bluuebunny/crossref_metadata_2025 huggingface dataset:
Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors
Authors: Kovács Tünde , Mikó Edit , Vida András , Sebő Éva , Toth Judit , Csonka Tamás , Boratkó Anita , Ujlaki Gyula , Lente Gréta , Kovács Patrik , Tóth Dezső , Árkosy Péter , Kiss Borbála , Méhes Gábor , Goedert James J. , Bai Péter
Published: February 2019

Recent studies showed that changes to the gut microbiome alters the microbiome-derived metabolome, potentially promoting carcinogenesis in organs that are distal to the gut. In this study, we assessed the relationship between breast cancer and cadaverine biosynthesis. Cadaverine treatment of Balb/c female mice (500 nmol/kg p.o. q.d.) grafted with 4T1 breast cancer cells ameliorated the disease (lower mass and infiltration of the primary tumor, fewer metastases, and lower grade tumors). Cadaverine treatment of breast cancer cell lines corresponding to its serum reference range (100–800 nM) reverted endothelial-to-mesenchymal transition, inhibited cellular movement and invasion, moreover, rendered cells less stem cell-like through reducing mitochondrial oxidation. Trace amino acid receptors (TAARs), namely, TAAR1, TAAR8 and TAAR9 were instrumental in provoking the cadaverine-evoked effects. Early stage breast cancer patients, versus control women, had reduced abundance of the CadA and LdcC genes in fecal DNA, both responsible for bacterial cadaverine production. Moreover, we found low protein expression of E. coli LdcC in the feces of stage 1 breast cancer patients. In addition, higher expression of lysine decarboxylase resulted in a prolonged survival among early-stage breast cancer patients. Taken together, cadaverine production seems to be a regulator of early breast cancer.
Oxo-aglaiastatin-Mediated Inhibition of Translation Initiation
Authors: Itoua Maïga Rayelle , Cencic Regina , Chu Jennifer , Waller Daniel D. , Brown Lauren E. , Devine William G. , Zhang Wenhan , Sebag Michael , Porco John A. , Pelletier Jerry
Published: February 2019

Translation is a highly regulated process that is perturbed in human cancers, often through activation of the PI3K/mTOR pathway which impacts directly on the ribosome recruitment phase of translation initiation. While significant research has focused on “drugging” components of the PI3K/mTOR network, efforts have also been directed towards inhibiting eukaryotic initiation factor (eIF) 4F-dependent translation. Small molecule inhibitors of this complex have been identified, characterized, and used to validate the rationale of targeting this step to curtail tumor cell growth and modulate chemotherapy response. One such class of compounds are the rocaglates, secondary metabolites from the plant genus Aglaia, which target the RNA helicase subunit of eIF4F, eIF4A. Here we explore the ability of synthetic derivatives of aglaiastatins and an aglaroxin derivative to target the translation process in vitro and in vivo and find the synthetic derivative oxo-aglaiastatin to possess such activity. Oxo-aglaiastatin inhibited translation in vitro and in vivo and synergized with doxorubicin, ABT-199 (a Bcl-2 antagonist), and dexamethasone when tested on hematological cancer cells. The biological activity of oxo-aglaiastatin was shown to be a consequence of inhibiting eIF4A1 activity.
Molecular evidence for distinct modes of nutrient acquisition between visceral and neurotropic schistosomes of birds
Authors: Leontovyč Roman , Young Neil D. , Korhonen Pasi K. , Hall Ross S. , Bulantová Jana , Jeřábková Veronika , Kašný Martin , Gasser Robin B. , Horák Petr
Published: February 2019

Trichobilharzia species are parasitic flatworms (called schistosomes or flukes) that cause important diseases in birds and humans, but very little is known about their molecular biology. Here, using a transcriptomics-bioinformatics-based approach, we explored molecular aspects pertaining to the nutritional requirements of Trichobilharzia szidati (‘visceral fluke’) and T. regenti (‘neurotropic fluke’) in their avian host. We studied the larvae of each species before they enter (cercariae) and as they migrate (schistosomules) through distinct tissues in their avian (duck) host. Cercariae of both species were enriched for pathways or molecules associated predominantly with carbohydrate metabolism, oxidative phosphorylation and translation of proteins linked to ribosome biogenesis, exosome production and/or lipid biogenesis. Schistosomules of both species were enriched for pathways or molecules associated with processes including signal transduction, cell turnover and motility, DNA replication and repair, molecular transport and/or catabolism. Comparative informatic analyses identified molecular repertoires (within, e.g., peptidases and secretory proteins) in schistosomules that can broadly degrade macromolecules in both T. szidati and T. regenti, and others that are tailored to each species to selectively acquire nutrients from particular tissues through which it migrates. Thus, this study provides molecular evidence for distinct modes of nutrient acquisition between the visceral and neurotropic flukes of birds.
Intraoperative but not postoperative blood transfusion adversely affect cancer recurrence and survival following nephrectomy for renal cell carcinoma
Authors: Abu-Ghanem Yasmin , Dotan Zohar , Zilberman Dorit E. , Kaver Issac , Ramon Jacob
Published: February 2019

The association between perioperative blood transfusion (PBT) with adverse oncological outcomes have been previously reported in multiple malignancies including RCC. Nevertheless, the importance of transfusion timing is still unclear. The primary purpose of this study is to appraise whether the receipt of intraoperative blood transfusion (BT) differ from postoperative BT in regards to cancer outcomes in renal cell carcinoma (RCC) patients treated with nephrectomy. Data on 1168 patients with RCC, who underwent radical or partial nephrectomy as primary therapy between 1988–2013 were analyzed. PBT was defined as transfusion of allogeneic red blood cells (RBC) during surgery or the postsurgical period. Survival was analyzed and compared using the Kaplan–Meier method with the log-rank test. Of 1168 patients, 198 patients (16.9%) received a PBT. Including 117 intraoperative BT and 81 postoperative BT. Only 21 (10.6%) patients required both intraoperative and postoperative BT. On multivariate analyses, receipt of PBT was associated with significantly worse local disease recurrence (HR: 2.4; P = 0.017), metastatic progression (HR: 2.7; P = 0.005), cancer-specific mortality (HR: 3.5; P = 0.002) and all-cause mortality (HR: 2.1; P = 0.005). Nevertheless, postoperative BT wasnotindependently associated with increased risk of local recurrence (p = 0.1), metastatic progression (P = 0.16) or kidney cancer death (P = 0.63), yet did significantly increase the risk of overall mortality (HR: 2.6; P = 0.004). In the current study, intraoperative transfusion of allogeneic RBC is associated with increased risks of cancer recurrence and mortality following nephrectomy.
Clinical significance of filamin A in patients with acromegaly and its association with somatostatin and dopamine receptor profiles
Authors: Coelho Maria Caroline Alves , Vasquez Marina Lipkin , Wildemberg Luiz Eduardo , Vázquez-Borrego Mari C. , Bitana Luciana , Camacho Aline Helen da Silva , Silva Débora , Ogino Liana Lumi , Ventura Nina , Sánchez-Sánchez Rafael , Chimelli Leila , Kasuki Leandro , Luque Raul M. , Gadelha Mônica R.
Published: February 2019

Filamin-A (FLNA) plays a crucial role in somatostatin receptor (sst) subtype-2 signaling in somatotropinomas. Our objective was to investigate the in vivo association between FLNA and sst2 expression, sst5 expression, dopamine receptor subtype-2 (D2) expression, somatostatin receptor ligand (SRL) responsiveness and tumor invasiveness in somatotropinomas. Quantitative real-time PCR was used to evaluate the absolute mRNA copy numbers of FLNA/sst2/sst5/D2 in 96 somatotropinomas. FLNA, sst2 and sst5 protein expression levels were also evaluated using immunohistochemistry. The Knosp-Steiner criteria were used to evaluate tumor invasiveness. Median FLNA, sst2, sst5 and D2 copy numbers were 4,244, 731, 156 and 3,989, respectively. Thirty-one of the 35 available tumors (89%) were immune positive for FLNA in the cytoplasm and membrane but not in the nucleus. FLNA and sst5 expression were positively correlated at the mRNA and protein levels (p < 0.001 and p = 0.033, respectively). FLNA was positively correlated with sst2 mRNA in patients who were responsive to SRL (p = 0.014, R = 0.659). No association was found between FLNA and tumor invasiveness. Our findings show that in somatotropinomas FLNA expression positively correlated with in vivo sst5 and D2 expression. Notably, FLNA was only correlated with sst2 in patients who were controlled with SRL. FLNA was not associated with tumor invasiveness.
The Correlation between the Frontostriatal Network and Impulsivity in Internet Gaming Disorder
Authors: Kim Jin-Young , Chun Ji-Won , Park Chang-Hyun , Cho Hyun , Choi Jihye , Yang Siyun , Ahn Kook-Jin , Kim Dai Jin
Published: February 2019

As excessive use of internet gaming has become a serious public health concern, increasing studies have revealed that impulsivity is one of the important risk factors of internet gaming disorder (IGD). This study was designed to investigate the altered resting-state functional connectivity (FC) of the bilateral orbitofrontal cortex (OFC) in IGD participants and to examine its relationship with impulsivity compared with the normal controls (NC). Seed-based analyses verified that participants with IGD displayed decreased FC between the OFC and frontal, striatal, temporal and occipital regions different from NC. Moreover, IGD participants showed weankened FC from the OFC with dorsal anterior cingulate cortex as well as with dorsolateral prefrontal cortex and dorsal striatum as the results of group difference. These results could suggest that the decreased frontostriatal connectivity was associated with excessive internet gaming. Also, the increased FC in frontostriatal regions was correlated with impulse control in the NC but not the IGD participants. Further insight into the brain circuitry on frontostriatal could provide the target for developing treatment approaches of impulse control in IGD.
Estimation of Cardiovascular Relative Pressure Using Virtual Work-Energy
Authors: Marlevi David , Ruijsink Bram , Balmus Maximilian , Dillon-Murphy Desmond , Fovargue Daniel , Pushparajah Kuberan , Bertoglio Cristóbal , Colarieti-Tosti Massimiliano , Larsson Matilda , Lamata Pablo , Figueroa C. Alberto , Razavi Reza , Nordsletten David A.
Published: February 2019

Many cardiovascular diseases lead to local increases in relative pressure, reflecting the higher costs of driving blood flow. The utility of this biomarker for stratifying the severity of disease has thus driven the development of methods to measure these relative pressures. While intravascular catheterisation remains the most direct measure, its invasiveness limits clinical application in many instances. Non-invasive Doppler ultrasound estimates have partially addressed this gap; however only provide relative pressure estimates for a range of constricted cardiovascular conditions. Here we introduce a non-invasive method that enables arbitrary interrogation of relative pressures throughout an imaged vascular structure, leveraging modern phase contrast magnetic resonance imaging, the virtual work-energy equations, and a virtual field to provide robust and accurate estimates. The versatility and accuracy of the method is verified in a set of complex patient-specific cardiovascular models, where relative pressures into previously inaccessible flow regions are assessed. The method is further validated within a cohort of congenital heart disease patients, providing a novel tool for probing relative pressures in-vivo.
Extreme Accelerations During Earthquakes Caused by Elastic Flapping Effect
Authors: Goto Hiroyuki , Kaneko Yoshihiro , Young John , Avery Hamish , Damiano Len
Published: February 2019

Accurate recording of large, earthquake-induced ground shaking is critical for our understanding of earthquake physics as well as seismic hazard assessment. Extremely large accelerations with the peak value of 3.2 times the gravity acceleration were recorded at seismic station WTMC located in northern South Island of New Zealand during the recent magnitude 7.8 Kaikoura earthquake. However, the mechanisms responsible for the generation of such large accelerations are not well understood. Here we use numerical simulations to examine a range of physical models that can reproduce the observed characteristics of the acceleration record. We find that the record of the asymmetric, vertical accelerations, also observed during a magnitude 6.3 earthquake, can be explained by a flapping effect, that is, the local, elastic bouncing of a foundation slab on which the sensor is installed. Our results suggest that the extremely large accelerations recorded at seismic station WTMC do not reflect the actual ground shaking, but were caused by a local, system response around the sensor. Our finding has important implications for both the evaluation of future seismic hazard based on the waveform records of the Kaikoura earthquake and the installation methodology of strong-motion seismometers in all earthquake prone countries.
SmvA is an important efflux pump for cationic biocides in Klebsiella pneumoniae and other Enterobacteriaceae
Authors: Wand Matthew E. , Jamshidi Shirin , Bock Lucy J. , Rahman Khondaker Miraz , Sutton J. Mark
Published: February 2019

The multidrug resistant (MDR) opportunistic pathogen Klebsiella pneumoniae has previously been shown to adapt to chlorhexidine by increasing expression of the MFS efflux pump smvA. Here we show that loss of the regulator SmvR, through adaptation to chlorhexidine, results in increased resistance to a number of cationic biocides in K. pneumoniae and other members of the Enterobacteriaceae. Clinical Enterobacteriaceae isolates which lack smvA and smvR also have an increased susceptibility to chlorhexidine. When smvA from Salmonella and K. pneumoniae are expressed in Escherichia coli, which lacks a homologue to SmvAR, resistance to chlorhexidine increased (4-fold) but plasmid carriage of smvA alone was detrimental to the cell. Challenge of K. pneumoniae with chlorhexidine and another cationic biocide, octenidine, resulted in increased expression of smvA (approx. 70 fold). Adaptation to octenidine was achieved through mutating key residues in SmvA (A363V; Y391N) rather than abolishing the function of SmvR, as with chlorhexidine adaptation. Molecular modelling was able to predict that octenidine interacted more strongly with these mutated SmvA forms. These results show that SmvA is a major efflux pump for cationic biocides in several bacterial species and that increased efflux through SmvA can lead to increased chlorhexidine and octenidine tolerance.
The methylome of the celiac intestinal epithelium harbours genotype-independent alterations in the HLA region
Authors: Fernandez-Jimenez Nora , Garcia-Etxebarria Koldo , Plaza-Izurieta Leticia , Romero-Garmendia Irati , Jauregi-Miguel Amaia , Legarda Maria , Ecsedi Szilvia , Castellanos-Rubio Ainara , Cahais Vincent , Cuenin Cyrille , Degli Esposti Davide , Irastorza Iñaki , Hernandez-Vargas Hector , Herceg Zdenko , Bilbao Jose Ramon
Published: February 2019

The Human Leucocyte Antigen (HLA) locus and other DNA sequence variants identified in Genome-Wide Association (GWA) studies explain around 50% of the heritability of celiac disease (CD). However, the pathogenesis of CD could be driven by other layers of genomic information independent from sequence variation, such as DNA methylation, and it is possible that allele-specific methylation explains part of the SNP associations. Since the DNA methylation landscape is expected to be different among cell types, we analyzed the methylome of the epithelial and immune cell populations of duodenal biopsies in CD patients and controls separately. We found a cell type-specific methylation signature that includes genes mapping to the HLA region, namely TAP1 and HLA-B. We also performed Immunochip SNP genotyping of the same samples and interrogated the expression of some of the affected genes. Our analysis revealed that the epithelial methylome is characterized by the loss of CpG island (CGI) boundaries, often associated to altered gene expression, and by the increased variability of the methylation across the samples. The overlap between differentially methylated positions (DMPs) and CD-associated SNPs or variants contributing to methylation quantitative trait loci (mQTLs) is minimal. In contrast, there is a notable enrichment of mQTLs among the most significant CD-associated SNPs. Our results support the notion that DNA methylation alterations constitute a genotype-independent event and confirm its role in the HLA region (apart from the well-known, DQ allele-specific effect). Finally, we find that a fraction of the CD-associated variants could exert its phenotypic effect through DNA methylation.
Development and Evaluation of a Multiplexed Immunoassay for Simultaneous Detection of Serum IgG Antibodies to Six Human Coronaviruses
Authors: Trivedi Suvang U. , Miao Congrong , Sanchez Joseph E. , Caidi Hayat , Tamin Azaibi , Haynes Lia , Thornburg Natalie J.
Published: February 2019

Known human coronaviruses (hCoV) usually cause mild to moderate upper-respiratory tract illnesses, except SARS-CoV and MERS-CoV, which, in addition to mild illness can also be associated with severe respiratory diseases and high mortality rates. Well-characterized multiplexed serologic assays are needed to aid in rapid detection and surveillance of hCoVs. The present study describes development and evaluation of a multiplexed magnetic microsphere immunoassay (MMIA) to simultaneously detect immunoglobulin G (IgG) antibodies specific for recombinant nucleocapsid proteins (recN) from hCoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV. We used paired human sera to screen for IgG with reactivity against six hCoVs to determine assay sensitivity, specificity and reproducibility. We found no signal interference between monoplex and multiplex assay formats (R2 range = 0.87–0.97). Screening of paired human sera using MMIA, resulted in 92 of 106 (sensitivity: 86%) as positive and 68 of 80 (specificity: 84%) as negative. This study serves as a proof of concept that it is feasible to develop and use a multiplexed microsphere immunoassay as a next generation screening tool for use in large scale seroprevalence studies of hCoVs.
Relaxation study of pre-densified silica glasses under 2.5 MeV electron irradiation
Authors: Ollier Nadège , Lancry Matthieu , Martinet Christine , Martinez Valérie , Le Floch Sylvie , Neuville Daniel
Published: February 2019

We examined the “relaxation properties” of pre-densified synthetic fused silica glass under 2.5 MeV electron irradiation. The densification of the glass was either obtained by hot compression (5 GPa-350 °C and 5 GPa-1000 °C) or via a thermal treatment increasing its fictive temperature (Tf = 1050, 1250 and 1400 °C). Under irradiation, the pre-densified silica glasses exhibit a relaxation of their macroscopic density with increasing integrated dose. Density was reduced for hot compressed silica and increased for Tf samples with different relaxation rates but it is remarkable that all sample densities follow a trend towards the same equilibrium value around 2.26 for a dose larger than 10 GGy despite a different final topology. After irradiation of hot compressed silica, the Raman spectra display a significant increment of 4 and almost 3-membered rings whereas they exhibit a glass density reduction; demonstrating that a D2 band increase cannot be considered as an absolute marker of the glass compaction. The correlation between density and D2 intensity remains valid until silica density remains lower than 2.26. In contrast, the FWHM of the main band peaking at 440 cm−1 appears to remain correlated to the silica glass density for all investigated samples.
Telencephalon transcriptome analysis of chronically stressed adult zebrafish
Authors: Huang Victoria , Butler Anderson A. , Lubin Farah D.
Published: February 2019

Chronic stress leads to disruptions in learning and memory processes. The effects of chronic stress experience on the adult zebrafish brain, particularly the memory associated telencephalon brain region, is unclear. The goal of this study was to identify gene expression changes in the adult zebrafish brain triggered by chronic unpredictable stress. Transcriptome analysis of the telencephalon revealed 155 differentially expressed genes. Of these genes, some are critical genes involved in learning and memory, such ascdk5andchrna7, indicating effects of chronic unpredictable stress on zebrafish memory. Interestingly, several genes were annotated in the Orange domain, which is an amino acid sequence present in eukaryotic DNA-binding transcription repressors. Furthermore, we identifiedhsd11b2, a cortisol inactivating gene, as chronic stress-responsive in the whole zebrafish brain. Collectively, these findings suggest that memory associated gene expression changes in adult zebrafish telencephalon are affected by chronic stress experience.
Induced vergence-accommodation conflict reduces cognitive performance in the Stroop test
Authors: Daniel François , Kapoula Zoï
Published: February 2019

Interaction mechanisms between cognition and binocular motor control in reading saccades remain unclear. In this study we examine objectively saccades and fixations parameters during the Stroop test, involving three different levels of cognitive demand (reading, color denomination and interference). In addition, we experimentally induce accommodation and vergence conflicts during the different tasks. Twenty-one visually normal subjects (age 20.9 ± 1.45) performed the Stroop test in three different randomized conditions: a control normal viewing condition, a 16Δ base-out prism condition, and a −2.50D spherical lenses condition. Prisms and spherical lenses induced Vergence-Accommodation conflict. Eye movements were recorded with the Eyeseecam video-oculography device. The results show (1) longer fixation duration in the interference task than in the denomination task, and shorter fixation duration in the reading task; (2) a higher interference effect in the conflict induced conditions compared to the control condition; (3) a lower tolerance to prism induced conflict, with a higher destabilization of the binocular motor control of saccades and fixations. This suggests an interplay between vergence accommodation conflict and cognitive load: tolerance to the conflict seems to be lower in the more cognitively demanding interference Stroop task. The results consolidate the link between cognition and high quality of single binocular vision.
Reconstitution of the embryonic kidney identifies a donor cell contribution to the renal vasculature upon transplantation
Authors: Murakami Yoichi , Naganuma Hidekazu , Tanigawa Shunsuke , Fujimori Toshihiko , Eto Masatoshi , Nishinakamura Ryuichi
Published: February 2019

The kidney possesses a highly organised vasculature that is required for its filtration function. While recent advances in stem cell biology have enabled the in vitro generation of kidney tissues, at least partially, recapitulation of the complicated vascular architecture remains a huge challenge. Herein we develop a method to reconstitute both the kidney and its vascular architecture in vitro, using dissociated and sorted mouse embryonic kidney cells. Upon transplantation, arteriolar networks were re-established that ran through the interstitial space between branching ureteric buds and eventually entered glomeruli. Using this system, we found that donor-derived endothelial cells significantly contributed to the arterioles and glomerular capillaries formed after transplantation. Unexpectedly, the near-complete depletion of canonical endothelial cells from the donor embryonic kidney suggested the existence of unidentified donor-derived endothelial precursors that were negative for canonical endothelial markers, but still contributed significantly to the vasculature in the transplants. Thus, our protocol will serve as a useful platform for identification of renal endothelial precursors and induction of these precursors from pluripotent stem cells.
The pro-inflammatory stimulus of zinc- and copper-containing welding fumes in whole blood assay via protein tyrosine phosphatase 1B inhibition
Authors: Bleidorn Johannes , Alamzad-Krabbe Hanif , Gerhards Benjamin , Kraus Thomas , Brand Peter , Krabbe Julia , Martin Christian
Published: February 2019

An asymptomatic systemic inflammation after exposure to zinc- and copper-containing welding fumes has been described as mild form of metal fume fever in recent studies. Since chronic systemic inflammation leads to a higher cardiovascular risk, examining the inflammation with the underlying pathomechanism is necessary to estimate and hopefully prevent long-term effects of welding. We established a whole blood assay to investigate the effects of zinc- and copper-containing welding fume particles on the blood immune response. Increased levels of IL-6, IL-8, TNFα and IL-1β determined after 24 hours of exposure indicated an acute systemic inflammatory reaction. In vitro increases of IL-6 were comparable to in vivo increases of serum IL-6 levels in a study with welding fume exposure of human subjects. Inhibition of PTP1B was identified as one pathway responsible for the effects of zinc- and copper-containing welding fumes and therefore welding fume fever. In conclusion, the whole blood assay is a reliable and feasible method to investigate effects of zinc- and copper-containing welding fumes on the immune system and as a surrogate for systemic inflammation and welding fume fever. Future research can utilize whole blood assays to reduce and partially replace human exposure studies for further investigations of welding fume fever.
Comparison of MRI-based automated segmentation methods and functional neurosurgery targeting with direct visualization of the Ventro-intermediate thalamic nucleus at 7T
Authors: Najdenovska Elena , Tuleasca Constantin , Jorge João , Maeder Philippe , Marques José P. , Roine Timo , Gallichan Daniel , Thiran Jean-Philippe , Levivier Marc , Bach Cuadra Meritxell
Published: February 2019

The ventro-intermediate nucleus (Vim), as part of the motor thalamic nuclei, is a commonly used target in functional stereotactic neurosurgery for treatment of drug-resistant tremor. As it cannot be directly visualized on routinely used magnetic resonance imaging (MRI), its clinical targeting is performed using indirect methods. Recent literature suggests that the Vim can be directly visualized on susceptibility-weighted imaging (SWI) acquired at 7 T. Our work aims to assess the distinguishable Vim on 7 T SWI in both healthy-population and patients and, using it as a reference, to compare it with: (1) The clinical targeting, (2) The automated parcellation of thalamic subparts based on 3 T diffusion MRI (dMRI), and (3) The multi-atlas segmentation techniques. In 95.2% of the data, the manual outline was adjacent to the inferior lateral border of the dMRI-based motor-nuclei group, while in 77.8% of the involved cases, its ventral part enclosed the Guiot points. Moreover, the late MRI signature in the patients was always observed in the anterior part of the manual delineation and it overlapped with the multi-atlas outline. Overall, our study provides new insight on Vim discrimination through MRI and imply novel strategies for its automated segmentation, thereby opening new perspectives for standardizing the clinical targeting.
Generation of bat-derived influenza viruses and their reassortants
Authors: Sato Masahiro , Maruyama Junki , Kondoh Tatsunari , Nao Naganori , Miyamoto Hiroko , Takadate Yoshihiro , Furuyama Wakako , Kajihara Masahiro , Ogawa Hirohito , Manzoor Rashid , Yoshida Reiko , Igarashi Manabu , Takada Ayato
Published: February 2019

Two novel influenza A virus-like genomes were detected in fruit bats in Central and South America. However, the biological properties of these bat-derived influenza viruses (BatIVs) are still largely unknown since infectious viral particles have never been isolated from the infected host species. In this study, a reverse genetics approach was used to generate infectious BatIV particles entirely from plasmids encoding full-length sequences in eight gene segments. We inoculated BatIV particles into various cell cultures including bat-derived cell lines and found that BatIVs infected particular bat-derived cells efficiently but not the other cell lines tested. Reassortant viruses between the two BatIVs were also successfully generated and their replication in the susceptible bat cell lines was confirmed. These findings suggest a limited host range and reassortment potential of BatIVs in nature, providing fundamental information for understanding of the ecology of BatIVs.
Herpes simplex virus type 1 epidemiology in the Middle East and North Africa: systematic review, meta-analyses, and meta-regressions
Authors: Chaabane Sonia , Harfouche Manale , Chemaitelly Hiam , Schwarzer Guido , Abu-Raddad Laith J.
Published: February 2019

This study aimed at characterizing herpes simplex virus type 1 (HSV-1) epidemiology in the Middle East and North Africa (MENA). HSV-1 records were systematically reviewed. Findings were reported following the PRISMA guidelines. Random-effects meta-analyses were implemented to estimate pooled mean HSV-1 seroprevalence. Random-effects meta-regressions were conducted to identify predictors of higher seroprevalence. Thirty-nine overall seroprevalence measures yielding 85 stratified measures were identified and included in the analyses. Pooled mean seroprevalence was 65.2% (95% CI: 53.6–76.1%) in children, and 91.5% (95% CI: 89.4–93.5%) in adults. By age group, seroprevalence was lowest at 60.5% (95% CI: 48.1–72.3%) in <10 years old, followed by 85.6% (95% CI: 80.5–90.1%) in 10–19 years old, 90.7% (95% CI: 84.7–95.5%) in 20–29 years old, and 94.3% (95% CI: 89.5–97.9%) in ≥30 years old. Age was the strongest predictor of seroprevalence explaining 44.3% of the variation. Assay type, sex, population type, year of data collection, year of publication, sample size, and sampling method were not significantly associated with seroprevalence. The aprioriconsidered factors explained 48.6% of the variation in seroprevalence. HSV-1 seroprevalence persists at high levels in MENA with most infections acquired in childhood. There is no evidence for declines in seroprevalence despite improving socio-economic conditions.
Growth, photosynthesis, and nutrient uptake in wheat are affected by differences in nitrogen levels and forms and potassium supply
Authors: Guo Jiuxin , Jia Yamin , Chen Huanhuan , Zhang Lijun , Yang Jinchang , Zhang Jun , Hu Xiangyu , Ye Xin , Li Yan , Zhou Yi
Published: February 2019

Nitrogen (N) and potassium (K) are essential macronutrients for plants growth; however, the mechanism by which K mediates negative effects on ammonium-sensitive plants is still poorly understood. We hypothesized that K supplies may enhance antagonistic ammonium stress while improving nitrate nutrition function, which wheat seedlings were grown in sand culture in the presence of two N forms (ammonium; nitrate) supplied at two rates (2, 10 mmol L−1) and three K levels (0.5, 5, 15 mmol L−1). We found that a high N rate increased plant biomass under nitrate nutrition, while it had a negative effect under ammonium nutrition. Compared with nitrate, biomass was depressed by 54% or 85% for low or high N rate under ammonium. This resulted in a reduction in gas exchange parameters and a subsequent decrease in growth variables and nutrient uptake, whereas these parameters increased significantly with increasing K levels. Moreover, in principal components analysis, these variations were highly clustered under nitrate nutrition and highly separated under ammonium nutrition. Our study shows a clear positive interaction between K and N, suggesting that high K supply relieves ammonium stress while improving growth vigor under nitrate nutrition by enhancing nutrient uptake and assimilate production in wheat plants.
Understanding HLA associations from SNP summary association statistics
Authors: Lim Jiwoo , Bae Sang-Cheol , Kim Kwangwoo
Published: February 2019

Strong genetic associations in the region containing human leukocyte antigen (HLA) genes have been well-documented in various human immune disorders. Imputation methods to infer HLA variants from single nucleotide polymorphism (SNP) genotypes are currently used to understand HLA associations with a trait of interest. However, it is challenging for some researchers to obtain individual-level SNP genotype data or reference haplotype data. In this study, we developed and evaluated a new method, DISH (direct imputing summary association statistics of HLA variants), for imputing summary association statistics of HLA variants from SNP summary association statistics based on linkage disequilibria in Asian and European populations. Disease association Z scores in DISH were highly correlated with those from imputed HLA genotypes in null model datasets (r = 0.934 in Asians; r = 0.960 in Europeans). We applied DISH to two previous GWAS datasets in Asian systemic lupus erythematosus and European rheumatoid arthritis populations. There was a high correlation between Z scores in the DISH and HLA genotype imputations, showing the same disease-susceptible and protective alleles. This study illustrated the usefulness of the DISH method in understanding and identifying disease-associated HLA variants in human diseases while maintaining individual-level data security.
Acute changes in cardiac structural and tissue characterisation parameters following haemodialysis measured using cardiovascular magnetic resonance
Authors: Kotecha Tushar , Martinez-Naharro Ana , Yoowannakul Suree , Lambe Tabitha , Rezk Tamer , Knight Daniel S. , Hawkins Philip N. , Moon James C. , Muthurangu Vivek , Kellman Peter , Rakhit Roby D. , Gillmore Julian D. , Jeetley Paramjit , Davenport Andrew , Fontana Marianna
Published: February 2019

In patients with chronic kidney disease (CKD), reverse left ventricular (LV) remodelling, including reduction in LV mass, can be observed following long-term haemodialysis (HD) and has been attributed to regression of LV hypertrophy. However, LV mass can vary in response to changes in myocyte volume, edema, or fibrosis. The aims of this study were to investigate the acute changes in structural (myocardial mass and biventricular volumes) and tissue characterization parameters (native T1 and T2) following HD using cardiovascular magnetic resonance (CMR). Twenty-five stable HD patients underwent non-contrast CMR including volumetric assessment and native T1 and T2 mapping immediately pre- and post-HD. The mean time between the first and second scan was 9.1 ± 1.1 hours and mean time from completion of dialysis to the second scan was 3.5 ± 1.3 hours. Post-HD, there was reduction in LV mass (pre-dialysis 98.9 ± 36.9 g/m2 vs post-dialysis 93.3 ± 35.8 g/m2, p = 0.003), which correlated with change in body weight (r = 0.717, p < 0.001). Both native T1 and T2 reduced significantly following HD (Native T1: pre-dialysis 1085 ± 43 ms, post-dialysis 1072 ± 43 ms; T2: pre-dialysis 53.3 ± 3.0 ms, post-dialysis 51.8 ± 3.1 ms, both p < 0.05). These changes presumably reflect acute reduction in myocardial water content rather than regression of LV hypertrophy. CMR with multiparametric mapping is a promising tool to assess the cardiac changes associated with HD.
Mathematical Structures in Group Decision-Making on Resource Allocation Distributions
Authors: Friedkin Noah E. , Proskurnikov Anton V. , Mei Wenjun , Bullo Francesco
Published: February 2019

Optimal decisions on the distribution of finite resources are explicitly structured by mathematical models that specify relevant variables, constraints, and objectives. Here we report analysis and evidence that implicit mathematical structures are also involved in group decision-making on resource allocation distributions under conditions of uncertainty that disallow formal optimization. A group’s array of initial distribution preferences automatically sets up a geometric decision space of alternative resource distributions. Weighted averaging mechanisms of interpersonal influence reduce the heterogeneity of the group’s initial preferences on a suitable distribution. A model of opinion formation based on weighted averaging predicts a distribution that is a feasible point in the group’s implicit initial decision space.
Improved Configuration and LSPR Response of Platinum Nanoparticles via Enhanced Solid State Dewetting of In-Pt Bilayers
Authors: Kunwar Sundar , Sui Mao , Pandey Puran , Gu Zenan , Pandit Sanchaya , Lee Jihoon
Published: February 2019

Noble metallic nanoparticles (NPs) can exhibit valuable properties such as localized surface plasmon resonance (LSPR) and large surface to volume ratio, which can find various optoelectronic and catalytic applications. In this work, the improved configuration and uniformity of platinum (Pt) NPs are demonstrated by using a sacrificial indium (In) layer via the enhanced solid state dewetting of In-Pt bilayers on sapphire (0001). In a sharp contrast to the conventional dewetting of intrinsic Pt film, the introduction of In component can significantly enhance the global dewetting process and thus can result in the fabrication of well-defined Pt NPs with the improved uniformity. This can be due to the fact that In possess high diffusivity, low surface energy and low sublimation temperature. Upon annealing, the intermixing of In and Pt atoms can occur at the interface due to the inter-diffusion, which forms In-Pt alloy system. As a result, the overall diffusivity and dewetting degree of system can be significantly improved and this can produce more isolated, uniform and semispherical Pt NPs at much lower temperatures as compared to the pure Pt film dewetting. Conveniently, the In atoms preferentially can be removed from the NP matrix by the sublimation even at relatively low temperatures. These Pt NPs exhibit dynamic LSPR band in the UV-visible wavelength based on the excitation of dipolar, quadrupolar and higher order resonance modes. Specifically, the LSPR wavelength can be tuned between ~480 and 580 nm by the fabrication of small to large size Pt NPs with the distinct configuration and interparticle spacing. Furthermore, at a constant Pt thickness, the size, spacing and density of Pt NPs can be readily tuned by the control of In layer thickness. The introduction of sacrificial In component can enable an additional flexibility for the control of surface morphologies of metallic NPs with the low diffusivity materials.
High-resolution fingerprinting of Candida parapsilosis isolates suggests persistence and transmission of infections among neonatal intensive care unit patients in Kuwait
Authors: Asadzadeh Mohammad , Ahmad Suhail , Al-Sweih Noura , Hagen Ferry , Meis Jacques F. , Khan Ziauddin
Published: February 2019

Candida parapsilosis causes ~35% of all candidemia cases in neonates. High-resolution fingerprinting of C. parapsilosis isolates from neonatal intensive care unit (NICU) patients in Maternity Hospital (MH) was performed to identify epidemiologically related strains. Sixty-eight bloodstream/colonizing strains isolated from 59 NICU patients, two isolates from health care workers (HCWs) from MH and 18 bloodstream isolates from two other hospitals were used. Six microsatellite markers were employed, isolates were assigned a numerical microsatellite genotype (MSG), dendrogram was constructed and similarities between genotypes were visualized by minimum spanning tree. Fifty bloodstream isolates from MH yielded 37 MSGs with 20 isolates clustering in 7 MSGs. Duplicate isolates and colonizing strains yielded same/highly similar MSG as bloodstream isolates. Colonizing strains from two non-candidemia patients yielded unique MSGs while others belonged to a cluster. All isolates from HCWs and from two other hospitals belonged to unique MSGs. Cluster isolates came from patients in NICU-1 or from neonates in NICU-1 and other NICUs. Clonal complexes comprising closely related genotypes indicative of microevolution were also detected. Our data show that some C. parapsilosis strains have persisted in MH environment over several years and these endemic genotypes were transmitted to other patients in NICU-1 and/or other nearby NICUs.
Heterodera glycines utilizes promiscuous spliced leaders and demonstrates a unique preference for a species-specific spliced leader over C. elegans SL1
Authors: Barnes Stacey N. , Masonbrink Rick E. , Maier Thomas R. , Seetharam Arun , Sindhu Anoop S. , Severin Andrew J. , Baum Thomas J.
Published: February 2019

Spliced leader trans-splicing (SLTS) plays a part in the maturation of pre-mRNAs in select species across multiple phyla but is particularly prevalent in Nematoda. The role of spliced leaders (SL) within the cell is unclear and an accurate assessment of SL occurrence within an organism is possible only after extensive sequencing data are available, which is not currently the case for many nematode species. SL discovery is further complicated by an absence of SL sequences from high-throughput sequencing results due to incomplete sequencing of the 5’-ends of transcripts during RNA-seq library preparation, known as 5′-bias. Existing datasets and novel methodology were used to identify both conserved SLs and unique hypervariable SLs within Heterodera glycines, the soybean cyst nematode. In H. glycines, twenty-one distinct SL sequences were found on 2,532 unique H. glycines transcripts. The SL sequences identified on the H. glycines transcripts demonstrated a high level of promiscuity, meaning that some transcripts produced as many as nine different individual SL-transcript combinations. Most uniquely, transcriptome analysis revealed that H. glycines is the first nematode to demonstrate a higher SL trans-splicing rate using a species-specific SL over well-conserved Caenorhabditis elegans SL-like sequences.
Tuberculosis-associated anemia is linked to a distinct inflammatory profile that persists after initiation of antitubercular therapy
Authors: Gil-Santana Leonardo , Cruz Luís A. B. , Arriaga María B. , Miranda Pryscila F. C. , Fukutani Kiyoshi F. , Silveira-Mattos Paulo S. , Silva Elisangela C. , Oliveira Marina G. , Mesquita Eliene D. D. , Rauwerdink Anneloek , Cobelens Frank , Oliveira Martha M. , Kritski Afranio , Andrade Bruno B.
Published: February 2019

Pulmonary tuberculosis (PTB) is associated with chronic inflammation and anemia. How anemia impacts systemic inflammation in PTB patients undergoing antitubercular therapy (ATT) is not fully understood. In the present study, data on several blood biochemical parameters were retrospectively analyzed from 118 PTB patients during the first 60 days of ATT. Multidimensional statistical analyses were employed to perform detailed inflammatory profiling of patients stratified by anemia status prior to treatment. Anemia was defined as hemoglobin levels <12.5 g/dL for female and <13.5 g/dL for male individuals. The findings revealed that most of anemia cases were likely caused by chronic inflammation. A distinct biosignature related to anemia was detected, defined by increased values of uric acid, C-reactive protein, and erythrocyte sedimentation rate. Importantly, anemic patients sustained increased levels of several biochemical markers at day 60 of therapy. Preliminary analysis failed to demonstrate association between persistent inflammation during ATT with frequency of positive sputum cultures at day 60. Thus, TB patients with anemia exhibit a distinct inflammatory profile, which is only partially reverted at day 60 of ATT.
Dust Vortex in the Taklimakan Desert by Himawari-8 High Frequency and Resolution Observation
Authors: Yumimoto Keiya , Kajino Mizuo , Tanaka Taichu Y. , Uno Itsushi
Published: February 2019

The Taklimakan Desert is known to be one of the world’s major sources of aeolian dust particles. Continuous images with 10-min temporal and 2-km spatial resolutions from a new-generation geostationary meteorological satellite captured the lifecycle (generation, evolution and outflow) of a previously unrecognized type of Taklimakan dust storm. The dust storm showed an anti-clockwise spiral structure and a clear core and behaved like a “dust vortex”. From image analysis, the horizontal scale and temporal lifetime of the dust vortex were estimated to be 600 km and 36 hours, respectively. We found that a strong pressure trough (cut-off low), along with a cold air mass located on the northwestern side of the Taklimakan Desert and the high mountains surrounding the Taklimakan Desert, played important roles in the formation and evolution of the dust vortex.
Diagnostic accuracy of low-radiation coronary computed tomography angiography with low tube voltage and knowledge-based model reconstruction
Authors: Lee Joohee , Kim Tae Hoon , Lee Byoung Kwon , Yoon Young Won , Kwon Hyuck Moon , Hong Bum Kee , Min Pil-Ki , Choi Eui-Young , Oh Chi Suk , Park Chul Hwan
Published: February 2019

We aimed to evaluate the accuracy of coronary computed tomography angiography (CCTA) with a low-radiation protocol and iterative model reconstruction (IMR), in comparison with invasive coronary angiography (ICA). Sixty-one patients (45 males; mean age, 61.9 ± 9.2 years) with suspected coronary artery disease who underwent CCTA and ICA were retrospectively enrolled. CCTA was performed with low tube voltage (80 or 100 kVp), low tube current (100–200 mAs), prospective ECG triggering, and IMR using a 64-slice computed tomography scanner. Coronary artery disease was defined as luminal narrowing of >50%, as assessed using CCTA and ICA. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive value, and accuracy of CCTA were examined. The mean radiation dose of CCTA was 1.05 ± 0.36 mSv. No non-diagnostic segment was noted. The sensitivity, specificity, PPV, NPV, and accuracy of CCTA were 86.4%, 96.1%, 80.3%, 97.5%, and 94.6% on a per segment basis, 93.1%, 94.7%, 88.3%, 97.0%, and 94.2% on a per vessel basis, and 100%, 83.3%, 93.5%, 100%, and 95.1% on a per patient basis, respectively. In conclusion, a low-radiation CCTA protocol with IMR may be useful for diagnosing coronary artery disease, as it reduces the radiation dose while maintaining diagnostic accuracy.
Experimental and simulation results of the adsorption of Mo and V onto ferrihydrite
Authors: Brinza Loredana , Vu Hong Phuc , Neamtu Mariana , Benning Liane G.
Published: February 2019

This study aims to highlight discrepancies between experimental and simulation linked to the mechanisms of Mo and V adsorption onto ferrihydrite (FHY) nanoparticles. We have measured adsorption capacities and uptake efficiencies and then fitted and compared these with outputs from various geochemical and adsorption models that were run as a function of pH, surface area (SA) and ferrihydrite particles size distributions. Our results revealed that the experimental data for the Mo system could be fitted very well, but this was not the case for the V system, when a model default value for the SA of FHY of 600 m2 g−1 was used. The discrepancy in the results for the V system can be explained by the lack of specific V species and/or associated constants in databases and variation in software versions, which change the outputted chemical species. Our comparative results also confirm that any experimental variables used as modelling inputs need to be checked carefully prior to any modelling exercises.