bluuebunny/crossref_metadata_2025 huggingface dataset:
First Report of Acetyl-CoA Carboxylase–Resistant Southern Crabgrass (Digitaria ciliaris) in the United States
Authors: Yu Jialin , McCullough Patrick E. , Czarnota Mark A.
Published: April 2017

Two populations of southern crabgrass identified in Georgia turfgrass were suspected to be resistant to sethoxydim. The objectives of this research were to evaluate the resistance levels of these biotypes to acetyl-CoA carboxylase (ACCase) inhibitors and alternative herbicides for control. From dose response experiments, the sethoxydim rate required to reduce shoot biomass 50% from the nontreated measured >64-times greater for both resistant (R) biotypes compared to the susceptible (S) biotype. Both R biotypes were cross-resistant to fenoxaprop and fluazifop. Clethodim at 290 gaiha−1reduced dry shoot biomass of the R biotypes and the S biotype to 47 and 21% of the nontreated, respectively. The R biotypes were equally susceptible to MSMA at 2240 g ai ha−1, quinclorac at 840 g ai ha−1, and topramezone at 37 g ai ha−1as compared to the S biotype. Sethoxydim at 315 and 945 g ha−1provided <20% control of the southern crabgrass populations in four field experiments. However, clethodim and topramezone provided 83% and 76% control at 4 wks after treatment, respectively. These southern crabgrass biotypes are resistant to sethoxydim and aryloxyphenoxypropionate herbicides. Although the R biotypes were less susceptible to clethodim than the S biotype, treatments provided acceptable control in the field. This is the first report of ACCase-resistant southern crabgrass in the United States.
A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages
Authors: Pereira Mafalda M. A. , Mahú Inês , Seixas Elsa , Martinéz-Sánchez Noelia , Kubasova Nadiya , Pirzgalska Roksana M , Cohen Paul , Dietrich Marcelo O , López Miguel , Bernardes Gonçalo J. L. , Domingos Ana I.
Published: April 2017

Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood–brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. We prevent blood–brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. We validate BRAINSPAReDT with regional genetic sympathectomy: BRAINSPAReDT ablates peripheral but not central catecholaminergic neurons, thus avoiding the Parkinson-like phenotype associated with full dopaminergic depletion. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissue-specific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system.
Methylation of WNT target genes AXIN2 and DKK1 as robust biomarkers for recurrence prediction in stage II colon cancer
Authors: Kandimalla R , Linnekamp J F , van Hooff S , Castells A , Llor X , Andreu M , Jover R , Goel A , Medema J P
Published: April 2017

Stage II colon cancer (CC) still remains a clinical challenge with patient stratification for adjuvant therapy (AT) largely relying on clinical parameters. Prognostic biomarkers are urgently needed for better stratification. Previously, we have shown that WNT target genes AXIN2, DKK1, APCDD1, ASCL2 and LGR5 are silenced by DNA methylation and could serve as prognostic markers in stage II CC patients using methylation-specific PCR. Here, we have extended our discovery cohort AMC90-AJCC-II (N=65) and methylation was analyzed by quantitative pyrosequencing. Subsequently, we validated the results in an independent EPICOLON1 CC cohort (N=79). Methylation of WNT target genes is negatively correlated to mRNA expression. A combination of AXIN2 and DKK1 methylation significantly predicted recurrences in univariate (area under the curve (AUC)=0.83, confidence interval (CI): 0.72–0.94, P<0.0001) analysis in stage II microsatellite stable (MSS) CC patients. This two marker combination showed an AUC of 0.80 (CI: 0.68–0.91, P<0.0001) in the EPICOLON1 validation cohort. Multivariate analysis in the Academic Medical Center (AMC) cohort revealed that both WNT target gene methylation and consensus molecular subtype 4 (CMS4) are significantly associated with poor recurrence-free survival (hazard ratio (HR)methylation: 3.84, 95% CI: 1.14–12.43; HRCMS4: 3.73, 95% CI: 1.22–11.48). CMS4 subtype tumors with WNT target methylation showed worse prognosis. Combining WNT target gene methylation and CMS4 subtype lead to an AUC of 0.89 (0.791–0.982, P<0.0001) for recurrence prediction. Notably, we observed that methylation of DKK1 is high in BRAF mutant and CIMP (CpG island methylator phenotype)-positive cancers, whereas AXIN2 methylation appears to be associated with CMS4. Methylation of AXIN2 and DKK1 were found to be robust markers for recurrence prediction in stage II MSS CC patients. Further validation of these findings in a randomized and prospective manner could pave a way to identify poor prognosis patients of stage II CC for AT.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells
Authors: Rupp Levi J. , Schumann Kathrin , Roybal Kole T. , Gate Rachel E. , Ye Chun J. , Lim Wendell A. , Marson Alexander
Published: April 2017

Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, we developed a protocol for combined Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing and lentiviral transduction to generate PD-1 deficient anti-CD19 CAR T cells. Pdcd1 (PD-1) disruption augmented CAR T cell mediated killing of tumor cells in vitro and enhanced clearance of PD-L1+ tumor xenografts in vivo. This study demonstrates improved therapeutic efficacy of Cas9-edited CAR T cells and highlights the potential of precision genome engineering to enhance next-generation cell therapies.
Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease
Authors: Skjørringe Tina , Amstrup Pedersen Per , Salling Thorborg Sidsel , Nissen Poul , Gourdon Pontus , Birk Møller Lisbeth
Published: April 2017

Menkes disease (MD) is caused by mutations in ATP7A, encoding a copper-transporting P-type ATPase which exhibits copper-dependent trafficking. ATP7A is found in the Trans-Golgi Network (TGN) at low copper concentrations, and in the post-Golgi compartments and the plasma membrane at higher concentrations. Here we have analyzed the effect of 36 ATP7A missense mutations identified in phenotypically different MD patients. Nine mutations identified in patients with severe MD, virtually eliminated ATP7A synthesis, in most cases due to aberrant RNA splicing. A group of 21 predominantly severe mutations led to trapping of the protein in TGN and displayed essentially no activity in a yeast-based functional assay. These were predicted to inhibit the catalytic phosphorylation of the protein. Four mutants showed diffuse post-TGN localization, while two displayed copper dependent trafficking. These six variants were identified in patients with mild MD and typically displayed activity in the yeast assay. The four post-TGN located mutants were presumably affected in the catalytic dephosphorylation of the protein. Together these results indicate that the severity of MD correlate with cellular localization of ATP7A and support previous studies indicating that phosphorylation is crucial for the exit of ATP7A from TGN, while dephosphorylation is crucial for recycling back to TGN.
Identification of a six-lncRNA signature associated with recurrence of ovarian cancer
Authors: Yang Kai , Hou Yan , Li Ang , Li Zhenzi , Wang Wenjie , Xie Hongyu , Rong Zhiwei , Lou Ge , Li Kang
Published: April 2017

Ovarian cancer (OvCa) is the leading cause of death among all gynecological malignancies, and recurrent OvCa is almost always incurable. In this study, we developed a signature based on long non-coding RNAs (lncRNAs) associated with OvCa recurrence to facilitate personalized OvCa therapy. lncRNA expression data were extracted from GSE9891 and GSE30161. LASSO (least absolute shrinkage and selection operator) penalized regression was used to identify an lncRNA-based signature using the GSE9891 training cohort. The signature was then validated in GSE9891 internal and GSE30161 external validation cohorts. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to explore the possible functions of identified lncRNAs. A six-lncRNA signature (RUNX1-IT1, MALAT1, H19, HOTAIRM1, LOC100190986 and AL132709.8) was identified in the training cohort and validated in internal and external validation cohorts using the LASSO method (P < 0.05). This signature was also independent of other clinical factors according to multivariate and sub-group analyses. The identified lncRNAs are involved in cancer-related biological processes and pathways. We selected a highly reliable signature based on six lncRNAs associated with OvCa recurrence. This six-lncRNA signature is a promising method to personalize ovarian cancer therapy and may improve patient quality of life quality according to patients’ condition in the future.
Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
Authors: Chan Sherwin , Ch’ng Jun-Hong , Wahlgren Mats , Thutkawkorapin Jessada
Published: April 2017

Plasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage bias and culminates in frequent insertion of asparagine homorepeats in the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal codons that are negatively associated to protein translation efficiency. Despite this, one third of all codons in the genome are GU wobble codons, suggesting that codon usage in P. falciparum has not been driven to maximize translation efficiency, but may have evolved as translational regulatory mechanism. Particularly, asparagine homorepeats are generally encoded by locally clustered GU wobble AAT codons, we demonstrated that this GU wobble-rich codon context is the determining factor that causes reduction of protein level. Moreover, insertion of clustered AAT codons also causes destabilization of the transcripts. Interestingly, more frequent asparagine homorepeats insertion is seen in single-exon genes, suggesting transcripts of these genes may have been programmed for rapid mRNA decay to compensate for the inefficiency of mRNA surveillance regulation on intronless genes. To our knowledge, this is the first study that addresses P. falciparum codon usage in vitro and provides new insights on translational regulation and genome evolution of this parasite.
The Vernix Caseosa is the Main Site of Dioxin Excretion in the Human Foetus
Authors: Morokuma Seiichi , Tsukimori Kiyomi , Hori Tsuguhide , Kato Kiyoko , Furue Masutaka
Published: April 2017

Dioxins are highly toxic to foetuses and prenatal exposure leads to adverse health effects; however, the metabolic pathways involved in dioxin excretion are poorly understood. We determined the dynamics of maternal-to-foetal dioxin transfer during normal pregnancy and how foetuses eliminate polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls. Dioxin levels in maternal blood, cord blood, placenta, vernix caseosa, meconium, and amniotic fluid were analysed by high-resolution gas chromatography/mass spectrometry. The average levels of total dioxins, expressed as picograms of toxic equivalency quantity per gram of lipid and in parentheses, dioxin fraction, with maternal blood levels arbitrarily set as 100%, were as follows: maternal blood, 15.8 (100%); placenta, 12.9 (81.5%); cord blood, 5.9 (37.2%); vernix caseosa, 8.4 (53.2%); meconium, 2.9 (18.2%); and amniotic fluid, 1.5 (9.2%). Similar proportions were observed for each dioxin congener. Thus, the highest content of foetal dioxins was observed in the vernix caseosa, indicating that this is the major site of dioxin excretion in human foetuses.
High expression of IMPDH2 is associated with aggressive features and poor prognosis of primary nasopharyngeal carcinoma
Authors: Xu Yi , Zheng Zhousan , Gao Ying , Duan Shiyu , Chen Cui , Rong Jian , Wang Kebing , Yun Miao , Weng Huiwen , Ye Sheng , Zhang Jiaxing
Published: April 2017

Inosine monophosphate dehydrogenase type II (IMPDH2) has been shown to play critical roles in the development and progression of several human cancers. However, little is known about IMPDH2 expression and its clinical significance in nasopharyngeal carcinoma (NPC). Western blotting, qRT-PCR and immunohistochemistry were employed to evaluate IMPDH2 expression in NPC cell lines and tissues. In our study, elevated expression of IMPDH2 was observed at both the protein and mRNA levels in NPC cell lines than in NPEC2 Bmi-1. IMPDH2 protein expression was markedly higher in NPC tissues than in adjacent non-tumorous tissues. Moreover, IMPDH2 expression in NPC correlated with several clinicopathological parameters, including T classification (P = 0.023), TNM stage (P = 0.020), distant metastasis (P = 0.001) and death (P = 0.002). Further Cox regression analysis suggested that IMPDH2 expression was an independent prognostic factor for overall survival (P = 0.001) and disease-free survival (P < 0.001). In addition, stratified survival analysis showed that high expression of IMPDH2 could be a prognostic factor for NPC patients with TNM stage I/II (OS: P = 0.012; DMFS: P = 0.007), TNM stage III/IV (OS: P = 0.028; DMFS: P = 0.020). Our study demonstrates IMPDH2 may be served as an independent prognostic biomarker for NPC patients, in which high IMPDH expression suggests poor prognosis of NPC patients.
Characteristics of the heme catabolic pathway in mild unconjugated hyperbilirubinemia and their associations with inflammation and disease prevention
Authors: Mölzer Christine , Wallner Marlies , Kern Carina , Tosevska Anela , Zadnikar René , Doberer Daniel , Marculescu Rodrig , Wagner Karl-Heinz
Published: April 2017

Heme catabolism exerts physiological functions that impact health through depressing inflammation. Upon reactive pathway progression, as in Gilbert’s Syndrome (GS; UGT1A1*28 polymorphism), aggravated health effects have been determined. Based on lower inflammation and improved metabolic health reported for GS, inter-group differences in heme catabolism were explored. Therefore, a case-control study including 120 fasted, healthy, age- and gender matched subjects with/without GS, was conducted. Genetic expressions of HMOX-1 and BLVRA were measured. Additionally participants were genotyped for those polymorphisms that are known (UGT1A1*28) or likely (HMOX-1 microsatellites) to impact bilirubinemia. Intracellular interleukins (IL-6, IL-1β, TNFα), circulatory C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hpt) were analysed as inflammatory markers. To assess intracellular heme oxygenase 1 (HO-1) isolated PBMCs were used. In GS vs. C, inflammation markers were significantly decreased. This was supported by an altered heme catabolism, indirectly reflecting in elevated unconjugated bilirubin (UCB; main phenotypic feature of GS) and iron, decreased hemopexin (Hpx) and Hpt and in up-regulated biliverdin reductase (BLVRA) gene expressions. Moreover, HMOX (GT)n short alleles were non-significantly more prominent in female GS individuals. Herewith, we propose a concept to elucidate why GS individuals encounter lower inflammation, and are thus less prone to oxidative-stress mediated diseases.
Power-scalable subcycle pulses from laser filaments
Authors: Voronin A.A. , Zheltikov A.M.
Published: April 2017

Compression of optical pulses to ultrashort pulse widths using methods of nonlinear optics is a well-established technology of modern laser science. Extending these methods to pulses with high peak powers, which become available due to the rapid progress of laser technologies, is, however, limited by the universal physical principles. With the ratio P/Pcr of the peak power of an ultrashort laser pulse, P, to the critical power of self-focusing, Pcr, playing the role of the fundamental number-of-particles integral of motion of the nonlinear Schrödinger equation, keeping this ratio constant is a key principle for the power scaling of laser-induced filamentation. Here, we show, however, that, despite all the complexity of the underlying nonlinear physics, filamentation-assisted self-compression of ultrashort laser pulses in the regime of anomalous dispersion can be scaled within a broad range of peak powers against the principle of constant P/Pcr. We identify filamentation self-compression scaling strategies whereby subcycle field waveforms with almost constant pulse widths can be generated without a dramatic degradation of beam quality within a broad range of peak powers, varying from just a few to hundreds of Pcr.
Memory and synaptic plasticity are impaired by dysregulated hippocampal O-GlcNAcylation
Authors: Yang Yong Ryoul , Song Seungju , Hwang Hongik , Jung Jung Hoon , Kim Su-Jeong , Yoon Sora , Hur Jin-Hoe , Park Jae-Il , Lee Cheol , Nam Dougu , Seo Young-Kyo , Kim Joung-Hun , Rhim Hyewhon , Suh Pann-Ghill
Published: April 2017

O-GlcNAcylated proteins are abundant in the brain and are associated with neuronal functions and neurodegenerative diseases. Although several studies have reported the effects of aberrant regulation of O-GlcNAcylation on brain function, the roles of O-GlcNAcylation in synaptic function remain unclear. To understand the effect of aberrant O-GlcNAcylation on the brain, we used Oga+/− mice which have an increased level of O-GlcNAcylation, and found that Oga+/− mice exhibited impaired spatial learning and memory. Consistent with this result, Oga+/− mice showed a defect in hippocampal synaptic plasticity. Oga heterozygosity causes impairment of both long-term potentiation and long-term depression due to dysregulation of AMPA receptor phosphorylation. These results demonstrate a role for hyper-O-GlcNAcylation in learning and memory.
Multivalley engineering in semiconductor microcavities
Authors: Sun M. , Savenko I. G. , Flayac H. , Liew T. C. H.
Published: April 2017

We consider exciton-photon coupling in semiconductor microcavities in which separate periodic potentials have been embedded for excitons and photons. We show theoretically that this system supports degenerate ground-states appearing at non-zero inplane momenta, corresponding to multiple valleys in reciprocal space, which are further separated in polarization corresponding to a polarization-valley coupling in the system. Aside forming a basis for valleytronics, the multivalley dispersion is predicted to allow for spontaneous momentum symmetry breaking and two-mode squeezing under non-resonant and resonant excitation, respectively.
B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial
Authors: Zhong Jia , Trevisi Letizia , Urch Bruce , Lin Xinyi , Speck Mary , Coull Brent A. , Liss Gary , Thompson Aaron , Wu Shaowei , Wilson Ander , Koutrakis Petros , Silverman Frances , Gold Diane R. , Baccarelli Andrea A.
Published: April 2017

Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5–induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.
Multiferroic Phases and Transitions in Ferroelectric Lead Titanate Nanodots
Authors: Xu Tao , Shimada Takahiro , Uratani Yoshitaka , Wang Xiaoyuan , Wang Jie , Kitamura Takayuki
Published: April 2017

Discovery of novel phases and their associated transitions in low-dimensional nanoscale systems is of central interest as the origin of emergent phenomena and new device paradigms. Although typical ferroelectrics such as PbTiO3 exhibit diverse phase transition sequences, the conventional incompatible mechanisms of ferroelectricity and magnetism keep them as simply nonmagnetic phases, despite the immense practical prospective of multiferroics in novel functional devices. Here, we demonstrate using density function theory that PbTiO3 nanodots exhibit unconventional multiferroic phase transitions. The nanosize and nonstoichiometric effects intrinsic to nanodots bring about the coexistence of ferromagnetism with the host electric polarization, mediated by the termination and surface morphology. We also predict the key features of the size-dependent phase diagram of nanodots that involve a rich sequence of ferroelectric-multiferroic-ferromagnetic/nonmagnetic (FE-MF-FM/NM) multiferroic phase transitions. The present work thus provides an avenue to realizing multiferroics and multifunctional oxides in low-dimensional systems.
Class of gauge-invariant models of quantum electrodynamics with nonlocal interaction
Authors: Mei Tao
Published: April 2017

We present a class of gauge-invariant models of quantum electrodynamics with nonlocal interaction. The models have translation, Lorentz and gauge invariance and reduce to the conventional local quantum electrodynamics under the appropriate limit conditions, both the equations of motion of the charged particle and electromagnetic field obtained by the action principle lead to the normal form of current conservation. Quantization of the models is realized by taking advantage of the formalism based on the Yang-Feldman equations and the Lehmann-Symanzik-Zimmermann reduction formulas. Finally, we employ a special choice of the models to calculate the vacuum polarization as an example to demonstrate the possibility of establishing a theory of quantum electrodynamics without divergence.
Phylogeny and historical biogeography of leafhopper subfamily Evacanthinae (Hemiptera: Cicadellidae) based on morphological and molecular data
Authors: Wang Yang , Dietrich Christopher H. , Zhang Yalin
Published: April 2017

Phylogenetic relationships among major lineages of the Evacanthinae, a highly diverse leafhopper subfamily distributed worldwide, were explored by analysing a dataset of 100 discrete morphological characters and DNA sequence data from five gene regions. Sixty-seven taxa representing all evacanthine tribes and all regional faunas, and fourteen putative outgroup taxa were included. Maximum-likelihood and Bayesian analyses yielded similar tree topologies that were well resolved with strong support for the monophyly of Evacanthinae and its four previously included tribes, but indicated that Draconirvana Dietrich, was incorrectly placed to tribe and that Sophonia Walker, Evacanthus Le Peletier & Serville, Bundera Distant, Paraonukia Ishihara and Onukia Matsumura are not monophyletic. Divergence time analysis suggests that the deepest divergences coincided with breakup of Gondwana but that more recent divergences occurred largely within a single biogeographic realm during the Paleogene, with a few long-distance dispersal events. Biogeographical analyses suggest that Evacanthinae originated in Neotropical region. A new tribe, Pentoffiini trib.n., is established to include Pentoffia Kramer and Evanirvana Hill, the genus Draconirvana Dietrich, placement n. is transferred to Evacanthini from Nirvanini, a key to tribes is also given and illustrations of representative genera are provided.
Study on the short-term effects of increased alcohol and cigarette consumption in healthy young men’s seminal quality
Authors: Silva Joana Vieira , Cruz Daniel , Gomes Mariana , Correia Bárbara Regadas , Freitas Maria João , Sousa Luís , Silva Vladimiro , Fardilha Margarida
Published: April 2017

Many studies have reported a negative impact of lifestyle factors on testicular function, spermatozoa parameters and pituitary-gonadal axis. However, conclusions are difficult to draw, since studies in the general population are rare. In this study we intended to address the early and late short-term impact of acute lifestyle alterations on young men’s reproductive function. Thirty-six healthy male students, who attended the Portuguese academic festivities, provided semen samples and answered questionnaires at three time-points. The consumption of alcohol and cigarette increased more than 8 and 2 times, respectively, during the academic festivities and resulted in deleterious effects on semen quality: one week after the festivities, a decrease on semen volume, spermatozoa motility and normal morphology was observed, in parallel with an increase on immotile spermatozoa, head and midpiece defects and spermatozoa oxidative stress. Additionally, three months after the academic festivities, besides the detrimental effect on volume, motility and morphology, a negative impact on spermatozoa concentration was observed, along with a decrease on epididymal, seminal vesicles and prostate function. This study contributed to understanding the pathophysiology underlying semen quality degradation induced by acute lifestyle alterations, suggesting that high alcohol and cigarette consumption are associated with decreased semen quality in healthy young men.
A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy
Authors: Oladipo Adewale O. , Oluwafemi Oluwatobi S. , Songca Sandile P. , Sukhbaatar Ariunbuyan , Mori Shiro , Okajima Junnosuke , Komiya Atsuki , Maruyama Shigenao , Kodama Tetsuya
Published: April 2017

Systemic delivery of an anti-cancer agent often leads to only a small fraction of the administered dose accumulating in target sites. Delivering anti-cancer agents through the lymphatic network can achieve more efficient drug delivery for the treatment of lymph node metastasis. We show for the first time that polymeric gold nanorods (PAuNRs) can be delivered efficiently from an accessory axillary lymph node to a tumor-containing proper axillary lymph node, enabling effective treatment of lymph node metastasis. In a mouse model of metastasis, lymphatic spread of tumor was inhibited by lymphatic-delivered PAuNRs and near-infrared laser irradiation, with the skin temperature controlled by cooling. Unlike intravenous injection, lymphatic injection delivered PAuNRs at a high concentration within a short period. The results show that lymphatic administration has the potential to deliver anti-cancer agents to metastatic lymph nodes for inhibition of tumor growth and could be developed into a new therapeutic method.
Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells
Authors: Zhou Xiangyu , Dong Tianyi , Fan Ziyan , Peng Yanping , Zhou Rongbin , Wang Xiaqiong , Song Ning , Han Mingyong , Fan Bingbing , Jia Jihui , Liu Shili
Published: April 2017

Perfluorodecanoic acid (PFDA), a perfluorinated carboxylic acid, presents in the environment and accumulates in human blood and organs, but its association with tumor promotion are not clear. Given that inflammation plays a significant role in the development of gastric malignancies, we evaluated the effects of PFDA on activation of the inflammasome and inflammation regulation in the gastric cell line AGS. When added to cell cultures, PFDA significantly stimulated IL-1β and IL18 secretion and their mRNA levels compared with control cells. By RT-PCR and western-blot we found that up-regulation of NLRP3 were associated with promotion of IL-1β and IL-18 production. Then expression variation of cIAP1/2, c-Rel and p52 were analyzed, the results demonstrated raised mRNA expression in all the tested genes concomitant with enhanced inflammasome activity after exposure to PFDA. Assays with cIAP2 siRNA and NFκB reporter provided additional evidence that these genes were involved in PFDA-induced inflammasome assembly. Furthermore, increased secretion of IL-1β and IL-18 were detected in stomach of PFDA-treated mice, disorganized alignment of epithelial cells and inflammatory cell infiltration were also observed in the stomach tissues upon PFDA treatment. This study reports for the first time that PFDA regulates inflammasome assembly in human cells and mice tissues.
Synthesis of Zn(II)-Doped Magnetite Leaf-Like Nanorings for Efficient Electromagnetic Wave Absorption
Authors: Yang Shuang , Jiang Jian-Tang , Xu Cheng-Yan , Wang Yang , Xu Yan-Yan , Cao Lei , Zhen Liang
Published: April 2017

We report the thermal annealing-induced formation of ring-like structure of Zn(II)-doped magnetite from iron alkoxide leaf-like nanoplate precusor. The phase, structure and morphology of magnetite nanorings were comprehensively characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy, atomic force microscope, scanning electron microscope, and transmission electron microscope. The obtained Zn(II)-doped magnetite nanorings are of 13–20 nm in edge width, 70–110 nm in short axis length and 100–150 nm in long axis length. The growth mechanism was possibly due to a combined effect of decomposition of the organic component and diffusion growth. Zn(II)-doped magnetite nanorings delivered saturation magnetization of 66.4 emu/g and coercivity of 33 Oe at room temperature. In addition, the coatings containing Zn(II)-doped magnetite nanorings as fillers exhibit excellent microwave absorption properties with a maximum reflection loss of −40.4 dB and wide effective absorbing band obtained in coating with thin thickness of 1.50 mm.
Hippocampus Segmentation Based on Local Linear Mapping
Authors: Pang Shumao , Jiang Jun , Lu Zhentai , Li Xueli , Yang Wei , Huang Meiyan , Zhang Yu , Feng Yanqiu , Huang Wenhua , Feng Qianjin
Published: April 2017

We propose local linear mapping (LLM), a novel fusion framework for distance field (DF) to perform automatic hippocampus segmentation. A k-means cluster method is propose for constructing magnetic resonance (MR) and DF dictionaries. In LLM, we assume that the MR and DF samples are located on two nonlinear manifolds and the mapping from the MR manifold to the DF manifold is differentiable and locally linear. We combine the MR dictionary using local linear representation to present the test sample, and combine the DF dictionary using the corresponding coefficients derived from local linear representation procedure to predict the DF of the test sample. We then merge the overlapped predicted DF patch to obtain the DF value of each point in the test image via a confidence-based weighted average method. This approach enabled us to estimate the label of the test image according to the predicted DF. The proposed method was evaluated on brain images of 35 subjects obtained from SATA dataset. Results indicate the effectiveness of the proposed method, which yields mean Dice similarity coefficients of 0.8697, 0.8770 and 0.8734 for the left, right and bi-lateral hippocampus, respectively.
Systems approach to characterize the metabolism of liver cancer stem cells expressing CD133
Authors: Hur Wonhee , Ryu Jae Yong , Kim Hyun Uk , Hong Sung Woo , Lee Eun Byul , Lee Sang Yup , Yoon Seung Kew
Published: April 2017

Liver cancer stem cells (LCSCs) have attracted attention because they cause therapeutic resistance in hepatocellular carcinoma (HCC). Understanding the metabolism of LCSCs can be a key to developing therapeutic strategy, but metabolic characteristics have not yet been studied. Here, we systematically analyzed and compared the global metabolic phenotype between LCSCs and non-LCSCs using transcriptome and metabolome data. We also reconstructed genome-scale metabolic models (GEMs) for LCSC and non-LCSC to comparatively examine differences in their metabolism at genome-scale. We demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. We also confirmed that MYC, a central point of regulation in cancer metabolism, was significantly up-regulated in LCSCs compared with non-LCSCs. Moreover, LCSCs tend to have less active fatty acid oxidation. In this study, the metabolic characteristics of LCSCs were identified using integrative systems analysis, and these characteristics could be potential cures for the resistance of liver cancer cells to anticancer treatments.
Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome
Authors: Kazim Syed Faraz , Blanchard Julie , Bianchi Riccardo , Iqbal Khalid
Published: April 2017

Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model.
Use of banker plant system for sustainable management of the most important insect pest in rice fields in China
Authors: Zheng Xusong , Lu Yanhui , Zhu Pingyang , Zhang Facheng , Tian Junce , Xu Hongxing , Chen Guihua , Nansen Christian , Lu Zhongxian
Published: April 2017

To meet the World’s food demand, there is a growing need for sustainable pest management practices. This study describes the results from complementary laboratory and field studies of a “banker plant system” for sustainable management of the rice brown planthopper (BPH) (Nilaparvata lugens Stål) – the economically most important rice pest in Asian rice growing areas. The banker plant system consisted of planting a grass species, Leersia sayanuka, adjacent to rice fields. L. sayanuka is the host plant of a planthopper, Nilaparvata muiri. An egg parasitoid, Anagrus nilaparvatae, parasitizes eggs of both BPH and N. muiri, and its establishment and persistence are improved through plantings of L. sayanuka and thereby attraction of N. muiri. Laboratory results showed that BPH was unable to complete its life cycle on L. sayanuka, and N. muiri could not complete its life cycle on rice. Thus, planting L. sayanuka did not increase the risk of planthopper damage to rice fields. Field studies showed that BPH densities were significantly lower in rice fields with banker plant system compared to control rice fields without banker plant system.
Housekeeping in Tephritid insects: the best gene choice for expression analyses in the medfly and the olive fly
Authors: Sagri Efthimia , Koskinioti Panagiota , Gregoriou Maria-Eleni , Tsoumani Konstantina T. , Bassiakos Yiannis C. , Mathiopoulos Kostas D.
Published: April 2017

Real-time quantitative-PCR has been a priceless tool for gene expression analyses. The reaction, however, needs proper normalization with the use of housekeeping genes (HKGs), whose expression remains stable throughout the experimental conditions. Often, the combination of several genes is required for accurate normalization. Most importantly, there are no universal HKGs which can be used since their expression varies among different organisms, tissues or experimental conditions. In the present study, nine common HKGs (RPL19, tbp, ubx, GAPDH, α-TUB, β-TUB, 14-3-3zeta, RPE and actin3) are evaluated in thirteen different body parts, developmental stages and reproductive and olfactory tissues of two insects of agricultural importance, the medfly and the olive fly. Three software programs based on different algorithms were used (geNorm, NormFinder and BestKeeper) and gave different ranking of HKG stabilities. This confirms once again that the stability of common HKGs should not be taken for granted and demonstrates the caution that is needed in the choice of the appropriate HKGs. Finally, by estimating the average of a standard score of the stability values resulted by the three programs we were able to provide a useful consensus key for the choice of the best HKG combination in various tissues of the two insects.
Nonresonant 104 Terahertz Field Enhancement with 5-nm Slits
Authors: Suwal Om Krishna , Rhie Jiyeah , Kim Nayeon , Kim Dai-Sik
Published: April 2017

Transmission of Terahertz (THz) electromagnetic wave through a substrate is encumbered because of scattering, multiple reflections, absorption, and Fabry–Perot effects when the wave interacts with the substrate. We present the experimental realization of nonresonant electromagnetic field enhancement by a factor of almost 104 in substrate-free 5-nm gold nanoslits. Our nanoslits yielded greater than 90% normalized electric field transmission in the low-frequency THz region; the slit width was 5 nm, and the gap coverage ratio was 10−4 of the entire membrane, 0.42 mm2. This large field enhancement was attributed to gap plasmons generated by the THz wave, which squeezes the charge cross-section, thus enabling very highly dense oscillating charges and strong THz field transmission from the nanoslits.
Controllable optical modulation of blue/green up-conversion fluorescence from Tm3+ (Er3+) single-doped glass ceramics upon two-step excitation of two-wavelengths
Authors: Chen Zhi , Kang Shiliang , Zhang Hang , Wang Ting , Lv Shichao , Chen Qiuqun , Dong Guoping , Qiu Jianrong
Published: April 2017

Optical modulation is a crucial operation in photonics for network data processing with the aim to overcome information bottleneck in terms of speed, energy consumption, dispersion and cross-talking from conventional electronic interconnection approach. However, due to the weak interactions between photons, a facile physical approach is required to efficiently manipulate photon-photon interactions. Herein, we demonstrate that transparent glass ceramics containing LaF3: Tm3+ (Er3+) nanocrystals can enable fast-slow optical modulation of blue/green up-conversion fluorescence upon two-step excitation of two-wavelengths at telecom windows (0.8–1.8 μm). We show an optical modulation of more than 1500% (800%) of the green (blue) up-conversion fluorescence intensity, and fast response of 280 μs (367 μs) as well as slow response of 5.82 ms (618 μs) in the green (blue) up-conversion fluorescence signal, respectively. The success of manipulating laser at telecom windows for fast-slow optical modulation from rear-earth single-doped glass ceramics may find application in all-optical fiber telecommunication areas.
Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells
Authors: Chang Po-Hsiang , Sekine Keisuke , Chao Hsiao-Mei , Hsu Shan-hui , Chern Edward
Published: April 2017

Cancer stem cells (CSCs), a small population of cancer cells, have been considered to be the origin of cancer initiation, recurrence, and metastasis. Tumor microenvironment provides crucial signals for CSCs to maintain stem cell properties and promotes tumorigenesis. Therefore, establishment of an appropriate cell culture system to mimic the microenvironment for CSC studies is an important issue. In this study, we grew colon and hepatocellular carcinoma (HCC) cells on chitosan membranes and evaluated the tumor progression and the CSC properties. Experimental results showed that culturing cancer cells on chitosan increased cell motility, drug resistance, quiescent population, self-renewal capacity, and the expression levels of stemness and CSC marker genes, such as OCT4, NANOG, CD133, CD44, and EpCAM. Furthermore, we demonstrated that chitosan might activate canonical Wnt/β-catenin-CD44 axis signaling in CD44positive colon cancer cells and noncanonical Wnt-STAT3 signaling in CD44negative HCC cells. In conclusion, chitosan as culture substrates activated the essential signaling of CSCs and promoted CSC properties. The chitosan culture system provides a convenient platform for the research of CSC biology and screening of anticancer drugs.
Entire CD3ε, δ, and γ humanized mouse to evaluate human CD3–mediated therapeutics
Authors: Ueda Otoya , Wada Naoko A. , Kinoshita Yasuko , Hino Hiroshi , Kakefuda Mami , Ito Tsuneo , Fujii Etsuko , Noguchi Mizuho , Sato Kiyoharu , Morita Masahiro , Tateishi Hiromi , Matsumoto Kaoru , Goto Chisato , Kawase Yosuke , Kato Atsuhiko , Hattori Kunihiro , Nezu Junichi , Ishiguro Takahiro , Jishage Kou-ichi
Published: April 2017

T cell–mediated immunotherapy is an attractive strategy for treatment in various disease areas. In this therapeutic approach, the CD3 complex is one of the key molecules to modulate T cell functions; however, in many cases, we cannot evaluate the drug candidates in animal experiments because the therapeutics, usually monoclonal antibodies specific to human CD3, cannot react to mouse endogenous Cd3. Although immunodeficient mice transfused with human hematopoietic stem or precursor cells, known as humanized mice, are available for these studies, mice humanized in this manner are not completely immune competent. In this study we have succeeded in establishing a novel mouse strain in which all the three components of the Cd3 complex — Cd3ε, Cd3δ, and Cd3γ — are replaced by their human counterparts, CD3E, CD3D, and CD3G. Basic immunological assessments have confirmed that this strain of human CD3 EDG–replaced mice are entirely immune competent, and we have also demonstrated that a bispecific antibody that simultaneously binds to human CD3 and a tumor-associated antigen (e.g. ERBB2 or GPC3) can be evaluated in human CD3 EDG–replaced mice engrafted with tumors. Our mouse model provides a novel means to evaluate the in vivo efficacy of human CD3–mediated therapy.
Eukaryotic Life Inhabits Rhodolith-forming Coralline Algae (Hapalidiales, Rhodophyta), Remarkable Marine Benthic Microhabitats
Authors: Krayesky-Self Sherry , Schmidt William E. , Phung Delena , Henry Caroline , Sauvage Thomas , Camacho Olga , Felgenhauer Bruce E. , Fredericq Suzanne
Published: April 2017

Rhodoliths are benthic calcium carbonate nodules accreted by crustose coralline red algae which recently have been identified as useful indicators of biomineral changes resulting from global climate change and ocean acidification. This study highlights the discovery that the interior of rhodoliths are marine biodiversity hotspots that function as seedbanks and temporary reservoirs of previously unknown stages in the life history of ecologically important dinoflagellate and haptophyte microalgae. Whereas the studied rhodoliths originated from offshore deep bank pinnacles in the northwestern Gulf of Mexico, the present study opens the door to assess the universality of endolithic stages among bloom-forming microalgae spanning different phyla, some of public health concerns (Prorocentrum) in marine ecosystems worldwide.
3D assembly based on 2D structure of Cellulose Nanofibril/Graphene Oxide Hybrid Aerogel for Adsorptive Removal of Antibiotics in Water
Authors: Yao Qiufang , Fan Bitao , Xiong Ye , Jin Chunde , Sun Qingfeng , Sheng Chengmin
Published: April 2017

Cellulose nanofibril/graphene oxide hybrid (CNF/GO) aerogel was fabricated via a one-step ultrasonication method for adsorptive removal of 21 kinds of antibiotics in water. The as-prepared CNF/GO aerogel possesses interconnected 3D network microstructure, in which GO nanosheets with 2D structure were intimately grown along CNF through hydrogen bonds. The aerogel exhibited superior adsorption capacity toward the antibiotics. The removal percentages (R%) of the antibiotics were more than 69% and the sequence of six categories antibiotics according to the adsorption efficiency was as follows: Tetracyclines > Quinolones > Sulfonamides > Chloramphenicols > β-Lactams > Macrolides. The adsorption mechanism was proposed to be electrostatic attraction, p-π interaction, π-π interaction and hydrogen bonds. In detail, the adsorption capacities of CNF/GO aerogel were 418.7 mg·g−1 for chloramphenicol, 291.8 mg·g−1 for macrolides, 128.3 mg·g−1 for quinolones, 230.7 mg·g−1 for β-Lactams, 227.3 mg·g−1 for sulfonamides, and 454.6 mg·g−1 for tetracyclines calculated by the Langmuir isotherm models. Furthermore, the regenerated aerogels still could be repeatedly used after ten cycles without obvious degradation of adsorption performance.
Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation
Authors: Li Shanshan , Lin Xiang , Xu Kailin , He Jiawei , Yang Hongqin , Li Hui
Published: April 2017

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.