortolini Eugenio , Cipriani Anna , Figus Carla , Marciani Giulia , Oxilia Gregorio , Romandini Matteo , Sorrentino Rita , Sola Marco , Benazzi Stefano
Published: September 2019

Recent work has disclosed the critical role played by enamel peptides in sex classification of old skeletal remains. In particular, protein AMELY (amelogenin isoform Y) is present in the enamel dental tissue of male individuals only, while AMELX (isoform X) can be found in both sexes. AMELY can be easily detected by LC-MS/MS in the ion extracted chromatograms of the SM(ox)IRPPY peptide (monoisotopic [M + 2 H]+2 mass = 440.2233 m/z). In this paper, we exploited the dimorphic features of the amelogenin protein to determine the sex of the so-called ‘Lovers of Modena’, two Late Antique individuals whose skeletons were intentionally buried hand-in-hand. Upon discovery, mass media had immediately assumed they were a male-female couple, even if bad preservation of the bones did not allow an effective sex classification. We were able to extract proteins from the dental enamel of both individuals (~1600 years old) and to confidently classify them as males. Results were compared to 14 modern and archaeological control samples, confirming the reliability of the ion chromatogram method for sex determination. Although we currently have no information on the actual relationship between the ‘Lovers of Modena’ (affective? Kin-based?), the discovery of two adult males intentionally buried hand-in-hand may have profound implications for our understanding of funerary practices in Late Antique Italy.
Minimal intervening control of biomolecular networks leading to a desired cellular state
Authors: Choo Sang-Mok , Park Sang-Min , Cho Kwang-Hyun
Published: September 2019

A cell phenotype can be represented by an attractor state of the underlying molecular regulatory network, to which other network states eventually converge. Here, the set of states converging to each attractor is called its basin of attraction. A central question is how to drive a particular cell state toward a desired attractor with minimal interventions on the network system. We develop a general control framework of complex Boolean networks to provide an answer to this question by identifying control targets on which one-time temporary perturbation can induce a state transition to the boundary of a desired attractor basin. Examples are shown to illustrate the proposed control framework which is also applicable to other types of complex Boolean networks.
Aflatoxin levels in maize and peanut and blood in women and children: The case of Timor-Leste
Authors: de Almeida Luis , Williams Robert , Soares Dirce M. , Nesbitt Harry , Wright Graeme , Erskine William
Published: September 2019

Aflatoxins are toxic fungal metabolites produced byAspergillussp. with carcinogenic properties that are a common food contaminant of many crops including maize and peanuts. In Timor-Leste malnutrition and children’s stunting are frequent and maize and peanuts are staple foods. This study aimed to provide information on aflatoxin exposure nationally. The study measured levels of aflatoxin in locally-produced maize and peanuts (296 samples) and of aflatoxin-albumin conjugate in blood samples of women and young children (514 and 620 respectively) across all municipalities. The average concentration of aflatoxin in the grain samples was low with most maize (88%) and peanut (92%) samples - lower than European Commission tolerated aflatoxin level. Although aflatoxin–albumin conjugate was detected in more than 80% of blood samples, the average concentration in children and adults of 0.64 and 0.98 pg mg−1alb, respectively, is much lower than in other similar rural-based countries. Although low in concentration, blood aflatoxin levels and aflatoxin contamination levels in maize across municipalities were correlated significantly for mothers (R2 = 37%, n = 495) but not for children (R2 = 10%). It is unlikely that the consumption of aflatoxin contaminated grain is a causative factor in the current level of malnutrition and stunting affecting Timor-Leste children.
The Concavity of the Maximal Expiratory Flow–Volume Curve Reflects the Extent of Emphysema in Obstructive Lung Diseases
Authors: Mochizuki Fumi , Iijima Hiroaki , Watanabe Azusa , Tanabe Naoya , Sato Susumu , Shiigai Masanari , Fujiwara Keiji , Shimada Takafumi , Ishikawa Hiroichi , Kanazawa Jun , Yatagai Yohei , Masuko Hironori , Sakamoto Tohru , Muro Shigeo , Hizawa Nobuyuki
Published: September 2019

A concave-shaped maximal expiratory flow-volume (MEFV) curve is a spirometric feature in chronic obstructive pulmonary disease (COPD). The MEFV curve is characterized by an increase in the Obstructive Index, which is defined as a ratio of forced vital capacity to the volume-difference between two points of half of the peak expiratory flow on the MEFV curve. We hypothesized that the Obstructive Index would reflect the severity of emphysema in patients with COPD and asthma-COPD overlap (ACO). Thus, the aim of this retrospective study was to evaluate whether the Obstructive Index on spirometry is associated with the extent of emphysema on computed tomography (CT) in patients with COPD, ACO, and asthma (N = 65, 15, and 53, respectively). The percentage of low-attenuation volume (LAV%) and wall area (WA%) were measured on CT. The Obstructive Index was higher in patients with COPD and ACO than in those with asthma. Spearman correlation showed that a greater Obstructive Index was associated with a higher LAV%, but not WA%. Multivariate analysis showed that Obstructive Index was associated with LAV% (standardized β = 0.43, P < 0.0001) independent of other spirometric indices. The Obstructive Index is a useful spirometric index that reflects the extent of emphysema.
Stable fabrication of a large nanopore by controlled dielectric breakdown in a high-pH solution for the detection of various-sized molecules
Authors: Yanagi Itaru , Akahori Rena , Takeda Ken-ichi
Published: September 2019

For nanopore sensing of various-sized molecules with high sensitivity, the size of the nanopore should be adjusted according to the size of each target molecule. For solid-state nanopores, a simple and inexpensive nanopore fabrication method utilizing dielectric breakdown of a membrane is widely used. This method is suitable for fabricating a small nanopore. However, it suffers two serious problems when attempting to fabricate a large nanopore: the generation of multiple nanopores and the non-opening failure of a nanopore. In this study, we found that nanopore fabrication by dielectric breakdown of a SiN membrane under high-pH conditions (pH ≥ 11.3) could overcome these two problems and enabled the formation of a single large nanopore up to 40 nm in diameter within one minute. Moreover, the ionic-current blockades derived from streptavidin-labelled and non-labelled DNA passing through the fabricated nanopore were clearly distinguished. The current blockades caused by streptavidin-labelled DNA could be identified even when its concentration is 1% of the total DNA.
21-Gene Recurrence Score and Adjuvant Chemotherapy Decision for Breast Cancer Patients with Positive Lymph Nodes
Authors: Tong Yiwei , Wu Jiayi , Huang Ou , He Jianrong , Zhu Li , Chen Weiguo , Li Yafen , Chen Xiaosong , Shen Kunwei
Published: September 2019

The 21-gene recurrence score (RS) assay is prognostic and predictive for hormone receptor (HR)+/HER2-/node- breast cancer (BC) patients. However, its clinical value in node + patients hasn’t been elucidated. HR+/HER2-/pN1 patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital from January 2014 to December 2018, with available RS results were retrospectively included. Clinico-pathological characteristics were compared. Adjuvant chemotherapy recommendations pre-/post- RS assay and actual usage were analyzed. A total of 303 patients were included, with 59, 178, 66 RS < 18, 18–30 and ≥ 31. Age (P < 0.001), comorbidity (P = 0.013), and RS category (P < 0.001) were independently associated with chemotherapy recommendation. Compared with low RS patients, those with intermediate (OR 6.58, 95% CI 2.37–18.31, P < 0.001) or high (OR 54.14, 95% CI 3.77–776.54, P = 0.003) RS were more likely to be recommended with chemotherapy. RS independently influence chemotherapy decision in postmenopausal population as well. Chemotherapy recommendation changed for 9.57% patients after RS assay. Patient adherence rate to chemotherapy recommendation was 94.72% (287/303). The 21-gene RS independently influenced chemotherapy recommendation in pN1 BC patients, which could provide additional information to guide chemotherapy decision with relatively good treatment adherence rate.
Marginal diversity analysis of conservation of Chinese domestic duck breeds
Authors: Zhang Yang , Wang Laidi , Bian Youqing , Wang Zhaoshan , Xu Qi , Chang Guobin , Chen Guohong
Published: September 2019

The present study aimed to systematically evaluate the genetic diversity of Chinese domestic duck breeds and ensure the most effective allocation and usage of conservation funds. We first performed an analysis of DNA genetic distance in 21 duck breeds by measuring short tandem repeats. Then, we calculated the extinction probability, contribution rate, and marginal diversity for each breed. The results showed that the extinction rate of the Zhongshan duck, Guangxi duck, and Ji’an duck were the highest at 0.67, 0.59, and 0.59, respectively, and that of the Linwu duck, Jinding duck, and Gaoyou duck were the lowest at 0.15, 0.18, and 0.19, respectively. The current diversity of populations was 7.72 and the expected diversity in five hundred years is 5.14 ± 1.15. The marginal diversity of the Chinese Muscovy duck was the largest (−2.20), accounting for 42.61% of the expected diversity, followed by the Guangxi duck (−0.49, 9.44%), whereas the Jinding duck was the smallest (−0.12; 2.32%). The protection potency of the Chinese Muscovy duck was the largest (0.61), followed by Guangxi duck (0.29), whereas the Jinding duck was the smallest (0.02). This study provides a reference for determining the conservation priority of Chinese domestic duck breeds or genetic resources.
Chronic Pressure Overload Results in Deficiency of Mitochondrial Membrane Transporter ABCB7 Which Contributes to Iron Overload, Mitochondrial Dysfunction, Metabolic Shift and Worsens Cardiac Function
Authors: Kumar Vikas , A. Aneesh Kumar , Sanawar Rahul , Jaleel Abdul , Santhosh Kumar T. R. , Kartha C. C.
Published: September 2019

We examined the hitherto unexplored role of mitochondrial transporters and iron metabolism in advancing metabolic and mitochondrial dysfunction in the heart during long term pressure overload. We also investigated the link between mitochondrial dysfunction and fluctuation in mitochondrial transporters associated with pressure overload cardiac hypertrophy. Left ventricular hypertrophy (LVH) was induced in 3-month-old male Wistar rats by constriction of the aorta using titanium clips. After sacrifice at the end of 6 and 15 months after constriction, tissues from the left ventricle (LV) from all animals were collected for histology, biochemical studies, proteomic and metabolic profiling, and gene and protein expression studies. LV tissues from rats with LVH had a significant decrease in the expression of ABCB7 and mitochondrial oxidative phosphorylation (mt-OXPHOS) enzymes, an increased level of lipid metabolites, decrease in the level of intermediate metabolites of pentose phosphate pathway and elevated levels of cytoplasmic and mitochondrial iron, reactive oxygen species (ROS) and autophagy-related proteins. Knockdown of ABCB7 in H9C2 cells and stimulation with angiotensin II resulted in increased ROS levels, ferritin, and transferrin receptor expression and iron overload in both mitochondria and cytoplasm. A decrease in mRNA and protein levels of mt-OXPHOS specific enzymes, mt-dynamics and autophagy clearance and activation of IGF-1 signaling were also seen in these cells. ABCB7 overexpression rescued all these changes. ABCB7 was found to interact with mitochondrial complexes IV and V. We conclude that in chronic pressure overload, ABCB7 deficiency results in iron overload and mitochondrial dysfunction, contributing to heart failure.
Switch Between El Nino and La Nina is Caused by Subsurface Ocean Waves Likely Driven by Lunar Tidal Forcing
Authors: Lin Jialin , Qian Taotao
Published: September 2019

The El Nino-Southern Oscillation (ENSO) is the dominant interannual variability of Earth’s climate system, and strongly modulates global temperature, precipitation, atmospheric circulation, tropical cyclones and other extreme events. However, forecasting ENSO is one of the most difficult problems in climate sciences affecting both interannual climate prediction and decadal prediction of near-term global climate change. The key question is what cause the switch between El Nino and La Nina. For the past 30 years, ENSO forecasts have been limited to short lead times after ENSO sea surface temperature (SST) anomaly has already developed, but unable to predict the switch between El Nino and La Nina. Here, we demonstrate that the switch between El Nino and La Nina is caused by a subsurface ocean wave propagating from western Pacific to central and eastern Pacific and then triggering development of SST anomaly. This is based on analysis of all ENSO events in the past 136 years using multiple long-term observational datasets. The wave’s slow phase speed and decoupling from atmosphere indicate that it is a forced wave. Further analysis of Earth’s angular momentum budget and NASA’s Apollo Landing Mirror Experiment suggests that the subsurface wave is likely driven by lunar tidal gravitational force.
New crosstalk between probiotics Lactobacillus plantarum and Bacillus subtilis
Authors: Yu Tao , Kong Jian , Zhang Li , Gu Xinyi , Wang Mingyu , Guo Tingting
Published: September 2019

It was reported that oral administration of Bacillus favored the growth of Lactobacillus in the intestinal tract. Here, this phenomenon was confirmed by co-cultivation of Bacillus subtilis 168 and Lactobacillus plantarum SDMCC050204-pL157 in vitro. To explain the possible molecular mechanisms, B. subtilis 168 cells were incubated in simulated intestinal fluid at 37 °C for 24 h, and up to 90% of cells autolysed in the presence of bile salts. Addition of the autolysate to medium inoculated with Lb. plantarum SDMCC050204 decreased the concentration of H2O2 in the culture, alleviated DNA damage and increased the survival of Lb. plantarum, as like the results of exogenous heme addition. These results suggested that the autolysate provided heme, which activated the heme-dependent catalase KatA in Lb. plantarum SDMCC050204. HPLC confirmed the presence of heme in the autolysate. Disruption of the Lb. plantarum SDMCC050204 katA gene abolished the protective effect of the B. subtilis 168 autolysate against H2O2 stress. We thus hypothesized that the beneficial effect of Bacillus toward Lactobacillus was established through activation of the heme-dependent catalase and remission of the damage of reactive oxygen species against Lactobacillus. This study raised new crosstalk between the two frequently-used probiotics, highlighting heme-dependent catalase as the key mediator.
The involvement of McpB chemoreceptor from Pseudomonas aeruginosa PAO1 in virulence
Authors: García-Fontana Cristina , Vílchez Juan I. , González-Requena Marta , González-López Jesús , Krell Tino , Matilla Miguel A. , Manzanera Maximino
Published: September 2019

Pseudomonas aeruginosa is an opportunistic human pathogen causing infections in a variety of plant and animal hosts. The gene mcpB, part of the chemosensory gene cluster II, encodes a soluble chemoreceptor whose function remains unknown. Previous studies show that the cheB2 gene, also located in the chemosensory cluster II, is involved in a specific response during infection and it is required for full pathogenicity of P. aeruginosa. To determine whether the McpB (or Aer2) chemoreceptor is involved in virulence processes, we generated a mcpB mutant and tested its phenotype using a virulence-measuring system. This system was developed by our group and is based on different bioassays using organisms living at different soil trophic levels, including microbial, nematode, arthropod, annelid, and plant model systems. The deletion of mcpB resulted in an attenuation of bacterial virulence in different infection models, and wild-type virulence was restored following genetic complementation of the mutant strain. Our study indicates that the McpB chemoreceptor is linked to virulence processes and may constitute the basis for the development of alternative strategies against this pathogen.
The Secretomes of Painful Versus Nonpainful Human Schwannomatosis Tumor Cells Differentially Influence Sensory Neuron Gene Expression and Sensitivity
Authors: Ostrow Kimberly Laskie , Donaldson Katelyn J. , Caterina Michael J. , Belzberg Allan , Hoke Ahmet
Published: September 2019

Schwannomatosis is a multiple tumor syndrome in which patients develop benign tumors along peripheral nerves throughout the body. The first symptom with which schwannomatosis patients often present, prior to discovery of tumors, is pain. This pain can be debilitating and is often inadequately alleviated by pharmacological approaches. Schwannomatosis-associated pain can be localized to the area of a tumor, or widespread. Moreover, not all tumors are painful, and the occurrence of pain is often unrelated to tumor size or location. We speculate that some individual tumors, but not others, secrete factors that act on nearby nerves to augment nociception by producing neuronal sensitization or spontaneous neuronal firing. We created cell lines from human SWN tumors with varying degrees of pain. We have found that conditioned medium (CM) collected from painful SWN tumors, but not that from nonpainful SWN tumors, sensitized DRG neurons, causing increased sensitivity to depolarization by KCl, increased response to noxious TRPV1 and TRPA1 agonists and also upregulated the expression of pain-associated genes in DRG cultures. Multiple cytokines were also detected at higher levels in CM from painful tumors. Taken together our data demonstrate a differential ability of painful versus non-painful human schwannomatosis tumor cells to secrete factors that augment sensory neuron responsiveness, and thus identify a potential determinant of pain heterogeneity in schwannomatosis.
Development of Polymer Blends Based on PVA:POZ with Low Dielectric Constant for Microelectronic Applications
Authors: Aziz Shujahadeen B. , Kadir M. F. Z. , Hamsan M. H. , Woo H. J. , Brza M. A.
Published: September 2019

There is a huge request for the development of low dielectric constant polymeric materials for microelectronic applications. In thisstudy, polymer blends based on PVA:POZ with low dielectric constant has been fabricated. The results of XRD indicate that crystalline domain is enhanced at higher POZ concentration. Brilliant phases between spherulitesare attributed to the enhanced crystalline domains at high POZ content. White portions are appeared in SEM images on the surface of PVA:POZ blends. From EDX analysis, these leaked portions are referred to the POZ material. The number and sizes of the white portions were also found to increase with increasing the POZ content. Using electrical equivalent circuits (EEC), electrical impedance plots (Z″ vs Z′) are fitted for all the samples. The results of impedance study illustrated that the resistivity of the samples increases with increasing POZ concentration. From dielectric measurements, dielectric constant was found to decrease with the introduction of more POZ into the PVA polymer. It is found to be about 1.68 at 40 wt.% POZ. Insulating materials with low dielectric constant (ε′ < 2) are found to be important in the electronics manufacturing, owing to decrease in crosstalk, resistance-capacitance time delay and power dissipation in high-density circuits. Therefore, further investigations concerning the dielectric constant and impedance for all the samples are also carried out. The real and imaginary parts of electric modulus are studied, where minimizing of electrode polarization can be achieved.
Author Correction: Improved reference genome for the domestic horse increases assembly contiguity and composition
Authors: Kalbfleisch Theodore S. , Rice Edward S. , DePriest Michael S. , Walenz Brian P. , Hestand Matthew S. , Vermeesch Joris R. , O’Connell Brendan L. , Fiddes Ian T. , Vershinina Alisa O. , Saremi Nedda F. , Petersen Jessica L. , Finno Carrie J. , Bellone Rebecca R. , McCue Molly E. , Brooks Samantha A. , Bailey Ernest , Orlando Ludovic , Green Richard E. , Miller Donald C. , Antczak Douglas F. , MacLeod James N.
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Correction: Bacterial detection and identification from human synovial fluids on an integrated microfluidic system
Authors: Liu Ting-Hang , Cheng Shu-Shen , You Huey-Ling , Lee Mel S. , Lee Gwo-Bin
Published: September 2019

Correction for ‘Bacterial detection and identification from human synovial fluids on an integrated microfluidic system’ by Ting-Hang Liu et al., Analyst, 2019, 144, 1210–1222.
Trace determination of vitamin B12 in food samples by using Fe3O4 magnetic particles including multi-walled carbon nanotubes and nanodiamonds
Authors: Ulusoy Halil İbrahim , Gülle Sümeyra , Yilmaz Erkan , Soylak Mustafa
Published: September 2019

A sensitive and simple determination method for trace vitamin B12 molecules was developed based on magnetic solid phase extraction (MSPE) by using newly synthesized magnetic nanoparticles.
Facile synthesis of Pd@Pt core–shell nanocubes with low Pt contentviadirect seed-mediated growth and their enhanced activity for formic acid oxidation
Authors: Xiao Xiangyun , Jeong Hwakyeung , Song Joseph , Ahn Jae-Pyung , Kim Jongwon , Yu Taekyung
Published: September 2019

Pd@Pt core–shell nanocubes with a partially covered Pt shell on the Pd nanocubes were synthesized by a direct seed-mediated growth method without a washing process.
Simple and scalable electrochemical synthesis of 2,1-benzisoxazoles and quinoline N-oxides
Authors: Rodrigo Eduardo , Baunis Haralds , Suna Edgars , Waldvogel Siegfried R.
Published: September 2019

At carbon electrodes in a scalable electrosynthetic way to two classes of useful heterocycles.
A soluble single atom catalyst promotes lithium polysulfide conversion in lithium sulfur batteries
Authors: Shi Zhenpu , Wang Lan , Xu Huifang , Wei Junqiang , Yue Hongyun , Dong Hongyu , Yin Yanhong , Yang Shuting
Published: September 2019

CoPcCl catalyzed the Li2S decomposition and enhanced the sulfur utilization remarkably.
Molecular protection of fatty acid methyl esters within a supramolecular capsule
Authors: Wang Kaiya , Jordan Jacobs H. , Gibb Bruce C.
Published: September 2019

We describe the use of a supramolecular nano-capsule for selective protection of cis- and trans-C18 mono-unsaturated fatty-acid esters.