bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-mW, few-cycle mid-infrared continuum spanning from 500 to 2250 cm−1
Authors: Zhang Jinwei , Fai Mak Ka , Nagl Nathalie , Seidel Marcus , Bauer Dominik , Sutter Dirk , Pervak Vladimir , Krausz Ferenc , Pronin Oleg 
Published: February 2018

AbstractThe demand for and usage of broadband coherent mid-infrared sources, such as those provided by synchrotron facilities, are growing. Since most organic molecules exhibit characteristic vibrational modes in the wavelength range between 500 and 4000 cm−1, such broadband coherent sources enable micro- or even nano-spectroscopic applications at or below the diffraction limit with a high signal-to-noise ratio1, 2, 3. These techniques have been applied in diverse fields ranging from life sciences, material analysis, and time-resolved spectroscopy. Here we demonstrate a broadband, coherent and intrinsically carrier-envelope-phase-stable source with a spectrum spanning from 500 to 2250 cm−1 (−30 dB) at an average power of 24 mW and a repetition rate of 77 MHz. This performance is enabled by the first mode-locked thin-disk oscillator operating at 2 μm wavelength, providing a tenfold increase in average power over femtosecond oscillators previously demonstrated in this wavelength range4. Multi-octave spectral coverage from this compact and power-scalable system opens up a range of time- and frequency-domain spectroscopic applications.
Circular RNA GRB10 as a competitive endogenous RNA regulating nucleus pulposus cells death in degenerative intervertebral disk
Authors: Guo Wei , Zhang Bin , Mu Kun , Feng Shi-Qing , Dong Zhan-Yin , Ning Guang-Zhi , Li Hao-Ran , Liu Shen , Zhao Ling , Li Yan , Yu Bing-Bing , Duan Hui-Quan , Sun Chao , Li Yong-Jin 
Published: February 2018

Abstract
Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the underlying mechanisms remain poorly understood. Compared with normal nucleus pulposus (NP) tissues, the expression of circ-GRB10 was downregulated in IDD. Furthermore, overexpression of circ-GRB10 inhibited NP cell apoptosis. circ-GRB10 could sequester miR-328-5p, which could potentially lead to the upregulation of target genes related to cell proliferation via the ErbB pathway. In conclusion, the present study revealed that circ-GRB10/miR-328-5p/ERBB2 signaling pathway is involved in IDD development, suggesting that circ-GRB10 might be a novel therapeutic target for IDD.
TCF7L2 positively regulates aerobic glycolysis via the EGLN2/HIF-1α axis and indicates prognosis in pancreatic cancer
Authors: Xiang Jinfeng , Hu Qiangsheng , Qin Yi , Ji Shunrong , Xu Wenyan , Liu Wensheng , Shi Si , Liang Chen , Liu Jiang , Meng Qingcai , Liang Dingkong , Ni Quanxing , Xu Jin , Zhang Bo , Yu Xianjun 
Published: February 2018

AbstractPatients with pancreatic ductal adenocarcinoma have much worse prognoses, and much effort has been directed toward understanding the molecular biological aspects of this disease. Accumulated evidence suggests that constitutive activation of the Wnt/β-catenin signalling contributes to the oncogenesis and progression of pancreatic cancer. Transcription factor 7-like2/transcription factor 4 (TCF7L2/TCF4), a β-catenin transcriptional partner, plays a vital role in the Wnt/β-catenin signalling pathway. In the present study, we investigated the clinicopathological significance of TCF7L2 in pancreatic cancer. Our results demonstrated that patients with higher TCF7L2 expression had worse prognosis. Our in vitro studies demonstrated that TCF7L2 positively regulated aerobic glycolysis by suppressing Egl-9 family hypoxia inducible factor 2 (EGLN2), leading to upregulation of hypoxia inducible factor 1 alpha subunit (HIF-1α). The impact of TCF7L2 on aerobic glycolysis was further confirmed in vivo by assessing 18FDG uptake in pancreatic cancer patients and in a subcutaneous xenograft mouse model. In summary, we identified novel predictive markers for prognosis and suggest a previously unrecognized role for TCF7L2 in control of aerobic glycolysis in pancreatic cancer.
Rapid measurement of inhibitor binding kinetics by isothermal titration calorimetry
Authors: Di Trani Justin M. , De Cesco Stephane , O’Leary Rebecca , Plescia Jessica , do Nascimento Claudia Jorge , Moitessier Nicolas , Mittermaier Anthony K. 
Published: February 2018

AbstractAlthough drug development typically focuses on binding thermodynamics, recent studies suggest that kinetic properties can strongly impact a drug candidate’s efficacy. Robust techniques for measuring inhibitor association and dissociation rates are therefore essential. To address this need, we have developed a pair of complementary isothermal titration calorimetry (ITC) techniques for measuring the kinetics of enzyme inhibition. The advantages of ITC over standard techniques include speed, generality, and versatility; ITC also measures the rate of catalysis directly, making it ideal for quantifying rapid, inhibitor-dependent changes in enzyme activity. We used our methods to study the reversible covalent and non-covalent inhibitors of prolyl oligopeptidase (POP). We extracted kinetics spanning three orders of magnitude, including those too rapid for standard methods, and measured sub-nM binding affinities below the typical ITC limit. These results shed light on the inhibition of POP and demonstrate the general utility of ITC-based enzyme inhibition kinetic measurements.
Frontal cortex function as derived from hierarchical predictive coding
Authors: Alexander William H. , Brown Joshua W. 
Published: February 2018

AbstractThe frontal lobes are essential for human volition and goal-directed behavior, yet their function remains unclear. While various models have highlighted working memory, reinforcement learning, and cognitive control as key functions, a single framework for interpreting the range of effects observed in prefrontal cortex has yet to emerge. Here we show that a simple computational motif based on predictive coding can be stacked hierarchically to learn and perform arbitrarily complex goal-directed behavior. The resulting Hierarchical Error Representation (HER) model simulates a wide array of findings from fMRI, ERP, single-units, and neuropsychological studies of both lateral and medial prefrontal cortex. By reconceptualizing lateral prefrontal activity as anticipating prediction errors, the HER model provides a novel unifying account of prefrontal cortex function with broad implications for understanding the frontal cortex across multiple levels of description, from the level of single neurons to behavior.
Multipotent Adult Progenitor Cells Support Lymphatic Regeneration at Multiple Anatomical Levels during Wound Healing and Lymphedema
Authors: Beerens Manu , Aranguren Xabier L. , Hendrickx Benoit , Dheedene Wouter , Dresselaers Tom , Himmelreich Uwe , Verfaillie Catherine , Luttun Aernout 
Published: February 2018

AbstractLymphatic capillary growth is an integral part of wound healing, yet, the combined effectiveness of stem/progenitor cells on lymphatic and blood vascular regeneration in wounds needs further exploration. Stem/progenitor cell transplantation also emerged as an approach to cure lymphedema, a condition caused by lymphatic system deficiency. While lymphedema treatment requires lymphatic system restoration from the capillary to the collector level, it remains undetermined whether stem/progenitor cells support a complex regenerative response across the entire anatomical spectrum of the system. Here, we demonstrate that, although multipotent adult progenitor cells (MAPCs) showed potential to differentiate down the lymphatic endothelial lineage, they mainly trophically supported lymphatic endothelial cell behaviour in vitro. In vivo, MAPC transplantation supported blood vessel and lymphatic capillary growth in wounds and restored lymph drainage across skin flaps by stimulating capillary and pre-collector vessel regeneration. Finally, human MAPCs mediated survival and functional reconnection of transplanted lymph nodes to the host lymphatic network by improving their (lymph)vascular supply and restoring collector vessels. Thus, MAPC transplantation represents a promising remedy for lymphatic system restoration at different anatomical levels and hence an appealing treatment for lymphedema. Furthermore, its combined efficacy on lymphatic and blood vascular growth is an important asset for wound healing.
Preoperative Heart Rate Variability as Predictors of Vagus Nerve Stimulation Outcome in Patients with Drug-resistant Epilepsy
Authors: Liu Hong-Yun , Yang Zhao , Meng Fan-Gang , Guan Yu-Guang , Ma Yan-Shan , Liang Shu-Li , Lin Jiu-Luan , Pan Long-Sheng , Zhao Ming-Ming , Qu Wei , Hao Hong-Wei , Luan Guo-Ming , Zhang Jian-Guo , Li Lu-Ming 
Published: February 2018

AbstractVagus nerve stimulation (VNS) is an adjunctive treatment for drug-resistant epilepsy (DRE). However, it is still difficult to predict which patients will respond to VNS treatment and to what extent. We aim to explore the relationship between preoperative heart rate variability (HRV) and VNS outcome. 50 healthy control subjects and 63 DRE patients who had received VNS implants and had at least one year of follow up were included. The preoperative HRV were analyzed by traditional linear methods and heart rhythm complexity analyses with multiscale entropy (MSE). DRE patients had significantly lower complexity indices (CI) as well as traditional linear HRV measurements than healthy controls. We also found that non-responders0 had significantly lower preoperative CI including Area 1–5, Area 6–15 and Area 6–20 than those in the responders0 while those of the non-responders50 had significantly lower RMSSD, pNN50, VLF, LF, HF, TP and LF/HF than the responders50. In receiver operating characteristic (ROC) curve analysis, Area 6–20 and RMSSD had the greatest discriminatory power for the responders0 and non-responders0, responders50 and non-responders50, respectively. Our results suggest that preoperative assessment of HRV by linear and MSE analysis can help in predicting VNS outcomes in patients with DRE.
Degradation shaped bacterial and archaeal communities with predictable taxa and their association patterns in Zoige wetland at Tibet plateau
Authors: Gu Yunfu , Bai Yan , Xiang Quanju , Yu Xiumei , Zhao Ke , Zhang Xiaoping , Li Chaonan , Liu Songqing , Chen Qiang 
Published: February 2018

AbstractSoil microbes provide important ecosystem services. Zoige Plateau wetland, the largest alpine peat wetland in the world, has suffered from serious degradation in the past 30 years. We studied the composition of the Zoige Plateau alpine wetland soil microbiota and relations among specific taxa using 16S rRNA amplicon sequencing combined with association network analysis. Compared to the pristine swamp soil, taxons DA101,Aeromicrobium,Bradyrhizobium, andCandidatus Nitrososphaerawere enriched and several methanogenic Euryarchaeota were depleted in the moderately degraded meadow soil and highly degraded sandy soil. Soil total potassium contents in soils with different degradation levels were significantly different, being the highest in meadow soil and lowest in swamp soil. The association network analysis showed that total potassium positively correlated with specific bacterial and archaeal taxa.Jiangella,Anaerolinea,Desulfobulbus,Geobacter,Flavobacterium,MethanobacteriumandMethanosaetawere identified as the keystone genera in the networks. Soil degradation affected soil properties, and caused changes in the bacterial and archaeal community composition and the association patterns of community members. The changes could serve as early warning signals of soil degradation in alpine wetlands.
Large-scale patterning of single cells and cell clusters in hydrogels
Authors: Gong Xiangyu , Mills Kristen L. 
Published: February 2018

AbstractBiophysical properties of the extracellular matrix (ECM) are known to play a significant role in cell behavior. To gain a better understanding of the effects of the biophysical microenvironment on cell behavior, the practical challenge is longitudinally monitoring behavioral variations within a population to make statistically powerful assessments. Population-level measurements mask heterogeneity in cell responses, and large-scale individual cell measurements are often performed in a one-time, snapshot manner after removing cells from their matrix. Here we present an easy and low-cost method for large-scale, longitudinal studies of heterogeneous cell behavior in 3D hydrogel matrices. Using a platform we term “the drop-patterning chip”, thousands of cells were simultaneously transferred from microwell arrays and fully embedded, only using the force of gravity, in precise patterns in 3D collagen I or Matrigel. This method allows for throughputs approaching 2D patterning methods that lack phenotypic information on cell-matrix interactions, and does not rely on special equipment and cell treatments that may result in a proximal stiff surface. With a large and yet well-organized group of cells captured in 3D matrices, we demonstrated the capability of locating selected individual cells and monitoring cell division, migration, and proliferation for multiple days.
A Highly Sensitive Detection System based on Proximity-dependent Hybridization with Computer-aided Affinity Maturation of a scFv Antibody
Authors: Wang Zhiheng , Li Yan , Liang Wenbin , Zheng Junsong , Li Shuhui , Hu Chuanmin , Chen An 
Published: February 2018

AbstractThe hepatitis B virus (HBV) infection is a critical health problem worldwide, and HBV preS1 is an important biomarker for monitoring HBV infection. Previously, we found that a murine monoclonal antibody, mAb-D8, targets the preS1 (aa91-107) fragment of HBV. To improve its performance, we prepared the single-chain variable region of mAb-D8 (scFvD8) and constructed the three-dimensional structure of the scFvD8-preS1 (aa91-107) complex by computer modelling. The affinity of scFvD8 was markedly increased by the introduction of mutations L96Tyr to Ser and H98Asp to Ser. Furthermore, a highly sensitive immunosensor was designed based on a proximity-dependent hybridization strategy in which the preS1 antigen competitively reacts with an antibody labelled with DNA, resulting in decreased proximity-dependent hybridization and increased electrochemical signal from the Fc fragment, which can be used for the quantisation of preS1. The results showed a wide detection range from 1 pM to 50 pM with a detection limit of 0.1 pM. The sensitivity and specificity of this immunosensor in clinical serum samples were 100% and 96%, respectively. This study provides a novel system based on proximity-dependent hybridization and the scFv antibody fragment for the rapid quantisation of antigens of interest with a high sensitivity.
An allosteric link connecting the lipid-protein interface to the gating of the nicotinic acetylcholine receptor
Authors: Domville Jaimee A. , Baenziger John E. 
Published: February 2018

AbstractThe mechanisms underlying lipid-sensing by membrane proteins is of considerable biological importance. A unifying mechanistic question is how a change in structure at the lipid-protein interface is translated through the transmembrane domain to influence structures critical to protein function. Gating of the nicotinic acetylcholine receptor (nAChR) is sensitive to its lipid environment. To understand how changes at the lipid-protein interface influence gating, we examined how a mutation at position 418 on the lipid-facing surface of the outer most M4 transmembrane α-helix alters the energetic couplings between M4 and the remainder of the transmembrane domain. Human muscle nAChR is sensitive to mutations at position 418, with the Cys-to-Trp mutation resulting in a 16-fold potentiation in function that leads to a congenital myasthenic syndrome. Energetic coupling between M4 and the Cys-loop, a key structure implicated in gating, do not change with C418W. Instead, Trp418 and an adjacent residue couple energetically with residues on the M1 transmembrane α-helix, leading to a reorientation of M1 that stabilizes the open state. We thus identify an allosteric link connecting the lipid-protein interface of the nAChR to altered channel function.
Transcriptional activation of zebrafish fads2 promoter and its transient transgene expression in yolk syncytial layer of zebrafish embryos
Authors: Tay Shu-Shen , Kuah Meng-Kiat , Shu-Chien Alexander Chong 
Published: February 2018

AbstractThe front-end desaturases (Fads) are rate-limiting enzymes responsible for production of long-chain polyunsaturated fatty acids (LC-PUFA). The full spectrum of the transcriptional regulation of fads is still incomplete, as cloning of fads promoter is limited to a few species. Here, we described the cloning and characterisation of the zebrafish fads2 promoter. Using 5′-deletion and mutation analysis on this promoter, we identified a specific region containing the sterol regulatory element (SRE) which is responsible for the activation of the fads2 promoter. In tandem, two conserved CCAAT boxes were also present adjacent to the SRE and mutation of either of these binding sites attenuates the transcriptional activation of the fads2 promoter. An in vivo analysis employing GFP reporter gene in transiently transfected zebrafish embryos showed that this 1754 bp upstream region of the fads2 gene specifically directs GFP expression in the yolk syncytial layer (YSL) region. This indicates a role for LC-PUFA in the transport of yolk lipids through this tissue layer. In conclusion, besides identifying novel core elements for transcriptional activation in zebrafish fads2 promoter, we also reveal a potential role for fads2 or LC-PUFA in YSL during development.
Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment
Authors: Itoh Go , Ikeda Masanori , Iemura Kenji , Amin Mohammed Abdullahel , Kuriyama Sei , Tanaka Masamitsu , Mizuno Natsuki , Osakada Hiroko , Haraguchi Tokuko , Tanaka Kozo 
Published: February 2018

AbstractFaithful chromosome segregation is ensured by the establishment of bi-orientation; the attachment of sister kinetochores to the end of microtubules extending from opposite spindle poles. In addition, kinetochores can also attach to lateral surfaces of microtubules; called lateral attachment, which plays a role in chromosome capture and transport. However, molecular basis and biological significance of lateral attachment are not fully understood. We have addressed these questions by focusing on the prometaphase rosette, a typical chromosome configuration in early prometaphase. We found that kinetochores form uniform lateral attachments in the prometaphase rosette. Many transient kinetochore components are maximally enriched, in an Aurora B activity-dependent manner, when the prometaphase rosette is formed. We revealed that rosette formation is driven by rapid poleward motion of dynein, but can occur even in its absence, through slow kinetochore movements caused by microtubule depolymerization that is supposedly dependent on kinetochore tethering at microtubule ends by CENP-E. We also found that chromosome connection to microtubules is extensively lost when lateral attachment is perturbed in cells defective in end-on attachment. Our findings demonstrate that lateral attachment is an important intermediate in bi-orientation establishment and chromosome alignment, playing a crucial role in incorporating chromosomes into the nascent spindle.
Melanopsin photoreception contributes to human visual detection, temporal and colour processing
Authors: Zele Andrew J. , Feigl Beatrix , Adhikari Prakash , Maynard Michelle L. , Cao Dingcai 
Published: February 2018

AbstractThe visual consequences of melanopsin photoreception in humans are not well understood. Here we studied melanopsin photoreception using a technique of photoreceptor silent substitution with five calibrated spectral lights after minimising the effects of individual differences in optical pre-receptoral filtering and desensitising penumbral cones in the shadow of retinal blood vessels. We demonstrate that putative melanopsin-mediated image-forming vision corresponds to an opponent S-OFF L + M-ON response property, with an average temporal resolution up to approximately 5 Hz, and >10x higher thresholds than red-green colour vision. With a capacity for signalling colour and integrating slowly changing lights, melanopsin-expressing intrinsically photosensitive retinal ganglion cells maybe the fifth photoreceptor type for peripheral vision.
Room temperature 90° phase-matching in zirconium and magnesium co-doped lithium niobate crystals
Authors: Kong Tengfei , Liu Hongde , Ge Xinyu , Qu Da , Liu Shiguo , Chen Shaolin , Zhang Ling , Kong Yongfa , Rupp Romano , Xu Jingjun 
Published: February 2018

AbstractLaser has been widely used in many aspects, by now it is difficult to get each frequency that we want, and frequency conversion is an effective way to obtain different frequency laser through a nonlinear optical crystal. MgO-doped LiNbO3 (Mg:LN) crystal has usually been used for second harmonic generation (SHG) through temperature-matching configuration with a stove, till now a room temperature 90° phase-matching is still lacking. Here we find that the SHG of Nd:YAG laser is achieved at 26.1 °C while the optical damage resistance is higher than 6.5 MW/cm2 in the ZrO2 and MgO co-doped LiNbO3 (Zr,Mg:LN) crystal. Moreover, the monotonic decrease of phase-matching temperature is firstly found with the increase of doping concentration. These unusual properties may be attributed to the formation of $${{\bf{Mg}}}_{{\bf{Li}}}^{{\boldsymbol{+}}}$$

Mg

Li

+

+ $${{\bf{Zr}}}_{{\bf{Nb}}}^{{\boldsymbol{-}}}$$

Zr

Nb

−

defect pairs. Our work suggests that Zr,Mg:LN crystal may be an attractive candidate for nonlinear optical applications.
Echinacoside Increases Sperm Quantity in Rats by Targeting the Hypothalamic Androgen Receptor
Authors: Jiang Zhihui , Zhou Bo , Li Xinping , Kirby Gordon M. , Zhang Xiaoying 
Published: February 2018

AbstractMale infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Our early work demonstrated that Cistanche extracts protect against sperm damage in mice and that echinacoside (ECH) is one of the major active components. Here we report an essential role for ECH, a natural product that reverses or protects against oligoasthenospermia in rats. ECH was assayed by HPLC, the quantity and quality of sperm was evaluated and hormone levels were determined by radioimmunosorbent assay. ECH reduced levels of androgen receptor (AR) and key steroidogenic-related genes as determined by Western blot and qPCR analysis. The interaction between ECH and AR were evaluated by indirect ELISA and molecular docking. The results show that ECH combined with hypothalamic AR in the pocket of Met-894 and Val-713 to inhibit transfer of AR from the cytoplasm to nuclei in the hypothalamus. While negative feedback of sex hormone regulation was inhibited, positive feedback was stimulated to increase the secretion of luteinizing hormone and testosterone subsequently enhancing the quantity of sperm. Taken together, these data demonstrate that ECH blocks AR activity in the hypothalamus to increase the quantity of sperm and protect against oligoasthenospermia in rats.