bluuebunny/crossref_metadata_2025_split huggingface dataset:
An unexpected N-terminal loop in PD-1 dominates binding by nivolumab
Authors: Tan Shuguang , Zhang Hao , Chai Yan , Song Hao , Tong Zhou , Wang Qihui , Qi Jianxun , Wong Gary , Zhu Xiaodong , Liu William J. , Gao Shan , Wang Zhongfu , Shi Yi , Yang Fuquan , Gao George F. , Yan Jinghua 
Published: February 2017

AbstractCancer immunotherapy by targeting of immune checkpoint molecules has been a research ‘hot-spot’ in recent years. Nivolumab, a human monoclonal antibody targeting PD-1, has been widely used clinically since 2014. However, the binding mechanism of nivolumab to PD-1 has not yet been shown, despite a recent report describing the complex structure of pembrolizumab/PD-1. It has previously been speculated that PD-1 glycosylation is involved in nivolumab recognition. Here we report the complex structure of nivolumab with PD-1 and evaluate the effects of PD-1 N-glycosylation on the interactions with nivolumab. Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all. Nivolumab binds to a completely different area than pembrolizumab. These results provide the basis for the design of future inhibitory molecules targeting PD-1.
The Promotion of Erythropoiesis via the Regulation of Reactive Oxygen Species by Lactic Acid
Authors: Luo Shun-Tao , Zhang Dong-Mei , Qin Qing , Lu Lian , Luo Min , Guo Fu-Chun , Shi Hua-Shan , Jiang Li , Shao Bin , Li Meng , Yang Han-Shuo , Wei Yu-Quan 
Published: February 2017

AbstractThe simultaneous increases in blood lactic acid and erythrocytes after intense exercise could suggest a link between lactate and the erythropoiesis. However, the effects of lactic acid on erythropoiesis remain to be elucidated. Here, we utilized a mouse model to determine the role of lactic acid in this process in parallel with studies using leukaemic K562 cells. Treatment of K562 cells in vitro with lactic acid increased the mRNA and protein expression of haemoglobin genes and the frequency of GPA+ cells. Also, increases in haematocrit and CD71−/Ter119+ erythroid cells were observed in lactic acid-treated mice, which showed a physiological increase in blood lactate. Mouse bone marrow CD34+/CD117− cells showed an increase in erythroid burst-forming units after stimulation with lactic acid in vitro. Furthermore, lactic acid increased the intracellular reactive oxygen species (ROS) content in bone marrow and in K562 cells. Erythroid differentiation induced in Haematopoietic Stem Cells (HSCs) and K562 cells by lactic acid was abolished by reducing ROS levels with SOD or 2-mercaptoethanol, which suggests that ROS is a critical regulator of this process. These findings provide a better understanding of the role of lactic acid in cellular metabolism and physiological functions.
Serum bilirubin levels and risk of type 2 diabetes: results from two independent cohorts in middle-aged and elderly Chinese
Authors: Wang Jing , Li Yaru , Han Xu , Hu Hua , Wang Fei , Li Xiulou , Yang Kun , Yuan Jing , Yao Ping , Miao Xiaoping , Wei Sheng , Wang Youjie , Cheng Weihong , Liang Yuan , Zhang Xiaomin , Guo Huan , Yang Handong , Yuan Jianmin , Koh Woon-Puay , Hu Frank B. , Wu Tangchun , Pan An , He Meian 
Published: February 2017

AbstractSerum bilirubin is a potent endogenous antioxidant and has been identified as cardiovascular risk in cohort studies, while the relation to type 2 diabetes (T2D) in the elderly remains unclear. We investigated both cross-sectional and prospective associations between serum bilirubin levels and T2D risk in the Dongfeng-Tongji (DFTJ) cohort, and replicated the prospective findings in a nested case-control study (509 cases and 509 controls) within the Singapore Chinese Health Study (SCHS). In the cross-sectional analysis of DFTJ cohort (15,575 participants with 2,532 diabetes cases), serum bilirubin levels (total, direct and indirect) increased in new on-set diabetes and decreased with the diabetic duration. In the longitudinal analysis of DFTJ cohort (772 incident diabetes cases during 4.5 years of follow-up among 12,530 diabetes-free participants at baseline), positive association was found between direct bilirubin and T2D risk comparing extreme quartiles, similar results were observed in the nested case-control study within SCHS. Total and indirect bilirubin levels were not significantly associated with T2D in either cohort. In conclusion, our findings do not support the protective association between serum bilirubin levels and incident T2D in the middle-aged and elderly adults; instead, direct bilirubin levels were associated with increased risk of T2D.
Characteristics, chemical compositions and biological activities of propolis from Al-Bahah, Saudi Arabia
Authors: Elnakady Yasser A. , Rushdi Ahmed I. , Franke Raimo , Abutaha Nael , Ebaid Hossam , Baabbad Mohannad , Omar Mohamed O. M. , Al Ghamdi Ahmad A. 
Published: February 2017

AbstractPropolis has been used to treat several diseases since ancient times, and is an important source of bioactive natural compounds and drug derivatives. These properties have kept the interest of investigators around the world, leading to the investigation of the chemical and biological properties and application of propolis. In this report, the chemical constituents that are responsible for the anticancer activities of propolis were analyzed. The propolis was sourced from Al-Baha in the southern part of the Kingdom of Saudi Arabia. Standard protocols for chemical fractionation and bioactivity-guided chemical analysis were used to identify the bio-active ethyl acetate fraction. The extraction was performed in methanol and then analyzed by gas chromatography-mass spectrometry (GC-MS). The major compounds are triterpenoids, with a relative concentration of 74.0%; steroids, with a relative concentration of 9.8%; and diterpenoids, with a relative concentration of 7.9%. The biological activity was characterized using different approaches and cell-based assays. Propolis was found to inhibit the proliferation of cancer cells in a concentration-dependent manner through apoptosis. Immunofluorescence staining with anti-α-tubulin antibodies and cell cycle analysis indicated that tubulin and/or microtubules are the cellular targets of the L-acetate fraction. This study demonstrates the importance of Saudi propolis as anti-cancer drug candidates.
High-resolution traction force microscopy on small focal adhesions - improved accuracy through optimal marker distribution and optical flow tracking
Authors: Holenstein Claude N. , Silvan Unai , Snedeker Jess G. 
Published: February 2017

AbstractThe accurate determination of cellular forces using Traction Force Microscopy at increasingly small focal attachments to the extracellular environment presents an important yet substantial technical challenge. In these measurements, uncertainty regarding accuracy is prominent since experimental calibration frameworks at this size scale are fraught with errors – denying a gold standard against which accuracy of TFM methods can be judged. Therefore, we have developed a simulation platform for generating synthetic traction images that can be used as a benchmark to quantify the influence of critical experimental parameters and the associated errors. Using this approach, we show that TFM accuracy can be improved >35% compared to the standard approach by placing fluorescent beads as densely and closely as possible to the site of applied traction. Moreover, we use the platform to test tracking algorithms based on optical flow that measure deformation directly at the beads and show that these can dramatically outperform classical particle image velocimetry algorithms in terms of noise sensitivity and error. We then report how optimized experimental and numerical strategy can improve traction map accuracy, and further provide the best available benchmark to date for defining practical limits to TFM accuracy as a function of focal adhesion size.
Entropy exchange for infinite-dimensional systems
Authors: Duan Zhoubo , Hou Jinchuan 
Published: February 2017

AbstractIn this paper the entropy exchange for channels and states in infinite-dimensional systems are defined and studied. It is shown that, this entropy exchange depends only on the given channel and the state. An explicit expression of the entropy exchange in terms of the state and the channel is proposed. The generalized Klein’s inequality, the subadditivity and the triangle inequality about the entropy including infinite entropy for the infinite-dimensional systems are established, and then, applied to compare the entropy exchange with the entropy change.
Photons, phonons, and plasmons with orbital angular momentum in plasmas
Authors: Chen Qiang , Qin Hong , Liu Jian 
Published: February 2017

AbstractExact eigen modes with orbital angular momentum (OAM) in the complex media of unmagnetized homogeneous plasmas are studied. Three exact eigen modes with OAM are derived, i.e., photons, phonons, and plasmons. The OAM of different plasma components are closely related to the charge polarities. For photons, the OAM of electrons and ions are of the same magnitude but opposite direction, and the total OAM is carried by the field. For the phonons and plasmons, their OAM are carried by the electrons and ions. The OAM modes in plasmas and their characteristics can be explored for potential applications in plasma physics and accelerator physics.
Effects of hydrological regime on development of Carex wet meadows in East Dongting Lake, a Ramsar Wetland for wintering waterbirds
Authors: Jing Lei , Lu Cai , Xia Yan , Shi Linlu , Zuo Aojie , Lei Jialing , Zhang Hong , Lei Guangchun , Wen Li 
Published: February 2017

AbstractWet meadows are one of the most important ecological components in floodplain, and are among the most dynamic ecosystems. Understanding the development of wet meadows and contributing environmental factors can provide better support for wetland management. Carex meadows in East Dongting Lake National Nature Reserve (EDLNNR) provide vital wintering ground for thousands of migratory waterbirds, and their ecological functions are under threated due to hydrological alternation. We measured wet meadow expansion in EDLNNR from 1989 to 2014, and explored its responses to hydrological and climatic factors within the generalised additive models (GAM) framework. We found an overall expansion of wet meadows over the study period. However, in contrast to many previous studies, our results showed that water level fluctuations at the hydrologic indicator site had only limited impacts on their development. Instead, sampling year, timing of water level recession, and local rainfall exerted significant effects. The effects of sampling year reflected the changes in sedimentation within Dongting Lake; and effects of timing of water withdrawal might be explained by the life history of the dominant sedge species. Our study suggested that the impacts of large scale hydrological alternation on vegetation may operate indirectly through its effects on sediment balance.
Apical dendrite degeneration, a novel cellular pathology for Betz cells in ALS
Authors: Genç Barış , Jara Javier H. , Lagrimas Amiko K. B. , Pytel Peter , Roos Raymond P. , Mesulam M. Marsel , Geula Changiz , Bigio Eileen H. , Özdinler P. Hande 
Published: February 2017

AbstractApical dendrites of Betz cells are important sites for the integration of cortical input, however their health has not been fully assessed in ALS patients. We investigated the primary motor cortices isolated from post-mortem normal control subjects, patients with familial ALS (fALS), sporadic ALS (sALS), ALS with frontotemporal dementia (FTD-ALS), and Alzheimer’s disease (AD), and found profound apical dendrite degeneration of Betz cells in both fALS and sALS, as well as FTD-ALS patients. In contrast, Betz cells of AD patients and normal controls retain cellular integrity in the motor cortex, and CA1 pyramidal neurons show abnormalities predominantly within their soma, rather than the apical dendrite. In line with extensive vacuolation and cytoarchitectural disintegration, the numbers of synapses were also significantly reduced only in ALS patients. Our findings indicate apical dendrite degeneration as a novel cellular pathology that distinguishes ALS and further support the importance of cortical dysfunction for disease pathology.
Two-dimensional Talbot self-imaging via Electromagnetically induced lattice
Authors: Wen Feng , Wang Wei , Ahmed Irfan , Wang Hongxing , Zhang Yiqi , Zhang Yanpeng , Mahesar Abdul Rasheed , Xiao Min 
Published: February 2017

AbstractWe propose a lensless optical method for imaging two-dimensional ultra-cold atoms (or molecules) in which the image can be non-locally observed by coincidence recording of entangled photon pairs. In particular, we focus on the transverse and longitudinal resolutions of images under various scanning methods. In addition, the role of the induced nonmaterial lattice on the image contrast is investigated. Our work shows a non-destructive and lensless way to image ultra-cold atoms or molecules that can be further used for two-dimensional atomic super-resolution optical testing and sub-wavelength lithography.
Spectrally monitoring the response of the biocrust moss Syntrichia caninervis to altered precipitation regimes
Authors: Young Kristina E. , Reed Sasha C. 
Published: February 2017

AbstractClimate change is expected to impact drylands worldwide by increasing temperatures and changing precipitation patterns. These effects have known feedbacks to the functional roles of dryland biological soil crust communities (biocrusts), which are expected to undergo significant climate-induced changes in community structure and function. Nevertheless, our ability to monitor the status and physiology of biocrusts with remote sensing is limited due to the heterogeneous nature of dryland landscapes and the desiccation tolerance of biocrusts, which leaves them frequently photosynthetically inactive and difficult to assess. To address this critical limitation, we subjected a dominant biocrust species Syntrichia caninervis to climate-induced stress in the form of small, frequent watering events, and spectrally monitored the dry mosses’ progression towards mortality. We found points of spectral sensitivity responding to experimentally-induced stress in desiccated mosses, indicating that spectral imaging is an effective tool to monitor photosynthetically inactive biocrusts. Comparing the Normalized Difference Vegetation Index (NDVI), the Simple Ratio (SR), and the Normalized Pigment Chlorophyll Index (NPCI), we found NDVI minimally effective at capturing stress in precipitation-stressed dry mosses, while the SR and NPCI were highly effective. Our results suggest the strong potential for utilizing spectroscopy and chlorophyll-derived indices to monitor biocrust ecophysiological status, even when biocrusts are dry, with important implications for improving our understanding of dryland functioning.
Small RNA-directed epigenetic programming of embryonic stem cell cardiac differentiation
Authors: Ghanbarian Hossein , Wagner Nicole , Michiels Jean-François , Cuzin François , Wagner Kay-Dietrich , Rassoulzadegan Minoo 
Published: February 2017

AbstractMicroinjection of small noncoding RNAs in one-cell embryos was reported in several instances to result in transcriptional activation of target genes. To determine the molecular mechanisms involved and to explore whether such epigenetic regulations could play a role in early development, we used a cell culture system as close as possible to the embryonic state. We report efficient cardiac differentiation of embryonic stem (ES) cells induced by small non-coding RNAs with sequences of Cdk9, a key player in cardiomyocyte differentiation. Transfer of oligoribonucleotides representing parts of the Cdk9 mRNA into ES and mouse embryo fibroblast cultures resulted in upregulation of transcription. Dependency on Argonaute proteins and endogenous antisense transcripts indicated that the inducer oligoribonucleotides were processed by the RNAi machinery. Upregulation of Cdk9 expression resulted in increased efficiency of cardiac differentiation suggesting a potential tool for stem cell-based regenerative medicine.
Future forest aboveground carbon dynamics in the central United States: the importance of forest demographic processes
Authors: Jin Wenchi , He Hong S. , Thompson Frank R. , Wang Wen J. , Fraser Jacob S. , Shifley Stephen R. , Hanberry Brice B. , Dijak William D. 
Published: February 2017

AbstractThe Central Hardwood Forest (CHF) in the United States is currently a major carbon sink, there are uncertainties in how long the current carbon sink will persist and if the CHF will eventually become a carbon source. We used a multi-model ensemble to investigate aboveground carbon density of the CHF from 2010 to 2300 under current climate. Simulations were done using one representative model for each of the simple, intermediate, and complex demographic approaches (ED2, LANDIS PRO, andLINKAGES, respectively). All approaches agreed that the current carbon sink would persist at least to 2100. However, carbon dynamics after current carbon sink diminishes to zero differ for different demographic modelling approaches. Both the simple and the complex demographic approaches predicted prolonged periods of relatively stable carbon densities after 2100, with minor declines, until the end of simulations in 2300. In contrast, the intermediate demographic approach predicted the CHF would become a carbon source between 2110 and 2260, followed by another carbon sink period. The disagreement between these patterns can be partly explained by differences in the capacity of models to simulate gross growth (both birth and subsequent growth) and mortality of short-lived, relatively shade-intolerant tree species.
Wnt7a Inhibits IL-1β Induced Catabolic Gene Expression and Prevents Articular Cartilage Damage in Experimental Osteoarthritis
Authors: Gibson Averi L. , Hui Mingalone Carrie K. , Foote Andrea T. , Uchimura Tomoya , Zhang Ming , Zeng Li 
Published: February 2017

AbstractWnt7a is a protein that plays a critical role in skeletal development. However, its effect on cartilage homeostasis under pathological conditions is not known. In this study, we found a unique inverse correlation between Wnt7a gene expression and that of MMP and IL-1β in individual human OA cartilage specimens. Upon ectopic expression in primary human articular chondrocytes, Wnt7a inhibited IL-1β-induced MMP and iNOS gene expression. Western blot analysis indicated that Wnt7a induced both canonical Wnt signaling and NFAT and Akt non-canonical signaling. Interestingly, inhibiting the canonical and Akt pathway did not affect Wnt7a activity. However, inhibiting the NFAT pathway impaired Wnt7a’s ability to inhibit MMP expression, suggesting that Wnt7a requires NFAT signaling to exert this function. In vivo, intraarticular injection of lentiviral Wnt7a strongly attenuated articular cartilage damage induced by destabilization of the medial meniscus (DMM) OA-inducing surgery in mice. Consistently, Wnt7a also inhibited the progressive increase of joint MMP activity in DMM animals. These results indicate that Wnt7a signaling inhibits inflammatory stimuli-induced catabolic gene expression in human articular chondrocytes and is sufficient to attenuate MMP activities and promote joint cartilage integrity in mouse experimental OA, demonstrating a novel effect of Wnt7a on regulating OA pathogenesis.
Anodically Grown Titania Nanotube Induced Cytotoxicity has Genotoxic Origins
Authors: Mohamed M. Sheikh , Torabi Aida , Paulose Maggie , Kumar D. Sakthi , Varghese Oomman K. 
Published: February 2017

AbstractNanoarchitectures of titania (TiO2) have been widely investigated for a number of medical applications including implants and drug delivery. Although titania is extensively used in the food, drug and cosmetic industries, biocompatibility of nanoscale titania is still under careful scrutiny due to the conflicting reports on its interaction with cellular matter. For an accurate insight, we performed in vitro studies on the response of human dermal fibroblast cells toward pristine titania nanotubes fabricated by anodic oxidation. The nanotubes at low concentrations were seen to induce toxicity to the cells, whereas at higher concentrations the cell vitality remained on par with controls. Further investigations revealed an increase in the G0 phase cell population depicting that majority of cells were in the resting rather than active phase. Though the mitochondrial set-up did not exhibit any signs of stress, significantly enhanced reactive oxygen species production in the nuclear compartment was noted. The TiO2 nanotubes were believed to have gained access to the nuclear machinery and caused increased stress leading to genotoxicity. This interesting property of the nanotubes could be utilized to kill cancer cells, especially if the nanotubes are functionalized for a specific target, thus eliminating the need for any chemotherapeutic agents.
Post-polyploidisation morphotype diversification associates with gene copy number variation
Authors: Schiessl Sarah , Huettel Bruno , Kuehn Diana , Reinhardt Richard , Snowdon Rod 
Published: February 2017

AbstractGenetic models for polyploid crop adaptation provide important information relevant for future breeding prospects. A well-suited model is Brassica napus, a recent allopolyploid closely related to Arabidopsis thaliana. Flowering time is a major adaptation trait determining life cycle synchronization with the environment. Here we unravel natural genetic variation in B. napus flowering time regulators and investigate associations with evolutionary diversification into different life cycle morphotypes. Deep sequencing of 35 flowering regulators was performed in 280 diverse B. napus genotypes. High sequencing depth enabled high-quality calling of single-nucleotide polymorphisms (SNPs), insertion-deletions (InDels) and copy number variants (CNVs). By combining these data with genotyping data from the Brassica 60 K Illumina® Infinium SNP array, we performed a genome-wide marker distribution analysis across the 4 ecogeographical morphotypes. Twelve haplotypes, including Bna.FLC.A10, Bna.VIN3.A02 and the Bna.FT promoter on C02_random, were diagnostic for the diversification of winter and spring types. The subspecies split between oilseed/kale (B. napus ssp. napus) and swedes/rutabagas (B. napus ssp. napobrassica) was defined by 13 haplotypes, including genomic rearrangements encompassing copies of Bna.FLC, Bna.PHYA and Bna.GA3ox1. De novo variation in copies of important flowering-time genes in B. napus arose during allopolyploidisation, enabling sub-functionalisation that allowed different morphotypes to appropriately fine-tune their lifecycle.