bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inactivation of nuclear GSK3β by Ser389 phosphorylation promotes lymphocyte fitness during DNA double-strand break response
Authors: Thornton Tina M. , Delgado Pilar , Chen Liang , Salas Beatriz , Krementsov Dimitry , Fernandez Miriam , Vernia Santiago , Davis Roger J. , Heimann Ruth , Teuscher Cory , Krangel Michael S. , Ramiro Almudena R. , Rincón Mercedes 
Published: January 2016

AbstractVariable, diversity and joining (V(D)J) recombination and immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that naturally generate DNA double-strand breaks (DSBs) and trigger a DNA repair response. It is unclear whether this response is associated with distinct survival signals that protect T and B cells. Glycogen synthase kinase 3β (GSK3β) is a constitutively active kinase known to promote cell death. Here we show that phosphorylation of GSK3β on Ser389 by p38 MAPK (mitogen-activated protein kinase) is induced selectively by DSBs through ATM (ataxia telangiectasia mutated) as a unique mechanism to attenuate the activity of nuclear GSK3β and promote survival of cells undergoing DSBs. Inability to inactivate GSK3β through Ser389 phosphorylation in Ser389Ala knockin mice causes a decrease in the fitness of cells undergoing V(D)J recombination and CSR. Preselection-Tcrβ repertoire is impaired and antigen-specific IgG antibody responses following immunization are blunted in Ser389GSK3β knockin mice. Thus, GSK3β emerges as an important modulator of the adaptive immune response.
Interplay between type IV pili activity and exopolysaccharides secretion controls motility patterns in single cells of Myxococcus xanthus
Authors: Hu Wei , Gibiansky Maxsim L. , Wang Jing , Wang Chuandong , Lux Renate , Li Yuezhong , Wong Gerard C. L. , Shi Wenyuan 
Published: January 2016

AbstractMyxococcus xanthus performs coordinated social motility of cell groups through the extension and retraction of type IV pili (TFP) on solid surfaces, which requires both TFP and exopolysaccharides (EPS). By submerging cells in a liquid medium containing 1% methylcellulose, M. xanthus TFP-driven motility was induced in isolated cells and independently of EPS. We measured and analyzed the movements of cells using community tracking algorithms, which combine single-cell resolution with statistics from large sample populations. Cells without significant multi-cellular social interactions have surprisingly complex behaviors: EPS− cells exhibited a pronounced increase in the tendency to stand vertically and moved with qualitatively different characteristics than other cells. A decrease in the EPS secretion of cells correlates with a higher instantaneous velocity, but with lower directional persistence in trajectories. Moreover, EPS− cells do not adhere to the surface as strongly as wild-type and EPS overproducing cells and display a greater tendency to have large deviations between the direction of movement and the cell axis, with cell velocity showing only minimal dependence on the direction of movement. The emerging picture is that EPS does not simply provide rheological resistance to a single mechanism but rather that the availability of EPS impacts motility pattern.
The β2 clamp in the Mycobacterium tuberculosis DNA polymerase III αβ2ε replicase promotes polymerization and reduces exonuclease activity
Authors: Gu Shoujin , Li Wenjuan , Zhang Hongtai , Fleming Joy , Yang Weiqiang , Wang Shihua , Wei Wenjing , Zhou Jie , Zhu Guofeng , Deng Jiaoyu , Hou Jian , Zhou Ying , Lin Shiqiang , Zhang Xian-En , Bi Lijun 
Published: January 2016

AbstractDNA polymerase III (DNA pol III) is a multi-subunit replication machine responsible for the accurate and rapid replication of bacterial genomes, however, how it functions in Mycobacterium tuberculosis (Mtb) requires further investigation. We have reconstituted the leading-strand replication process of the Mtb DNA pol III holoenzyme in vitro and investigated the physical and functional relationships between its key components. We verify the presence of an αβ2ε polymerase-clamp-exonuclease replicase complex by biochemical methods and protein-protein interaction assays in vitro and in vivo and confirm that, in addition to the polymerase activity of its α subunit, Mtb DNA pol III has two potential proofreading subunits; the α and ε subunits. During DNA replication, the presence of the β2 clamp strongly promotes the polymerization of the αβ2ε replicase and reduces its exonuclease activity. Our work provides a foundation for further research on the mechanism by which the replication machinery switches between replication and proofreading and provides an experimental platform for the selection of antimicrobials targeting DNA replication in Mtb.
Constructal approach to cell membranes transport: Amending the ‘Norton-Simon’ hypothesis for cancer treatment
Authors: Lucia Umberto , Ponzetto Antonio , Deisboeck Thomas S. 
Published: January 2016

AbstractTo investigate biosystems, we propose a new thermodynamic concept that analyses ion, mass and energy flows across the cell membrane. This paradigm-shifting approach has a wide applicability to medically relevant topics including advancing cancer treatment. To support this claim, we revisit ‘Norton-Simon’ and evolving it from an already important anti-cancer hypothesis to a thermodynamic theorem in medicine. We confirm that an increase in proliferation and a reduction in apoptosis trigger a maximum of ATP consumption by the tumor cell. Moreover, we find that positive, membrane-crossing ions lead to a decrease in the energy used by the tumor, supporting the notion of their growth inhibitory effect while negative ions apparently increase the cancer’s consumption of energy hence reflecting a growth promoting impact. Our results not only represent a thermodynamic proof of the original Norton-Simon hypothesis but, more concretely, they also advance the clinically intriguing and experimentally testable, diagnostic hypothesis that observing an increase in negative ions inside a cellin vitroand inside a diseased tissuein vivo, may indicate growth or recurrence of a tumor. We conclude with providing theoretical evidence that applying electromagnetic field therapy early on in the treatment cycle may maximize its anti-cancer efficacy.
Integrated optofluidic-microfluidic twin channels: toward diverse application of lab-on-a-chip systems
Authors: Lv Chao , Xia Hong , Guan Wei , Sun Yun-Lu , Tian Zhen-Nan , Jiang Tong , Wang Ying-Shuai , Zhang Yong-Lai , Chen Qi-Dai , Ariga Katsuhiko , Yu Yu-De , Sun Hong-Bo 
Published: January 2016

AbstractOptofluidics, which integrates microfluidics and micro-optical components, is crucial for optical sensing, fluorescence analysis and cell detection. However, the realization of an integrated system from optofluidic manipulation and a microfluidic channel is often hampered by the lack of a universal substrate for achieving monolithic integration. In this study, we report on an integrated optofluidic-microfluidic twin channels chip fabricated by one-time exposure photolithography, in which the twin microchannels on both surfaces of the substrate were exactly aligned in the vertical direction. The twin microchannels can be controlled independently, meaning that fluids could flow through both microchannels simultaneously without interfering with each other. As representative examples, a tunable hydrogel microlens was integrated into the optofluidic channel by femtosecond laser direct writing, which responds to the salt solution concentration and could be used to detect the microstructure at different depths. The integration of such optofluidic and microfluidic channels provides an opportunity to apply optofluidic detection practically and may lead to great promise for the integration and miniaturization of Lab-on-a-Chip systems.
Large-Area Growth of Turbostratic Graphene on Ni(111) via Physical Vapor Deposition
Authors: Garlow Joseph A. , Barrett Lawrence K. , Wu Lijun , Kisslinger Kim , Zhu Yimei , Pulecio Javier F. 
Published: January 2016

AbstractSingle-layer graphene has demonstrated remarkable electronic properties that are strongly influenced by interfacial bonding and break down for the lowest energy configuration of stacked graphene layers (AB Bernal). Multilayer graphene with relative rotations between carbon layers, known as turbostratic graphene, can effectively decouple the electronic states of adjacent layers, preserving properties similar to that of SLG. While the growth of AB Bernal graphene through chemical vapor deposition has been widely reported, we investigate the growth of turbostratic graphene on heteroepitaxial Ni(111) thin films utilizing physical vapor deposition. By varying the carbon deposition temperature between 800 –1100 °C, we report an increase in the graphene quality concomitant with a transition in the size of uniform thickness graphene, ranging from nanocrystallites to thousands of square microns. Combination Raman modes of as-grown graphene within the frequency range of 1650 cm−1 to 2300 cm−1, along with features of the Raman 2D mode, were employed as signatures of turbostratic graphene. Bilayer and multilayer graphene were directly identified from areas that exhibited Raman characteristics of turbostratic graphene using high-resolution TEM imaging. Raman maps of the pertinent modes reveal large regions of turbostratic graphene on Ni(111) thin films at a deposition temperature of 1100 °C.
Towards a novel bioelectrocatalytic platform based on “wiring” of pyrroloquinoline quinone-dependent glucose dehydrogenase with an electrospun conductive polymeric fiber architecture
Authors: Gladisch Johannes , Sarauli David , Schäfer Daniel , Dietzel Birgit , Schulz Burkhard , Lisdat Fred 
Published: January 2016

AbstractElectrospinning is known as a fabrication technique for electrode architectures that serve as immobilization matrices for biomolecules. The current work demonstrates a novel approach to construct a conductive polymeric platform, capable not only of immobilization, but also of electrical connection of the biomolecule with the electrode. It is produced upon electrospinning from mixtures of three different highly conductive sulfonated polyanilines and polyacrylonitrile on ITO electrodes. The resulting fiber mats are with a well-retained conductivity. After coupling the enzyme pyrroloquinoline quinone-dependent glucose dehydrogenase (PQQ-GDH) to polymeric structures and addition of the substrate glucose an efficient bioelectrocatalysis is demonstrated. Depending on the choice of the sulfonated polyanilline mediatorless bioelectrocatalysis starts at low potentials; no large overpotential is needed to drive the reaction. Thus, the electrospun conductive immobilization matrix acts here as a transducing element, representing a promising strategy to use 3D polymeric scaffolds as wiring agents for active enzymes. In addition, the mild and well reproducible fabrication process and the active role of the polymer film in withdrawing electrons from the reduced PQQ-GDH lead to a system with high stability. This could provide access to a larger group of enzymes for bioelectrochemical applications including biosensors and biofuel cells.
The aberrantly expressed miR-193b-3p contributes to preeclampsia through regulating transforming growth factor-β signaling
Authors: Zhou Xinyao , Li Qiaoli , Xu Jiawei , Zhang Xiaojing , Zhang Huijuan , Xiang Yuqian , Fang Chuantao , Wang Teng , Xia Shihui , Zhang Qiang , Xing Qinghe , He Lin , Wang Lei , Xu Mingqing , Zhao Xinzhi 
Published: January 2016

AbstractPreeclampsia (PE) is a leading cause of maternal mortality worldwide. Several studies have detected some differentially expressed microRNAs in the preeclamptic placenta, but few of the identified microRNAs demonstrated consistent findings among different research studies. In this study, high-throughput microRNA sequencing (HTS) of 9 preeclamptic and 9 normal placentas was performed. Seventeen microRNAs were identified to be up-regulated and 8 down-regulated in preeclamptic placentas. Eight differentially expressed microRNAs except one identified in our study were determined to be consistent with at least one previous study, while sixteen were newly found. We performed qRT-PCR with independent 22 preeclamptic placentas and 20 control placentas to verify the differentially expressed microRNAs and ten microRNAs were validated. The predicted target genes of the aberrantly expressed miR-193b-3p were enriched in the following gene ontology categories: cell motility and migration, cell proliferation and angiogenesis. We also found that miR-193b-3p significantly decreased the migration and invasion of trophoblast (HTR-8/SVneo) cells and that miR-193b-3p could regulate trophoblasts migration and invasion through binding onto the 3′UTR target site of TGF-β2. In conclusion, we identified a list of differentially expressed microRNAs in PE placentas by HTS and provided preliminary evidence for the role of miR-193b-3p in the pathogenesis of preeclampsia.
Structure of a variable lymphocyte receptor-like protein from the amphioxus Branchiostoma floridae
Authors: Cao Dong-Dong , Liao Xin , Cheng Wang , Jiang Yong-Liang , Wang Wen-Jie , Li Qiong , Chen Jun-Yuan , Chen Yuxing , Zhou Cong-Zhao 
Published: January 2016

AbstractDiscovery of variable lymphocyte receptors (VLRs) in agnathans (jawless fish) has brought the origin of adaptive immunity system (AIS) forward to 500 million years ago accompanying with the emergence of vertebrates. Previous findings indicated that amphioxus, a representative model organism of chordate, also possesses some homologs of the basic components of TCR/BCR-based AIS, but it remains unknown if there exist any components of VLR-based AIS in amphioxus. Bioinformatics analyses revealed the amphioxus Branchiostoma floridae encodes a group of putative VLR-like proteins. Here we reported the 1.79 Å crystal structure of Bf66946, which forms a crescent-shaped structure of five leucine-rich repeats (LRRs). Structural comparisons indicated that Bf66946 resembles the lamprey VLRC. Further electrostatic potential analyses showed a negatively-charged patch at the concave of LRR solenoid structure that might be responsible for antigen recognition. Site-directed mutagenesis combined with bacterial binding assays revealed that Bf66946 binds to the surface of Gram-positive bacteria Staphylococcus aureus and Streptococcus pneumonia via a couple of acidic residues at the concave. In addition, the closest homolog of Bf66946 is highly expressed in the potential immune organ gill of Branchiostoma belcheri. Altogether, our findings provide the first structural evidence for the emergence of VLR-like molecules in the basal chordates.
Spatially resolved and orientation dependent Raman mapping of epitaxial lateral overgrowth nonpolar a-plane GaN on r-plane sapphire
Authors: Jiang Teng , Xu Sheng-rui , Zhang Jin-cheng , Xie Yong , Hao Yue 
Published: January 2016

AbstractUncoalesced a-plane GaN epitaxial lateral overgrowth (ELO) structures have been synthesized along two mask stripe orientations on a-plane GaN template by MOCVD. The morphology of two ELO GaN structures is performed by Scanning electronic microscopy. The anisotropy of crystalline quality and stress are investigated by micro-Raman spectroscopy. According to the Raman mapping spectra, the variations on the intensity, peak shift and the full width at half maximum (FWHM) of GaN E2 (high) peak indicate that the crystalline quality improvement occurs in the window region of the GaN stripes along [0001], which is caused by the dislocations bending towards the sidewalls. Conversely, the wing regions have better quality with less stress as the dislocations propagated upwards when the GaN stripes are along ["Equation missing"]. Spatial cathodoluminescence mapping results further support the explanation for the different dislocation growth mechanisms in the ELO processes with two different mask stripe orientations.
Translation Microscopy (TRAM) for super-resolution imaging
Authors: Qiu Zhen , Wilson Rhodri S , Liu Yuewei , R Dun Alison , Saleeb Rebecca S , Liu Dongsheng , Rickman Colin , Frame Margaret , Duncan Rory R , Lu Weiping 
Published: January 2016

AbstractSuper-resolution microscopy is transforming our understanding of biology but accessibility is limited by its technical complexity, high costs and the requirement for bespoke sample preparation. We present a novel, simple and multi-color super-resolution microscopy technique, called translation microscopy (TRAM), in which a super-resolution image is restored from multiple diffraction-limited resolution observations using a conventional microscope whilst translating the sample in the image plane. TRAM can be implemented using any microscope, delivering up to 7-fold resolution improvement. We compare TRAM with other super-resolution imaging modalities, including gated stimulated emission deletion (gSTED) microscopy and atomic force microscopy (AFM). We further developed novel ‘ground-truth’ DNA origami nano-structures to characterize TRAM, as well as applying it to a multi-color dye-stained cellular sample to demonstrate its fidelity, ease of use and utility for cell biology.
Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy
Authors: Cao Buqing , Yu Qing , Zhao Wei , Tang Zhiping , Cong Binhai , Du Jiankui , Lu Jianqiang , Zhu Xiaoyan , Ni Xin 
Published: January 2016

AbstractThe tissue kallikrein-related peptidase family (KLK) is a group of trypsin- and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown. In the present study, we demonstrated for the first time that KLK8 was expressed in myocardium. KLK8 expression was upregulated in left ventricle of cardiac hypertrophy models. Both intra-cardiac adenovirus-mediated and transgenic-mediated KLK8 overexpression led to cardiac hypertrophy in vivo. In primary neonatal rat cardiomyocytes, KLK8 knockdown inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas KLK8 overexpression promoted cardiomyocyte hypertrophy via a serine protease activity-dependent but kinin receptor-independent pathway. KLK8 overexpression increased epidermal growth factor (EGF) production, which was blocked by the inhibitors of serine protease. EGF receptor (EGFR) antagonist and EGFR knockdown reversed the hypertrophy induced by KLK8 overexpression. KLK8-induced cardiomyocyte hypertrophy was also significantly decreased by blocking the protease-activated receptor 1 (PAR1) or PAR2 pathway. Our data suggest that KLK8 may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway. It is implied that different KLK family members can subtly regulate cardiac function and remodeling.
At least two Fc Neu5Gc residues of monoclonal antibodies are required for binding to anti-Neu5Gc antibody
Authors: Yu Chuanfei , Gao Kai , Zhu Lei , Wang Wenbo , Wang Lan , Zhang Feng , Liu Chunyu , Li Meng , Wormald Mark R. , Rudd Pauline M. , Wang Junzhi 
Published: January 2016

AbstractTwo non-human glycan epitopes, galactose-α-1,3-galactose (α-gal) and Neu5Gc-α-2-6-galactose (Neu5Gc) have been shown to be antigenic when attached to Fab oligosaccharides of monoclonal antibodies (mAbs) , while α-gal attached to Fc glycans was not. However, the antigenicity of Neu5Gc on the Fc glycans remains unclear in the context that most mAbs carry only Fc glycans. After studying two clinical mAbs carrying significant amounts of Fc Neu5Gc, we show that their binding activity with anti-Neu5Gc antibody resided in a small subset of mAbs carrying two or more Fc Neu5Gc, while mAbs harboring only one Neu5Gc showed no reactivity. Since most Neu5Gc epitopes were distributed singly on the Fc of mAbs, our results suggest that the potential antigenicity of Fc Neu5Gc is low. Our study could be referenced in the process design and optimization of mAb production in murine myeloma cells and in the quality control of mAbs for industries and regulatory authorities.
Very-low and low-density lipoproteins induce neutral lipid accumulation and impair migration in monocyte subsets
Authors: Jackson William D. , Weinrich Tobias W. , Woollard Kevin J. 
Published: January 2016

AbstractBlood monocytes are heterogeneous effector cells of the innate immune system. In circulation these cells are constantly in contact with lipid-rich lipoproteins, yet this interaction is poorly characterised. Our aim was to examine the functional effect of hyperlipidaemia on blood monocytes. In the Ldlr−/− mouse monocytes rapidly accumulate cytoplasmic neutral lipid vesicles during hyperlipidaemia. Functional analysis in vivo revealed impaired monocyte chemotaxis towards peritonitis following high fat diet due to retention of monocytes in the greater omentum. In vitro assays using human monocytes confirmed neutral lipid vesicle accumulation after exposure to LDL or VLDL. Neutral lipid accumulation did not inhibit phagocytosis, endothelial adhesion, intravascular crawling and transmigration. However, lipid loading led to a migratory defect towards C5a and disruption of cytoskeletal rearrangement, including an inhibition of RHOA signaling. These data demonstrate distinct effects of hyperlipidaemia on the chemotaxis and cytoskeletal regulation of monocyte subpopulations. These data emphasise the functional consequences of blood monocyte lipid accumulation and reveal important implications for treating inflammation, infection and atherosclerosis in the context of dyslipidaemia.
Ground state potential energy surfaces around selected atoms from resonant inelastic x-ray scattering
Authors: Schreck Simon , Pietzsch Annette , Kennedy Brian , Såthe Conny , Miedema Piter S. , Techert Simone , Strocov Vladimir N. , Schmitt Thorsten , Hennies Franz , Rubensson Jan-Erik , Föhlisch Alexander 
Published: January 2016

AbstractThermally driven chemistry as well as materials’ functionality are determined by the potential energy surface of a systems electronic ground state. This makes the potential energy surface a central and powerful concept in physics, chemistry and materials science. However, direct experimental access to the potential energy surface locally around atomic centers and to its long-range structure are lacking. Here we demonstrate how sub-natural linewidth resonant inelastic soft x-ray scattering at vibrational resolution is utilized to determine ground state potential energy surfaces locally and detect long-range changes of the potentials that are driven by local modifications. We show how the general concept is applicable not only to small isolated molecules such as O2 but also to strongly interacting systems such as the hydrogen bond network in liquid water. The weak perturbation to the potential energy surface through hydrogen bonding is observed as a trend towards softening of the ground state potential around the coordinating atom. The instrumental developments in high resolution resonant inelastic soft x-ray scattering are currently accelerating and will enable broad application of the presented approach. With this multidimensional potential energy surfaces that characterize collective phenomena such as (bio)molecular function or high-temperature superconductivity will become accessible in near future.