bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractWe 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

AbstractAlzheimer’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

AbstractMolecular 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

AbstractInherited 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

AbstractThe 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

AbstractThe 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

AbstractHuman 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

AbstractThe 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

AbstractFast 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

AbstractA 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

AbstractA 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

AbstractVisceral 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

AbstractThe 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

AbstractDual-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

AbstractNitrate 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.