bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer
Authors: Echeverria Gloria V. , Powell Emily , Seth Sahil , Ge Zhongqi , Carugo Alessandro , Bristow Christopher , Peoples Michael , Robinson Frederick , Qiu Huan , Shao Jiansu , Jeter-Jones Sabrina L. , Zhang Xiaomei , Ramamoorthy Vandhana , Cai Shirong , Wu Wenhui , Draetta Giulio , Moulder Stacy L. , Symmans William F. , Chang Jeffrey T. , Heffernan Timothy P. , Piwnica-Worms Helen 
Published: November 2018

AbstractMost triple negative breast cancers (TNBCs) are aggressively metastatic with a high degree of intra-tumoral heterogeneity (ITH), but how ITH contributes to metastasis is unclear. Here, clonal dynamics during metastasis were studied in vivo using two patient-derived xenograft (PDX) models established from the treatment-naive primary breast tumors of TNBC patients diagnosed with synchronous metastasis. Genomic sequencing and high-complexity barcode-mediated clonal tracking reveal robust alterations in clonal architecture between primary tumors and corresponding metastases. Polyclonal seeding and maintenance of heterogeneous populations of low-abundance subclones is observed in each metastasis. However, lung, liver, and brain metastases are enriched for an identical population of high-abundance subclones, demonstrating that primary tumor clones harbor properties enabling them to seed and thrive in multiple organ sites. Further, clones that dominate multi-organ metastases share a genomic lineage. Thus, intrinsic properties of rare primary tumor subclones enable the seeding and colonization of metastases in secondary organs in these models.
Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome
Authors: Goswami Panchali , Abid Ali Ferdos , Douglas Max E. , Locke Julia , Purkiss Andrew , Janska Agnieszka , Eickhoff Patrik , Early Anne , Nans Andrea , Cheung Alan M. C. , Diffley John F. X. , Costa Alessandro 
Published: November 2018

AbstractEukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase. A key step is the recruitment of GINS that requires the leading-strand polymerase Pol epsilon, composed of Pol2, Dpb2, Dpb3, Dpb4. While a truncation of the catalytic N-terminal Pol2 supports cell division, Dpb2 and C-terminal Pol2 (C-Pol2) are essential for viability. Dpb2 and C-Pol2 are non-catalytic modules, shown or predicted to be related to an exonuclease and DNA polymerase, respectively. Here, we present the cryo-EM structure of the isolated C-Pol2/Dpb2 heterodimer, revealing that C-Pol2 contains a DNA polymerase fold. We also present the structure of CMG/C-Pol2/Dpb2 on a DNA fork, and find that polymerase binding changes both the helicase structure and fork-junction engagement. Inter-subunit contacts that keep the helicase-polymerase complex together explain several cellular phenotypes. At least some of these contacts are preserved during Pol epsilon-dependent CMG assembly on path to origin firing, as observed with DNA replication reconstituted in vitro.
A synthetic microbial biosensor for high-throughput screening of lactam biocatalysts
Authors: Yeom Soo-Jin , Kim Moonjeong , Kwon Kil Koang , Fu Yaoyao , Rha Eugene , Park Sung-Hyun , Lee Hyewon , Kim Haseong , Lee Dae-Hee , Kim Dong-Myung , Lee Seung-Goo 
Published: November 2018

AbstractBiocatalytic cyclization is highly desirable for efficient synthesis of biologically derived chemical substances, such as the commodity chemicals ε-caprolactam and δ-valerolactam. To identify biocatalysts in lactam biosynthesis, we develop a caprolactam-detecting genetic enzyme screening system (CL-GESS). TheAlcaligenes faecalisregulatory protein NitR is adopted for the highly specific detection of lactam compounds against lactam biosynthetic intermediates. We further systematically optimize the genetic components of the CL-GESS to enhance sensitivity, achieving 10-fold improvement. Using this highly sensitive GESS, we screen marine metagenomes and find an enzyme that cyclizes ω-amino fatty acids to lactam. Moreover, we determine the X-ray crystal structure and catalytic residues based on mutational analysis of the cyclase. The cyclase is also used as a helper enzyme to sense intracellular ω-amino fatty acids. We expect this simple and accurate biosensor to have wide-ranging applications in rapid screening of new lactam-synthesizing enzymes and metabolic engineering for lactam bio-production.
The disease resistance protein SNC1 represses the biogenesis of microRNAs and phased siRNAs
Authors: Cai Qiang , Liang Chao , Wang Suikang , Hou Yingnan , Gao Lei , Liu Li , He Wenrong , Ma Wenbo , Mo Beixin , Chen Xuemei 
Published: November 2018

AbstractPlants evolved an array of disease resistance genes (R genes) to fight pathogens. In the absence of pathogen infection, NBS-LRR genes, which comprise a major subfamily of R genes, are suppressed by a small RNA cascade involving microRNAs (miRNAs) that trigger the biogenesis of phased siRNAs (phasiRNAs) from R gene transcripts. However, whether or how R genes influence small RNA biogenesis is unknown. In this study, we isolate a mutant with global defects in the biogenesis of miRNAs and phasiRNAs in Arabidopsis thaliana and trace the defects to the over accumulation and nuclear localization of an R protein SNC1. We show that nuclear SNC1 represses the transcription of miRNA and phasiRNA loci, probably through the transcriptional corepressor TPR1. Intriguingly, nuclear SNC1 reduces the accumulation of phasiRNAs from three source R genes and concomitantly, the expression of a majority of the ~170R genes is up-regulated. Taken together, this study suggests an R gene-miRNA-phasiRNA regulatory module that amplifies plant immune responses.
A fast quantum interface between different spin qubit encodings
Authors: Noiri A. , Nakajima T. , Yoneda J. , Delbecq M. R. , Stano P. , Otsuka T. , Takeda K. , Amaha S. , Allison G. , Kawasaki K. , Kojima Y. , Ludwig A. , Wieck A. D. , Loss D. , Tarucha S. 
Published: November 2018

AbstractSingle-spin qubits in semiconductor quantum dots hold promise for universal quantum computation with demonstrations of a high single-qubit gate fidelity above 99.9% and two-qubit gates in conjunction with a long coherence time. However, initialization and readout of a qubit is orders of magnitude slower than control, which is detrimental for implementing measurement-based protocols such as error-correcting codes. In contrast, a singlet-triplet qubit, encoded in a two-spin subspace, has the virtue of fast readout with high fidelity. Here, we present a hybrid system which benefits from the different advantages of these two distinct spin-qubit implementations. A quantum interface between the two codes is realized by electrically tunable inter-qubit exchange coupling. We demonstrate a controlled-phase gate that acts within 5.5 ns, much faster than the measured dephasing time of 211 ns. The presented hybrid architecture will be useful to settle remaining key problems with building scalable spin-based quantum computers.
Compositional adaptability in NPM1-SURF6 scaffolding networks enabled by dynamic switching of phase separation mechanisms
Authors: Ferrolino Mylene C. , Mitrea Diana M. , Michael J. Robert , Kriwacki Richard W. 
Published: November 2018

AbstractThe nucleolus, the site for ribosome biogenesis contains hundreds of proteins and several types of RNA. The functions of many non-ribosomal nucleolar proteins are poorly understood, including Surfeit locus protein 6 (SURF6), an essential disordered protein with roles in ribosome biogenesis and cell proliferation. SURF6 co-localizes with Nucleophosmin (NPM1), a highly abundant protein that mediates the liquid-like features of the granular component region of the nucleolus through phase separation. Here, we show that electrostatically-driven interactions between disordered regions of NPM1 and SURF6 drive liquid-liquid phase separation. We demonstrate that co-existing heterotypic (NPM1-SURF6) and homotypic (NPM1-NPM1) scaffolding interactions within NPM1-SURF6 liquid-phase droplets dynamically and seamlessly interconvert in response to variations in molecular crowding and protein concentrations. We propose a mechanism wherein NPM1-dependent nucleolar scaffolds are modulated by non-ribosomal proteins through active rearrangements of interaction networks that can possibly contribute to the directionality of ribosomal biogenesis within the liquid-like nucleolus.
Olfactory marker protein (OMP) regulates formation and refinement of the olfactory glomerular map
Authors: Albeanu Dinu F. , Provost Allison C. , Agarwal Prateek , Soucy Edward R. , Zak Joseph D. , Murthy Venkatesh N. 
Published: November 2018

AbstractInputs from olfactory sensory neuron (OSN) axons expressing the same type of odorant receptor (OR) converge in the glomerulus of the main olfactory bulb. A key marker of mature OSNs is olfactory marker protein (OMP), whose deletion has been associated with deficits in OSN signal transduction and odor discrimination. Here, we investigate glomerular odor responses and anatomical architecture in mice in which one or both alleles of OMP are replaced by the fluorescent synaptic activity reporter, synaptopHluorin. Functionally heterogeneous glomeruli, that is, ones with microdomains with distinct odor responses, are rare in OMP+/– mice, but occur frequently in OMP–/– mice. Genetic targeting of single ORs reveals that these microdomains arise from co-innervation of individual glomeruli by OSNs expressing different ORs. This glomerular mistargeting is locally restricted to a few glomerular diameters. Our studies document functional heterogeneity in sensory input within individual glomeruli and uncover its anatomical correlate, revealing an unexpected role for OMP in the formation and refinement of the glomerular map.
Formation of electron radiation belts at Saturn by Z-mode wave acceleration
Authors: Woodfield E. E. , Horne R. B. , Glauert S. A. , Menietti J. D. , Shprits Y. Y. , Kurth W. S. 
Published: November 2018

AbstractAt Saturn electrons are trapped in the planet’s magnetic field and accelerated to relativistic energies to form the radiation belts, but how this dramatic increase in electron energy occurs is still unknown. Until now the mechanism of radial diffusion has been assumed but we show here that in-situ acceleration through wave particle interactions, which initial studies dismissed as ineffectual at Saturn, is in fact a vital part of the energetic particle dynamics there. We present evidence from numerical simulations based on Cassini spacecraft data that a particular plasma wave, known as Z-mode, accelerates electrons to MeV energies inside 4 RS (1 RS = 60,330 km) through a Doppler shifted cyclotron resonant interaction. Our results show that the Z-mode waves observed are not oblique as previously assumed and are much better accelerators than O-mode waves, resulting in an electron energy spectrum that closely approaches observed values without any transport effects included.
Evolution of a General RNA-Cleaving FANA Enzyme
Authors: Wang Yajun , Ngor Arlene K. , Nikoomanzar Ali , Chaput John C. 
Published: November 2018

AbstractThe isolation of synthetic genetic polymers (XNAs) with catalytic activity demonstrates that catalysis is not limited to natural biopolymers, but it remains unknown whether such systems can achieve robust catalysis with Michaelis-Menten kinetics. Here, we describe an efficient RNA-cleaving 2’-fluoroarabino nucleic acid enzyme (FANAzyme) that functions with a rate enhancement of >106-fold over the uncatalyzed reaction and exhibits substrate saturation kinetics typical of most natural enzymes. The FANAzyme was generated by in vitro evolution using natural polymerases that were found to recognize FANA substrates with high fidelity. The enzyme comprises a small 25 nucleotide catalytic domain flanked by substrate-binding arms that can be engineered to recognize diverse RNA targets. Substrate cleavage occurs at a specific phosphodiester bond located between an unpaired guanine and a paired uracil in the substrate recognition arm. Our results expand the chemical space of nucleic acid enzymes to include nuclease-resistant scaffolds with strong catalytic activity.
Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier
Authors: Mäe Maarja Andaloussi , Li Tian , Bertuzzi Giacomo , Raschperger Elisabeth , Vanlandewijck Michael , He Liqun , Nahar Khayrun , Dalheim Annika , Hofmann Jennifer J. , Laviña Bàrbara , Keller Annika , Betsholtz Christer , Genové Guillem 
Published: November 2018

AbstractDiabetes mellitus is associated with cognitive impairment and various central nervous system pathologies such as stroke, vascular dementia, or Alzheimer’s disease. The exact pathophysiology of these conditions is poorly understood. Recent reports suggest that hyperglycemia causes cerebral microcirculation pathology and blood-brain barrier (BBB) dysfunction and leakage. The majority of these reports, however, are based on methods including in vitro BBB modeling or streptozotocin-induced diabetes in rodents, opening questions regarding the translation of the in vitro findings to the in vivo situation, and possible direct effects of streptozotocin on the brain vasculature. Here we used a genetic mouse model of hyperglycemia (Ins2AKITA) to address whether prolonged systemic hyperglycemia induces BBB dysfunction and leakage. We applied a variety of methodologies to carefully evaluate BBB function and cellular integrity in vivo, including the quantification and visualization of specific tracers and evaluation of transcriptional and morphological changes in the BBB and its supporting cellular components. These experiments did neither reveal altered BBB permeability nor morphological changes of the brain vasculature in hyperglycemic mice. We conclude that prolonged hyperglycemia does not lead to BBB dysfunction, and thus the cognitive impairment observed in diabetes may have other causes.
Philippines–Taiwan Oscillations and its connection to tropical cyclone frequency in the western North Pacific Ocean
Authors: Chang Yu-Lin K. , Miyazawa Yasumasa , Kodaira Tsubasa , Behera Swadhin 
Published: November 2018

AbstractAn atmospheric component of the Philippine–Taiwan Oscillations (PTOa) is used to examine its potential connection with tropical cyclone (TC) frequency in the western North Pacific in the period of 1979–2014. During positive PTOa years, more TCs are observed in the tropical western Pacific south of 18 °N where cyclonic wind anomaly appears. On the other hand, anti-cyclonic wind anomaly appears in the subtropics north of 18 °N and is associated with less TC formation there. The opposite wind vorticities in tropics/subtropics and associated variability in TC frequency reverse in negative PTOa phase. Besides, the negative contribution of ocean heat content suggests the relative importance of wind vorticity according to the oceanic cyclone genesis potential index. The PTOa provides a more direct explanation of the TC activity compared to other remotely linked phenomena at least for the past 36 years (1979–2014). Therefore, PTOa can potentially serve as a promising index for diagnosing or forecasting TC activity in the western North Pacific Ocean.
Diverse novel resident Wolbachia strains in Culicine mosquitoes from Madagascar
Authors: Jeffries Claire L. , Tantely Luciano M. , Raharimalala Fara N. , Hurn Eliot , Boyer Sébastien , Walker Thomas 
Published: November 2018

AbstractWolbachia endosymbiotic bacteria are widespread throughout insect species and Wolbachia transinfected in Aedes mosquito species has formed the basis for biocontrol programs as Wolbachia strains inhibit arboviral replication and can spread through populations. Resident strains in wild Culicine mosquito populations (the vectors of most arboviruses) requires further investigation given resident strains can also affect arboviral transmission. As Madagascar has a large diversity of both Culicine species and has had recent arboviral outbreaks, an entomology survey was undertaken, in five ecologically diverse sites, to determine the Wolbachia prevalence. We detected diverse novel resident Wolbachia strains within the Aedeomyia, Culex, Ficalbia, Mansonia and Uranotaenia genera. Wolbachia prevalence rates and strain characterisation through Sanger sequencing with multilocus sequence typing (MLST) and phylogenetic analysis revealed significant diversity and we detected co-infections with the environmentally acquired bacteria Asaia. Mosquitoes were screened for major arboviruses to investigate if any evidence could be provided for their potential role in transmission and we report the presence of Rift Valley fever virus in three Culex species: Culex tritaeniorhynchus, Culex antennatus and Culex decens. The implications of the presence of resident Wolbachia strains are discussed and how the discovery of novel strains can be utilized for applications in the development of biocontrol strategies.
Holevo Capacity of Discrete Weyl Channels
Authors: ur Rehman Junaid , Jeong Youngmin , Kim Jeong San , Shin Hyundong 
Published: November 2018

AbstractHolevo capacity is the maximum rate at which a quantum channel can reliably transmit classical information without entanglement. However, calculating the Holevo capacity of arbitrary quantum channels is a nontrivial and computationally expensive task since it requires the numerical optimization over all possible input quantum states. In this paper, we consider discrete Weyl channels (DWCs) and exploit their symmetry properties to model DWC as a classical symmetric channel. We characterize lower and upper bounds on the Holevo capacity of DWCs using simple computational formulae. Then, we provide a sufficient and necessary condition where the upper and lower bounds coincide. The framework in this paper enables us to characterize the exact Holevo capacity for most of the known special cases of DWCs.
Die Nutzung der Peritonealdialyse
Authors: Gerber Lukas , Segerer Stephan 
Published: November 2018

ZusammenfassungDie Peritonealdialyse (PD) ist die häufigste Form der Heimdialyse und wird
weltweit bei etwa 10 % der Dialysepatienten verwendet. Der Anteil der
PD-Patienten variiert sowohl zwischen einzelnen Ländern als auch zwischen
Zentren innerhalb desselben Landes sehr stark. In dieser Übersicht diskutieren
wir, welche Faktoren die PD-Nutzung beeinflussen und wie diese potenziell
verbessert werden könnte.
Role of zinc in insulin regulation and diabetes
Authors: Poudel Resham , Bhusal Yuvaraj , Tharu Biswaraj , Kafle Nisha 
Published: November 2018

AbstractZinc (Zn) affects glucose metabolism through insulin regulation and has potential implication in diabetes. Zn deficiency has not been proven in diabetes; however, observations of hyperzincuria, hypozincemia, and Zn malabsorption in diabetes indicate additional requirements for Zn. Mutation in Zn transporter 8 – a key protein in insulin secretion – has been associated with Type 2 diabetes. Zn supplementation in prediabetics and diabetics has been supported to improve plasma glucose, hemoglobin A1c (HbA1c), and lipids and potentially improve insulin sensitivity, reduce oxidative stress, and protect from renal damage.
The AMR problem: demanding economies, biological margins, and co-producing alternative strategies
Authors: Hinchliffe Steve , Butcher Andrea , Rahman Muhammad Meezanur 
Published: November 2018

AbstractWidespread antimicrobial resistance (AMR) poses a threat to public and animal health, and has consequences for the structure and sustainability of food production. The problem is often framed as one of inappropriate antimicrobial use, which drives emergence and selection of resistant microbes. The answer to this framing of the problem is to lower disease incidence and transmission rates, regulate antimicrobial uses and to educate prescribers and users of medicines. In this paper we argue that this seemingly straightforward programme of action is beset by at least two difficulties. First, in many parts of the world, disease dynamics and antimicrobial uses are embedded within biosocially demanding settings. Second, antibiotic use is one among many possible drivers of resistance. We focus on the aquatic environment and aquacultural food production where resistance drivers may relate to a variety of processes. Using interviews, survey data, and participatory modelling exercises with competency groups in Bangladesh’s shrimp and prawn aquaculture sector, we demonstrate the need to understand economic and biological drivers of disease, farmer adaptations to disease risks and the potential paradox of pursuing pathogen-free food production as a means to reduce AMR risks. We argue that the AMR problem needs to be framed as an adaptive rather than technical challenge, and involves ownership, change and experimentation across a range of relevant sites.
Composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular mortality in older community-dwelling men
Authors: Baumert Mathias , Immanuel Sarah A , Stone Katie L , Litwack Harrison Stephanie , Redline Susan , Mariani Sara , Sanders Prashanthan , McEvoy R Doug , Linz Dominik 
Published: November 2018

Abstract

Aims
To investigate the composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular (CV) mortality in community-dwelling older men.

Methods and results
We analysed overnight oximetry data from polysomnograms obtained in 2840 men from the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study (ClinicalTrials.gov Identifier: NCT00070681) to determine the number of acute episodic desaturations per hour (oxygen desaturation index, ODI) and time spent below 90% oxygen saturation (T90) attributed to acute desaturations (T90desaturation) and to non-specific drifts in oxygen saturation (T90non-specific), respectively, and their relationship with CV mortality. After 8.8 ± 2.7 years follow-up, 185 men (6.5%) died from CV disease. T90 [hazard ratio (HR) 1.21, P &lt; 0.001], but not ODI (HR 1.13, P = 0.06), was significantly associated with CV death in univariate analysis. T90 remained significant when adjusting for potential confounders (HR 1.16, P = 0.004). Men with T90 &gt; 12 min were at an elevated risk of CV mortality (HR 1.59; P = 0.006). Approximately 20.7 (5.7–48.5) percent of the variation in T90 could be attributed to non-specific drifts in oxygen saturation. T90desaturation and T90non-specific were individually associated with CV death but combining both variables did not improve the prediction.

Conclusion
In community-dwelling older men, T90 is an independent predictor of CV mortality. T90 is not only a consequence of frank desaturations, but also reflects non-specific drifts in oxygen saturation, both contributing towards the association with CV death. Whether T90 can be used as a risk marker in the clinical setting and whether its reduction may constitute a treatment target warrants further study.