bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB
Authors: Oswald Christine , Tam Heng-Keat , Pos Klaas M. 
Published: December 2016

AbstractThe deployment of multidrug efflux pumps is a powerful defence mechanism for Gram-negative bacterial cells when exposed to antimicrobial agents. The major multidrug efflux transport system in Escherichia coli, AcrAB–TolC, is a tripartite system using the proton-motive force as an energy source. The polyspecific substrate-binding module AcrB uses various pathways to sequester drugs from the periplasm and outer leaflet of the inner membrane. Here we report the asymmetric AcrB structure in complex with fusidic acid at a resolution of 2.5 Å and mutational analysis of the putative fusidic acid binding site at the transmembrane domain. A groove shaped by the interface between transmembrane helix 1 (TM1) and TM2 specifically binds fusidic acid and other lipophilic carboxylated drugs. We propose that these bound drugs are actively displaced by an upward movement of TM2 towards the AcrB periplasmic porter domain in response to protonation events in the transmembrane domain.
Interplay of Dirac electrons and magnetism in CaMnBi2 and SrMnBi2
Authors: Zhang Anmin , Liu Changle , Yi Changjiang , Zhao Guihua , Xia Tian-long , Ji Jianting , Shi Youguo , Yu Rong , Wang Xiaoqun , Chen Changfeng , Zhang Qingming 
Published: December 2016

AbstractDirac materials exhibit intriguing low-energy carrier dynamics that offer a fertile ground for novel physics discovery. Of particular interest is the interplay of Dirac carriers with other quantum phenomena such as magnetism. Here we report on a two-magnon Raman scattering study of AMnBi2 (A=Ca, Sr), a prototypical magnetic Dirac system comprising alternating Dirac carrier and magnetic layers. We present the first accurate determination of the exchange energies in these compounds and, by comparison with the reference compound BaMn2Bi2, we show that the Dirac carrier layers in AMnBi2 significantly enhance the exchange coupling between the magnetic layers, which in turn drives a charge-gap opening along the Dirac locus. Our findings break new grounds in unveiling the fundamental physics of magnetic Dirac materials, which offer a novel platform for probing a distinct type of spin–Fermion interaction. The results also hold great promise for applications in magnetic Dirac devices.
Engineering orthogonal dual transcription factors for multi-input synthetic promoters
Authors: Brödel Andreas K. , Jaramillo Alfonso , Isalan Mark 
Published: December 2016

AbstractSynthetic biology has seen an explosive growth in the capability of engineering artificial gene circuits from transcription factors (TFs), particularly in bacteria. However, most artificial networks still employ the same core set of TFs (for example LacI, TetR and cI). The TFs mostly function via repression and it is difficult to integrate multiple inputs in promoter logic. Here we present to our knowledge the first set of dual activator-repressor switches for orthogonal logic gates, based on bacteriophage λ cI variants and multi-input promoter architectures. Our toolkit contains 12 TFs, flexibly operating as activators, repressors, dual activator–repressors or dual repressor–repressors, on up to 270 synthetic promoters. To engineer non cross-reacting cI variants, we design a new M13 phagemid-based system for the directed evolution of biomolecules. Because cI is used in so many synthetic biology projects, the new set of variants will easily slot into the existing projects of other groups, greatly expanding current engineering capacities.
Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease
Authors: Zuo Li-Jun , Yu Shu-Yang , Hu Yang , Wang Fang , Piao Ying-Shan , Lian Teng-Hong , Yu Qiu-Jin , Wang Rui-Dan , Li Li-Xia , Guo Peng , Du Yang , Zhu Rong-Yan , Jin Zhao , Wang Ya-Jie , Wang Xiao-Min , Chan Piu , Chen Sheng-Di , Wang Yong-Jun , Zhang Wei 
Published: December 2016

AbstractFatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.
A self-consistent spin-diffusion model for micromagnetics
Authors: Abert Claas , Ruggeri Michele , Bruckner Florian , Vogler Christoph , Manchon Aurelien , Praetorius Dirk , Suess Dieter 
Published: December 2016

AbstractWe propose a three-dimensional micromagnetic model that dynamically solves the Landau-Lifshitz-Gilbert equation coupled to the full spin-diffusion equation. In contrast to previous methods, we solve for the magnetization dynamics and the electric potential in a self-consistent fashion. This treatment allows for an accurate description of magnetization dependent resistance changes. Moreover, the presented algorithm describes both spin accumulation due to smooth magnetization transitions and due to material interfaces as in multilayer structures. The model and its finite-element implementation are validated by current driven motion of a magnetic vortex structure. In a second experiment, the resistivity of a magnetic multilayer structure in dependence of the tilting angle of the magnetization in the different layers is investigated. Both examples show good agreement with reference simulations and experiments respectively.
The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new insights into its duplicated “magic” RNA polymerase
Authors: D’Argenio Valeria , Petrillo Mauro , Pasanisi Daniela , Pagliarulo Caterina , Colicchio Roberta , Talà Adelfia , de Biase Maria Stella , Zanfardino Mario , Scolamiero Emanuela , Pagliuca Chiara , Gaballo Antonio , Cicatiello Annunziata Gaetana , Cantiello Piergiuseppe , Postiglione Irene , Naso Barbara , Boccia Angelo , Durante Miriana , Cozzuto Luca , Salvatore Paola , Paolella Giovanni , Salvatore Francesco , Alifano Pietro 
Published: December 2016

AbstractIn contrast to the widely accepted consensus of the existence of a single RNA polymerase in bacteria, several actinomycetes have been recently shown to possess two forms of RNA polymerases due the to co-existence of two rpoB paralogs in their genome. However, the biological significance of the rpoB duplication is obscure. In this study we have determined the genome sequence of the lipoglycopeptide antibiotic A40926 producer Nonomuraea gerenzanensis ATCC 39727, an actinomycete with a large genome and two rpoB genes, i.e. rpoB(S) (the wild-type gene) and rpoB(R) (the mutant-type gene). We next analyzed the transcriptional and metabolite profiles in the wild-type gene and in two derivative strains over-expressing either rpoB(R) or a mutated form of this gene to explore the physiological role and biotechnological potential of the “mutant-type” RNA polymerase. We show that rpoB(R) controls antibiotic production and a wide range of metabolic adaptive behaviors in response to environmental pH. This may give interesting perspectives also with regard to biotechnological applications.
Lyn prevents aberrant inflammatory responses to Pseudomonas infection in mammalian systems by repressing a SHIP-1-associated signaling cluster
Authors: Li Rongpeng , Fang Lizhu , Pu Qinqin , Lin Ping , Hoggarth Austin , Huang Huang , Li Xuefeng , Li Guoping , Wu Min 
Published: December 2016

AbstractThe pleiotropic Src kinase Lyn has critical roles in host defense in alveolar macrophages against bacterial infection, but the underlying mechanism for Lyn-mediated inflammatory response remains largely elusive. Using mouse Pseudomonas aeruginosa infection models, we observed that Lyn−/− mice manifest severe lung injury and enhanced inflammatory responses, compared with wild-type littermates. We demonstrate that Lyn exerts this immune function through interaction with IL-6 receptor and cytoskeletal protein Ezrin via its SH2 and SH3 domains. Depletion of Lyn results in excessive STAT3 activation, and enhanced the Src homology 2-containing inositol-5-phopsphatase 1 (SHIP-1) expression. Deletion of SHIP-1 in Lyn−/− mice (double knockout) promotes mouse survival and reduces inflammatory responses during P. aeruginosa infection, revealing the rescue of the deadly infectious phenotype in Lyn deficiency. Mechanistically, loss of SHIP-1 reduces NF-κB-dependent cytokine production and dampens MAP kinase activation through a TLR4-independent PI3K/Akt pathway. These findings reveal Lyn as a regulator for host immune response against P. aeruginosa infection through SHIP-1 and IL-6/STAT3 signaling pathway in alveolar macrophages.
A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study
Authors: Peck Yvonne , He Pengfei , Chilla Geetha Soujanya V. N. , Poh Chueh Loo , Wang Dong-An 
Published: December 2016

AbstractIn this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.
Proteomic analysis of scallop hepatopancreatic extract provides insights into marine polysaccharide digestion
Authors: Lyu Qianqian , Jiao Wenqian , Zhang Keke , Bao Zhenmin , Wang Shi , Liu Weizhi 
Published: December 2016

AbstractMarine polysaccharides are used in a variety of applications, and the enzymes that degrade these polysaccharides are of increasing interest. The main food source of herbivorous marine mollusks is seaweed, and several polysaccharide-degrading enzymes have been extracted from mollusk digestive glands (hepatopancreases). Here, we used a comprehensive proteomic approach to examine the hepatopancreatic proteins of the Zhikong scallop (Chlamys farreri). We identified 435 proteins, the majority of which were lysosomal enzymes and carbohydrate and protein metabolism enzymes. However, several new enzymes related to polysaccharide metabolism were also identified. Phylogenetic and structural analyses of these enzymes suggest that these polysaccharide-degrading enzymes may have a variety of potential substrate specificities. Taken together, our study characterizes several novel polysaccharide-degrading enzymes in the scallop hepatopancreas and provides an enhanced view of these enzymes and a greater understanding of marine polysaccharide digestion.
A Jurassic wood providing insights into the earliest step in Ginkgo wood evolution
Authors: Jiang Zikun , Wang Yongdong , Philippe Marc , Zhang Wu , Tian Ning , Zheng Shaolin 
Published: December 2016

AbstractThe fossil record ofGinkgoleaf and reproductive organs has been well dated to the Mid-Jurassic (170 Myr). However, the fossil wood record that can safely be assigned to Ginkgoales has not yet been reported from strata predating the late Early Cretaceous (ca. 100 Myr). Here, we report a new fossil wood from the Mid-Late Jurassic transition deposit (153–165 Myr) of northeastern China. The new fossil wood specimen displays severalGinkgofeatures, including inflated axial parenchyma and intrusive tracheid tips. Because it is only slightly younger than the oldest recordedGinkgoreproductive organs (the Yima Formation, 170 Myr), this fossil wood very probably represents the oldest bona fide fossilGinkgowood and the missing ancestral form ofGinkgowood evolution.
Analysis of High-altitude Syndrome and the Underlying Gene Polymorphisms Associated with Acute Mountain Sickness after a Rapid Ascent to High-altitude
Authors: Yu Jie , Zeng Ying , Chen Guozhu , Bian Shizhu , Qiu Youzhu , Liu Xi , Xu Baida , Song Pan , Zhang Jihang , Qin Jun , Huang Lan 
Published: December 2016

AbstractTo investigated the objective indicators and potential genotypes for acute mountain sickness (AMS). 176 male subjects were evaluated for symptoms scores and physiological parameters at 3700 m. EPAS1 gene polymorphisms were explored and verified effects of potential genotypes on pulmonary function by inhaled budesonide. The incidence of AMS was 53.98% (95/176). The individuals who suffered from headache with anxiety and greater changes in heart rate (HR), the forced vital capacity (FVC), and mean flow velocity of basilar artery (Vm-BA), all of which were likely to develop AMS. The rs4953348 polymorphism of EPAS1 gene had a significant correlation with the SaO2 level and AMS, and a significant difference in the AG and GG genotype distribution between the AMS and non-AMS groups. The spirometric parameters were significantly lower, but HR (P = 0.036) and Vm-BA (P = 0.042) significantly higher in the AMS subjects
with the G allele than those with the A allele. In summary, changes in HR (≥82 beats/min), FVC (≤4.2 Lt) and Vm-BA (≥43 cm/s) levels may serve as predictors for diagnosing AMS accompanied by high-altitude syndrome. The A allele of rs4953348 is a protective factor for AMS through HR and Vm-BA compensation, while the G allele may contribute to hypoxic pulmonary hypertension in AMS.
Generation of kidney tubular organoids from human pluripotent stem cells
Authors: Yamaguchi Shintaro , Morizane Ryuji , Homma Koichiro , Monkawa Toshiaki , Suzuki Sayuri , Fujii Shizuka , Koda Muneaki , Hiratsuka Ken , Yamashita Maho , Yoshida Tadashi , Wakino Shu , Hayashi Koichi , Sasaki Junichi , Hori Shingo , Itoh Hiroshi 
Published: December 2016

AbstractRecent advances in stem cell research have resulted in methods to generate kidney organoids from human pluripotent stem cells (hPSCs), which contain cells of multiple lineages including nephron epithelial cells. Methods to purify specific types of cells from differentiated hPSCs, however, have not been established well. For bioengineering, cell transplantation, and disease modeling, it would be useful to establish those methods to obtain pure populations of specific types of kidney cells. Here, we report a simple two-step differentiation protocol to generate kidney tubular organoids from hPSCs with direct purification of KSP (kidney specific protein)-positive cells using anti-KSP antibody. We first differentiated hPSCs into mesoderm cells using a glycogen synthase kinase-3β inhibitor for 3 days, then cultured cells in renal epithelial growth medium to induce KSP+ cells. We purified KSP+ cells using flow cytometry with anti-KSP antibody, which exhibited characteristics of all segments of kidney tubular cells and cultured KSP+ cells in 3D Matrigel, which formed tubular organoids in vitro. The formation of tubular organoids by KSP+ cells induced the acquisition of functional kidney tubules. KSP+ cells also allowed for the generation of chimeric kidney cultures in which human cells self-assembled into 3D tubular structures in combination with mouse embryonic kidney cells.
Immune Responses Induced by Recombinant Bacillus Subtilis Expressing the Hemagglutinin Protein of H5N1 in chickens
Authors: Mou Chunxiao , Zhu Liqi , Yang Jingjing , Xu Wenwen , Cheng Xiaoying , Yang Qian 
Published: December 2016

AbstractTo develop an effective, safe, and convenient vaccine for the prevention of highly pathogenic avian influenza (HPAI) H5N1, we have constructed a recombinant Bacillus subtilis strain (B.S.-HA) expressing the hemagglutinin (HA) protein. Then we evaluated the immune function in chicken bone marrow derived dendritic cells (BM-DCs), and the immune response after oral immunization. Our results show that the recombinant Bacillus subtilis B.S.-HA could be sampled by BM-DCs in vitro and increase the BM-DCs major histocompatibility complex (MHC) II phenotype. The weight, height of the small intestine villus, and lymphoid tissue area of the ileum increased significantly in B.S.-HA immunized chickens (P < 0.05 or P < 0.01). B.S.-HA induced the secretion of cytokines and the expression of Toll-like receptors in the trachea and small intestine (P < 0.05 or P < 0.01). In addition, B.S.-HA elevated the specific IgA titers in the trachea, IgG and HI antibody titers in serum (P < 0.05 or P < 0.01). Therefore, B.S.-HA provides a potential novel strategy and approach for developing an H5N1 vaccine.
Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
Authors: Zhou Wencheng , Mo Xiaoting , Cui Wenhui , Zhang Zhihui , Li Delin , Li Liucheng , Xu Liang , Yao Hongwei , Gao Jian 
Published: December 2016

AbstractEpithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2−/−) and wild-type mice to compare the development of PF. Rat type II alveolar epithelial cells (RLE-6TN) were treated with a specific Nrf2 activator sulforaphane, or transfected with Nrf2 and snail siRNAs to determine their effects on transforming growth factor β1 (TGF-β1)-induced EMT. We found that BLM-induced EMT and lung fibrosis were more severe in Nrf2−/− mice compared to wild-type mice. In vitro, sulforaphane treatment attenuated TGF-β1-induced EMT, accompanied by the down-regulation of snail. Inversely, silencing Nrf2 by siRNA enhanced TGF-β1-induced EMT along with increased expression of snail. Interestingly, when snail was silenced by siRNA, sulforaphane treatment was unable to reduce the progression of EMT in RLE-6TN cells. These findings suggest that Nrf2 attenuates EMT and fibrosis process by regulating the expression of snail in PF.
Microstructure Imaging of Crossing (MIX) White Matter Fibers from diffusion MRI
Authors: Farooq Hamza , Xu Junqian , Nam Jung Who , Keefe Daniel F. , Yacoub Essa , Georgiou Tryphon , Lenglet Christophe 
Published: December 2016

AbstractDiffusion MRI (dMRI) reveals microstructural features of the brain white matter by quantifying the anisotropic diffusion of water molecules within axonal bundles. Yet, identifying features such as axonal orientation dispersion, density, diameter, etc., in complex white matter fiber configurations (e.g. crossings) has proved challenging. Besides optimized data acquisition and advanced biophysical models, computational procedures to fit such models to the data are critical. However, these procedures have been largely overlooked by the dMRI microstructure community and new, more versatile, approaches are needed to solve complex biophysical model fitting problems. Existing methods are limited to models assuming single fiber orientation, relevant to limited brain areas like the corpus callosum, or multiple orientations but without the ability to extract detailed microstructural features. Here, we introduce a new and versatile optimization technique (MIX), which enables microstructure imaging of crossing white matter fibers. We provide a MATLAB implementation of MIX, and demonstrate its applicability to general microstructure models in fiber crossings using synthetic as well as ex-vivo and in-vivo brain data.
A CRISPR/Cas9 Functional Screen Identifies Rare Tumor Suppressors
Authors: Katigbak Alexandra , Cencic Regina , Robert Francis , Sénécha Patrick , Scuoppo Claudio , Pelletier Jerry 
Published: December 2016

AbstractAn enormous amount of tumor sequencing data has been generated through large scale sequencing efforts. The functional consequences of the majority of mutations identified by such projects remain an open, unexplored question. This problem is particularly complicated in the case of rare mutations where frequency of occurrence alone or prediction of functional consequences are insufficient to distinguish driver from passenger or bystander mutations. We combine genome editing technology with a powerful mouse cancer model to uncover previously unsuspected rare oncogenic mutations in Burkitt’s lymphoma. We identify two candidate tumor suppressors whose loss cooperate with MYC over-expression to accelerate lymphomagenesis. Our results highlight the utility of in vivo CRISPR/Cas9 screens combined with powerful mouse models to identify and validate rare oncogenic modifier events from tumor mutational data.
The influence of ionic strength on carbonate-based spectroscopic barometry for aqueous fluids: an in-situ Raman study on Na2CO3-NaCl solutions
Authors: Wu Jia , Wang Shixia , Zheng Haifei 
Published: December 2016

AbstractThe Raman wavenumber of the symmetric stretching vibration of carbonate ion (ν1-CO32−) was measured in three aqueous solutions containing 2.0 mol·L−1 Na2CO3 and 0.20, 0.42, or 0.92 mol·L−1 NaCl, respectively, from 122 to 1538 MPa at 22 °C using a moissanite anvil cell. The ν1 Raman signal linearly shifted to higher wavenumbers with increasing pressure. Most importantly, the slope of ν1-CO32− Raman frequency shift (∂ν1/∂P)I was independent of NaCl concentration. Moreover, elevated ionic strength was found to shift the apparent outline of the carbonate peak toward low wavenumbers, possibly by increasing the proportion of the contact ion pair NaCO3−. Further investigations revealed no cross-interaction between the pressure effect and the ionic strength effect on the Raman spectra, possibly because the distribution of different ion-pair species in the carbonate equilibrium was largely pressure-independent. These results suggested that the ionic strength should be incorporated as an additional constraint for measuring the internal pressure of various solution-based systems. Combining the ν1-CO32− Raman frequency slope with the pressure herein with the values for the temperature or the ionic strength dependencies determined from previous studies, we developed an empirical equation that can be used to estimate the pressure of carbonate-bearing aqueous solutions.