bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous and specific chemical cross-linking in live cells to capture and identify protein interactions
Authors: Yang Bing , Tang Shibing , Ma Cheng , Li Shang-Tong , Shao Guang-Can , Dang Bobo , DeGrado William F. , Dong Meng-Qiu , Wang Peng George , Ding Sheng , Wang Lei 
Published: December 2017

AbstractCovalently locking interacting proteins in situ is an attractive strategy for addressing the challenge of identifying weak and transient protein interactions, yet it is demanding to execute chemical reactions in live systems in a biocompatible, specific, and autonomous manner. Harnessing proximity-enabled reactivity of an unnatural amino acid incorporated in the bait toward a target residue of unknown proteins, here we genetically encode chemical cross-linkers (GECX) to cross-link interacting proteins spontaneously and selectively in live cells. Obviating an external trigger for reactivity and affording residue specificity, GECX enables the capture of low-affinity protein binding (affibody with Z protein), elusive enzyme-substrate interaction (ubiquitin-conjugating enzyme UBE2D3 with substrate PCNA), and endogenous proteins interacting with thioredoxin in E. coli cells, allowing for mass spectrometric identification of interacting proteins and crosslinking sites. This live cell chemistry-based approach should be valuable for investigating currently intangible protein interactions in vivo for better understanding of biology in physiological settings.
Phased uplift of the northeastern Tibetan Plateau inferred from a pollen record from Yinchuan Basin, northwestern China
Authors: Li Xinling , Hao Qingzhen , Wei Mingjian , Andreev Andrei A. , Wang Junping , Tian Yanyan , Li Xiaolei , Cai Maotang , Hu Jianmin , Shi Wei 
Published: December 2017

AbstractThe uplift of the Tibetan Plateau (TP) significantly affected both regional and global climates. Although there is evidence that the Tibetan Plateau experienced uplift during the Quaternary, the timing and amplitude are poorly constrained. However, the increased availability of long sedimentary records of vegetation change provides an opportunity to reconstruct the timing of the uplift. Here, we present a well-dated, high-resolution pollen record for the last 2.6 Ma from the Yinchuan Basin, which was incised by the Yellow River with its source in the northeastern Tibetan Plateau. Variations in the Artemisia/Chenopodiaceae (A/C) ratio of the reveal changes in moisture conditions in the Yinchuan Basin during glacial-interglacial cycles, as well as a gradual long-term aridification trend which is consistent with progressive global cooling. However, fluctuations in the percentages of Picea and Abies differ from those of the A/C ratio and we propose that they reflect changes in the vegetation and environment of high elevation areas. The Picea and Abies records reveal two phases of increased representation, at 2.1 and 1.2 Ma, which may indicate phases in the uplift of the northeastern Tibetan Plateau. Thus, they provide independent evidence for the timing of the uplift of the Tibetan Plateau during the Quaternary.
Fabrication of pH-responsive PLGA(UCNPs/DOX) nanocapsules with upconversion luminescence for drug delivery
Authors: Zhao Junwei , Yang Hui , Li Jili , Wang Yujiang , Wang Xin 
Published: December 2017

AbstractThe integration of anticancer drugs and inorganic nanocrystals in polymer nanocapsules is a widely used strategy to improve their functionality, stability and sustained release. However, the complexity in the preparation of functional nanocapsules and their reproducibility still challenge these promising drug carriers in clinical application. Here we introduce a simple one-step self-assembly strategy to prepare multifunctional nanocapsules based on simultaneous poly (DL-lactic-co-glycolic acid) (PLGA) encapsulation of antitumor drug doxorubicin hydrochloride (DOX) and NaYF4:Yb,Er@NaGdF4 upconversion nanoparticles (UCNPs) for cancer cell imaging and drug delivery. The obtained PLGA(UCNPs/DOX) nanocapsules with a small size of ≈150 nm possessed bright upconversion fluorescence and could act as T1-
weighted contrast agents for magnetic resonance imaging (MRI). Moreover, the PLGA(UCNPs/DOX) nanocapsules exhibited pH-responsive drug releasing behavior, causing the loaded DOX easily releasing at cancer cells, and an obvious cytotoxicity via MTT assay. The endocytosis process of PLGA (UCNPs/DOX) nanocapsules is evaluated using optical microscopy and upconversion fluorescence microscopy. These results demonstrated that the developed PLGA nanocapsules could serve as multifunctional drug delivery systems for cancer imaging and therapy.
Generation of therapeutic protein variants with the human serum albumin binding capacity via site-specific fatty acid conjugation
Authors: Cho Jinhwan , Lim Sung In , Yang Byung Seop , Hahn Young S. , Kwon Inchan 
Published: December 2017

AbstractExtension of the serum half-life is an important issue in developing new therapeutic proteins and expanding applications of existing therapeutic proteins. Conjugation of fatty acid, a natural human serum albumin ligand, to a therapeutic protein/peptide was developed as a technique to extend the serum half-life in vivo by taking advantages of unusually long serum half-life of human serum albumin (HSA). However, for broad applications of fatty acid-conjugation, several issues should be addressed, including a poor solubility of fatty acid and a substantial loss in the therapeutic activity. Therefore, herein we systematically investigate the conditions and components in conjugation of fatty acid to a therapeutic protein resulting in the HSA binding capacity without compromising therapeutic activities. By examining the crystal structure and performing dye conjugation assay, two sites (W160 and D112) of urate oxidase (Uox), a model therapeutic protein, were selected as sites for fatty acid-conjugation. Combination of site-specific incorporation of a clickable p-azido-L-phenylalanine to Uox and strain-promoted azide-alkyne cycloaddition allowed the conjugation of fatty acid (palmitic acid analog) to Uox with the HSA binding capacity and retained enzyme activity. Deoxycholic acid, a strong detergent, greatly enhanced the conjugation yield likely due to the enhanced solubility of palmitic acid analog.
Proteomic investigation of effects of hydroxysafflor yellow A in oxidized low-density lipoprotein-induced endothelial injury
Authors: Ye Feng , Wang Jianhe , Meng Wei , Qian Jingru , Jin Ming 
Published: December 2017

AbstractOxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial damage is a key event in early atherosclerosis. Safflower has been used to treat atherosclerotic heart disease in China for many years, but its molecular basis remains unclear. Hydroxysafflor yellow A (HSYA) is the main active ingredient of aqueous safflower extract. We identified the proteins involved in HSYA activity against ox-LDL-induced endothelial injury using isobaric tags for relative and absolute quantification-coupled two-dimensional liquid chromatography–tandem mass spectrometry. HSYA (1, 5, or 25 μM) alleviated ox-LDL-induced endothelial damage in a dose-dependent manner. We quantitated approximately 2700 protein species, of which 77 were differentially expressed following HSYA treatment. Most protein changes were related to structural molecules, metabolic enzymes, and proteins involved in signal transduction. Several differentially expressed proteins were further validated by western blot analysis. We also analysed the role of the mitochondrial membranous voltage-dependent anion-selective channel protein 2 (VDAC2) in HSYA treatment using small interfering RNA. VDAC2 functioned as a downstream anti-apoptosis effector during HSYA treatment of ox-LDL-induced endothelial impairment. These results further our understanding of the mechanisms responsible for the effects of HSYA.
CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters
Authors: Parra-Damas Arnaldo , Rubió-Ferrarons Laura , Shen Jie , Saura Carlos A. 
Published: December 2017

AbstractGene expression mediated by the transcription factor cAMP-responsive element-binding protein (CREB) is essential for a wide range of brain processes. The transcriptional coactivartor CREB-regulated transcription coactivator-1 (CRTC1) is required for efficient induction of CREB target genes during neuronal activity. However, the mechanisms regulating induction of specific CREB/CRTC1-dependent genes during neuronal activity remain largely unclear. Here, we investigated the molecular mechanisms regulating activity-dependent gene transcription upon activation of the CREB/CRTC1 signaling pathway in neurons. Depolarization and cAMP signals induce preferential transcription of activity-dependent genes containing promoters with proximal CRE/TATA sequences, such as c-fos, Dusp1, Nr4a1, Nr4a2 and Ptgs2, but not genes with proximal CRE/TATA-less promoters (e.g. Nr4a3, Presenilin-1 and Presenilin-2). Notably, biochemical and chromatin immunoprecipitation analyses reveal constitutive binding of CREB to target gene promoters in the absence of neuronal activity, whereas recruitment of CRTC1 to proximal CRE/TATA promoters depends on neuronal activity. Neuronal activity induces rapid CRTC1 dephosphorylation, nuclear translocation and binding to endogenous CREB. These results indicate that neuronal activity induces a preferential binding of CRTC1 to the transcriptional complex in CRE/TATA-containing promoters to engage activity-dependent transcription in neurons.
Environment spectrum and coherence behaviours in a rare-earth doped crystal for quantum memory
Authors: Gong Bo , Tu Tao , Zhou Zhong-Quan , Zhu Xing-Yu , Li Chuan-Feng , Guo Guang-Can 
Published: December 2017

AbstractWe theoretically investigate the dynamics of environment and coherence behaviours of the central ion in a quantum memory based on a rare-earth doped crystal. The interactions between the central ion and the bath spins suppress the flip-flop rate of the neighbour bath spins and yield a specific environment spectral density S(ω). Under dynamical decoupling pulses, this spectrum provides a general scaling for the coherence envelope and coherence time, which significantly extend over a range on an hour-long time scale. The characterized environment spectrum with ultra-long coherence time can be used to implement various quantum communication and information processing protocols.
Ablation of peri-insult generated granule cells after epilepsy onset halts disease progression
Authors: Hosford Bethany E. , Rowley Shane , Liska John P. , Danzer Steve C. 
Published: December 2017

AbstractAberrant integration of newborn hippocampal granule cells is hypothesized to contribute to the development of temporal lobe epilepsy. To test this hypothesis, we used a diphtheria toxin receptor expression system to selectively ablate these cells from the epileptic mouse brain. Epileptogenesis was initiated using the pilocarpine status epilepticus model in male and female mice. Continuous EEG monitoring was begun 2–3 months after pilocarpine treatment. Four weeks into the EEG recording period, at a time when spontaneous seizures were frequent, mice were treated with diphtheria toxin to ablate peri-insult generated newborn granule cells, which were born in the weeks just before and after pilocarpine treatment. EEG monitoring continued for another month after cell ablation. Ablation halted epilepsy progression relative to untreated epileptic mice; the latter showing a significant and dramatic 300% increase in seizure frequency. This increase was prevented in treated mice. Ablation did not, however, cause an immediate reduction in seizures, suggesting that peri-insult generated cells mediate epileptogenesis, but that seizures per se are initiated elsewhere in the circuit. These findings demonstrate that targeted ablation of newborn granule cells can produce a striking improvement in disease course, and that the treatment can be effective when applied months after disease onset.
Structural basis for high specificity of octopine binding in the plant pathogen Agrobacterium tumefaciens
Authors: Vigouroux Armelle , El Sahili Abbas , Lang Julien , Aumont-Nicaise Magali , Dessaux Yves , Faure Denis , Moréra Solange 
Published: December 2017

AbstractAgrobacterium pathogens of octopine- and nopaline-types force host plants to produce either octopine or nopaline compounds, which they use as nutrients. Two Agrobacterium ABC-transporters and their cognate periplasmic binding proteins (PBPs) OccJ and NocT import octopine and nopaline/octopine, respectively. Here, we show that both octopine transport and degradation confer a selective advantage to octopine-type A. tumefaciens when it colonizes plants. We report the X-ray structures of the unliganded PBP OccJ and its complex with octopine as well as a structural comparison with NocT and the related PBP LAO from Salmonella enterica, which binds amino acids (lysine, arginine and ornithine). We investigated the specificity of OccJ, NocT and LAO using several ligands such as amino acids, octopine, nopaline and octopine analogues. OccJ displays a high selectivity and nanomolar range affinity for octopine. Altogether, the structural and affinity data allowed to define an octopine binding signature in PBPs and to construct a OccJ mutant impaired in octopine binding, a selective octopine-binding NocT and a non-selective octopine-binding LAO by changing one single residue in these PBPs. We proposed the PBP OccJ as a major trait in the ecological specialization of octopine-type Agrobacterium pathogens when they colonize and exploit the plant host.
Bacterial Nanocellulose Loaded with Bromelain: Assessment of Antimicrobial, Antioxidant and Physical-Chemical Properties
Authors: Ataide Janaína Artem , de Carvalho Nathália Mendes , Rebelo Márcia de Araújo , Chaud Marco Vinícius , Grotto Denise , Gerenutti Marli , Rai Mahendra , Mazzola Priscila Gava , Jozala Angela Faustino 
Published: December 2017

AbstractBacterial nanocellulose (BNC) has desirable properties for wound healing such as high purity, good shape retention, and high water binding capacity. Bromelain is a protease found in pineapple tissues and has been applied in several fields, it has anti-inflammatory and anticancer properties, promotes cell apoptosis, amongst others. In this work, a BNC based device for the controlled release of bromelain was developed. BNC were submersed in sterilized bromelain solution and incubated at 25 °C under 100 rpm for 24 h. Physical-chemical properties, protein concentration, antioxidant and antimicrobial activities were measured. Results demonstrate that BNC could improve bromelain antimicrobial activity 9 times. Those findings allow concluding that bromelain is a promising molecule to be incorporated into BNC’s. The BNC’s characteristics seem to represent a new promising delivery system of the loaded biomolecule, and protected from external actions.
Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy
Authors: Leonard Charles E. , Brensinger Colleen M. , Bilker Warren B. , Kimmel Stephen E. , Whitaker Heather J. , Hennessy Sean 
Published: December 2017

AbstractWarfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited. We quantified the risk of venous thromboembolism (VTE) and ischemic stroke (IS) due to statin and fibrate discontinuation in warfarin users, in which warfarin was initially dose-titrated during ongoing antihyperlipidemic therapy. Using 1999–2011 United States Medicaid claims among 69 million beneficiaries, we conducted a set of bidirectional self-controlled case series studies—one for each antihyperlipidemic. Outcomes were hospital admissions for VTE/IS. The risk segment was a maximum of 90 days immediately following antihyperlipidemic discontinuation, the exposure of interest. Time-varying confounders were included in conditional Poisson models. We identified 629 study eligible-persons with at least one outcome. Adjusted incidence rate ratios (IRRs) for all antihyperlipidemics studied were consistent with the null, and ranged from 0.21 (0.02, 2.82) for rosuvastatin to 2.16 (0.06, 75.0) for gemfibrozil. Despite using an underlying dataset of millions of persons, we had little precision in estimating IRRs for VTE/IS among warfarin-treated persons discontinuing individual antihyperlipidemics. Further research should investigate whether discontinuation of gemfibrozil in warfarin users results in serious underanticoagulation.
Non-invasive multimodal optical coherence and photoacoustic tomography for human skin imaging
Authors: Chen Zhe , Rank Elisabet , Meiburger Kristen M. , Sinz Christoph , Hodul Andreas , Zhang Edward , Hoover Erich , Minneman Micheal , Ensher Jason , Beard Paul C. , Kittler Harald , Leitgeb Rainer A. , Drexler Wolfgang , Liu Mengyang 
Published: December 2017

AbstractThe cutaneous vasculature is involved in many diseases. Current clinical examination techniques, however, cannot resolve the human vasculature with all plexus in a non-invasive manner. By combining an optical coherence tomography system with angiography extension and an all optical photoacoustic tomography system, we can resolve in 3D the blood vessels in human skin for all plexus non-invasively. With a customized imaging unit that permits access to various parts of patients’ bodies, we applied our multimodality imaging system to investigate several different types of skin conditions. Quantitative vascular analysis is given for each of the dermatological conditions to show the potential diagnostic value of our system in non-invasive examination of diseases and physiological processes. Improved performance of our system over its previous generation is also demonstrated with an updated characterization.
Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition
Authors: Dey Joyoti , Deckwerth Thomas L. , Kerwin William S. , Casalini Joseph R. , Merrell Angela J. , Grenley Marc O. , Burns Connor , Ditzler Sally H. , Dixon Chantel P. , Beirne Emily , Gillespie Kate C. , Kleinman Edward F. , Klinghoffer Richard A. 
Published: December 2017

AbstractAberrant regulation of BCL-2 family members enables evasion of apoptosis and tumor resistance to chemotherapy. BCL-2 and functionally redundant counterpart, MCL-1, are frequently over-expressed in high-risk diffuse large B-cell lymphoma (DLBCL). While clinical inhibition of BCL-2 has been achieved with the BH3 mimetic venetoclax, anti-tumor efficacy is limited by compensatory induction of MCL-1. Voruciclib, an orally bioavailable clinical stage CDK-selective inhibitor, potently blocks CDK9, the transcriptional regulator of MCL-1. Here, we demonstrate that voruciclib represses MCL-1 protein expression in preclinical models of DLBCL. When combined with venetoclax in vivo, voruciclib leads to model-dependent tumor cell apoptosis and tumor growth inhibition. Strongest responses were observed in two models representing high-risk activated B-cell (ABC) DLBCL, while no response was observed in a third ABC model, and intermediate responses were observed in two models of germinal center B-cell like (GCB) DLBCL. Given the range of responses, we show that CIVO, a multiplexed tumor micro-dosing technology, represents a viable functional precision medicine approach for differentiating responders from non-responders to BCL-2/MCL-1 targeted therapy. These findings suggest that the combination of voruciclib and venetoclax holds promise as a novel, exclusively oral combination therapy for a subset of high-risk DLBCL patients.
Quality of Life of People with Thoracic Outlet Syndrome after Surgery
Authors: Frandoloso Silvio , Pimentel Henrique , Bedin Thais , Silva Bruna , Cunha Bellinati Natalia 
Published: December 2017

Purpose To evaluate the quality of life of patients with neurogenic thoracic outlet syndrome (N-TOS) who underwent surgery via the supraclavicular approach.
Method Sociodemographic and clinical data were collected, and an evaluation of the pain and quality of life of 29 patients was performed.
Results The average age of the patients was 42 years, and most of them were female. All of them had one or more associated pathologies. They all worked in occupations that involved repetitive movement of the upper limbs. The evaluation of the degree of pain showed that the pain remains preponderant and incapacitating in the life of these individuals, who consequently enjoy a low quality of life.
Conclusion These patients presented low quality of life, with persistent pain probably resulting from the associated pathologies, in addition to their psychosocial context. Thus, in order to treat the TOS, an intervention of a multidisciplinary team with a holistic view of the patient is required.
Markenbildung durch Standardisierung
Authors: Solcher Bertram 
Published: December 2017

Zusammenfassung
Fallbeispiel Eine konsequente Standardisierung von Abläufen – das ist das Erfolgsrezept des Unternehmens Surgical Process Institute.
Ziel ist es, Ergebnisse, Wirtschaftlichkeit und Service zu verbessern – vor allem im OP. Ein Fallbeispiel.
Phytotherapie im Klimakterium
Authors: Dorstewitz Hartmut 
Published: December 2017

ZusammenfassungIn Anbetracht der Nebenwirkungen und Risiken hormoneller Therapien bei klimakterischen Beschwerden suchen Patientinnen häufig nach wirksamen
Alternativen. Die Phytotherapie bietet gute Möglichkeiten die Beschwerden zu lindern. Bewährte Phytotherapeutika sind: Mönchspfeffer,
Traubensilberkerze und Sibirischer Rhabarber.Erfahrungsgemäß sollte beim Einsetzen klimakterischer Beschwerden zuerst mit der Phytotherapie begonnen werden und nicht umgekehrt, da durch
die supprimierende Wirkung der Hormone die pflanzlichen Wirkstoffe schlechtere Chancen zur Selbstregulation haben.
Litigating for Liberty: Enslaved Morisco Children in Sixteenth-Century Valladolid
Authors: Cavanaugh Stephanie M. 
Published: December 2017

AbstractMorisco children captured during the Granadan war of 1568–70, known as the Second War of the Alpujarras, could attain legal but limited freedom in accordance with Philip II’s 1572 law against the enslavement of Morisco minors. Those manumitted were meant to remain servants in Old Christian households until the age of majority. The Spanish monarchy recognized the political value of controlling children. Aiming to turn the children of Morisco rebels into proper Christian subjects, the king authorized and facilitated their liberation as part of a larger project of Morisco conversion. Granadan Moriscos worked within the law in pursuit of liberation, yet took action to reunite families separated by slavery and deportation when possible.
Corrigendum to “The classical Artin approximation theorems”
Authors: Hauser Herwig 
Published: December 2017

The purpose of this note is to clarify and complement various places in the article The classical Artin approximation theorems, published in Bull. Amer. Math. Soc. 54 (2017), no. 4, 595–633. A few reasonings in the article may have been difficult to follow or were even problematic. The author is indebted to F. Castro-Jiménez, C. Chiu, R. Ephraim, B. Lamel, S. Perlega, G. Pfister, G. Rond, M. Singer, S. Woblistin, and particularly to an anonymous referee for valuable feedback.