bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro-metastatic collagen lysyl hydroxylase dimer assemblies stabilized by Fe2+-binding
Authors: Guo Hou-Fu , Tsai Chi-Lin , Terajima Masahiko , Tan Xiaochao , Banerjee Priyam , Miller Mitchell D. , Liu Xin , Yu Jiang , Byemerwa Jovita , Alvarado Sarah , Kaoud Tamer S. , Dalby Kevin N. , Bota-Rabassedas Neus , Chen Yulong , Yamauchi Mitsuo , Tainer John A. , Phillips George N. , Kurie Jonathan M. 
Published: January 2018

AbstractCollagen lysyl hydroxylases (LH1-3) are Fe2+- and 2-oxoglutarate (2-OG)-dependent oxygenases that maintain extracellular matrix homeostasis. High LH2 levels cause stable collagen cross-link accumulations that promote fibrosis and cancer progression. However, developing LH antagonists will require structural insights. Here, we report a 2 Å crystal structure and X-ray scattering on dimer assemblies for the LH domain of L230 in Acanthamoeba polyphaga mimivirus. Loop residues in the double-stranded β-helix core generate a tail-to-tail dimer. A stabilizing hydrophobic leucine locks into an aromatic tyrosine-pocket on the opposite subunit. An active site triad coordinates Fe2+. The two active sites flank a deep surface cleft that suggest dimerization creates a collagen-binding site. Loss of Fe2+-binding disrupts the dimer. Dimer disruption and charge reversal in the cleft increase Km and reduce LH activity. Ectopic L230 expression in tumors promotes collagen cross-linking and metastasis. These insights suggest inhibitor targets for fibrosis and cancer.
Ub-ProT reveals global length and composition of protein ubiquitylation in cells
Authors: Tsuchiya Hikaru , Burana Daocharad , Ohtake Fumiaki , Arai Naoko , Kaiho Ai , Komada Masayuki , Tanaka Keiji , Saeki Yasushi 
Published: January 2018

AbstractProtein ubiquitylation regulates diverse cellular processes via distinct ubiquitin chains that differ by linkage type and length. However, a comprehensive method for measuring these properties has not been developed. Here we describe a method for assessing the length of substrate-attached polyubiquitin chains, “ubiquitin chain protection from trypsinization (Ub-ProT).” Using Ub-ProT, we found that most ubiquitylated substrates in yeast-soluble lysate are attached to chains of up to seven ubiquitin molecules. Inactivation of the ubiquitin-selective chaperone Cdc48 caused a dramatic increase in chain lengths on substrate proteins, suggesting that Cdc48 complex terminates chain elongation by substrate extraction. In mammalian cells, we found that ligand-activated epidermal growth factor receptor (EGFR) is rapidly modified with K63-linked tetra- to hexa-ubiquitin chains following EGF treatment in human cells. Thus, the Ub-ProT method can contribute to our understanding of mechanisms regulating physiological ubiquitin chain lengths and composition.
Lymphocyte-specific protein 1 regulates mechanosensory oscillation of podosomes and actin isoform-based actomyosin symmetry breaking
Authors: Cervero Pasquale , Wiesner Christiane , Bouissou Anais , Poincloux Renaud , Linder Stefan 
Published: January 2018

AbstractSubcellular fine-tuning of the actomyosin cytoskeleton is a prerequisite for polarized cell migration. We identify LSP (lymphocyte-specific protein) 1 as a critical regulator of actomyosin contractility in primary macrophages. LSP1 regulates adhesion and migration, including the parameters cell area and speed, and also podosome turnover, oscillation and protrusive force. LSP1 recruits myosin IIA and its regulators, including myosin light chain kinase and calmodulin, and competes with supervillin, a myosin hyperactivator, for myosin regulators, and for actin isoforms, notably β-actin. Actin isoforms are anisotropically distributed in myosin IIA-expressing macrophages, and contribute to the differential recruitment of LSP1 and supervillin, thus enabling an actomyosin symmetry break, analogous to the situation in cells expressing two myosin II isoforms. Collectively, these results show that the cellular pattern of actin isoforms builds the basis for the differential distribution of two actomyosin machineries with distinct properties, leading to the establishment of discrete zones of actomyosin contractility.
Biochemical mechanisms determine the functional compatibility of heterologous genes
Authors: Porse Andreas , Schou Thea S. , Munck Christian , Ellabaan Mostafa M. H. , Sommer Morten O. A. 
Published: January 2018

AbstractElucidating the factors governing the functional compatibility of horizontally transferred genes is important to understand bacterial evolution, including the emergence and spread of antibiotic resistance, and to successfully engineer biological systems. In silico efforts and work using single-gene libraries have suggested that sequence composition is a strong barrier for the successful integration of heterologous genes. Here we sample 200 diverse genes, representing >80% of sequenced antibiotic resistance genes, to interrogate the factors governing genetic compatibility in new hosts. In contrast to previous work, we find that GC content, codon usage, and mRNA-folding energy are of minor importance for the compatibility of mechanistically diverse gene products at moderate expression. Instead, we identify the phylogenetic origin, and the dependence of a resistance mechanism on host physiology, as major factors governing the functionality and fitness of antibiotic resistance genes. These findings emphasize the importance of biochemical mechanism for heterologous gene compatibility, and suggest physiological constraints as a pivotal feature orienting the evolution of antibiotic resistance.
Sensory deprivation in Staphylococcus aureus
Authors: Villanueva Maite , García Begoña , Valle Jaione , Rapún Beatriz , Ruiz de los Mozos Igor , Solano Cristina , Martí Miguel , Penadés José R. , Toledo-Arana Alejandro , Lasa Iñigo 
Published: January 2018

AbstractBacteria use two-component systems (TCSs) to sense and respond to environmental changes. The core genome of the major human pathogen Staphylococcus aureus encodes 16 TCSs, one of which (WalRK) is essential. Here we show that S. aureus can be deprived of its complete sensorial TCS network and still survive under growth arrest conditions similarly to wild-type bacteria. Under replicating conditions, however, the WalRK system is necessary and sufficient to maintain bacterial growth, indicating that sensing through TCSs is mostly dispensable for living under constant environmental conditions. Characterization of S. aureus derivatives containing individual TCSs reveals that each TCS appears to be autonomous and self-sufficient to sense and respond to specific environmental cues, although some level of cross-regulation between non-cognate sensor-response regulator pairs occurs in vivo. This organization, if confirmed in other bacterial species, may provide a general evolutionarily mechanism for flexible bacterial adaptation to life in new niches.
Acetylation accumulates PFKFB3 in cytoplasm to promote glycolysis and protects cells from cisplatin-induced apoptosis
Authors: Li Fu-Long , Liu Jin-Ping , Bao Ruo-Xuan , Yan GuoQuan , Feng Xu , Xu Yan-Ping , Sun Yi-Ping , Yan Weili , Ling Zhi-Qiang , Xiong Yue , Guan Kun-Liang , Yuan Hai-Xin 
Published: January 2018

AbstractEnhanced glycolysis in cancer cells has been linked to cell protection from DNA damaging signals, although the mechanism is largely unknown. The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) catalyzes the generation of fructose-2,6-bisphosphate, a potent allosteric stimulator of glycolysis. Intriguingly, among the four members of PFKFB family, PFKFB3 is uniquely localized in the nucleus, although the reason remains unclear. Here we show that chemotherapeutic agent cisplatin promotes glycolysis, which is suppressed by PFKFB3 deletion. Mechanistically, cisplatin induces PFKFB3 acetylation at lysine 472 (K472), which impairs activity of the nuclear localization signal (NLS) and accumulates PFKFB3 in the cytoplasm. Cytoplasmic accumulation of PFKFB3 facilitates its phosphorylation by AMPK, leading to PFKFB3 activation and enhanced glycolysis. Inhibition of PFKFB3 sensitizes tumor to cisplatin treatment in a xenograft model. Our findings reveal a mechanism for cells to stimulate glycolysis to protect from DNA damage and potentially suggest a therapeutic strategy to sensitize tumor cells to genotoxic agents by targeting PFKFB3.
Afforestation neutralizes soil pH
Authors: Hong Songbai , Piao Shilong , Chen Anping , Liu Yongwen , Liu Lingli , Peng Shushi , Sardans Jordi , Sun Yan , Peñuelas Josep , Zeng Hui 
Published: January 2018

AbstractSoil pH regulates soil biogeochemical processes and has cascading effects on terrestrial ecosystem structure and functions. Afforestation has been widely adopted to increase terrestrial carbon sequestration and enhance water and soil preservation. However, the effect of afforestation on soil pH is still poorly understood and inconclusive. Here we investigate the afforestation-caused soil pH changes with pairwise samplings from 549 afforested and 148 control plots in northern China. We find significant soil pH neutralization by afforestation—afforestation lowers pH in relatively alkaline soil but raises pH in relatively acid soil. The soil pH thresholds (TpH), the point when afforestation changes from increasing to decreasing soil pH, are species-specific, ranging from 5.5 (Pinus koraiensis) to 7.3 (Populus spp.) with a mean of 6.3. These findings indicate that afforestation can modify soil pH if tree species and initial pH are properly matched, which may potentially improve soil fertility and promote ecosystem productivity.
A microengineered vascularized bleeding model that integrates the principal components of hemostasis
Authors: Sakurai Yumiko , Hardy Elaissa T. , Ahn Byungwook , Tran Reginald , Fay Meredith E. , Ciciliano Jordan C. , Mannino Robert G. , Myers David R. , Qiu Yongzhi , Carden Marcus A. , Baldwin W. Hunter , Meeks Shannon L. , Gilbert Gary E. , Jobe Shawn M. , Lam Wilbur A. 
Published: January 2018

AbstractHemostasis encompasses an ensemble of interactions among platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces, but current assays assess only isolated aspects of this complex process. Accordingly, here we develop a comprehensive in vitro mechanical injury bleeding model comprising an “endothelialized” microfluidic system coupled with a microengineered pneumatic valve that induces a vascular “injury”. With perfusion of whole blood, hemostatic plug formation is visualized and “in vitro bleeding time” is measured. We investigate the interaction of different components of hemostasis, gaining insight into several unresolved hematologic issues. Specifically, we visualize and quantitatively demonstrate: the effect of anti-platelet agent on clot contraction and hemostatic plug formation, that von Willebrand factor is essential for hemostasis at high shear, that hemophilia A blood confers unstable hemostatic plug formation and altered fibrin architecture, and the importance of endothelial phosphatidylserine in hemostasis. These results establish the versatility and clinical utility of our microfluidic bleeding model.
Cryo-EM structure of 5-HT3A receptor in its resting conformation
Authors: Basak Sandip , Gicheru Yvonne , Samanta Amrita , Molugu Sudheer Kumar , Huang Wei , Fuente Maria la de , Hughes Taylor , Taylor Derek J. , Nieman Marvin T. , Moiseenkova-Bell Vera , Chakrapani Sudha 
Published: January 2018

AbstractSerotonin receptors (5-HT3AR) directly regulate gut movement, and drugs that inhibit 5-HT3AR function are used to control emetic reflexes associated with gastrointestinal pathologies and cancer therapies. The 5-HT3AR function involves a finely tuned orchestration of three domain movements that include the ligand-binding domain, the pore domain, and the intracellular domain. Here, we present the structure from the full-length 5-HT3AR channel in the apo-state determined by single-particle cryo-electron microscopy at a nominal resolution of 4.3 Å. In this conformation, the ligand-binding domain adopts a conformation reminiscent of the unliganded state with the pore domain captured in a closed conformation. In comparison to the 5-HT3AR crystal structure, the full-length channel in the apo-conformation adopts a more expanded conformation of all the three domains with a characteristic twist that is implicated in gating.
Multidimensional correlation of nuclear relaxation rates and diffusion tensors for model-free investigations of heterogeneous anisotropic porous materials
Authors: de Almeida Martins João P. , Topgaard Daniel 
Published: January 2018

AbstractDespite their widespread use in non-invasive studies of porous materials, conventional MRI methods yield ambiguous results for microscopically heterogeneous materials such as brain tissue. While the forward link between microstructure and MRI observables is well understood, the inverse problem of separating the signal contributions from different microscopic pores is notoriously difficult. Here, we introduce an experimental protocol where heterogeneity is resolved by establishing 6D correlations between the individual values of isotropic diffusivity, diffusion anisotropy, orientation of the diffusion tensor, and relaxation rates of distinct populations. Such procedure renders the acquired signal highly specific to the sample’s microstructure, and allows characterization of the underlying pore space without prior assumptions on the number and nature of distinct microscopic environments. The experimental feasibility of the suggested method is demonstrated on a sample designed to mimic the properties of nerve tissue. If matched to the constraints of whole body scanners, this protocol could allow for the unconstrained determination of the different types of tissue that compose the living human brain.
Controlling motile disclinations in a thick nematogenic material with an electric field
Authors: Bhattacharjee Amit Kumar 
Published: January 2018

AbstractManipulating topological disclination networks that arise in a symmetry-breaking phase transformation in widely varied systems including anisotropic materials can potentially lead to the design of novel materials like conductive microwires, self-assembled resonators, and active anisotropic matter. However, progress in this direction is hindered by a lack of control of the kinetics and microstructure due to inherent complexity arising from competing energy and topology. We have studied thermal and electrokinetic effects on disclinations in a three-dimensional nonabsorbing nematic material with a positive and negative sign of the dielectric anisotropy. The electric flux lines are highly nonuniform in uniaxial media after an electric field below the Fréedericksz threshold is switched on, and the kinetics of the disclination lines is slowed down. In biaxial media, depending on the sign of the dielectric anisotropy, apart from the slowing down of the disclination kinetics, a nonuniform electric field filters out disclinations of different topology by inducing a kinetic asymmetry. These results enhance the current understanding of forced disclination networks and establish the presented method, which we call fluctuating electronematics, as a potentially useful tool for designing materials with novel properties in silico.
The reunion of two lineages of the Neotropical brown stink bug on soybean lands in the heart of Brazil
Authors: Soares Patricia L. , Cordeiro Erick M. G. , Santos Frederico N. S. , Omoto Celso , Correa Alberto S. 
Published: January 2018

AbstractThe rapid pace of conversion of natural areas to agricultural systems is highly concerning, and the consequences for conservation and pest management are not yet fully understood. We examined mitochondrial (COI and Cytb) and nuclear (ITS1) gene regions of 21 populations of the stink bug Euschistus heros, to investigate the genetic diversity, genetic structure, and demographic history of this emerging soybean pest in South America. Two deep lineages that diverged in the Pliocene (4.5 Myr) occur over wide areas of Brazil. Historical changes during the Plio-Pleistocene led to significant genetic differences between E. heros populations, which differentiated further in several biomes. The northern lineage is older, more diverse, and prevalent in the Amazon and Caatinga, while the southern lineage is younger, less diverse, and prevalent in the Atlantic Forest and Chaco biomes. Euschistus heros populations are expanding in size and range but at different rates, strongly affected by environmental variables. Secondary contact between the main lineages is now occurring, mainly in areas of intensive farming and particularly in the Cerrado, an important agricultural frontier. Individuals adapted to different environmental conditions and to large monocultures might currently be combining into a panmictic and hard-to-control pest population.
Novel non-periodic spoof surface plasmon polaritons with H-shaped cells and its application to high selectivity wideband bandpass filter
Authors: Gao Xin , Che Wenquan , Feng Wenjie 
Published: January 2018

AbstractIn this paper, one kind of novel non-periodic spoof surface plasmon polaritons (SSPPs) with H-shaped cells is proposed. As we all know, the cutoff frequency exists inherently for the conventional comb-shaped SSPPs, which is a kind of periodic groove shape structures and fed by a conventional coplanar waveguide (CPW). In this work, instead of increasing the depth of all the grooves, two H-shaped cells are introduced to effectively reduce the cutoff frequency of the conventional comb-shaped SSPPs (about 12 GHz) for compact design. More importantly, the guide waves can be gradually transformed to SSPP waves with high efficiency, and better impedance matching from 50 Ω to the novel SSPP strip is achieved. Based on the proposed non-periodic SSPPs with H-shaped cells, a wideband bandpass filter (the 3-dB fractional bandwidths 68%) is realized by integrating the spiral-shaped defected ground structure (DGS) etched on CPW. Specifically, the filter shows high passband selectivity (Δf3 dB/Δf20 dB = 0.91) and wide upper stopband with −20 dB rejection. A prototype is fabricated for demonstration. Good agreements can be observed between the measured and simulated results, indicating potential applications in the integrated plasmonic devices and circuits at microwave and even THz frequencies.
Fast and accurate detection of spread source in large complex networks
Authors: Paluch Robert , Lu Xiaoyan , Suchecki Krzysztof , Szymański Bolesław K. , Hołyst Janusz A. 
Published: January 2018

AbstractSpread over complex networks is a ubiquitous process with increasingly wide applications. Locating spread sources is often important, e.g. finding the patient one in epidemics, or source of rumor spreading in social network. Pinto, Thiran and Vetterli introduced an algorithm (PTVA) to solve the important case of this problem in which a limited set of nodes act as observers and report times at which the spread reached them. PTVA uses all observers to find a solution. Here we propose a new approach in which observers with low quality information (i.e. with large spread encounter times) are ignored and potential sources are selected based on the likelihood gradient from high quality observers. The original complexity of PTVA is O(N
α
), where α ∈ (3,4) depends on the network topology and number of observers (N denotes the number of nodes in the network). Our Gradient Maximum Likelihood Algorithm (GMLA) reduces this complexity to O (N2log (N)). Extensive numerical tests performed on synthetic networks and real Gnutella network with limitation that id’s of spreaders are unknown to observers demonstrate that for scale-free networks with such limitation GMLA yields higher quality localization results than PTVA does.
Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Elevated Cancer Incidence in Firefighters
Authors: Stec Anna A. , Dickens Kathryn E. , Salden Marielle , Hewitt Fiona E. , Watts Damian P. , Houldsworth Philip E. , Martin Francis L. 
Published: January 2018

AbstractCancer incidence appears to be higher amongst firefighters compared to the general population. Given that many cancers have an environmental component, their occupational exposure to products of carbon combustion such as polycyclic aromatic hydrocarbons (PAHs) is of concern. This is the first UK study identifying firefighters exposure to PAH carcinogens. Wipe samples were collected from skin (jaw, neck, hands), personal protective equipment of firefighters, and work environment (offices, fire stations and engines) in two UK Fire and Rescue Service Stations. Levels of 16 US Environmental Protection Agency (EPA) PAHs were quantified together with more potent carcinogens: 7,12-dimethylbenzo[a]anthracene, and 3-methylcholanthrene (3-MCA) (12 months post-initial testing). Cancer slope factors, used to estimate cancer risk, indicate a markedly elevated risk. PAH carcinogens including benzo[a]pyrene (B[a]P), 3-MCA, and 7,12-dimethylbenz[a]anthracene PAHs were determined on body surfaces (e.g., hands, throat), on PPE including helmets and clothing, and on work surfaces. The main exposure route would appear to be via skin absorption. These results suggest an urgent need to monitor exposures to firefighters in their occupational setting and conduct long-term follow-up regarding their health status.
The role of transposable elements in functional evolution of amphioxus genome: the case of opsin gene family
Authors: Pantzartzi Chrysoula N. , Pergner Jiri , Kozmik Zbynek 
Published: January 2018

AbstractTransposable elements (TEs) are able to jump to new locations (transposition) in the genome, usually after replication. They constitute the so-called selfish or junk DNA and take over large proportions of some genomes. Due to their ability to move around they can change the DNA landscape of genomes and are therefore a rich source of innovation in genes and gene regulation. Surge of sequence data in the past years has significantly facilitated large scale comparative studies. Cephalochordates have been regarded as a useful proxy to ancestral chordate condition partially due to the comparatively slow evolutionary rate at morphological and genomic level. In this study, we used opsin gene family from three Branchiostoma species as a window into cephalochordate genome evolution. We compared opsin complements in terms of family size, gene structure and sequence allowing us to identify gene duplication and gene loss events. Furthermore, analysis of the opsin containing genomic loci showed that they are populated by TEs. In summary, we provide evidence of the way transposable elements may have contributed to the evolution of opsin gene family and to the shaping of cephalochordate genomes in general.