bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells
Authors: Montaner Aneley , da Silva Santana Themis Taynah , Schroeder Timm , Einicker-Lamas Marcelo , Girardini Javier , Costa Marcos Romualdo , Banchio Claudia 
Published: January 2018

AbstractHitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation at the expense of astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial differentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell differentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specification and further support the notion that cell differentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specification in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.
Engineered 3D-printed artificial axons
Authors: Espinosa-Hoyos Daniela , Jagielska Anna , Homan Kimberly A. , Du Huifeng , Busbee Travis , Anderson Daniel G. , Fang Nicholas X. , Lewis Jennifer A. , Van Vliet Krystyn J. 
Published: January 2018

AbstractMyelination is critical for transduction of neuronal signals, neuron survival and normal function of the nervous system. Myelin disorders account for many debilitating neurological diseases such as multiple sclerosis and leukodystrophies. The lack of experimental models and tools to observe and manipulate this process in vitro has constrained progress in understanding and promoting myelination, and ultimately developing effective remyelination therapies. To address this problem, we developed synthetic mimics of neuronal axons, representing key geometric, mechanical, and surface chemistry components of biological axons. These artificial axons exhibit low mechanical stiffness approaching that of a human axon, over unsupported spans that facilitate engagement and wrapping by glial cells, to enable study of myelination in environments reflecting mechanical cues that neurons present in vivo. Our 3D printing approach provides the capacity to vary independently the complex features of the artificial axons that can reflect specific states of development, disease, or injury. Here, we demonstrate that oligodendrocytes’ production and wrapping of myelin depend on artificial axon stiffness, diameter, and ligand coating. This biofidelic platform provides direct visualization and quantification of myelin formation and myelinating cells’ response to both physical cues and pharmacological agents.
Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters
Authors: Ito Kenyu , Ohkawara Bisei , Yagi Hideki , Nakashima Hiroaki , Tsushima Mikito , Ota Kyotaro , Konishi Hiroyuki , Masuda Akio , Imagama Shiro , Kiyama Hiroshi , Ishiguro Naoki , Ohno Kinji 
Published: January 2018

AbstractFGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ), but its in vivo ligand remains to be determined. Laser capture microdissection of the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day 7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at E18.5 and in adults. Fgf18−/− mice at E18.5 showed decreased expressions of the NMJ-specific Chrne and Colq genes in the diaphragm. In Fgf18−/− diaphragms, the synaptophysin-positive areas at the nerve terminals and the acetylcholine receptor (AChR)-positive areas at the motor endplates were both approximately one-third of those in wild-type embryos. Fgf18−/− diaphragms ultrastructurally showed abnormal aggregation of multiple nerve terminals making a gigantic presynapse with sparse synaptic vesicles, and simplified motor endplates. In Fgf18−/− diaphragms, miniature endplate potentials were low in amplitude with markedly reduced frequency. In C2C12 myotubes, FGF18 enhanced AChR clustering, which was blocked by inhibiting FGFRs or MEK1. We propose that FGF18 plays a pivotal role in AChR clustering and NMJ formation in mouse embryogenesis.
Variations in bacterial and archaeal communities along depth profiles of Alaskan soil cores
Authors: Tripathi Binu Mani , Kim Mincheol , Kim Yongwon , Byun Eunji , Yang Ji-Woong , Ahn Jinho , Lee Yoo Kyung 
Published: January 2018

AbstractUnderstating the microbial communities and ecological processes that influence their structure in permafrost soils is crucial for predicting the consequences of climate change. In this study we investigated the bacterial and archaeal communities along depth profiles of four soil cores collected across Alaska. The bacterial and archaeal diversity (amplicon sequencing) overall decreased along the soil depth but the depth-wise pattern of their abundances (qPCR) varied by sites. The community structure of bacteria and archaea displayed site-specific pattern, with a greater role of soil geochemical characteristics rather than soil depth. In particular, we found significant positive correlations between methane trapped in cores and relative abundance of methanogenic archaeal genera, indicating a strong association between microbial activity and methane production in subsurface soils. We observed that bacterial phylogenetic community assembly tended to be more clustered in surface soils than in deeper soils. Analyses of phylogenetic community turnover among depth profiles across cores indicated that the relative influence of deterministic and stochastic processes was mainly determined by soil properties rather than depth. Overall, our findings emphasize that the vertical distributions of bacterial and archaeal communities in permafrost soils are to a large extent determined by the variation in site-specific soil properties.
Climate change risk to forests in China associated with warming
Authors: Yin Yunhe , Ma Danyang , Wu Shaohong 
Published: January 2018

AbstractVariations in forest net primary productivity (NPP) reflects the combined effects of key climate variables on ecosystem structure and function, especially on the carbon cycle. We performed risk analysis indicated by the magnitude of future negative anomalies in NPP in comparison with the natural interannual variability to investigate the impact of future climatic projections on forests in China. Results from the multi-model ensemble showed that climate change risk of decreases in forest NPP would be more significant in higher emission scenario in China. Under relatively low emission scenarios, the total area of risk was predicted to decline, while for RCP8.5, it was predicted to first decrease and then increase after the middle of 21st century. The rapid temperature increases predicted under the RCP8.5 scenario would be probably unfavorable for forest vegetation growth in the long term. High-level risk area was likely to increase except RCP2.6. The percentage area at high risk was predicted to increase from 5.39% (2021–2050) to 27.62% (2071–2099) under RCP8.5. Climate change risk to forests was mostly concentrated in southern subtropical and tropical regions, generally significant under high emission scenario of RCP8.5, which was mainly attributed to the intensified dryness in south China.
Adipose-specific lipin1 overexpression in mice protects against alcohol-induced liver injury
Authors: Zhang Wenliang , Zhong Wei , Sun Qian , Sun Xinguo , Zhou Zhanxiang 
Published: January 2018

AbstractExcessive fatty acid release from the white adipose tissue (WAT) contributes to the development of alcoholic liver disease (ALD). Lipin1 (LPIN1), as a co-regulator of DNA-bound transcription factors and a phosphatidic acid (PA) phosphatase (PAP) enzyme that dephosphorylates PA to form diacylglycerol (DAG), is dramatically reduced by alcohol in the WAT. This study aimed at determining the role of adipose LPIN1 in alcohol-induced lipodystrophy and the development of ALD. Transgenic mice overexpressing LPIN1 in adipose tissue (LPIN1-Tg) and wild type (WT) mice were fed a Lieber-DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks. Alcohol feeding to WT mice resulted in significant liver damage, which was significantly alleviated in the LPIN1-Tg mice. Alcohol feeding significantly reduced epididymal WAT (EWAT) mass, inhibited lipogenesis, and increased lipolysis in WT mice, which were attenuated in the LPIN1-Tg mice. LPIN1 overexpression also partially reversed alcohol-reduced plasma leptin levels. In WT mice, alcohol feeding induced hepatic lipid accumulation and down-regulation of beta-oxidation genes, which were dramatically alleviated in the LPIN1-Tg mice. LPIN1 overexpression also significantly attenuated alcohol-induced hepatic ER stress. These results suggest that overexpression of LPIN1 in adipose tissue restores WAT lipid storage function and secretive function to alleviate alcohol-induced liver injury.
Reconstruction of the domain orientation distribution function of polycrystalline PZT ceramics using vector piezoresponse force microscopy
Authors: Kratzer Markus , Lasnik Michael , Röhrig Sören , Teichert Christian , Deluca Marco 
Published: January 2018

AbstractLead zirconate titanate (PZT) is one of the prominent materials used in polycrystalline piezoelectric devices. Since the ferroelectric domain orientation is the most important parameter affecting the electromechanical performance, analyzing the domain orientation distribution is of great importance for the development and understanding of improved piezoceramic devices. Here, vector piezoresponse force microscopy (vector-PFM) has been applied in order to reconstruct the ferroelectric domain orientation distribution function of polished sections of device-ready polycrystalline lead zirconate titanate (PZT) material. A measurement procedure and a computer program based on the software Mathematica have been developed to automatically evaluate the vector-PFM data for reconstructing the domain orientation function. The method is tested on differently in-plane and out-of-plane poled PZT samples, and the results reveal the expected domain patterns and allow determination of the polarization orientation distribution function at high accuracy.
Unveiling the piezoelectric nature of polar α-phase P(VDF-TrFE) at quasi-two-dimensional limit
Authors: Qian Jun , Jiang Sai , Wang Qijing , Zheng Shushu , Guo Shuya , Yi Chang , Wang Jianpu , Wang Xinran , Tsukagoshi Kazuhito , Shi Yi , Li Yun 
Published: January 2018

AbstractPiezoelectric response of P(VDF-TrFE), which is modulated by the dipole density due to the polarization switching on applying an electric field, allows it act as the fundamental components for electromechanical systems. As proposed since the 1970s, its polar α-phase is supposed to yield an enhanced piezoelectric activity. However, its experimental verification has never been reported, hampered by a substantial challenge for the achievement of a smooth, neat α-phase film. Here, we prepare ultrathin crystalline α-phase P(VDF-TrFE) films on the AlOx/Al-coated SiO2/Si substrates via a solution-based approach at room temperature. Thus, we unveil the piezoelectric nature of the polar α-phase P(VDF-TrFE) at a quasi-two-dimensional limit. The obtained values of the relative morphological deformation, the local effective piezoelectric coefficient, and the electric field-induced strain reach up to 37 pm, −46.4 pm V−1, and 4.1%, respectively. Such a robust piezoelectric response is even higher than that of the β-phase. Besides, the evolution of piezoelectricity, which is related to the piezoelectric properties of two polarization states, is also studied. Our work can enable the exploration of the prospective applications of polar α-phase P(VDF-TrFE) films.
Biogenesis of podosome rosettes through fission
Authors: Kuo Szu-Lin , Chen Chien-Lin , Pan Yi-Ru , Chiu Wen-Tai , Chen Hong-Chen 
Published: January 2018

AbstractPodosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Individual podosomes are often found to organize into large rosette-like structures in some types of cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and certain highly invasive cancer cells. In this study, we show that new podosome rosettes arise through one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts. Fission is a more efficient way than de novo assembly to generate new podosome rosettes in these cells. Podosome rosettes undergoing fission possess higher motility and a stronger matrix-degrading capability. Podosome rosette fission may be the result of polarized myosin II-mediated contractility of these structures, which is coordinately regulated by myosin light chain kinase and Rho-associated kinase II. Collectively, this study unveils a previously unknown mechanism—fission for the biogenesis of podosome rosettes.
Functional Antibody Response Against V1V2 and V3 of HIV gp120 in the VAX003 and VAX004 Vaccine Trials
Authors: Balasubramanian Preetha , Williams Constance , Shapiro Mariya B. , Sinangil Faruk , Higgins Keith , Nádas Arthur , Totrov Maxim , Kong Xiang-Peng , Fiore-Gartland Andrew J. , Haigwood Nancy L. , Zolla-Pazner Susan , Hioe Catarina E. 
Published: January 2018

AbstractImmunization with HIV AIDSVAX gp120 vaccines in the phase III VAX003 and VAX004 trials did not confer protection. To understand the shortcomings in antibody (Ab) responses induced by these vaccines, we evaluated the kinetics of Ab responses to the V1V2 and V3 regions of gp120 and the induction of Ab-mediated antiviral functions during the course of 7 vaccinations over a 30.5-month period. Plasma samples from VAX003 and VAX004 vaccinees and placebo recipients were measured for ELISA-binding Abs and for virus neutralization, Ab-dependent cellular phagocytosis (ADCP), and Ab-dependent cellular cytotoxicity (ADCC). Ab responses to V1V2 and V3 peaked after 3 to 4 immunizations and declined after 5 to 7 immunizations. The deteriorating responses were most evident against epitopes in the underside of the V1V2 β-barrel and in the V3 crown. Correspondingly, vaccinees demonstrated higher neutralization against SF162 pseudovirus sensitive to anti-V1V2 and anti-V3 Abs after 3 or 4 immunizations than after 7 immunizations. Higher levels of ADCP and ADCC were also observed at early or mid-time points as compared with the final time point. Hence, VAX003 and VAX004 vaccinees generated V1V2- and V3-binding Abs and functional Abs after 3 to 4 immunizations, but subsequent boosts did not maintain these responses.
Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial Response and Improve Clinical Outcomes in Experimental Spinal Cord Injury
Authors: Ruppert Katherine A. , Nguyen Tin T. , Prabhakara Karthik S. , Toledano Furman Naama E. , Srivastava Amit K. , Harting Matthew T. , Cox Charles S. , Olson Scott D. 
Published: January 2018

AbstractNo current clinical intervention can alter the course of acute spinal cord injury (SCI), or appreciably improve neurological outcome. Mesenchymal stromal cells (MSCs) have been shown to modulate the injury sequelae of SCI largely via paracrine effects, although the mechanisms remain incompletely understood. One potential modality is through secretion of extracellular vesicles (EVs). In this study, we investigate whether systemic administration of EVs isolated from human MSCs (MSCEv) has the potential to be efficacious as an alternative to cell-based therapy for SCI. Additionally, we investigate whether EVs isolated from human MSCs stimulated with pro-inflammatory cytokines have enhanced anti-inflammatory effects when administered after SCI. Immunohistochemistry supported the quantitative analysis, demonstrating a diminished inflammatory response with apparent astrocyte and microglia disorganization in cord tissue up to 10 mm caudal to the injury site. Locomotor recovery scores showed significant improvement among animals treated with MSCEv. Significant increases in mechanical sensitivity threshold were observed in animals treated with EVs from either naïve MSC (MSCEvwt) or stimulated MSC (MSCEv+), with a statistically significant increase in threshold for MSCEv+-treated animals when compared to those that received MSCEvwt. In conclusion, these data show that treatment of acute SCI with extracellular vesicles derived from human MSCs attenuates neuroinflammation and improves functional recovery.
Neoadjuvant therapy in relation to lymphadenectomy and resection margins during surgery for oesophageal cancer
Authors: Kauppila Joonas H. , Wahlin Karl , Lagergren Pernilla , Lagergren Jesper 
Published: January 2018

AbstractDifferences in lymph node yield and tumour-involved resection margins comparing neoadjuvant therapy plus surgery with surgery alone for oesophageal cancer are unclear. Patients who underwent oesophageal cancer surgery in Sweden in 1987–2010 were included. Patients treated with neoadjuvant therapy were compared with those who underwent surgery alone. Outcomes were the number of examined lymph nodes (main outcome), number metastatic lymph nodes, and resection margin status. Rate ratios (RRs) and 95% CIs of lymph node yield were calculated by Poisson regression, and odds ratios (ORs) and 95% CIs of resection margin status by multivariable logistic regression, both adjusted for confounders. Among 1818 patients, 587 (32%) had received neoadjuvant therapy and 1231 (68%) had not. Lymph node yield was lower in the neoadjuvant therapy group (median 6 versus 8; adjusted RR 0.75, 0.73–0.78). Fewer metastatic nodes were identified following neoadjuvant therapy (median 0 versus 1; adjusted RR 0.76, 0.69–0.84). Neoadjuvant therapy associated to decreased risk of tumour-involved resection margins when adjusted for confounders except T-stage (OR 0.52, 0.38–0.70), but the association did not remain after adjustment for T-stage (OR 0.91, 0.64–1.29). Neoadjuvant therapy seems to decrease the lymph node yield and decrease the risk of tumour-involved resection margins by shrinking primary tumour.
Leakage correction improves prognosis prediction of dynamic susceptibility contrast perfusion MRI in primary central nervous system lymphoma
Authors: Kim Yeon Soo , Choi Seung Hong , Yoo Roh-Eul , Kang Koung Mi , Yun Tae Jin , Kim Ji-hoon , Sohn Chul-Ho , Park Sung-Hye , Won Jae-Kyung , Kim Tae Min , Park Chul-Kee , Kim Il Han 
Published: January 2018

AbstractTo evaluate whether the cerebral blood volume (CBV) measurement with leakage correction from dynamic susceptibility contrast perfusion weighted imaging can be useful in predicting prognosis for primary central nervous system lymphoma (PCNSL). 46 PCNSL patients were included and classified by radiation therapy (RT) stratification into RT (n = 30) and non-RT (n = 16) groups. The corresponding histogram parameters of normalized CBV (nCBV) maps with or without leakage correction were calculated on contrast-enhanced T1 weighted image (CE T1WI) or on fluid attenuated inversion recovery image. The 75th percentile nCBV with leakage correction based on CE T1WI (T1 nCBVL75%) had a significant difference between the short and long progression free survival (PFS) subgroups of the RT group and the non-RT group, respectively. Based on the survival analysis, patients in the RT group with high T1 nCBVL75% had earlier progression than the others with a low T1 nCBVL75%. However, patients in the non-RT group with a high T1 nCBVL75% had slower progression than the others with a low T1 nCBVL75%. Based on RT stratification, the CBV with leakage correction has potential as a noninvasive biomarker for the prognosis prediction of PCNSL to identify high risk patients and it has a different correlation with the PFS based on the presence of combined RT.
A biofilm and organomineralisation model for the growth and limiting size of ooids
Authors: Batchelor Murray T. , Burne Robert V. , Henry Bruce I. , Li Fei , Paul Josef 
Published: January 2018

AbstractOoids are typically spherical sediment grains characterised by concentric layers encapsulating a core. There is no universally accepted explanation for ooid genesis, though factors such as agitation, abiotic and/or microbial mineralisation and size limitation have been variously invoked. Here we examine the possible influence of microbial organomineralisation on the formation of some naturally occurring ooids. We develop a mathematical model for ooid growth, inspired by work on avascular brain tumours, that assumes mineralisation in a biofilm to form a central core which then nucleates the progressive growth of concentric laminations. The model predicts a limiting size with the sequential width variation of growth rings comparing favourably with those observed in experimentally grown ooids generated from biomicrospheres. In reality, this model pattern may be complicated during growth by syngenetic aggrading neomorphism of the unstable mineral phase, followed by diagenetic recrystallisation that further complicates the structure. Our model provides a potential key to understanding the genetic archive preserved in the internal structures of some ooids.
Dengue virus-induced ER stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo
Authors: Lee Ying-Ray , Kuo Szu-Han , Lin Ching-Yen , Fu Po-Jung , Lin Yee-Shin , Yeh Trai-Ming , Liu Hsiao-Sheng 
Published: January 2018

AbstractDengue virus (DENV) utilizes the endoplasmic reticulum (ER) for replication and assembling. Accumulation of unfolded proteins in the ER lumen leads to ER stress and unfolded protein response (UPR). Three branches of UPRs temporally modulated DENV infection. Moreover, ER stress can also induce autophagy. DENV infection induces autophagy which plays a promotive role in viral replication has been reported. However, the role of ER stress in DENV-induced autophagy, viral titer, and pathogenesis remain unclear. Here, we reveal that ER stress and its downstream UPRs are indispensable for DENV-induced autophagy in various human cells. We demonstrate that PERK-eIF2α and IRE1α-JNK signaling pathways increased autophagy and viral load after DENV infection. However, ATF6-related pathway showed no effect on autophagy and viral replication. IRE1α-JNK downstream molecule Bcl-2 was phosphorylated by activated JNK and dissociated from Beclin 1, which playing a critical role in autophagy activation. These findings were confirmed as decreased viral titer, attenuated disease symptoms, and prolonged survival rate in the presence of JNK inhibitor in vivo. In summary, we are the first to reveal that DENV2-induced ER stress increases autophagy activity, DENV replication, and pathogenesis through two UPR signaling pathways both in vitro and in vivo.