bluuebunny/crossref_metadata_2025_split huggingface dataset:
Length effects on the dynamic process of cellular uptake and exocytosis of single-walled carbon nanotubes in murine macrophage cells
Authors: Cui Xuejing , Wan Bin , Yang Yu , Ren Xiaomin , Guo Liang-Hong 
Published: May 2017

AbstractCellular uptake and exocytosis of SWCNTs are fundamental processes determining their intracellular concentration and effects. Despite the great potential of acid-oxidized SWCNTs in biomedical field, understanding of the influencing factors on these processes needs to be deepened. Here, we quantitatively investigated uptake and exocytosis of SWCNTs in three lengths-630 (±171) nm (L-SWCNTs), 390 (±50) nm (M-SWCNTs), and 195 (±63) nm (S-MWCNTs) in macrophages. The results showed that the cellular accumulation of SWCNTs was a length-independent process and non-monotonic in time, with the most SWCNTs (3950 fg/cell) accumulated at 8 h and then intracellular SWCNTs dropped obviously with time. The uptake rate of SWCNTs decreased with increasing concentration, suggesting that intracellular SWCNTs accumulation is a saturable process. After refreshing culture medium, we found increasing SWCNTs in supernatant and decreasing intracellular SWCNTs over time, confirming the exocytosis occurred. Selective inhibition of endocytosis pathways showed that the internalization of SWCNTs involves several pathways, in the order of macropinocytosis> caveolae-mediated endocytosis> clathrin-dependent endocytosis. Intriguingly, clathrin-mediated endocytosis is relatively important for internalizing shorter SWCNTs. The dynamic processes of SWCNTs uptake and exocytosis and the mechanisms revealed by this study may render a better understanding on SWCNT toxicity and facilitate the design of CNT products with mitigated toxicity and desired functions.
Biological early diagenesis and insolation-paced paleoproductivity signified in deep core sediment organic matter
Authors: Chen Meilian , Kim Ji-Hoon , Choi Jiyoung , Lee Yun Kyung , Hur Jin 
Published: May 2017

AbstractThe dynamics of a large stock of organic matter contained in deep sediments of marginal seas plays pivotal role in global carbon cycle, yet it is poorly constrained. Here, dissolved organic matter (DOM) in sediments was investigated for core sediment up to ~240 meters deep in the East/Japan Sea. The upper downcore profile (≤118 mbsf, or meters below seafloor) at a non-chimney site (U1) featured the exponential production of dissolved organic carbon (DOC) and optically active DOM with time in the pore water above sulfate-methane-transition-zone (SMTZ), concurrent with the increases of nutrients and alkalinity, and the reduction of sulfate. Such depth profiles signify a biological pathway of the DOM production during the early diagenesis of particulate organic matter presumably dominated by sulfate reduction. Below the SMTZ, an insolation-paced oscillation of DOM in a ~405-Kyr cycle of orbital eccentricity was observed at site U1, implying astronomically paced paleoproductivity stimulated by light availability. Furthermore, DOM dynamics of the deep sediments were likely governed by intensive humification as revealed by the less pronounced protein-like fluorescence and the lower H/C and O/C ratios below SMTZ among 15,281 formulas identified. Our findings here provide novel insights into organic matter dynamics in deep sediments.
Inflammatory state exists in familial amyloid polyneuropathy that may be triggered by mutated transthyretin
Authors: Suenaga Genki , Ikeda Tokunori , Masuda Teruaki , Motokawa Hiroaki , Yamashita Taro , Takamatsu Kotaro , Misumi Yohei , Ueda Mitsuharu , Matsui Hirotaka , Senju Satoru , Ando Yukio 
Published: May 2017

AbstractThe relationship between familial amyloid polyneuropathy (FAP), which is caused by mutated transthyretin (TTR), and inflammation has only recently been noted. To determine whether inflammation is present in FAP carriers and patients, serum interleukin (IL)−6 concentration in 57 healthy donors (HD), 21 FAP carriers, and 66 FAP patients was examined, with the relationship between IL-6 and TTR assessed in each group by multiple regression analysis and structural equation models (SEM). Compared with HD, IL-6 concentration was elevated in FAP carriers (p = 0.001, 95% CI 0.398–1.571) and patients (p = 0.002, 95% CI 0.362–1.521). Further, SEM indicated a positive relationship between IL-6 and TTR in FAP carriers (p = 0.010, 95% CI 0.019–0.140), but not in HD and FAP patients. In addition, we determined whether TTR induces production of pro-inflammatory cytokines ex vivo. HD-derived CD14 + monocytes and induced pluripotent stem cell-derived myeloid lineage cells from a HD and FAP patient dose-dependently produced IL-6 under mutated and aggregated TTR conditions, compared with wild-type TTR. In conclusion, FAP carriers and patients are in an inflammatory state, with the presence of mutated TTR being a trigger of inflammation, especially in FAP carriers.
A novel non genomic glucocorticoid signaling mediated by a membrane palmitoylated glucocorticoid receptor cross talks with GnRH in gonadotrope cells
Authors: Ayrout Mohsen , Simon Violaine , Bernard Valérie , Binart Nadine , Cohen-Tannoudji Joëlle , Lombès Marc , Chauvin Stéphanie 
Published: May 2017

AbstractGlucocorticoid hormones (GC) are the main stress mediators associated with reproductive disorders. GC exert their effects through activation of the glucocorticoid receptor (GR) principally acting as a transcription factor. Beside well-established GR-mediated genomic actions, several lines of evidence suggest a role for rapid membrane-initiated GC signaling in gonadotrope cells triggered by a membrane-associated GR. Herein, we demonstrate the existence of a specific membrane-initiated GC signaling in LβT2 gonadotrope cells involving two related phosphoproteins: Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and synapsin-I. Within 5 min, LβT2 cells treated with stress range of 10−7 M Corticosterone or a membrane impermeable-GC, BSA-conjugated corticosterone, exhibited a 2-fold increase in levels of phospho-CaMKII and phospho-synapsin-I. Biochemical approaches revealed that this rapid signaling is promoted by a palmitoylated GR. Importantly, GC significantly alter GnRH-induced CaMKII phosphorylation, consistent with a novel cross-talk between the GnRH receptor and GC. This negative effect of GC on GnRH signaling was further observed on LH release by mouse pituitary explants. Altogether, our work provides new findings in GC field by bringing novel understanding on how GR integrates plasma membrane, allowing GC membrane-initiated signaling that differs in presence of GnRH to disrupt GnRH-dependent signaling and LH secretion.
No protection of permafrost due to desertification on the Qinghai–Tibet Plateau
Authors: Wu Qingbai , Yu Wenbing , Jin Huijun 
Published: May 2017

AbstractDesertification of tundra regions may form an escalating cycle with permafrost degradation where more permafrost thaw leads to continued desertification. This traditional viewpoint has been challenged in recent reports that state desertification protects the underlying permafrost. However, our measurements of soil temperature from nine sites in the Honglianghe River Basin, interior Qinghai-Tibet Plateau, show that desertification can degrade permafrost. If one compares the permafrost temperatures at sites with thin sand covers (e.g. site Yu-7, permafrost temperature of −0.64 °C; site Yu-6, permafrost temperature of −1.15 °C) with that of site Xie-1 (−0.65 °C, with a 120-cm-thick sand cover), the permafrost temperature is not significantly different. It is clear that a thick sand cover does not influence the underlying permafrost temperature. Our observations support traditional geocryological knowledge which states that, under most circumstances, desertification does not protect, but rather degrades, permafrost.
FRET-based Visualization of PDGF Receptor Activation at Membrane Microdomains
Authors: Seong Jihye , Huang Min , Sim Kyoung Mi , Kim Hyunbin , Wang Yingxiao 
Published: May 2017

AbstractPlatelet-derived growth factor receptor (PDGFR) senses extracellular growth factors and transfer the signals inside the cells regulating cell proliferation, migration and survival. It has been controversial at which membrane microdomains PDGFRs reside and how they control such diverse intracellular signaling pathways. Here, we developed a novel PDGFR biosensor based on fluorescence resonance energy transfer (FRET), which can detect the real-time PDGFR activity in live cells with high spatiotemporal resolutions. To study subcellular PDGFR activity at membrane microdomains, this PDGFR biosensor was further targeted in or outside lipid rafts via different lipid modification signals. The results suggest that, in response to PDGF stimulation, PDGFR activity is evenly distributed at different membrane microdomains, while integrin-mediated signaling events have inhibitory effects on the activation of PDGFR specifically located in lipid rafts but not outside rafts, implying the role of lipid microdomains as segregated signaling platforms.
Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin
Authors: Chelakkot Chaithanya , Ghim Jaewang , Rajasekaran Nirmal , Choi Jong-Sun , Kim Jung-Hwan , Jang Myoung Ho , Shin Young Kee , Suh Pann-Ghill , Ryu Sung Ho 
Published: May 2017

AbstractUlcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal-specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis.
Tumor protein 53 mutations are enriched in diffuse large B-cell lymphoma with irregular CD19 marker expression
Authors: Kazantseva Marina , Hung Noelyn A. , Mehta Sunali , Roth Imogen , Eiholzer Ramona , Rich Alison M. , Seo Benedict , Baird Margaret A. , Braithwaite Antony W. , Slatter Tania L. 
Published: May 2017

AbstractAccumulating evidence suggests tumor protein 53 (p53) promotes correct cellular differentiation. Thus, mutant TP53 may be more frequent in tumors with irregular differentiation. This study investigated whether TP53 mutations were more frequent in diffuse large B cell lymphoma (DLBCL) that lacked the B cell lineage marker CD19. Sixteen CD19 negative and 78 CD19 positive DLBCL were sequenced for TP53 mutations. Twenty nine tumors had TP53 mutations and were associated with poorer survival. Mutant TP53 was more frequent in CD19 negative lymphomas (81% versus 21%, p < 0.0001). Analysis of other B cell markers revealed a lack of paired box 5 (PAX5) in CD19 positive lymphomas with mutant TP53 (50%), which was more frequent compared to tumors with wild-type TP53 (15%, p = 0.002). In summary, DLBCL lacking CD19 or PAX5 expression were more likely to have mutant TP53, suggesting irregular B cell marker phenotypes are associated with TP53 mutation.
Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis
Authors: Abadpour Shadab , Göpel Sven O. , Schive Simen W. , Korsgren Olle , Foss Aksel , Scholz Hanne 
Published: May 2017

AbstractOne of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin:insulin ratio in nutrient deprived human islets. Furthermore, GDNF alleviated thapsigargin-induced ER stress evidenced by reduced expressions of IRE1α and BiP and consequently apoptosis. Importantly, this was associated with an increase in phosphorylation of PI3K/AKT and GSK3B signaling pathway. Transplantation of ER stressed human islets pre-treated with GDNF under kidney capsule of diabetic mice resulted in reduced expressions of IRE1α and BiP in human islet grafts with improved grafts function shown by higher levels of human C-peptide post-transplantation. We suggest that GDNF has protective and anti-apoptotic effects on nutrient deprived and ER stress activated human islets and could play a significant role in rescuing human islets from stress responses.
Multi-Colored Light-Emitting Electrochemical Cells Based on Thermal Activated Delayed Fluorescence Host
Authors: Liu Jiang , Oliva Jorge , Tong Kwing , Zhao Fangchao , Chen Dustin , Pei Qibing 
Published: May 2017

AbstractLight-emitting electrochemical cells (LECs) with the thermally activated delayed fluorescence(TADF) host and phosphorescent guests were fabricated using solution process. It is demonstrated for the first time that TADF, a well-known phenomenon that helps to increase electroluminescence efficiency by harvesting excitons from triplet states, is used as a host in LECs. Devices with green, yellow, red and warm white emissions were fabricated, with the best devices showing more than 7000 cd/m2 stable emission and a peak efficiency over 7 cd/A. Under high voltage stress, a burst of extremely high luminance of over 30,000 cd/m2 was observed. All these LEC devices are extremely simple with only one active layer. Thus, our results could pave way to produce low- cost light source with high luminance, using TADF molecules.
Human ancestry correlates with language and reveals that race is not an objective genomic classifier
Authors: Baker Jennifer L. , Rotimi Charles N. , Shriner Daniel 
Published: May 2017

AbstractGenetic and archaeological studies have established a sub-Saharan African origin for anatomically modern humans with subsequent migrations out of Africa. Using the largest multi-locus data set known to date, we investigated genetic differentiation of early modern humans, human admixture and migration events, and relationships among ancestries and language groups. We compiled publicly available genome-wide genotype data on 5,966 individuals from 282 global samples, representing 30 primary language families. The best evidence supports 21 ancestries that delineate genetic structure of present-day human populations. Independent of self-identified ethno-linguistic labels, the vast majority (97.3%) of individuals have mixed ancestry, with evidence of multiple ancestries in 96.8% of samples and on all continents. The data indicate that continents, ethno-linguistic groups, races, ethnicities, and individuals all show substantial ancestral heterogeneity. We estimated correlation coefficients ranging from 0.522 to 0.962 between ancestries and language families or branches. Ancestry data support the grouping of Kwadi-Khoe, Kx’a, and Tuu languages, support the exclusion of Omotic languages from the Afroasiatic language family, and do not support the proposed Dené-Yeniseian language family as a genetically valid grouping. Ancestry data yield insight into a deeper past than linguistic data can, while linguistic data provide clarity to ancestry data.
HIV-1 CRF01_AE strain is associated with faster HIV/AIDS progression in Jiangsu Province, China
Authors: Chu Minjie , Zhang Wuhong , Zhang Xuan , Jiang Wenjie , Huan Xiping , Meng Xiaojun , Zhu Bowen , Yang Yue , Tao Yusha , Tian Tian , Lu Yihua , Jiang Liying , Zhang Lei , Zhuang Xun 
Published: May 2017

AbstractThe goal of this study was to assess risk factors associated with HIV/AIDS progression. Between May 2007 and December 2014, 114 subjects were enrolled in Wuxi City and examined every 6 months. The pol gene sequence was amplified to ascertain the HIV-1 subtype. A Cox proportional hazards regression model was used to estimate the factors associated with HIV/AIDS progression. The median follow-up time for all 114 subjects was 26.70 months (IQR: 18.50–41.47), while the median progression time of the 38 progressed subjects was 24.80 months (IQR: 14.13–34.38). Overall, the CRF01_AE subtype was correlated with a significant risk of accelerated progression compared to non-CRF01_AE subtypes (HR = 3.14, 95%CI: 1.39–7.08, P = 0.006). In addition, a lower CD4 count (350–499) at baseline was associated with a risk of accelerated HIV/AIDS progression compared to higher CD4 count (≥500) (HR = 4.38, 95%CI: 1.95–9.82, P < 0.001). Furthermore, interaction analyses showed that HIV-1 subtypes interacted multiplicatively with transmission routes or CD4 count at baseline to contribute to HIV/AIDS progression (P = 0.023 and P < 0.001, respectively). In conclusion, the CRF01_AE subtype and a lower CD4 count at baseline tend to be associated with the faster progression of HIV/AIDS. Understanding the factors affecting HIV/AIDS progression is crucial for developing personalized management and clinical counselling strategies.
One amino acid makes a difference–Characterization of a new TPMT allele and the influence of SAM on TPMT stability
Authors: Iu Yan Ping Heidi , Helander Sara , Kahlin Anna Zimdahl , Cheng Chun Wah , Shek Chi Chung , Leung Moon Ho , Wallner Björn , Mårtensson Lars-Göran , Appell Malin Lindqvist 
Published: May 2017

AbstractThiopurine induced toxicity is associated with defects in the thiopurine methyltransferase (TPMT) gene. TPMT is a polymorphic enzyme, with most of the single nucleotide polymorphisms (SNPs) causing an amino acid change, altering the enzymatic activity of the TPMT protein. In this study, we characterize a novel patient allele c.719A > C, named TPMT*41, together with the more common variant *3C c.719A > G, resulting in an amino acid shift at tyrosine 240 to serine, p.Y240S and cysteine, p.Y240C respectively. We show that the patient heterozygote for c.719A > C has intermediate enzymatic activity in red blood cells. Furthermore, in vitro studies, using recombinant protein, show that TPMT p.Y240S is less stable than both TPMTwt and TPMT p.Y240C. The addition of SAM increases the stability and, in agreement with Isothermal Titration Calorimetry (ITC) data, higher molar excess of SAM is needed in order to stabilize TPMT p.Y240C and TPMT p.Y240S compared to TPMTwt. Molecular dynamics simulations show that the loss of interactions is most severe for Y240S, which agrees with the thermal stability of the mutations. In conclusion, our study shows that SAM increases the stability of TPMT and that changing only one amino acid can have a dramatic effect on TPMT stability and activity.
Viral nervous necrosis in gilthead sea bream (Sparus aurata) caused by reassortant betanodavirus RGNNV/SJNNV: an emerging threat for Mediterranean aquaculture
Authors: Toffan Anna , Pascoli Francesco , Pretto Tobia , Panzarin Valentina , Abbadi Miriam , Buratin Alessandra , Quartesan Rosita , Gijón Daniel , Padrós Francesc 
Published: May 2017

AbstractViral nervous necrosis (VNN) certainly represents the biggest challenge for the sustainability and the development of aquaculture. A large number of economically relevant fish species have proven to be susceptible to the disease. Conversely, gilthead sea bream has generally been considered resistant to VNN, although it has been possible to isolate the virus from apparently healthy sea bream and sporadically from affected larvae and postlarvae. Unexpectedly, in 2014–2016 an increasing number of hatcheries in Europe have experienced mass mortalities in sea bream larvae. Two clinical outbreaks were monitored over this time span and findings are reported in this paper. Despite showing no specific clinical signs, the affected fish displayed high mortality and histological lesions typical of VNN. Fish tested positive for betanodavirus by different laboratory techniques. The isolates were all genetically characterized as being reassortant strains RGNNV/SJNNV. A genetic characterization of all sea bream betanodaviruses which had been isolated in the past had revealed that the majority of the strains infecting sea bream are actually RGNNV/SJNNV. Taken together, this information strongly suggests that RGNNV/SJNNV betanodavirus possesses a particular tropism to sea bream, which can pose a new and unexpected threat to the Mediterranean aquaculture.
Incorrect dosage of IQSEC2, a known intellectual disability and epilepsy gene, disrupts dendritic spine morphogenesis
Authors: Hinze S J , Jackson M R , Lie S , Jolly L , Field M , Barry S C , Harvey R J , Shoubridge C 
Published: May 2017

AbstractThere is considerable genetic and phenotypic heterogeneity associated with intellectual disability (ID), specific learning disabilities, attention-deficit hyperactivity disorder, autism and epilepsy. The intelligence quotient (IQ) motif and SEC7 domain containing protein 2 gene (IQSEC2) is located on the X-chromosome and harbors mutations that contribute to non-syndromic ID with and without early-onset seizure phenotypes in both sexes. Although IQ and Sec7 domain mutations lead to partial loss of IQSEC2 enzymatic activity, the in vivo pathogenesis resulting from these mutations is not known. Here we reveal that IQSEC2 has a key role in dendritic spine morphology. Partial loss-of-function mutations were modeled using a lentiviral short hairpin RNA (shRNA) approach, which achieved a 57% knockdown of Iqsec2 expression in primary hippocampal cell cultures from mice. Investigating gross morphological parameters after 8 days of in vitro culture (8DIV) identified a 32% reduction in primary axon length, in contrast to a 27% and 31% increase in the number and complexity of dendrites protruding from the cell body, respectively. This increase in dendritic complexity and spread was carried through dendritic spine development, with a 34% increase in the number of protrusions per dendritic segment compared with controls at 15DIV. Although the number of dendritic spines had normalized by 21DIV, a reduction was noted in the number of immature spines. In contrast, when modeling increased dosage, overexpression of wild-type IQSEC2 led to neurons with shorter axons that were more compact and displayed simpler dendritic branching. Disturbances to dendritic morphology due to knockdown of Iqsec2 were recapitulated in neurons from Iqsec2 knockout mice generated in our laboratory using CRISPR/Cas9 technology. These observations provide evidence of dosage sensitivity for IQSEC2, which normally escapes X-inactivation in females, and links these disturbances in expression to alterations in the morphology of developing neurons.