bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Xpert MTB/RIF with measures to assess Mycobacterium tuberculosis bacillary burden in high HIV burden areas of Southern Africa
Authors: Beynon Fenella , Theron Grant , Respeito Durval , Mambuque Edson , Saavedra Belen , Bulo Helder , Sanz Sergi , Dheda Keertan , Garcia-Basteiro Alberto L.
Published: March 2018

Traditionally, smear microscopy has been used as a point-of-care measure of bacillary burden in tuberculosis patients to inform infection control and contact tracing. Xpert MTB/RIF has the potential to replace smear. However, data to support the use of its quantitative output [cycle threshold (CT)] as an alternate point-of-care measure of bacillary burden are limited. This study assessed the correlation (Spearman’s) between CT, smear, culture time-to-positivity (TTP), and clinical factors in patients with Xpert-positive sputum from Mozambique (n = 238) and South Africa (n = 462). Mean CT and smear grade correlated well (ρ0.72); compared to TTP and smear (ρ0.61); and mean CT and TTP (ρ0.50). In multivariate analyses, lower CT (higher bacillary load) was associated with negative HIV serostatus and low BMI. A smear positivity rule-out (95% sensitivity) CT cut-off of 28.0 was identified, with 54.1% specificity, 2.07 positive likelihood ratio, 0.09 negative likelihood ratio and 79.0% correctly classified. Cut-offs were higher for HIV positive compared to HIV negative individuals for any set sensitivity level. This study suggests Xpert CT values correlate well with smear, both in HIV positive and negative individuals, and that CT cut-offs might be broadly applicable to multiple settings. Studies to directly assess the association of CT with infectiousness are needed.
Adipose mesenchymal stem cells from osteoporotic donors preserve functionality and modulate systemic inflammatory microenvironment in osteoporotic cytotherapy
Authors: Zheng Chen-Xi , Sui Bing-Dong , Liu Nu , Hu Cheng-Hu , He Tao , Zhang Xin-Yi , Zhao Pan , Chen Ji , Xuan Kun , Jin Yan
Published: March 2018

Maintenance of bone homeostasis against diseased microenvironments remains as a major challenge. Recently, mesenchymal stem cells (MSCs) have been unravelled as potent microenvironmental modulators, the systemic infusion of which in cytotherapy can prevent or rescue extensive bone loss via anti-inflammation. However, MSCs also accept microenvironmental regulations; particularly, MSCs from bone marrow (BMMSCs) are prone to pathological microenvironmental factors of bone. In this study, we discovered that BMMSCs from osteoporotic donors of ovariectomized (OVX) mice lost their anti-inflammatory capability and failed to prevent bone loss when infused back into OVX recipients. Nevertheless, MSCs from adipose tissues (ADMSCs) preserved their anti-inflammatory capacity, despite diseased microenvironments of OVX donors, and continued to show protective effects on bone in OVX recipients. In the cellular level, the anti-inflammatory superiority of osteoporotic donor-derived ADMSCs over BMMSCs existed in their distinctive capability to induce T-cell apoptosis, which was molecularly attributed to retained expression levels of critical immunomodulatory genes. Furthermore, these functional discrepancies of BMMSCs and ADMSCs were due to differential stemness, energy metabolism and anti-oxidative defence system, underlying general disparity in their cellular states. Collectively, our findings optimize osteoporotic cytotherapy by using ADMSCs in resistance to and in modulation of diseased microenvironments.
Untargeted metabolomics reveals a new mode of action of pretomanid (PA-824)
Authors: Baptista Rafael , Fazakerley David M. , Beckmann Manfred , Baillie Les , Mur Luis A. J.
Published: March 2018

Pretomanid is a promising anti-tubercular drug currently at clinical phase III, but its mechanisms of action are currently unclear. This study aimed to: (i) reveal the metabolome of Mycobacterium smegmatis under pretomanid treatment; (ii) compare major sources of metabolite variation in bacteria treated with pretomanid treatment and other antibiotics; and (iii) to target metabolites responsible for the killing activity of pretomanid in mycobacteria. Untargeted high-resolution metabolite profiling was carried out using flow infusion electrospray ion high resolution mass spectrometry (FIE-HRMS) to identify and quantify metabolites. The identification of key metabolites was independently confirmed by gas-chromatography time-of flight mass spectrometry (GC-tofMS) in comparison to standards. Pretomanid treatments generated a unique distinctive metabolite profile when compared to ampicillin, ethambutol, ethionamide, isoniazid, kanamycin, linezolid, rifampicin and streptomycin. Metabolites which differed significantly only with pretomanid treatment were identified and mapped on to bacterial metabolic pathways. This targeted the pentose phosphate pathway with significant accumulation seen with fructose-6-phosphate, ribose-5-phosphate and glyceraldehyde-3-phosphate. These effects were linked to the accumulation of a toxic metabolite methylglyoxal. This compound showed significant antimicrobial activity (MIC 0.65 mM) against M. smegmatis.
Results of the radiation dose of head, body and tail of hippocampus in nasopharyngeal carcinoma patients treated with intensity modulated radiotherapy
Authors: Zong-wen Sun , lei Shi , Qinglin Li , yue Kong , feng-lei Du , Tie-ming Xie , Yong-hong Hua , Qiao-ying Hu , Xiao-zhong Chen , Yuan-yuan Chen , Ming Chen
Published: March 2018

This study is to analyze the radiation dose of head, body and tail of hippocampus (HC) of nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). Evaluate cognitive function of patients with Wechsler adult intelligence scale-Chinese revised (WAIS-CR). HC were segmented into HC head (HH), HC body (HB) and HC tail (HT) and the indexes were then analyzed. WAIS-CR was tested before and 3months after radiotherapy. The mean radiation dose of left and right HC was (1147 ± 976)cGy, (1011 ± 602)cGy respectively. The radiation dose and the volume exposed in different dose of HH, HB and HT decreased in turn. For 5 patients, before and after radiotherapy, the regular-order score was 8.60 ± 1.34, 8.0 ± 1.00 (P = 0.43), while the reverse-order score was 5.80 ± 0.84, 5.20 ± 0.84 (P = 0.07). The radiation dose of HH, HB and HT was different, and the radiation dose of HH was the highest, which should be emphasized especially.
Author Correction: Evaporative deposition of polystyrene microparticles on PDMS surface
Authors: Yu Ying-Song , Wang Ming-Chao , Huang Xianfu
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
No perceptual prioritization of non-nociceptive vibrotactile and visual stimuli presented on a sensitized body part
Authors: Torta D. M. , Filbrich L. , Van Den Broeke E. N. , Legrain V.
Published: March 2018

High frequency electrical conditioning stimulation (HFS) is an experimental method to induce increased mechanical pinprick sensitivity in the unconditioned surrounding skin (secondary hyperalgesia). Secondary hyperalgesia is thought to be the result of central sensitization, i.e. increased responsiveness of nociceptive neurons in the central nervous system. Vibrotactile and visual stimuli presented in the area of secondary hyperalgesia also elicit enhanced brain responses, a finding that cannot be explained by central sensitization as it is currently defined. HFS may recruit attentional processes, which in turn affect the processing of all stimuli. In this study we have investigated whether HFS induces perceptual biases towards stimuli presented onto the sensitized arm by using Temporal Order Judgment (TOJ) tasks. In TOJ tasks, stimuli are presented in rapid succession on either arm, and participants have to indicate their perceived order. In case of a perceptual bias, the stimuli presented on the attended side are systematically reported as occurring first. Participants performed a tactile and a visual TOJ task before and after HFS. Analyses of participants’ performance did not reveal any prioritization of the visual and tactile stimuli presented onto the sensitized arm. Our results provide therefore no evidence for a perceptual bias towards tactile and visual stimuli presented onto the sensitized arm.
Metabolomic Prediction of Human Prostate Cancer Aggressiveness: Magnetic Resonance Spectroscopy of Histologically Benign Tissue
Authors: Vandergrift Lindsey A. , Decelle Emily A. , Kurth Johannes , Wu Shulin , Fuss Taylor L. , DeFeo Elita M. , Halpern Elkan F. , Taupitz Matthias , McDougal W. Scott , Olumi Aria F. , Wu Chin-Lee , Cheng Leo L.
Published: March 2018

Prostate cancer alters cellular metabolism through events potentially preceding cancer morphological formation. Magnetic resonance spectroscopy (MRS)-based metabolomics of histologically-benign tissues from cancerous prostates can predict disease aggressiveness, offering clinically-translatable prognostic information. This retrospective study of 185 patients (2002–2009) included prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia (BPH) (n = 15), and biopsy cores from cancer-negative patients (n = 14). Tissues were measured with high resolution magic angle spinning (HRMAS) MRS, followed by quantitative histology using the Prognostic Grade Group (PGG) system. Metabolic profiles, measured solely from 338 of 365 histologically-benign tissues from cancerous prostates and divided into training-testing cohorts, could identify tumor grade and stage, and predict recurrence. Specifically, metabolic profiles: (1) show elevated myo-inositol, an endogenous tumor suppressor and potential mechanistic therapy target, in patients with highly-aggressive cancer, (2) identify a patient sub-group with less aggressive prostate cancer to avoid overtreatment if analysed at biopsy; and (3) subdivide the clinicopathologically indivisible PGG2 group into two distinct Kaplan-Meier recurrence groups, thereby identifying patients more at-risk for recurrence. Such findings, achievable by biopsy or prostatectomy tissue measurement, could inform treatment strategies. Metabolomics information can help transform a morphology-based diagnostic system by invoking cancer biology to improve evaluation of histologically-benign tissues in cancer environments.
Multilocus genetic profile in dopaminergic pathway modulates the striatum and working memory
Authors: Wang Chao , Liu Bing , Zhang Xiaolong , Cui Yue , Yu Chunshui , Jiang Tianzi
Published: March 2018

Dopamine is critical in pathophysiology and therapy of schizophrenia. Many studies have reported altered dopaminergic activity in the dorsal but not ventral striatum in schizophrenia. Based on the largest genome-wide association study of schizophrenia to date, we calculated the polygenic risk score (PGRS) of each subject in a healthy general group, including all variations in the set of functionally related genes involved in dopamine neurotransmitter system. We aimed to test whether the genetic variations in the dopaminergic pathway that have been identified as associated with schizophrenia are related to the function of the striatum and to working memory. We found that a higher PGRS was significantly associated with impairment in working memory. Moreover, resting-state functional connectivity analysis revealed that as the polygenic risk score increased, the connections between left putamen and caudate and the default mode network grew stronger, while the connections with the fronto-parietal network grew weaker. Our findings may shed light on the biological mechanism underlying the “dopamine hypothesis” of schizophrenia and provide some implications regarding the polygenic effects on the dopaminergic activity in the risk for schizophrenia.
A Poroelastic Model of a Fibrous-Porous Tissue Engineering Scaffold
Authors: Yuan Daniel , Somers Sarah M. , Grayson Warren L. , Spector Alexander A.
Published: March 2018

Tissue engineering scaffolds are used in conjunction with stem cells for the treatment of various diseases. A number of factors provided by the scaffolds affect the differentiation of stem cells. Mechanical cues that are part of the natural cellular microenvironment can both accelerate the differentiation toward particular cell lineages or induce differentiation to an alternative cell fate. Among such factors, there are externally applied strains and mechanical (stiffness and relaxation time) properties of the extracellular matrix. Here, the mechanics of a fibrous-porous scaffold is studied by applying a coordinated modeling and experimental approach. A force relaxation experiment is used, and a poroelastic model associates the relaxation process with the fluid diffusion through the fibrous matrix. The model parameters, including the stiffness moduli in the directions along and across the fibers as well as fluid diffusion time, are estimated by fitting the experimental data. The time course of the applied force is then predicted for different rates of loading and scaffold porosities. The proposed approach can help in a reduction of the technological and experimental efforts to produce 3-D scaffolds for regenerative medicine as well as in a higher accuracy of the estimation of the local factors sensed by stem cells.
Identification of highly effective target genes for RNAi-mediated control of emerald ash borer, Agrilus planipennis
Authors: Rodrigues Thais B. , Duan Jian J. , Palli Subba R. , Rieske Lynne K.
Published: March 2018

Recent study has shown that RNA interference (RNAi) is efficient in emerald ash borer (EAB), Agrilus planipennis, and that ingestion of double-stranded RNA (dsRNA) targeting specific genes causes gene silencing and mortality in neonates. Here, we report on the identification of highly effective target genes for RNAi-mediated control of EAB. We screened 13 candidate genes in neonate larvae and selected the most effective target genes for further investigation, including their effect on EAB adults and on a non-target organism, Tribolium castaneum. The two most efficient target genes selected, hsp (heat shock 70-kDa protein cognate 3) and shi (shibire), caused up to 90% mortality of larvae and adults. In EAB eggs, larvae, and adults, the hsp is expressed at higher levels when compared to that of shi. Ingestion of dsHSP and dsSHI caused mortality in both neonate larvae and adults. Administration of a mixture of both dsRNAs worked better than either dsRNA by itself. In contrast, injection of EAB.dsHSP and EAB.dsSHI did not cause mortality in T. castaneum. Thus, the two genes identified cause high mortality in the EAB with no apparent phenotype effects in a non-target organism, the red flour beetle, and could be used in RNAi-mediated control of this invasive pest.
An integrated flow cytometry-based platform for isolation and molecular characterization of circulating tumor single cells and clusters
Authors: Bhagwat Neha , Dulmage Keely , Pletcher Charles H. , Wang Ling , DeMuth William , Sen Moen , Balli David , Yee Stephanie S. , Sa Silin , Tong Frances , Yu Liping , Moore Jonni S. , Stanger Ben Z. , Dixon Eric P. , Carpenter Erica L.
Published: March 2018

Comprehensive molecular analysis of rare circulating tumor cells (CTCs) and cell clusters is often hampered by low throughput and purity, as well as cell loss. To address this, we developed a fully integrated platform for flow cytometry-based isolation of CTCs and clusters from blood that can be combined with whole transcriptome analysis or targeted RNA transcript quantification. Downstream molecular signature can be linked to cell phenotype through index sorting. This newly developed platform utilizes in-line magnetic particle-based leukocyte depletion, and acoustic cell focusing and washing to achieve >98% reduction of blood cells and non-cellular debris, along with >1.5 log-fold enrichment of spiked tumor cells. We could also detect 1 spiked-in tumor cell in 1 million WBCs in 4/7 replicates. Importantly, the use of a large 200μm nozzle and low sheath pressure (3.5 psi) minimized shear forces, thereby maintaining cell viability and integrity while allowing for simultaneous recovery of single cells and clusters from blood. As proof of principle, we isolated and transcriptionally characterized 63 single CTCs from a genetically engineered pancreatic cancer mouse model (n = 12 mice) and, using index sorting, were able to identify distinct epithelial and mesenchymal sub-populations based on linked single cell protein and gene expression.
Author Correction: Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans
Authors: Laker R. C. , Garde C. , Camera D. M. , Smiles W. J. , Zierath J. R. , Hawley J. A. , Barrès R.
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Using remote sensing environmental data to forecast malaria incidence at a rural district hospital in Western Kenya
Authors: Sewe Maquins Odhiambo , Tozan Yesim , Ahlm Clas , Rocklöv Joacim
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Publisher Correction: Fungus-larva relation in the formation of Cordyceps sinensis as revealed by stable carbon isotope analysis
Authors: Guo Lian-Xian , Hong Yue-Hui , Zhou Qian-Zhi , Zhu Qing , Xu Xiao-Ming , Wang Jiang-Hai
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Tracing intensive fish and meat consumption using Zn isotope ratios: evidence from a historical Breton population (Rennes, France)
Authors: Jaouen Klervia , Colleter Rozenn , Pietrzak Anita , Pons Marie-Laure , Clavel Benoît , Telmon Norbert , Crubézy Éric , Hublin Jean-Jacques , Richards Michael P.
Published: March 2018

Here we report Sr and Zn isotope ratios of teeth of medieval to early modern Breton people a population whose diet is known from historical, archeological and collagen isotope data. Most of the population, buried in the Dominican convent of Rennes, France, consists of parliamentary nobles, wealthy commoners and ecclesiastics, who had a diet rich in animal products. Our aim is to assess how the Zn isotope ratios of their teeth compare to those of other French historical populations previously studied, which were characterized by cereal-based diets, and those of modern French individuals, who daily eat animal products. We describe a clear offset (∼0.35‰) between local and non-local human individuals in Zn isotope ratios. The δ66Zntooth values of local individuals overlap that of modern French people, and are lower than those of local carnivores. Non-local δ66Zn values are similar to those of historical individuals analyzed previously. We conclude the lower Zn isotope ratios of local humans relative to the associated fauna can be explained by the consumption of carnivorous fish and pork, in agreement with historical, zooarchaeological and collagen (C, N, S) isotope data. Zn isotopes could therefore be a tracer of fish and/or substantial meat consumption in ancient populations.
Quantifying the propagation of distress and mental disorders in social networks
Authors: Scatà Marialisa , Di Stefano Alessandro , La Corte Aurelio , Liò Pietro
Published: March 2018

Heterogeneity of human beings leads to think and react differently to social phenomena. Awareness and homophily drive people to weigh interactions in social multiplex networks, influencing a potential contagion effect. To quantify the impact of heterogeneity on spreading dynamics, we propose a model of coevolution of social contagion and awareness, through the introduction of statistical estimators, in a weighted multiplex network. Multiplexity of networked individuals may trigger propagation enough to produce effects among vulnerable subjects experiencing distress, mental disorder, which represent some of the strongest predictors of suicidal behaviours. The exposure to suicide is emotionally harmful, since talking about it may give support or inadvertently promote it. To disclose the complex effect of the overlapping awareness on suicidal ideation spreading among disordered people, we also introduce a data-driven approach by integrating different types of data. Our modelling approach unveils the relationship between distress and mental disorders propagation and suicidal ideation spreading, shedding light on the role of awareness in a social network for suicide prevention. The proposed model is able to quantify the impact of overlapping awareness on suicidal ideation spreading and our findings demonstrate that it plays a dual role on contagion, either reinforcing or delaying the contagion outbreak.
Cold Atmospheric Plasma Induces ATP-Dependent Endocytosis of Nanoparticles and Synergistic U373MG Cancer Cell Death
Authors: He Zhonglei , Liu Kangze , Manaloto Eline , Casey Alan , Cribaro George P. , Byrne Hugh J. , Tian Furong , Barcia Carlos , Conway Gillian E. , Cullen Patrick J. , Curtin James F.
Published: March 2018

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are significantly increased when exposed to 75 kV CAP generated by dielectric barrier discharge. No significant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological effects of CAP, long-lived reactive species were not involved, and plasma-activated liquids did not replicate the effect. Chemical effects induced by direct and indirect exposure to CAP appears the dominant mediator of enhanced uptake. Transient physical alterations of membrane integrity played a minor role. 3D-reconstruction of deconvoluted confocal images confirmed AuNP accumulation in lysosomes and other acidic vesicles, which will be useful for future drug delivery and diagnostic strategies. Toxicity of AuNP significantly increased by 25-fold when combined with CAP. Our data indicate that direct exposure to CAP activates AuNP-dependent cytotoxicity by increasing AuNP endocytosis and trafficking to lysosomes in U373MG cells.
Whole Genome Resequencing of Capsicum baccatum and Capsicum annuum to Discover Single Nucleotide Polymorphism Related to Powdery Mildew Resistance
Authors: Ahn Yul-Kyun , Manivannan Abinaya , Karna Sandeep , Jun Tae-Hwan , Yang Eun-Young , Choi Sena , Kim Jin-Hee , Kim Do-Sun , Lee Eun-Su
Published: March 2018

The present study deals with genome wide identification of single-nucleotide polymorphism (SNP) markers related to powdery mildew (PM) resistance in two pepper varieties. Capsicum baccatum (PRH1- a PM resistant line) and Capsicum annuum (Saengryeg- a PM susceptible line), were resequenced to develop SNP markers. A total of 6,213,009 and 6,840,889 SNPs for PRH1 and Saengryeg respectively have been discovered. Among the SNPs, majority were classified as homozygous type SNPs, particularly in the resistant line. Moreover, the SNPs were differentially distributed among the chromosomes in both the resistant and susceptible lines. In total, 4,887,031 polymorphic SNP loci were identified between the two lines and 306,871 high-resolution melting (HRM) marker primer sets were designed. In order to understand the SNPs associated with the vital genes involved in diseases resistance and stress associated processes, chromosome-wise gene ontology analysis was performed. The results revealed the occurrence that SNPs related to diseases resistance genes were predominantly distributed in chromosome 4. In addition, 6281 SNPs associated with 46 resistance genes were identified. Among the lines, PRH1 consisted of maximum number of polymorphic SNPs related to NBS-LRR genes. The SNP markers were validated using HRM assay in 45 F4 populations and correlated with the phenotypic disease index.
Incongruent pitch cues are associated with increased activation and functional connectivity in the frontal areas
Authors: Lin Jo-Fu Lotus , Imada Toshiaki , Kuhl Patricia K. , Lin Fa-Hsuan
Published: March 2018

Pitch plays a crucial role in music and speech perception. Pitch perception is characterized by multiple perceptual dimensions, such as pitch height and chroma. Information provided by auditory signals that are related to these perceptual dimensions can be either congruent or incongruent. To create conflicting cues for pitch perception, we modified Shepard tones by varying the pitch height and pitch chroma dimensions in either the same or opposite directions. Our behavioral data showed that most listeners judged pitch changes based on pitch chroma, instead of pitch height, when incongruent information was provided. The reliance on pitch chroma resulted in a stable percept of upward or downward pitch shift, rather than alternating between two different percepts. Across the incongruent and congruent conditions, consistent activation was found in the bilateral superior temporal and inferior frontal areas. In addition, significantly stronger activation was observed in the inferior frontal areas during the incongruent compared to congruent conditions. Enhanced functional connectivity was found between the left temporal and bilateral frontal areas in the incongruent than congruent conditions. Increased intra-hemispheric and inter-hemispheric connectivity was also observed in the frontal areas. Our results suggest the involvement of the frontal lobe in top-down and bottom-up processes to generate a stable percept of pitch change with conflicting perceptual cues.
NF-kB2 Genetic Variations are Significantly Associated with Non-Small Cell Lung Cancer Risk and Overall Survival
Authors: Dimitrakopoulos Foteinos-Ioannis D. , Antonacopoulou Anna G. , Kottorou Anastasia E. , Maroussi Stella , Panagopoulos Nikolaos , Koukourikou Ioulia , Scopa Chrisoula , Kalofonou Melpomeni , Koutras Angelos , Makatsoris Thomas , Papadaki Helen , Dougenis Dimitrios , Brock Malcolm , Kalofonos Haralabos P.
Published: March 2018

During the last decade, a growing number of publications implicate NF-kB2 in NSCLC pathogenesis. Here, we investigated the clinical relevance of NF-kB2 single nucleotide polymorphisms (SNPs) rs7897947, rs11574852 and rs12769316 in NSCLC and their association with NF-kB2 protein and mRNA levels. Our data show that TT (rs7897947T >G) and AA (rs12769316G >A) genotypes were strongly associated with an increased risk for NSCLC (P = 0.019 and P = 0.003, respectively). Additionally, in multivariate analysis, TT (rs7897947T >G) homozygosity was associated with worse 2- and 3-year survival rates (P = 0.030 and P = 0.028, respectively), especially among patients with stages III/IV, who had worse 2, 3 and 5-year survival (P = 0.001, P = 0.022 and P = 0.035, respectively). In chemotherapy-treated patients, TT (rs12769316G >A) homozygosity was also associated with worse 2- and 3-year survival compared to G allele carriers (P = 0.006 and P = 0.014, respectively). Furthermore, rs12769316 was correlated with survival outcome of stage I and II patients (P = 0.031 and P = 0.006, respectively). Interestingly, amongst the patients who developed metastases, A allele carriers had better 5-year survival (P = 0.020). In addition, rs12769316 was associated with NF-kB2 protein (P = 0.001) and mRNA expression (P = 0.017) as well as with tumor maximum diameter (P = 0.025). Overall, this study suggests that rs7897947 and rs12769316 are involved in NSCLC susceptibility, in treatment response and in clinical outcome.
Author Correction: Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis
Authors: Gao Xueqin , Ke Chaofu , Liu Haixia , Liu Wei , Li Kang , Yu Bo , Sun Meng
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
First adequately-known quadrupedal sirenian from Eurasia (Eocene, Bay of Biscay, Huesca, northeastern Spain)
Authors: Díaz-Berenguer Ester , Badiola Ainara , Moreno-Azanza Miguel , Canudo José Ignacio
Published: March 2018

Sirenians are the only extant herbivorous mammals fully adapted to an aquatic lifestyle. They originated in Africa during the Paleocene from an undetermined clade of afrotherian mammals, and by the end of the Eocene they were widely distributed across the tropical latitudes. Here we introduce Sobrarbesiren cardieli gen. et sp. nov. It is the first adequately-known quadrupedal sirenian from Eurasia and the oldest record of this clade from western Europe. Fossils have been recovered from the middle Lutetian (SBZ15) site of Castejón de Sobrarbe-41 (Huesca, Spain), and comprise many cranial and postcranial remains, including pelvic girdle and hind limb bones, from at least six sirenian individuals of different ontogenetic stages. Sobrarbesiren shows a suite of characters previously considered synapomorphies of different clades of derived sirenians, such as the presence of the processus retroversus of the squamosal and the pterygoid fossa, combined with ancestral characters such as the presence of an alisphenoid canal, a permanent P5, at least two sacral vertebrae, a primitive pelvis and functional femora and fibulae. Sobrarbesiren is recovered as the sister taxon of Dugongidae and represents a transitional stage of adaptation to aquatic life between the amphibious quadrupedal prorastomids and the aquatic quadrupedal protosirenids.
Coherent all-optical transistor based on frustrated total internal reflection
Authors: Goodarzi A. , Ghanaatshoar M.
Published: March 2018

This study aims to design an all-optical transistor based on tunneling of light through frustrated total internal reflection. Under total internal reflection, the electromagnetic wave penetrates into the lower index medium. If a medium with high refractive index is placed close to the boundary of the first one, a portion of light leaks into the second medium. The penetrated electromagnetic field distribution can be influenced by another coherent light in the low refractive index medium via interference, leading to light amplification. Upon this technique, we introduce coherent all-optical transistors based on photonic crystal structures. Subsequently, we inspect the shortest pulse which is amplified by the designed system and also its terahertz repetition rate. We will show that such a system can operate in a cascade form. Operating in terahertz range and the amplification efficiency of around 20 are of advantages of this system.
RNA-Seq identifies genes whose proteins are transformative in the differentiation of cytotrophoblast to syncytiotrophoblast, in human primary villous and BeWo trophoblasts
Authors: Azar Christopher , Valentine Mark , Trausch-Azar Julie , Druley Todd , Nelson D. Michael , Schwartz Alan L.
Published: March 2018

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression and quantitative protein expression, we identified genes and their cognate proteins which are coordinately up- or down-regulated in two cellular models of cytotrophoblast to syncytiotrophoblast development, human primary villous and human BeWo cytotrophoblasts. These include hCGβ, TREML2, PAM, CRIP2, INHA, FLRG, SERPINF1, C17orf96, KRT17 and SAA1. These findings provide avenues for further understanding the mechanisms underlying mammalian placental synctiotrophoblast development.
Author Correction: Differentiated surface fungal communities at point of harvest on apple fruits from rural and peri-urban orchards
Authors: Shen Youming , Nie Jiyun , Li Zhixia , Li Haifei , Wu Yonglong , Dong Yafeng , Zhang Jianyi
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Mesoproterozoic juvenile crust in microcontinents of the Central Asian Orogenic Belt: evidence from oxygen and hafnium isotopes in zircon
Authors: He Zhen-Yu , Klemd Reiner , Yan Li-Li , Lu Tian-Yu , Zhang Ze-Ming
Published: March 2018

We report in situ O and Hf isotope data of zircon grains from coeval Mesoproterozoic (ca. 1.4 Ga) igneous metamafic (amphibolite) and granitic rocks of the Chinese Central Tianshan microcontinent (CTM) in the southern Central Asian Orogenic Belt (CAOB). Zircon grains from amphibolite have mantle-like δ18OVSMOW values of 4.7–5.6‰ and juvenile Hf isotopic compositions (εHf(t) = 8.4–15.3; TDMC = 1.57–1.22 Ga), whereas those from granitic rocks have δ18OVSMOW values of 5.6–7.0‰ and evolved Hf isotopic compositions (εHf(t) = −1.0–8.2; TDMC = 2.09–1.62 Ga). Zircon O–Hf isotopic compositions of the metamafic and granitic rocks provide evidence for Mesoproterozoic (ca. 1.4 Ga) crustal growth and a substantial Palaeoproterozoic supracrustal component in the CTM. These findings and previous studies, reporting ca. 1.4 Ga magmatic rocks from other microcontinents of the CAOB, suggest that a large belt of Mesoproterozoic (ca. 1.4 Ga) juvenile continental crust formed in a continental terrane, fragments of which now occur over a distance of more than a thousand kilometres in the southern CAOB.
Comparative study of afterpulsing behavior and models in single photon counting avalanche photo diode detectors
Authors: Ziarkash Abdul Waris , Joshi Siddarth Koduru , Stipčević Mario , Ursin Rupert
Published: March 2018

Single-photon avalanche diode (SPAD) detectors, have a great importance in fields like quantum key distribution, laser ranging, florescence microscopy, etc. Afterpulsing is a non-ideal behavior of SPADs that adversely affects any application that measures the number or timing of detection events. Several studies based on a few individual detectors, derived distinct mathematical models from semiconductor physics perspectives. With a consistent testing procedure and statistically large data sets, we show that different individual detectors - even if identical in type, make, brand, etc. - behave according to fundamentally different mathematical models. Thus, every detector must be characterized individually and it is wrong to draw universal conclusions about the physical meaning behind these models. We also report the presence of high-order afterpulses that are not accounted for in any of the standard models.
Multi-nanolayered VO2/Sapphire Thin Film via Spinodal Decomposition
Authors: Sun Guangyao , Cao Xun , Yue Yuanzheng , Gao Xiang , Long Shiwei , Li Ning , Li Rong , Luo Hongjie , Jin Ping
Published: March 2018

Coating of VO2-based thin film has been extensively studied for fabricating energy-saving smart windows. One of the most efficient ways for fabricating high performance films is to create multi-nanolayered structure. However, it has been highly challenge to make such layers in the VO2-based films using conventional methods. In this work, a facile two-step approach is established to fabricate multilayered VO2-TiO2thin films. We first deposited the amorphous thin films upon sputtering, and then anneal them to transform the amorphous phase into alternating Ti- and V-rich multilayered nanostructure via a spinodal decomposition mechanism. In particular, we take advantage of different sapphire substrate planes (A-plane (11–20), R-plane (1–102), C-plane (0001), and M-plane (10-10)) to achieve different decomposition modes. The new approach has made it possible to tailoring the microstructure of the thin films for optimized performances by controlling the disorder-order transition in terms of both kinetic and thermodynamic aspects. The derived thin films exhibit superior optical modulation upon phase transition, significantly reduced transition temperature and hysteresis loop width, and high degradation resistance, these improvements indicate a high potential to be used for fabricating the next generation of energy saving smart windows.
Transcription factor PAX6 as a novel prognostic factor and putative tumour suppressor in non-small cell lung cancer
Authors: Kiselev Yury , Andersen Sigve , Johannessen Charles , Fjukstad Bjørn , Standahl Olsen Karina , Stenvold Helge , Al-Saad Samer , Donnem Tom , Richardsen Elin , Bremnes Roy M. , Rasmussen Busund Lill-Tove
Published: March 2018

Lung cancer is the leading cause of cancer deaths. Novel predictive biomarkers are needed to improve treatment selection and more accurate prognostication. PAX6 is a transcription factor with a proposed tumour suppressor function. Immunohistochemical staining was performed on tissue microarrays from 335 non-small cell lung cancer (NSCLC) patients for PAX6. Multivariate analyses of clinico-pathological variables and disease-specific survival (DSS) was carried out, and phenotypic changes of two NSCLC cell lines with knockdown of PAX6 were characterized. While PAX6 expression was only associated with a trend of better disease-specific survival (DSS) (p = 0.10), the pN+ subgroup (N = 103) showed significant correlation between high PAX6 expression and longer DSS (p = 0.022). Median survival for pN + patients with high PAX6 expression was 127.4 months, versus 22.9 months for patients with low PAX6 expression. In NCI-H661 cells, knockdown of PAX6 strongly activated serum-stimulated migration. In NCI-H460 cells, PAX6 knockdown activated anchorage-independent growth. We did not observe any significant effect of PAX6 on proliferation in either of cell lines. Our findings strongly support the proposition of PAX6 as a valid and positive prognostic marker in NSCLC in node-positive patients. There is a need for further studies, which should provide mechanistical explanation for the role of PAX6 in NSCLC.
Bacteriophages are more virulent to bacteria with human cells than they are in bacterial culture; insights from HT-29 cells
Authors: Shan Jinyu , Ramachandran Ananthi , Thanki Anisha M. , Vukusic Fatima B. I. , Barylski Jakub , Clokie Martha R. J.
Published: March 2018

Bacteriophage therapeutic development will clearly benefit from understanding the fundamental dynamics of in vivo phage-bacteria interactions. Such information can inform animal and human trials, and much can be ascertained from human cell-line work. We have developed a human cell-based system using Clostridium difficile, a pernicious hospital pathogen with limited treatment options, and the phage phiCDHS1 that effectively kills this bacterium in liquid culture. The human colon tumorigenic cell line HT-29 was used because it simulates the colon environment where C. difficile infection occurs. Studies on the dynamics of phage-bacteria interactions revealed novel facets of phage biology, showing that phage can reduce C. difficile numbers more effectively in the presence of HT-29 cells than in vitro. Both planktonic and adhered Clostridial cell numbers were successfully reduced. We hypothesise and demonstrate that this observation is due to strong phage adsorption to the HT-29 cells, which likely promotes phage-bacteria interactions. The data also showed that the phage phiCDHS1 was not toxic to HT-29 cells, and phage-mediated bacterial lysis did not cause toxin release and cytotoxic effects. The use of human cell lines to understand phage-bacterial dynamics offers valuable insights into phage biology in vivo, and can provide informative data for human trials.
MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1
Authors: Carmichael Ruth E. , Wilkinson Kevin A. , Craig Tim J. , Ashby Michael C. , Henley Jeremy M.
Published: March 2018

Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic membrane is a key determinant of the strength of excitatory neurotransmission, and is thought to underlie learning and memory. The transcription factor MEF2 is a negative regulator of memory in vivo, in part by regulating trafficking of the AMPAR subunit GluA2, but the molecular mechanisms behind this have not been established. Here we show, via knockdown of endogenous MEF2A in primary neuronal culture, that MEF2A is specifically required for Group I metabotropic glutamate receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR expression or trafficking under basal conditions. Furthermore, this process occurs independently of changes in expression of Arc/Arg3.1, a previously characterised MEF2 transcriptional target and mediator of mGluR-dependent long-term depression. These data demonstrate a novel MEF2A-dependent mechanism for the regulation of activity-dependent AMPAR trafficking.
Author Correction: Interferometric rotating point spread function
Authors: Wang Wei , Situ Guohai
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Possible bite-induced abscess and osteomyelitis in Lufengosaurus (Dinosauria: sauropodomorph) from the Lower Jurassic of the Yimen Basin, China
Authors: Xing Lida , Rothschild Bruce M. , Randolph-Quinney Patrick S. , Wang Yi , Parkinson Alexander H. , Ran Hao
Published: March 2018

We report an osseous abnormality on a specimen of the sauropod dinosaur Lufengosaurus huenei from the Fengjiahe Formation in Yuxi Basin, China. A gross pathological defect occurs on the right third rib, which was subjected to micro-computed tomographic imaging as an aid in diagnosis. The analysis of pathological characteristics and the shape of the abnormality is incompatible with impact or healed trauma, such as a common rib fracture, and instead suggests focal penetration of the rib, possibly due to a failed predator attack. The identification of characteristics based on gross morphology and internal micro-morphology presented by the specimen, suggests an abscess with osteomyelitis as the most parsimonious explanation. Osteomyelitis is a severe infection originating in the bone marrow, usually resulting from the introduction of pyogenic (pus-producing) bacteria into the bone. Micro-tomographic imaging of the lesion suggests a degree of healing and bone remodelling following post-traumatic wound infection with evidence of sclerotic bone formation at the site of pathological focus, indicating that L. huenei survived the initial trauma. However, as osteomyelitis can express through widespread systemic effects, including a lowering of immune response and overall condition, this disease may have been a contributing factor to the eventual death of the individual.
Diffusion tensor tractography of the mammillothalamic tract in the human brain using a high spatial resolution DTI technique
Authors: Kamali Arash , Zhang Caroline C. , Riascos Roy F. , Tandon Nitin , Bonafante-Mejia Eliana E. , Patel Rajan , Lincoln John A. , Rabiei Pejman , Ocasio Laura , Younes Kyan , Hasan Khader M.
Published: March 2018

The mammillary bodies as part of the hypothalamic nuclei are in the central limbic circuitry of the human brain. The mammillary bodies are shown to be directly or indirectly connected to the amygdala, hippocampus, and thalami as the major gray matter structures of the human limbic system. Although it is not primarily considered as part of the human limbic system, the thalamus is shown to be involved in many limbic functions of the human brain. The major direct connection of the thalami with the hypothalamic nuclei is known to be through the mammillothalamic tract. Given the crucial role of the mammillothalamic tracts in memory functions, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the mammillothalamic tract in the human brain. Fifteen healthy adults were studied after obtaining written informed consent. We used high spatial resolution diffusion tensor imaging data at 3.0 T. We delineated, for the first time, the detailed trajectory of the mammillothalamic tract of the human brain using deterministic diffusion tensor tractography.
Lack of evidence supporting a role of TMC4-rs641738 missense variant—MBOAT7- intergenic downstream variant—in the Susceptibility to Nonalcoholic Fatty Liver Disease
Authors: Sookoian Silvia , Flichman Diego , Garaycoechea Martin E. , Gazzi Carla , Martino Julio San , Castaño Gustavo O. , Pirola Carlos J.
Published: March 2018

Current knowledge on the genetic basis of nonalcoholic fatty liver disease (NAFLD) suggests that variants contributing not only to the disease predisposition but histological severity as well are located in genes that regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4 (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case-control study. Our sample included 634 individuals (372 patients with NAFLD diagnosed by liver biopsy and 262 control subjects); genotyping was performed by a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor allele frequency 40.8%. Our sample had 84–99% power if an additive genetic model is assumed for estimated odds ratios of 1.3–1.5, respectively. We found no evidence of association between rs641738 and either NAFLD (Cochran-Armitage test for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7 protein expression were found in the liver of patients with NAFLD, which were unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the pathogenesis of NAFLD is inconclusive.
Pattern Formation through Temporal Fractional Derivatives
Authors: Yin Hongwei , Wen Xiaoqing
Published: March 2018

It is well known that temporal first-derivative reaction-diffusion systems can produce various fascinating Turing patterns. However, it has been found that many physical, chemical and biological systems are well described by temporal fractional-derivative reaction-diffusion equations. Naturally arises an issue whether and how spatial patterns form for such a kind of systems. To address this issue clearly, we consider a classical prey-predator diffusive model with the Holling II functional response, where temporal fractional derivatives are introduced according to the memory character of prey’s and predator’s behaviors. In this paper, we show that this fractional-derivative system can form steadily spatial patterns even though its first-derivative counterpart can’t exhibit any steady pattern. This result implies that the temporal fractional derivatives can induce spatial patterns, which enriches the current mechanisms of pattern formation.