bluuebunny/crossref_metadata_2025 huggingface dataset:
EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB
Authors: De Pasquale Valeria , Pezone Antonio , Sarogni Patrizia , Tramontano Alfonso , Schiattarella Gabriele Giacomo , Avvedimento Vittorio Enrico , Paladino Simona , Pavone Luigi Michele
Published: January 2018

Mucopolysaccharidosis (MPS) IIIB is an inherited lysosomal storage disease caused by the deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU) required for heparan sulfate (HS) degradation. The defective lysosomal clearance of undigested HS results in dysfunction of multiple tissues and organs. We recently demonstrated that the murine model of MPS IIIB develops cardiac disease, valvular abnormalities, and ultimately heart failure. To address the molecular mechanisms governing cardiac dysfunctions in MPS IIIB, we generated a model of the disease by silencing NAGLU gene expression in H9C2 rat cardiomyoblasts. NAGLU-depleted H9C2 exhibited accumulation of abnormal lysosomes and a hypertrophic phenotype. Furthermore, we found the specific activation of the epidermal growth factor receptor (EGFR), and increased phosphorylation levels of extracellular signal-regulated kinases (ERKs) in NAGLU-depleted H9C2. The inhibition of either EGFR or ERKs, using the selective inhibitors AG1478 and PD98059, resulted in the reduction of both lysosomal aberration and hypertrophy in NAGLU-depleted H9C2. We also found increased phosphorylation of c-Src and a reduction of the hypertrophic response in NAGLU-depleted H9C2 transfected with a dominant-negative c-Src. However, c-Src phosphorylation remained unaffected by AG1478 treatment, posing c-Src upstream EGFR activation. Finally, heparin-binding EGF-like growth factor (HB-EGF) protein was found overexpressed in our MPS IIIB cellular model, and its silencing reduced the hypertrophic response. These results indicate that both c-Src and HB-EGF contribute to the hypertrophic phenotype of NAGLU-depleted cardiomyoblasts by synergistically activating EGFR and subsequent signaling, thus suggesting that EGFR pathway inhibition could represent an effective therapeutic approach for MPS IIIB cardiac disease.
Monoglyceride lipase gene knockout in mice leads to increased incidence of lung adenocarcinoma
Authors: Liu Renyan , Wang Xin , Curtiss Christopher , Landas Steve , Rong Rong , Sheikh M. Saeed , Huang Ying
Published: January 2018

Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The role of MGL in tumorigenesis remains to be fully elucidated. We have previously shown that MGL expression was reduced or absent in multiple human malignancies, and overexpression of MGL inhibited cancer cell growth. Here, we have generated the MGL knockout mice to further investigate the role of MGL in tumorigenesis in vivo. Our results indicate that MGL-deficient (MGL+/−, MGL−/−) mice exhibited a higher incidence of neoplasia in multiple organs, including the lung, spleen, liver and lymphoid tissues. Interestingly, lung neoplasms were the most common neoplastic changes in the MGL-deficient mice. Importantly, MGL-deficient animals developed premalignant high-grade dysplasia and adenocarcinomas in their lungs. Investigation of the MGL expression status in lung cancer specimens from patients also revealed that MGL expression was significantly reduced in the majority of primary human lung cancers when compared to corresponding matched normal tissues. Furthermore, mouse embryonic fibroblasts (MEFs) from MGL-deficient animals showed characteristics of cellular transformation including increased cell proliferation, foci formation and anchorage-independent growth. Our results also indicate that MGL deficiency was associated with activation of EGFR and ERK. In addition, pro-inflammatory molecules COX-2 and TNF-α were also activated in the MGL-deficient lung tissues. Thus, our results provide new insights into the novel role of MGL as an important negative regulator of EGFR, COX-2 and TNF-α. Accordingly, EGFR and COX-2/TNF-α activation/induction is expected to play important roles in MGL deficiency-driven lung tumors. Collectively, our results implicate the tumor suppressive role of MGL in preventing tumor development in vivo, particularly in context to the lung cancer, and highlight its role as a potential tumor suppressor.
Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells
Authors: Augello Giuseppa , Modica Martina , Azzolina Antonina , Puleio Roberto , Cassata Giovanni , Emma Maria Rita , Di Sano Caterina , Cusimano Antonella , Montalto Giuseppe , Cervello Melchiorre
Published: January 2018

Hepatocellular carcinoma (HCC) is one of the common malignancies and is an increasingly important cause of cancer death worldwide. Surgery, chemotherapy, and radiation therapy extend the 5-year survival limit in HCC patients by only 6%. Therefore, there is a need to develop new therapeutic approaches for the treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity. In the present study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC cells through in vitro and in vivo models, and examined its molecular mechanisms of action. MLN2238 inhibited cell viability in human HCC cells HepG2, Hep3B, and SNU475 in a time- and dose-dependent manner. Flow cytometry analysis demonstrated that MLN2238 induced G2/M cell cycle arrest and cellular apoptosis in HCC cells. Cell cycle arrest was associated with increased expression levels of p21 and p27. MLN2238-induced apoptosis was confirmed by caspase-3/7 activation, PARP cleavage and caspase-dependent β-catenin degradation. In addition, MLN2238 activated ER stress genes in HCC cells and increased the expression of the stress-inducible gene nuclear protein-1. Furthermore, MLN2238 treatment induced upregulation of myeloid cell leukemia-1 (Mcl-1) protein, and Mcl-1 knockdown sensitized HCC cells to MLN2238 treatment, suggesting the contribution of Mcl-1 expression to MLN2238 resistance. This result was also confirmed using the novel Mcl-1 small molecule inhibitor A1210477. Association of A1210477 and MLN2238 determined synergistic antitumor effects in HCC cells. Finally, in vivo orally administered MLN2238 suppressed tumor growth of Hep3B cells in xenograft models in nude mice. In conclusion, our results offer hope for a new therapeutic opportunity in the treatment of HCC patients.
Electric fields control the orientation of peptides irreversibly immobilized on radical-functionalized surfaces
Authors: Martin Lewis J. , Akhavan Behnam , Bilek Marcela M. M.
Published: January 2018

Surface functionalization of an implantable device with bioactive molecules can overcome adverse biological responses by promoting specific local tissue integration. Bioactive peptides have advantages over larger protein molecules due to their robustness and sterilizability. Their relatively small size presents opportunities to control the peptide orientation on approach to a surface to achieve favourable presentation of bioactive motifs. Here we demonstrate control of the orientation of surface-bound peptides by tuning electric fields at the surface during immobilization. Guided by computational simulations, a peptide with a linear conformation in solution is designed. Electric fields are used to control the peptide approach towards a radical-functionalized surface. Spontaneous, irreversible immobilization is achieved when the peptide makes contact with the surface. Our findings show that control of both peptide orientation and surface concentration is achieved simply by varying the solution pH or by applying an electric field as delivered by a small battery.
Angiogenic factor-driven inflammation promotes extravasation of human proangiogenic monocytes to tumours
Authors: Sidibe Adama , Ropraz Patricia , Jemelin Stéphane , Emre Yalin , Poittevin Marine , Pocard Marc , Bradfield Paul F. , Imhof Beat A.
Published: January 2018

Recruitment of circulating monocytes is critical for tumour angiogenesis. However, how human monocyte subpopulations extravasate to tumours is unclear. Here we show mechanisms of extravasation of human CD14dimCD16+ patrolling and CD14+CD16+ intermediate proangiogenic monocytes (HPMo), using human tumour xenograft models and live imaging of transmigration. IFNγ promotes an increase of the chemokine CX3CL1 on vessel lumen, imposing continuous crawling to HPMo and making these monocytes insensitive to chemokines required for their extravasation. Expression of the angiogenic factor VEGF and the inflammatory cytokine TNF by tumour cells enables HPMo extravasation by inducing GATA3-mediated repression of CX3CL1 expression. Recruited HPMo boosts angiogenesis by secreting MMP9 leading to release of matrix-bound VEGF-A, which amplifies the entry of more HPMo into tumours. Uncovering the extravasation cascade of HPMo sets the stage for future tumour therapies.
Neuronal messenger ribonucleoprotein transport follows an aging Lévy walk
Authors: Song Minho S. , Moon Hyungseok C. , Jeon Jae-Hyung , Park Hye Yoon
Published: January 2018

Localization of messenger ribonucleoproteins (mRNPs) plays an essential role in the regulation of gene expression for long-term memory formation and neuronal development. Knowledge concerning the nature of neuronal mRNP transport is thus crucial for understanding how mRNPs are delivered to their target synapses. Here, we report experimental and theoretical evidence that the active transport dynamics of neuronal mRNPs, which is distinct from the previously reported motor-driven transport, follows an aging Lévy walk. Such nonergodic, transient superdiffusion occurs because of two competing dynamic phases: the motor-involved ballistic run and static localization of mRNPs. Our proposed Lévy walk model reproduces the experimentally extracted key dynamic characteristics of mRNPs with quantitative accuracy. Moreover, the aging status of mRNP particles in an experiment is inferred from the model. This study provides a predictive theoretical model for neuronal mRNP transport and offers insight into the active target search mechanism of mRNP particles in vivo.
Evolutionary adaptations to new environments generally reverse plastic phenotypic changes
Authors: Ho Wei-Chin , Zhang Jianzhi
Published: January 2018

Organismal adaptation to a new environment may start with plastic phenotypic changes followed by genetic changes, but whether the plastic changes are stepping stones to genetic adaptation is debated. Here we address this question by investigating gene expression and metabolic flux changes in the two-phase adaptation process using transcriptomic data from multiple experimental evolution studies and computational metabolic network analysis, respectively. We discover that genetic changes more frequently reverse than reinforce plastic phenotypic changes in virtually every adaptation. Metabolic network analysis reveals that, even in the presence of plasticity, organismal fitness drops after environmental shifts, but largely recovers through subsequent evolution. Such fitness trajectories explain why plastic phenotypic changes are genetically compensated rather than strengthened. In conclusion, although phenotypic plasticity may serve as an emergency response to a new environment that is necessary for survival, it does not generally facilitate genetic adaptation by bringing the organismal phenotype closer to the new optimum.
C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity
Authors: Selvaraj Bhuvaneish T. , Livesey Matthew R. , Zhao Chen , Gregory Jenna M. , James Owain T. , Cleary Elaine M. , Chouhan Amit K. , Gane Angus B. , Perkins Emma M. , Dando Owen , Lillico Simon G. , Lee Youn-Bok , Nishimura Agnes L. , Poreci Urjana , Thankamony Sai , Pray Meryll , Vasistha Navneet A. , Magnani Dario , Borooah Shyamanga , Burr Karen , Story David , McCampbell Alexander , Shaw Christopher E. , Kind Peter C. , Aitman Timothy J. , Whitelaw C. Bruce A. , Wilmut Ian , Smith Colin , Miles Gareth B. , Hardingham Giles E. , Wyllie David J. A. , Chandran Siddharthan
Published: January 2018

Mutations in C9ORF72 are the most common cause of familial amyotrophic lateral sclerosis (ALS). Here, through a combination of RNA-Seq and electrophysiological studies on induced pluripotent stem cell (iPSC)-derived motor neurons (MNs), we show that increased expression of GluA1 AMPA receptor (AMPAR) subunit occurs in MNs with C9ORF72 mutations that leads to increased Ca2+-permeable AMPAR expression and results in enhanced selective MN vulnerability to excitotoxicity. These deficits are not found in iPSC-derived cortical neurons and are abolished by CRISPR/Cas9-mediated correction of the C9ORF72 repeat expansion in MNs. We also demonstrate that MN-specific dysregulation of AMPAR expression is also present in C9ORF72 patient post-mortem material. We therefore present multiple lines of evidence for the specific upregulation of GluA1 subunits in human mutant C9ORF72 MNs that could lead to a potential pathogenic excitotoxic mechanism in ALS.
Facile storage and release of white phosphorus and yellow arsenic
Authors: Seitz Andreas E. , Hippauf Felix , Kremer Werner , Kaskel Stefan , Scheer Manfred
Published: January 2018

The storage of metastable compounds and modifications of elements are of great interest for synthesis and other, e.g., semiconductor, applications. Whereas white phosphorus is a metastable modification that can be stored under certain conditions, storage of the extremely (light- and air-)sensitive form of arsenic, yellow arsenic, is a challenge rarely tackled so far. Herein, we report on the facile storage and release of these tetrahedral E4 molecules (E = P, As) using activated carbon as a porous storage material. These loaded materials are air- and light-stable and have been comprehensively characterized by solid-state 31P{1H} MAS NMR spectroscopy, powder X-ray diffraction analysis, nitrogen adsorption measurements, and thermogravimetric analysis. Additionally, we show that these materials can be used as a suitable E4 source for releasing intact white phosphorus or yellow arsenic, enabling subsequent reactions in solution. Because the uptake and release of E4 are reversible, these materials are excellent carriers of these highly reactive modifications.
Erratum: Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry
Authors: Cornejo-Olivas Mario , Torres Luis , Velit-Salazar Mario R. , Inca-Martinez Miguel , Mazzetti Pilar , Cosentino Carlos , Micheli Federico , Perandones Claudia , Dieguez Elena , Raggio Victor , Tumas Vitor , Borges Vanderci , Ferraz Henrique B. , Rieder Carlos R. M. , Shumacher-Schuh Artur , Velez-Pardo Carlos , Jimenez-Del-Rio Marlene , Lopera Francisco , Chang-Castello Jorge , Andreé-Munoz Brennie , Waldherr Sarah , Yearout Dora , Zabetian Cyrus P. , Mata Ignacio F.
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this article.
Investigation of radiomic signatures for local recurrence using primary tumor texture analysis in oropharyngeal head and neck cancer patients
Authors:   M. D. Anderson Cancer Center Head and Neck Quantitative Imaging Working Group, Elhalawani Hesham , Kanwar Aasheesh , Mohamed Abdallah S. R. , White Aubrey , Zafereo James , Wong Andrew , Berends Joel , Abohashem Shady , Williams Bowman , Aymard Jeremy M. , Perni Subha , Messer Jay , Warren Ben , Youssef Bassem , Yang Pei , Meheissen Mohamed A. M. , Kamal Mona , Elgohari Baher , Ger Rachel B. , Cardenas Carlos E. , Fave Xenia , Zhang Lifei , Mackin Dennis , Marai G. Elisabeta , Vock David M. , Canahuate Guadalupe M. , Lai Stephen Y. , Gunn G. Brandon , Garden Adam S. , Rosenthal David I. , Court Laurence , Fuller Clifton D.
Published: January 2018

Radiomics is one such “big data” approach that applies advanced image refining/data characterization algorithms to generate imaging features that can quantitatively classify tumor phenotypes in a non-invasive manner. We hypothesize that certain textural features of oropharyngeal cancer (OPC) primary tumors will have statistically significant correlations to patient outcomes such as local control. Patients from an IRB-approved database dispositioned to (chemo)radiotherapy for locally advanced OPC were included in this retrospective series. Pretreatment contrast CT scans were extracted and radiomics-based analysis of gross tumor volume of the primary disease (GTVp) were performed using imaging biomarker explorer (IBEX) software that runs in Matlab platform. Data set was randomly divided into a training dataset and test and tuning holdback dataset. Machine learning methods were applied to yield a radiomic signature consisting of features with minimal overlap and maximum prognostic significance. The radiomic signature was adapted to discriminate patients, in concordance with other key clinical prognosticators. 465 patients were available for analysis. A signature composed of 2 radiomic features from pre-therapy imaging was derived, based on the Intensity Direct and Neighbor Intensity Difference methods. Analysis of resultant groupings showed robust discrimination of recurrence probability and Kaplan-Meier-estimated local control rate (LCR) differences between “favorable” and “unfavorable” clusters were noted.
Verification of Argentine ant defensive compounds and their behavioral effects on heterospecific competitors and conspecific nestmates
Authors: Welzel Kevin F. , Lee Shao Hung , Dossey Aaron T. , Chauhan Kamlesh R. , Choe Dong-Hwan
Published: January 2018

The invasive Argentine ant (Linepithema humile) has become established worldwide in regions with Mediterranean or subtropical climates. The species typically disrupts the balance of natural ecosystems by competitively displacing some native ant species via strong exploitation and interference competition. Here we report that Argentine ants utilize glandular secretions for inter and intra-specific communications during aggressive interactions with a heterospecific competitor, California harvester ant (Pogonomyrmex californicus). Chemical analyses indicated that Argentine ants deploy glandular secretions containing two major volatile iridoids, dolichodial and iridomyrmecin, on the competitor’s cuticular surface during aggressive interactions. Bioassays indicated that the glandular secretions function as a defensive allomone, causing high levels of irritation in the heterospecific. Furthermore, the same glandular secretions elicited alarm and attraction of conspecific nestmates, potentially enabling more rapid/coordinated defense by the Argentine ants. Two major volatile constituents of the glandular secretion, dolichodial and iridomyrmecin, were sufficient to elicit these responses in conspecifics (as a mixture or individual compounds). The current study suggests that invasive Argentine ants’ superior exploitation and interference competition may rely on the species’ effective semiochemical parsimony.
Intravitreal injection of aflibercept, an anti-VEGF antagonist, down-regulates plasma von Willebrand factor in patients with age-related macular degeneration
Authors: Yamashita Mariko , Matsumoto Masanori , Hayakawa Masaki , Sakai Kazuya , Fujimura Yoshihiro , Ogata Nahoko
Published: January 2018

We investigated the association between von Willebrand factor (VWF) and exudative age-related macular degeneration (AMD) in 114 Japanese patients. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitor is the most effective therapy for AMD. Therefore, we analyzed changes of VWF antigen (VWF:Ag) and VWF multimers (VWFMs) after intravitreal injection of aflibercept, an anti-VEGF antagonist. The relationship between polymorphisms in complement factor H (p.Y402H and p.I62V) and AMD was previously reported. In our patients, p.I62V, but not p.Y402H, was significantly associated with an increased risk of AMD. Pre-treatment plasma levels of VWF:Ag in patients with AMD were significantly higher than those in controls. Unusually large VWFMs (UL-VWFMs) were detected in the majority of AMD patients with concurrent vitreous or subretinal hemorrhage. After intravitreal injection of aflibercept, plasma levels of VWF:Ag and VEGF-A were significantly decreased. UL-VWFMs disappeared after aflibercept injection in three cases, but persisted even 1 month after injection in the other five cases. In conclusion, plasma VWF:Ag levels were significantly elevated in patients with AMD, and decreased after intravitreal aflibercept injection. VWF may play an important role in the pathophysiology of AMD, and aflibercept might improve AMD by reducing plasma levels of VWF in addition to VEGF-A.
Innate immune alterations are elicited in microglial cells before plaque deposition in the Alzheimer’s disease mouse model 5xFAD
Authors: Boza-Serrano Antonio , Yang Yiyi , Paulus Agnes , Deierborg Tomas
Published: January 2018

Alzheimer’s disease (AD) is the most common form of dementia characterized by the formation of amyloid plaques (Aβ). Over the last decade, the important role of the innate immune system for the disease development has been established. Chronic activation of microglial cells creates a proinflammatory environment, which is believed to be central for the development of the disease as well as its progression. We used the AD mouse model 5xFAD to investigate if inflammatory alterations are present in microglial cells before plaque deposition. We applied mass spectrometry and bioinformation analysis to elucidate early microglial alterations. Interestingly, we found the cytokines IL1β and IL10 to be elevated in the 5xFAD brain after the formation of Aβ plaque at 10 weeks only. Using mass spectrometry analysis of microglial cells with bioinformation analysis, we found JAK/STAT, p38 MAPK and Interleukin pathways affected in microglial cells before plaque deposition at 6 weeks. At 10 weeks, GO analysis showed affected pathways related to interferon-gamma regulation and MAPK pathways. Our study points toward early inflammatory changes in microglial cells even before the accumulation of Aβ.
Coupling molecular data and experimental crosses sheds light about species delineation: a case study with the genus Ciona
Authors: Malfant Marine , Darras Sébastien , Viard Frédérique
Published: January 2018

Molecular studies sometimes reveal evolutionary divergence within accepted species. Such findings can initiate taxonomic revision, as exemplified in the formerly recognized species Ciona intestinalis. While an increasing number of studies have examined the ecology, reproductive barriers and genetics of C. intestinalis and C. robusta, there are still much uncertainties regarding other species of this genus. Using experimental crosses and mitochondrial data, we investigated the evolutionary relationships among four native and introduced Ciona spp., found in sympatry in the Mediterranean Sea or English Channel. Outcome of 62 bi-parental reciprocal crosses between C. intestinalis, C. robusta, C. roulei and C. edwardsi showed that C. edwardsi is reproductively isolated from the other taxa, which is in agreement with its distinct location in the phylogenetic tree. Conversely, hybrids are easily obtained in both direction when crossing C. intestinalis and C. roulei, reinforcing the hypothesis of two genetically differentiated lineages but likely being from a same species. Altogether, this study sheds light on the evolutionary relationship in this complex genus. It also calls for further investigation notably based on genome-wide investigation to better describe the evolutionary history within the genus Ciona, a challenging task in a changing world where biological introductions are shuffling species distribution.
Embryonic Surface Ectoderm-specific Mitofusin 2 Conditional Knockout Induces Congenital Cataracts in Mice
Authors: Zhao Jiangyue , Wu Xinwei , Wu Danhong , Yu Yinhui , Yu Yibo , Wang Yao , Fu Qiuli , Zhang Jinsong , Yao Ke
Published: January 2018

Inherited mitochondrial mutations can result in mitochondrial dysfunction or stochastic oxidative damage. Cumulative mitochondrial damage is an important factor in age-related disorders, such as cataracts and macular degeneration. Mfn2 mediates the fusion of mitochondria and contribute to the dynamic balance between fusion and fission that determines mitochondria morphology. We report here that conditional loss of Mfn2 function in the head surface ectoderm leads to a range of congenital eye defects, including small, opacified lens and small eyeball in the most severe phenotypes. The Le-Cre transgenic mouse line and Mfn2 flox mouse line were used in this study to generate Mfn2 conditional knockout mice. Our study revealed Mfn2 gene function in lens development and addressed the relationship between the mitochondria and lens transparency. Conditional loss of Mfn2 affected lens epithelium cell proliferation, apoptosis and ultrastructure of mitochondria. We conclude that proper development of the lens and lens transparency depend on normal Mfn2 gene function.
Lighting-from-above prior in biological motion perception
Authors: Fedorov Leonid A. , Dijkstra Tjeerd M. H. , Giese Martin A.
Published: January 2018

The visual system is able to recognize body motion from impoverished stimuli. This requires combining stimulus information with visual priors. We present a new visual illusion showing that one of these priors is the assumption that bodies are typically illuminated from above. A change of illumination direction from above to below flips the perceived locomotion direction of a biological motion stimulus. Control experiments show that the underlying mechanism is different from shape-from-shading and directly combines information about body motion with a lighting-from-above prior. We further show that the illusion is critically dependent on the intrinsic luminance gradients of the most mobile parts of the moving body. We present a neural model with physiologically plausible mechanisms that accounts for the illusion and shows how the illumination prior might be encoded within the visual pathway. Our experiments demonstrate, for the first time, a direct influence of illumination priors in high-level motion vision.
Guanylate cyclase C reduces invasion of intestinal epithelial cells by bacterial pathogens
Authors: Amarachintha Surya , Harmel-Laws Eleana , Steinbrecher Kris A.
Published: January 2018

The guanylate cyclase C (GC-C) receptor regulates electrolyte and water secretion into the gut following activation by the E. coli enterotoxin STa, or by weaker endogenous agonists guanylin and uroguanylin. Our previous work has demonstrated that GC-C plays an important role in controlling initial infection as well as carrying load of non-invasive bacterial pathogens in the gut. Here, we use Salmonella enterica serovar Typhimurium to determine whether GC-C signaling is important in host defense against pathogens that actively invade enterocytes. In vitro studies indicated that GC-C signaling significantly reduces Salmonella invasion into Caco2-BBE monolayers. Relative to controls, GC-C knockout mice develop severe systemic illness following oral Salmonella infection, characterized by disrupted intestinal mucus layer, elevated cytokines and organ CFUs, and reduced animal survival. In Salmonella-infected wildtype mice, oral gavage of GC-C agonist peptide reduced host/pathogen physical interaction and diminished bacterial translocation to mesenteric lymph nodes. These studies suggest that early life susceptibility to STa-secreting enterotoxigenic E. coli may be counter-balanced by a critical role of GC-C in protecting the mucosa from non-STa producing, invasive bacterial pathogens.
Vaccine vectors based on Adenovirus 19a/64 exhibit broad cellular tropism and potently restimulate HCMV-specific T cell responses ex vivo
Authors: Kiener Richard , Fleischmann Markus , Schwegler Christiane , Ruzsics Zsolt , Thirion Christian , Schrödel Silke , Asbach Benedikt , Wagner Ralf
Published: January 2018

Human Cytomegalovirus (HCMV) remains a major health burden and the development of a vaccine is a global priority. We developed new viral vectors delivering the T cell immunogens IE-1 and pp65 based on Adenovirus 19a/64 (Ad19a/64), a member of subgroup D. In this ex vivo study, the novel vectors were compared side by side to Ad5 or modified Vaccinia Ankara (MVA) strains expressing the same transgenes. We found that unlike Ad5, Ad19a/64 vectors readily transduce a broad panel of immune cells, including monocytes, T cells, NK cells and monocyte-derived dendritic cells (moDCs). Both Ad19a/64- and MVA-transduced moDCs efficiently restimulated IE-1 or pp65-specific T cells but MVA induced a higher amount of cytotoxicity in this cell type. Ad5 and Ad19 induced upregulation of CD86 and HLA-DR in moDCs whereas expression of CD80 and CD83 was largely unaltered. By contrast, MVA transduction led to downregulation of all markers. Taken together, our data demonstrate that Ad19a/64 is a promising vector for the delivery of HCMV immunogens since it transduces dendritic cells with an efficiency that is comparable to MVA, but cytotoxicity and interference with dendritic cell maturation are less pronounced.
Warming deferentially altered multidimensional soil legacy induced by past land use history
Authors: Dong Weiling , Song Alin , Liu Xueduan , Yu Bing , Wang Boren , Lu Yuqiu , Li Yanling , Yin Huaqun , Li Jianwei , Fan Fenliang
Published: January 2018

The legacy effects of previous land use and climate history may affect current soil function. However, the manner in which these legacy effects of land use are modulated by the subsequent climate remains unclear. For this reason, we investigated how the legacies of soil multiple functions left by conversion of grassland to agricultural management were mediated by climate warming with a reciprocal transplant approach. The overall legacy was further separated into the contributions by changes in the abiotic properties of the soil (abiotic process) and microbial community (biotic process). We here hypothesized that warming may mediate the legacy effects of previous land use, mainly by changing biotic processes. Results indicated that warming significantly influenced the total legacies of soil respiration and three exoenzyme activities representing recalcitrant carbon, nitrogen, and phosphorus cycling, but did not affect the total legacy of β-1,4-glucosidase activity, which is involved in labile carbon cycling. The relative contributions of abiotic and biotic processes to the warming effects on the total legacy depended on the type of soil function. The effects of warming on land use change legacies were derived from altered bacterial community structure. The results of the present study suggest that climate conditions could interact with land use legacy to determine the ecosystem functions in a process-specific way.
Slow moving neural source in the epileptic hippocampus can mimic progression of human seizures
Authors: Chiang Chia-Chu , Wei Xile , Ananthakrishnan Arvind Keshav , Shivacharan Rajat S. , Gonzalez-Reyes Luis E. , Zhang Mingming , Durand Dominique M.
Published: January 2018

Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here, we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain. A fast traveling spike and a slow moving wave were recorded simultaneously with a genetically encoded voltage sensitive fluorescent protein (VSFP Butterfly 1.2) and a high speed camera. The results of this study indicate that the fast traveling spike is NMDA-sensitive but the slow moving wave is not. Image analysis and model simulation demonstrate that the slow moving wave is moving slowly, generating the fast traveling spike and is, therefore, a moving source of the epileptiform activity. This slow moving wave is associated with a propagating neural calcium wave detected with calcium dye (OGB-1) but is independent of NMDA receptors, not related to ATP release, and much faster than those previously recorded potassium waves. Computer modeling suggests that the slow moving wave can propagate by the ephaptic effect like epileptiform activity. These findings provide an alternative explanation for slow propagation seizure wavefronts associated with fast propagating spikes.
Enhanced Thermal Conductivity of Polyimide Composites with Boron Nitride Nanosheets
Authors: Wang Ting , Wang Mengjie , Fu Li , Duan Zehui , Chen Yapeng , Hou Xiao , Wu Yuming , Li Shuangyi , Guo Liangchao , Kang Ruiyang , Jiang Nan , Yu Jinhong
Published: January 2018

A strategy was reported to prepare boron nitride nanosheets (BNNSs) by a molten hydroxide assisted liquid exfoliation from hexagonal boron nitride (h-BN) powder. BNNSs with an average thickness of 3 nm were obtained by a facile, low-cost, and scalable exfoliation method. Highly thermally conductive polyimide (PI) composite films with BNNSs filler were prepared by solution-casting process. The in-plane thermal conductivity of PI composite films with 7 wt% BNNSs is up to 2.95 W/mK, which increased by 1,080% compared to the neat PI. In contrast, the out-of plane thermal conductivity of the composites is 0.44 W/mK, with an increase by only 76%. The high anisotropy of thermal conductivity was verified to be due to the high alignment of the BNNSs. The PI/BNNSs composite films are attractive for the thermal management applications in the field of next-generation electronic devices.
In vivo imaging of adeno-associated viral vector labelled retinal ganglion cells
Authors: Smith Corey A. , Chauhan Balwantray C.
Published: January 2018

A defining characteristic of optic neuropathies, such as glaucoma, is progressive loss of retinal ganglion cells (RGCs). Current clinical tests only provide weak surrogates of RGC loss, but the possibility of optically visualizing RGCs and quantifying their rate of loss could represent a radical advance in the management of optic neuropathies. In this study we injected two different adeno-associated viral (AAV) vector serotypes in the vitreous to enable green fluorescent protein (GFP) labelling of RGCs in wild-type mice for in vivo and non-invasive imaging. GFP-labelled cells were detected by confocal scanning laser ophthalmoscopy 1-week post-injection and plateaued in density at 4 weeks. Immunohistochemical analysis 5-weeks post-injection revealed labelling specificity to RGCs to be significantly higher with the AAV2-DCX-GFP vector compared to the AAV2-CAG-GFP vector. There were no adverse functional or structural effects of the labelling method as determined with electroretinography and optical coherence tomography, respectively. The RGC-specific positive and negative scotopic threshold responses had similar amplitudes between control and experimental eyes, while inner retinal thickness was also unchanged after injection. As a positive control experiment, optic nerve transection resulted in a progressive loss of labelled RGCs. AAV vectors provide strong and long-lasting GFP labelling of RGCs without detectable adverse effects.
Omentectomy Prevents Metabolic Syndrome By Reducing Appetite and Body Weight In A Diet-Induced Obesity Rat Model
Authors: García-Ruiz Inmaculada , Solís-Muñoz Pablo , Fernández-Moreira Daniel , Grau Montserrat , Muñoz-Yagüe Maria Teresa , Solís-Herruzo José A.
Published: January 2018

Visceral fat deposition is associated with impairment of glucose and lipid metabolism while leptin levels are frequently related to subcutaneous fat area. At present, there is considerable controversy regarding the role of visceral adipose tissue accumulation in the development of metabolic syndrome (MS). Here we show the effects of omentectomy on the liver and MS in a diet induced obesity rat model. Our results reveal that undergoing omentectomy previously the establishment of the diet-induced-obesity reduced significantly body weight gain and avoid the development of MS, including non-alcoholic fatty liver disease. Intriguingly, the significantly lower body weight gain was due to decreased food intake. Omentum drives obesity progression through leptin resistance mediated by C-reactive protein, Interleucin (IL)-6 and high lipolysis activity. Omentum removal reversed immediately the increased plasma levels of CRP and IL-6 and gradually food intake, weight gain, and features of MS in diet-induced-obesity. Omentectomy caused no changes in normal-weigh-rats. This report displays causal mechanism by which omentum promotes obesity and propose omentectomy as a promising procedure in MS prevention.
Contrasting maternal and paternal genetic variation of hunter-gatherer groups in Thailand
Authors: Kutanan Wibhu , Kampuansai Jatupol , Changmai Piya , Flegontov Pavel , Schröder Roland , Macholdt Enrico , Hübner Alexander , Kangwanpong Daoroong , Stoneking Mark
Published: January 2018

The Maniq and Mlabri are the only recorded nomadic hunter-gatherer groups in Thailand. Here, we sequenced complete mitochondrial (mt) DNA genomes and ~2.364 Mbp of non-recombining Y chromosome (NRY) to learn more about the origins of these two enigmatic populations. Both groups exhibited low genetic diversity compared to other Thai populations, and contrasting patterns of mtDNA and NRY diversity: there was greater mtDNA diversity in the Maniq than in the Mlabri, while the converse was true for the NRY. We found basal uniparental lineages in the Maniq, namely mtDNA haplogroups M21a, R21 and M17a, and NRY haplogroup K. Overall, the Maniq are genetically similar to other negrito groups in Southeast Asia. By contrast, the Mlabri haplogroups (B5a1b1 for mtDNA and O1b1a1a1b and O1b1a1a1b1a1 for the NRY) are common lineages in Southeast Asian non-negrito groups, and overall the Mlabri are genetically similar to their linguistic relatives (Htin and Khmu) and other groups from northeastern Thailand. In agreement with previous studies of the Mlabri, our results indicate that the Malbri do not directly descend from the indigenous negritos. Instead, they likely have a recent origin (within the past 1,000 years) by an extreme founder event (involving just one maternal and two paternal lineages) from an agricultural group, most likely the Htin or a closely-related group.
Single Plasmonic Structure Enhanced Dual-band Room Temperature Infrared Photodetection
Authors: Tong Jinchao , Tobing Landobasa Y. M. , Luo Yu , Zhang Dawei , Zhang Dao Hua
Published: January 2018

Dual-band photodetection in mid- and near-wave infrared spectral bands is of scientific interest and technological importance. Most of the state-of-the-art mid-infrared photodetectors normally operate at low temperature and/or suffer from toxicity and high cost due to limitations of material properties and device structures. The capability of surface plasmons in confining electromagnetic waves into extremely small volume provides an opportunity for improving the performance for room temperature operation. Here, we report an n-InAsSb/n-GaSb heterostructure photodiode integrated with plasmonic two-dimensional subwavelength hole array (2DSHA) for room temperature two band photodetection. We demonstrate that with a properly designed 2DSHA, room temperature detectivities of the heterostructure device can be enhanced to ~1.4 × 109 Jones and ~1.5 × 1011 Jones for the two bands peaked at 3.4 μm and 1.7 μm, respectively. In addition, we study the photocurrent enhancement in both photoconductor and heterojunction modes in the same integrated structure. The demonstration of single 2DSHA enhanced heterojunction photodiode brings a step closer to high sensitivity room temperature devices and systems which require multiband absorption.
The Arabidopsis NLP7 gene regulates nitrate signaling via NRT1.1–dependent pathway in the presence of ammonium
Authors: Zhao Lufei , Zhang Wenjing , Yang Yi , Li Zehui , Li Na , Qi Shengdong , Crawford Nigel M. , Wang Yong
Published: January 2018

Nitrate is not only an important nutrient but also a signaling molecule for plants. A few of key molecular components involved in primary nitrate responses have been identified mainly by forward and reverse genetics as well as systems biology, however, many underlining mechanisms of nitrate regulation remain unclear. In this study, we show that the expression of NRT1.1, which encodes a nitrate sensor and transporter (also known as CHL1 and NPF6.3), is modulated by NIN-like protein 7 (NLP7). Genetic and molecular analyses indicate that NLP7 works upstream of NRT1.1 in nitrate regulation when NH4+ is present, while in absence of NH4+, it functions in nitrate signaling independently of NRT1.1. Ectopic expression of NRT1.1 in nlp7 resulted in partial or complete restoration of nitrate signaling (expression from nitrate-regulated promoter NRP), nitrate content and nitrate reductase activity in the transgenic lines. Transcriptome analysis revealed that four nitrogen-related clusters including amino acid synthesis-related genes and members of NRT1/PTR family were modulated by both NLP7 and NRT1.1. In addition, ChIP and EMSA assays results indicated that NLP7 may bind to specific regions of the NRT1.1 promoter. Thus, NLP7 acts as an important factor in nitrate signaling via regulating NRT1.1 under NH4+ conditions.
One-pot synthesis of a fluorescent molecularly imprinted nanosensor for highly selective detection of sulfapyridine in water
Authors: Hu Yufeng , Li Xiangdao , Liu Jie , Wu Minghuo , Li Ming , Zang Xinke
Published: January 2018

A fluorescent molecularly imprinted nanosensor based on free-radical polymerization was developed for the detection of sulfapyridine.
Mercury methylation in stormwater retention ponds at different stages in the management lifecycle
Authors: Strickman R. J. , Mitchell C. P. J.
Published: January 2018

Stormwater retention ponds produce MeHg, but accumulate less than other types of small wetlands. Their mercury biogeochemistry is subtly different from that of superficially similar environments.
Development of a novel scoring system for identifying emerging chemical risks in the food chain
Authors: Oltmanns J. , Licht O. , Bitsch A. , Bohlen M.-L. , Escher S. E. , Silano V. , MacLeod M. , Serafimova R. , Kass G. E. N. , Merten C.
Published: January 2018

The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food and feed safety, including the establishment of procedures aimed at the identification of emerging risks to food safety.
Quantifying nanoplastic-bound chemicals accumulated in Daphnia magna with a passive dosing method
Authors: Jiang Ruifen , Lin Wei , Wu Jiayi , Xiong Yaxin , Zhu Fang , Bao Lian-Jun , You Jing , Ouyang Gangfeng , Zeng Eddy Y.
Published: January 2018

The contribution of different uptake pathways of chemicals in D. magna in the presence of nanoplastics was clarified.
NANoPoLC algorithm for correcting nanoparticle concentration by sample polydispersity
Authors: Lazurko Caitlin , Ahumada Manuel , Valenzuela-Henríquez Francisco , Alarcon Emilio I.
Published: January 2018

An algorithm for incorporating nanoparticle size dispersity for calculating concentration is presented.
Design of highly selective ethanol dehydration nanocatalysts for ethylene production
Authors: Austin Natalie , Kostetskyy Pavlo , Mpourmpakis Giannis
Published: January 2018

Rational design of catalysts for selective conversion of alcohols to olefins is key since product selectivity remains an issue due to competing etherification reactions.
An amorphous Si material with a sponge-like structure as an anode for Li-ion and Na-ion batteries
Authors: Han Ying , Lin Ning , Xu Tianjun , Li Tieqiang , Tian Jie , Zhu Yongchun , Qian Yitai
Published: January 2018

Sponge-like porous amorphous silicon was prepared by reacting SiCl4 with Mg; it exhibited excellent electrochemical performance for Li-ion batteries and Na-ion batteries.
One-step chemical vapor deposition of MoS2 nanosheets on SiNWs as photocathodes for efficient and stable solar-driven hydrogen production
Authors: Hu Die , Xiang Jie , Zhou Qingwei , Su Shaoqiang , Zhang Zongbao , Wang Xin , Jin Mingliang , Nian Li , Nözel Richard , Zhou Guofu , Zhang Zhang , Liu Junming
Published: January 2018

A one-step chemical vapor deposition for the synthesis of SiNWs/MoS2 photocathodes for efficient and stable solar-driven hydrogen production.
Kinetic and thermodynamic analysis of triplex formation between peptide nucleic acid and double-stranded RNA
Authors: Sato Takaya , Sakamoto Naonari , Nishizawa Seiichi
Published: January 2018

We revealed an association mechanism for PNA–dsRNA triplex formation based on a set of kinetic and thermodynamic data.
Active oxygen species adsorbed on the catalyst surface and its effect on formaldehyde oxidation over Pt/TiO2 catalysts at room temperature; role of the Pt valence state on this reaction?
Authors: Kim Geo Jong , Lee Sang Moon , Chang Hong Sung , Kim Sung Su
Published: January 2018

Two catalyst factors were identified that affected the reaction rate in the room temperature oxidation of HCHO.
Copolymerization of CO2 and epoxides mediated by zinc organyls
Authors: Wulf Christoph , Doering Ulrike , Werner Thomas
Published: January 2018

Simple zinc organyls (R2Zn) efficiently catalyze the copolymerization of CO2 and cyclohexene oxide. The effect of various reaction parameters has been studied. The reaction proceeds under halogen-free conditions and no co-catalyst is required.
Titanate nanotubes-bonded organosulfonic acid as solid acid catalyst for synthesis of butyl levulinate
Authors: Zhou Shuolin , Jiang Dabo , Liu Xianxiang , Chen Yiping , Yin Dulin
Published: January 2018

TiO2 nanotubes-bonded organosulfonic acid as a hybrid catalyst exhibited better activity and good reusability for esterification reaction.
Probing the surface structure of hydroxyapatite through its interaction with hydroxyl: a first-principles study
Authors: Wang Xian , Zhang Li , Liu Zeyu , Zeng Qun , Jiang Gang , Yang Mingli
Published: January 2018

Hydroxyl adsorption alters the surface structure of hydroxyapatite.
Surface-tension-confined assembly of a metal–organic framework in femtoliter droplet arrays
Authors: Wu Zhongsheng , Lin Yinyin , Xing Juanjuan , Zhang Mengying , Wu Jinbo
Published: January 2018

The key factors determining HKUST-1 single-crystal growth are the internal flows in an evaporating droplet and consequently aggregation induced by the combination of metallic Cu(ii) and BTC ions.
Green synthesis of a Cu/MgO nanocomposite by Cassytha filiformis L. extract and investigation of its catalytic activity in the reduction of methylene blue, congo red and nitro compounds in aqueous media
Authors: Nasrollahzadeh Mahmoud , Issaabadi Zahra , Sajadi S. Mohammad
Published: January 2018

This work reports the green synthesis of a Cu/MgO nanocomposite using Cassytha filiformis L. extract as a reducing agent without stabilizers or surfactants.
Hydrogel-embedded tight ultrafiltration membrane with superior anti-dye-fouling property for low-pressure driven molecule separation
Authors: Jiang Gaoshuo , Zhang Shenxiang , Zhu Yuzhang , Gao Shoujian , Jin Huile , Luo Liqiang , Zhang Feng , Jin Jian
Published: January 2018

A hydrogel-embedded tight ultrafiltration membrane composed of sodium polyacrylate-modified polyacrylonitrile with excellent anti-dye-fouling property can effectively separate dyes from salts.
Interfacial engineering via inserting functionalized water-soluble fullerene derivative interlayers for enhancing the performance of perovskite solar cells
Authors: Cao Tiantian , Huang Peng , Zhang Kaicheng , Sun Ziqi , Zhu Kai , Yuan Ligang , Chen Kang , Chen Ning , Li Yongfang
Published: January 2018

Two novel fullerene derivatives were synthesized and utilized as buffer layers in perovskite solar cells for the first time.
A novel design concept for fabricating 3D graphene with the assistant of anti-solvent precipitated sulphates and its Li-ion storage properties
Authors: Wu Kaipeng , Du Ke , Hu Guorong
Published: January 2018

A novel design concept and green synthesis strategy of the Hummers method for fabricating 3D graphene directly from the GO mixed liquor.