bluuebunny/crossref_metadata_2025_split huggingface dataset:
The network properties of the brain at the time of normal birth support the acquisition of language processing
Authors: Salvan Piergiorgio , Arichi Tomoki , Vidaurre Diego , Tournier J Donald , Falconer Shona , Chew Andrew , Counsell Serena J , Edwards A David 
Published: March 2018

AbstractLanguage acquisition appears to rely at least in part on recruiting pre-existing brain structures. We hypothesized that the neural substrate for language can be characterized by distinct, non-trivial network properties of the brain, that modulate language acquisition early in development. We tested whether these brain network properties present at the normal age of birth predicted later language abilities, and whether these were robust against perturbation by studying infants exposed to the extreme environmental stress of preterm birth.We found that brain network controllability and integration predicted respectively phonological, ‘bottom-up’ and syntactical, ‘top-down’ language skills at 20 months, and that syntactical but not phonological functions were modulated by premature extrauterine life. These data show that the neural substrate for language acquisition is a network property present at term corrected age. These distinct developmental trajectories may be relevant to the emergence of social interaction after birth.
Self-assembly of the RZZ complex into filaments drives kinetochore expansion in the absence of microtubule attachment
Authors: Pereira Cláudia , Reis Rita M. , Gama José B. , Cheerambathur Dhanya K. , Carvalho Ana X. , Gassmann Reto 
Published: March 2018

SUMMARYThe kinetochore is a dynamic multi-protein assembly that forms on each sister chromatid and interacts with microtubules of the mitotic spindle to drive chromosome segregation. In animals, kinetochores without attached microtubules expand their outermost layer into crescent and ring shapes to promote microtubule capture and spindle assembly checkpoint (SAC) signalling. Kinetochore expansion is an example of protein co-polymerization, but the mechanism is not understood. Here, we present evidence that kinetochore expansion is driven by oligomerization of the Rod-Zw10-Zwilch (RZZ) complex, an outer kinetochore component that recruits the motor dynein and the SAC proteins Mad1-Mad2. Depletion of ROD in human cells suppresses kinetochore expansion, as does depletion of Spindly, the adaptor that connects RZZ to dynein, while dynein itself is dispensable. Expansion is also suppressed by mutating ZWILCH residues implicated in Spindly binding. Conversely, supplying cells with excess ROD facilitates kinetochore expansion under otherwise prohibitive conditions. Using the C. elegans early embryo, we demonstrate that ROD-1 has a concentration-dependent propensity for oligomerizing into µm-scale filaments, and we identify the ROD-1 β-propeller as a key regulator of self-assembly. Finally, we show that a minimal ROD-1-Zw10 complex efficiently oligomerizes into filaments in vitro. Our results suggest that RZZ’s capacity for oligomerization is harnessed by kinetochores to assemble the expanded outermost domain, in which RZZ filaments serve as recruitment platforms for SAC components and microtubule-binding proteins. Thus, we propose that RZZ self-assembly into filaments underlies the adaptive change in kinetochore size that contributes to chromosome segregation fidelity.
Structure of the mouse TRPC4 ion channel
Authors: Duan Jingjing , Li Jian , Zeng Bo , Chen Gui-Lan , Peng Xiaogang , Zhang Yixing , Wang Jianbin , Clapham David E. , Li Zongli , Zhang Jin 
Published: March 2018

AbstractMembers of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally-mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Structures belonging to the TRPV, TRPM, TRPP, TRPA and TRPML subfamilies have been solved, but to date, none of the founding canonical (TRPC) structures. Here we report an electron cryo-microscopy (cryo-EM) structure of TRPC4 in its apo state to an overall resolution of 3.3 Å. The structure reveals an unusually complex architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain, this unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP and the C-terminal domains. The comparison of our structure with other known TRP structures provides molecular insights into TRPC4 ion selectivity and extends our knowledge of the diversity and evolution of the TRP channels.
Calcium-activated chloride channels clamp odor-evoked spike activity in olfactory receptor neurons
Authors: Zak Joseph D. , Grimaud Julien , Li Rong-Chang , Lin Chih-Chun , Murthy Venkatesh N. 
Published: March 2018

AbstractThe calcium-activated chloride channel anoctamin-2 (Ano2) is thought to amplify transduction currents in ORNs, a hypothesis supported by previous studies in dissociated neurons from Ano2-/- mice. Paradoxically, despite a reduction in transduction currents in Ano2-/- ORNs, their spike output for odor stimuli may be higher. We examined the role of Ano2 in ORNs in their native environment in freely breathing mice by imaging activity in ORN axons as they arrive in the olfactory bulb glomeruli. Odor-evoked responses in ORN axons of Ano2-/- mice were consistently larger for a variety of odorants and concentrations. In an open arena, Ano2-/- mice took longer to approach a localized odor source than wild-type mice, revealing clear olfactory behavioral deficits. Our studies provide the first in vivo evidence toward an alternative role for Ano2 in the olfactory transduction cascade, where it may serve as a feedback mechanism to clamp ORN spike output.
Structure of the receptor-activated human TRPC6 ion channel
Authors: Tang Qinglin , Guo Wenjun , Zheng Li , Wu Jing-Xiang , Liu Meng , Zhou Xindi , Zhang Xiaolin , Chen Lei 
Published: March 2018

AbstractTRPC6 is a receptor-activated nonselective cation channel that belongs to the family of canonical transient receptor potential (TRPC) channels. It is activated by diacylglycerol, a lipid second messenger. TRPC6 is involved in many physiological processes and implicated in human genetic diseases. Here we present the structure of human TRPC6 homotetramer in complex with a newly identified high affinity inhibitor BTDM solved by single-particle cryo-electron microscopy to 3.8 Å resolution. The structure shows a two-layer architecture, in which the bell-shaped cytosolic layer holds the transmembrane layer. Extensive inter-subunit interactions of cytosolic domain, including N terminal ankyrin repeats and C terminal coiled-coil, contribute to the tetramer assembly. The high affinity inhibitor BTDM wedges between S5-S6 pore domain and voltage sensor-like domain to inhibit channel opening. Our structure uncovers the molecular architecture of TRPC channels and provides a structural basis for understanding the mechanism of these channels.
Deactivation and Mislocalization of a kinase protein induced by a single amino acid mutation on the proton transport catalytic aspartic acid
Authors: Zhang Yang 
Published: March 2018

AbstractRhoptry protein 18 (ROP18) is a major determinant of strain-specific virulence in Toxoplasma gondii. The kinase activity of ROP18 is required for acute virulence, while the aspartate in the catalytic loop of ROP18 is considered essential for phosphoryl transfer. We showed that a single amino acid mutation at the catalytic aspartate residue (D409A mutation) significantly altered ROP18 kinase activity in vitro, and abolished ROP18-mediated ATF6β degradation. Furthermore, the investigated single amino acid mutation in ROP18 led to alternation of subcellular localization of ROP18 protein. Structural modeling analysis suggests that these phenotypes might be associated with D409A mutation induced conformation changes in ROP18.Our findings demonstrate that a single amino acid mutation on the proton transport catalytic aspartic acid induced conformational alternations in ROP18 resulting in functional changes associated with ROP18 protein.
A role for Fibroblast Growth Factor Receptor 1 in the pathogenesis ofNeisseria meningitidis
Authors: Azimi Sheyda , Wheldon Lee M. , Oldfield Neil J. , Ala’Aldeen Dlawer A. A. , Wooldridge Karl G. 
Published: March 2018

SummaryNeisseria meningitidisremains an important cause of human disease. It is highly adapted to the human host – its only known reservoir. Adaptations to the host environment include many specific interactions with human molecules including iron-binding proteins, components of the innate and adaptive immune systems, and cell surface receptors such as the Epidermal Growth Factor Receptor (EGFR). Interaction of the meningococcus with EGFR has been elucidated in some detail and leads to intracellular signalling and cytoskeletal changes contributing to the pathogenesis of the organism. Here, we show that the meningococcus also recruits Fibroblast Growth Factor Receptor 1 (FGFR1) onto the surface of human blood microvascular epithelial cells (HBMECs). Furthermore, meningococci internalised into these cells recruit the activated form of this receptor, and that expression and activation of FGFR1 is necessary for efficient internalisation of meningococci into HBMECs. We show thatNeisseria meningitidisinteracts specifically with the IIIc isoform of FGFR1.
Cytoplasmic sequestration of the RhoA effector mDiaphanous1 by Prohibitin2 promotes muscle differentiation
Authors: Saleh Amena , Subramaniam Gunasekaran , Raychaudhuri Swasti , Dhawan Jyotsna 
Published: March 2018

AbstractAdhesion and growth factor dependent signalling control muscle gene expression through common effectors, coupling cytoskeletal dynamics to transcriptional activation. Earlier, we showed that mDiaphanous1, an effector of adhesion-dependent RhoA-signalling promotes MyoD expression in myoblasts, linking contractility to lineage determination. Here, we report that paradoxically, mDia1 negatively regulates MyoD function in myotubes. Knockdown of endogenous mDia1 during differentiation enhances MyoD and Myogenin expression, while over-expression of mDia1ΔN3, a RhoA-independent mutant, suppresses Myogenin promoter activity and expression. We investigated mechanisms that may counteract mDia1 to promote Myogenin expression and timely differentiation by analysing mDia1-interacting proteins. We report that mDia1 has a stage-specific interactome, including Prohibitin2, MyoD, Akt2, and β-Catenin, of which Prohibitin2 colocalises with mDia1 in cytoplasmic punctae and opposes mDia1 function in myotubes. Co-expression of mDia1-binding domains of Prohibitin2 reverses the anti-myogenic effects of mDia1ΔN3. Our results suggest that Prohibitin2 sequesters mDiaphanous1 to dampen its activity and finetune RhoA-mDiaphanous1 signalling to promote differentiation. Overall, we report that mDia1 is multi-functional signaling effector with opposing functions in different cellular stages, but is modulated by a differentiation-dependent interactome.Summary statementmDia1 has common and stage-specific functions in muscle cells. In myotubes, mDia1 is sequestered by an interacting protein Prohibitin2, which promotes Myogenin expression and mitigates mDia1’s inhibitory effects on differentiation.Graphical abstract
Would an RRS by any other name sound as RAD?
Authors: Campbell Erin O , Brunet Bryan M T , Dupuis Julian R , Sperling Felix A H 
Published: March 2018

ABSTRACTSampling markers throughout a genome with restriction enzymes emerged in the 2000s as reduced representation shotgun sequencing (RRS). Rapid advances in sequencing technology have since spurred modifications of RRS, giving rise to many derivatives with unique names, such as RADseq. But naming conventions have often been more creative than consistent, with unclear criteria for recognition as a unique method resulting in a proliferation of names characterized by ambiguity. We conducted a literature review to assess methodological and etymological relationships among 36 restriction enzyme-based methods, as well as rates of correct referencing of commonly-used methods. We identify several instances of methodological convergence or misattribution in the literature, and note that many published derivatives have modified only minor elements of parent protocols. We urge greater restraint in naming derivative methods, to strike a better balance between clarity, recognition of scientific innovation, and correct attribution.
Tychus: a whole genome sequencing pipeline for assembly, annotation and phylogenetics of bacterial genomes
Authors: Dean Christopher , Noyes Noelle , Lakin Steven , Rovira-Sanz Pablo , Yang Xiang , Belk Keith , Morley Paul S. , Meinersmann Rick , Abdo Zaid 
Published: March 2018

AbstractSummaryTychus is a tool that allows researchers to perform massively parallel whole genome sequence (WGS) analysis with the goal of producing a high confidence and comprehensive description of the bacterial genome. Key features of the Tychus pipeline include the assembly, annotation, alignment, variant discovery and phylogenetic inference of large numbers of WGS isolates in parallel using open-source bioinformatics tools and virtualization technology. All prerequisite tools and dependencies come packaged together in a single suite that can be easily downloaded and installed on Linux and Mac operating systems.AvailabilityTychus is freely available as an open-source package under the MIT license, and can be downloaded via GitHub (https://github.com/Abdo-Lab/Tychus).Contactzaid.abdo@colostate.edu
Functional Characterization of Enhancer Evolution in the Primate Lineage
Authors: Klein Jason C. , Keith Aidan , Agarwal Vikram , Durham Timothy , Shendure Jay 
Published: March 2018

BackgroundEnhancers play an important role in morphological evolution and speciation by controlling the spatiotemporal expression of genes. Due to technological limitations, previous efforts to understand the evolution of enhancers in primates have typically studied many enhancers at low resolution, or single enhancers at high resolution. Although comparative genomic studies reveal large-scale turnover of enhancers, a specific understanding of the molecular steps by which mammalian or primate enhancers evolve remains elusive.ResultsWe identified candidate hominoid-specific liver enhancers from H3K27ac ChIP-seq data. After locating orthologs in 11 primates spanning ∼40 million years, we synthesized all orthologs as well as computational reconstructions of 9 ancestral sequences for 348 “active tiles” of 233 putative enhancers. We concurrently tested all sequences (20 per tile) for regulatory activity with STARR-seq in HepG2 cells, with the goal of characterizing the evolutionary-functional trajectories of each enhancer. We observe groups of enhancer tiles with coherent trajectories, most of which can be explained by one or two mutational events per tile. We quantify the correlation between the number of mutations along a branch and the magnitude of change in functional activity. Finally, we identify 57 mutations that correlate with functional changes; these are enriched for cytosine deamination events within CpGs, compared to background events.ConclusionsWe characterized the evolutionary-functional trajectories of hundreds of liver enhancers throughout the primate phylogeny. We observe subsets of regulatory sequences that appear to have gained or lost activity at various positions in the primate phylogeny. We use these data to quantify the relationship between sequence and functional divergence, and to identify CpG deamination as a potentially important force in driving changes in enhancer activity during primate evolution.
Structural elements required for coupling ion and substrate transport in the neurotransmitter transporter homolog LeuT
Authors: Zhang Yuan-Wei , Tavoulari Sotiria , Sinning Steffen , Aleksandrova Antoniya A. , Forrest Lucy R. , Rudnick Gary 
Published: March 2018

AbstractThe coupled transport of ions and substrates allows transporters to accumulate substrates using the energy in transmembrane ion gradients and electrical potentials. During transport, conformational changes that switch accessibility of substrate and ion binding sites from one side of the membrane to the other must be controlled so as to prevent uncoupled movement of ions or substrates. In the Neurotransmitter:Sodium Symporter (NSS) family, Na+ stabilizes the transporter in an outward-open state, thus decreasing the likelihood of uncoupled Na+ transport. In a step essential for coupled transport, substrate binding must overcome the effect of Na+, allowing intracellular substrate and Na+ release from an inward-open state. However, it is unclear which specific elements of the protein mediate this conformational response to substrate binding. Previously, we showed that in the prokaryotic NSS transporter LeuT, the effect of Na+ on conformation occurs at the Na2 site, where it influences conformation by fostering interaction between two domains of the protein (JBC 291: 1456, 2016). Here, we identify a conserved tyrosine residue in the substrate binding site required for substrate to enable conversion to inward-open states by establishing an interaction between the two transporter domains. We further identify additional interactions between the two transporter domains in the extracellular pathway that are required. Together with our previous work on the conformational effect of Na+, these results identify mechanistic components underlying ion-substrate coupling in NSS transporters.
Disrupted structure and aberrant function of CHIP mediates the loss of motor and cognitive function in preclinical models of cerebellar CHIPopathy
Authors: Shi Chang-he , Rubel Carrie , Soss Sarah E. , Sanchez-Hodge Rebekah , Zhang Shuo , Stevens Donte A. , McDonough Holly , Page Richard C. , Chazin Walter J. , Patterson Cam , Mao Cheng-yuan , Willis Monte S. , Luo Hai-Yang , Tang Mi-bo , Du Pan , Wang Yao-he , Hu Zheng-wei , Xu Yu-ming , Schisler Jonathan C. 
Published: March 2018

AbstractCHIP (carboxyl terminus of heat shock 70-interacting protein) has long been recognized as an active member of the cellular protein quality control system given the ability of CHIP to function as both a co-chaperone and ubiquitin ligase. Mutations in CHIP are the driver of spinocerebellar autosomal recessive 16 (SCAR16), or cerebellar CHIPopathy, as we initially discovered this disease was caused by a loss of CHIP ubiquitin ligase function. The initial mutation describing SCAR16 was a missense mutation in the ubiquitin ligase domain of CHIP (p.T246M). Using multiple biophysical and cellular approaches, we demonstrate that T246M mutation results in structural disorganization and misfolding of the CHIP U-box domain, promoting oligomerization, and increased proteasome-dependent turnover. CHIP-T246M has no ligase activity, but maintains interactions with chaperones and alters the co-chaperone function of CHIP. To establish preclinical models of SCAR16, we engineered T246M at the endogenous locus in both mice and rats. Animals homozygous for T246M had both cognitive and motor cerebellar dysfunction distinct from those observed in the CHIP null animal model, as well as deficits in learning and memory, reflective of the cognitive deficits reported in SCAR16 patients. We conclude that the T246M mutation is not equivalent to the total loss of CHIP, supporting the concept that disease-causing CHIP mutations have different biophysical and functional repercussions on CHIP function that may directly correlate to the spectrum of clinical phenotypes observed in SCAR16 patients. Our findings both further expand our basic understanding of CHIP biology and provide meaningful mechanistic insight underlying the molecular drivers of SCAR16 disease pathology, which may be used to inform the development of novel therapeutics for this devastating disease.
General inverse solution of six-degrees-of-freedom serial robots based on the product of exponentials model
Authors: Wang Haixia , Lu Xiao , Cui Wei , Zhang Zhiguo , Li Yuxia , Sheng Chunyang 
Published: March 2018

Purpose
Developing general closed-form solutions for six-degrees-of-freedom (DOF) serial robots is a significant challenge. This paper thus aims to present a general solution for six-DOF robots based on the product of exponentials model, which adapts to a class of robots satisfying the Pieper criterion with two parallel or intersecting axes among its first three axes.

Design/methodology/approach
The proposed solution can be represented as uniform expressions by using geometrical properties and a modified Paden–Kahan sub-problem, which mainly adopts the screw theory.

Findings
A simulation and experiments validated the correctness and effectiveness of the proposed method (general resolution for six-DOF robots based on the product of exponentials model).

Originality/value
The Rodrigues rotation formula is additionally used to turn the complex problem into a solvable trigonometric function and uniformly express six solutions using two formulas.
Why do I conform to your ideas?
Authors: Qu Yongzheng , Wu Wen , Tang Fangcheng , Si Haijian , Xia Yuhuan 
Published: March 2018

PurposeThe purpose of this study is to advance and test a new construct, harmony voice. Furthermore, according to the social influence theory, the relationship betweenzhongyong, an essential Confucian orientation mode and voice behavior, and the moderating role of coworker’s regulatory focus (promotion focus and prevention focus) has been examined.Design/methodology/approachA field study has been designed to test our hypotheses. We used samples of 291 employee–coworker dyads from a variety of organizations in China to test this study’s hypotheses.FindingsThe results of this empirical study show thatzhongyongis positively related to harmony voice. Coworkers’ promotion focus strengthens the positive effect ofzhongyongon harmony voice, and coworkers’ prevention focus weakens the positive effect ofzhongyongon harmony voice.Research limitations/implicationsTraditionally defined voice and harmony voice might cause different risks to the voicer. However, how and what kinds of risks may be differently caused by these two types of voice behaviors have not been examined in this study. Future empirical research can explore the different effects of traditionally defined voice and harmony voice.Practical implicationsManagers responsible for managing Chinese employees should notice the difference in some important ways of thinking between Easterners and Westerners. Specifically,zhongyongmay direct people to express issues related to work in ways that are different from those of their Western counterparts. Harmony voice can benefit the Chinese organization without disrupting organizational development.Social implicationsBy examining the relationship betweenzhongyongand harmony voice, we contribute to identifying antecedents of voice by using an emic research perspective.Originality/valueWe made significant theoretical contributions to voice literature. We developed the construct of harmony voice, and we examined the relationship betweenzhongyongand voice.