bluuebunny/crossref_metadata_2025_split huggingface dataset:
A globalBrassicapest and a sympatric cryptic ally,Plutella australiana(Lepidoptera: Plutellidae), show strong divergence despite the capacity to hybridize
Authors: Perry Kym D. , Baker Gregory J. , Powis Kevin J. , Kent Joanne K. , Ward Christopher M. , Baxter Simon W. 
Published: September 2017

AbstractThe diamondback moth,Plutella xylostella, has been intensively studied due to its ability to evolve insecticide resistance and status as the world’s most destructive pest of brassicaceous crops. The surprise discovery of a cryptic ally,Plutella australianaLandry & Hebert, with apparent endemism to Australia, immediately raised questions regarding the extent of ecological and genetic diversity between these two species, whether gene flow could occur, and ultimately if specific management was required. Here, we show that despite sympatric distributions and the capacity to hybridize in controlled laboratory experiments, striking differences in genetic and phenotypic traits exist that are consistent with contrasting colonization histories and reproductive isolation after secondary contact. Almost 1500Plutellaindividuals were collected from wild and cultivated brassicaceous plants at 75 locations throughout Australia.Plutella australianawas commonly found on allBrassicahost types sampled except commercial vegetables, which are routinely sprayed with insecticide. Bioassays using four commonly-used insecticides found thatP. australianawas 19-306 fold more susceptible thanP. xylostella. Genome-wide SNPs derived from RADseq revealed substantially higher levels of genetic diversity acrossP. australianacompared withP. xylostellanuclear genomes, yet both species showed limited variation in mtDNA. Infection with a singleWolbachiasubgroup B strain was fixed inP. australiana, suggesting that a selective sweep contributed to low mtDNA diversity, while a subgroup A strain infected just 1.5 % ofP. xylostella. AlthoughP. australianais a potential pest of brassica crops, it is of secondary importance toP. xylostella.
Assessing the virulence ofCryptococcus neoformanscausing meningitis in HIV infected and uninfected patients in Vietnam
Authors: Thanh Lam Tuan , Toffaletti Dena L. , Tenor Jennifer L. , Giamberardino Charles , Sempowski Gregory D. , Asfaw Yohannes , Phan Hai Trieu , Van Duong Anh , Nguyen Trinh Mai , Thwaites Guy E. , Ashton Philip M. , Van Vinh Nguyen Chau , Baker Stephen G. , Perfect John R. , Day Jeremy N. 
Published: September 2017

AbstractWe previously observed a substantial burden of cryptococcal meningitis in Vietnam atypically arising in HIV-uninfected individuals. This disease was associated with a single genotype ofCryptococcus neoformans(Sequence Type (ST)5), which was significantly less common in HIV-infected individuals. Aiming to compare the phenotypic characteristics of ST5 and non-ST5 C. neoformans we selected 30 representative Vietnamese isolates, compared theirin vitropathogenic potential andin vivovirulence. ST5 and non-ST5 organisms exhibited comparable characteristics with respect toin vitrovirulence markers including melanin production, replication at 37°C, and growth in cerebrospinal fluid. However, the ST5 isolates had significantly increased variability in cellular and capsular sizing compared with non-ST5 organisms (p<0.001). Counter-intuitively, mice infected with ST5 isolates had significantly longer survival with lower fungal burdens at day 7 than non-ST5 isolates. Notably, ST5 isolates induced significantly greater initial inflammatory responses than non-ST5 strains, measured by TNF-α concentrations (p<0.001). Despite being generally less virulent in the mouse model, we hypothesize that the significant within strain variation seen in ST5 isolates in the tested phenotypes may represent an evolutionary advantage enabling adaptation to novel niches including apparently immunocompetent human hosts.
Attentional fluctuations induce shared variability in macaque primary visual cortex
Authors: Denfield George H. , Ecker Alexander S. , Shinn Tori J. , Bethge Matthias , Tolias Andreas S. 
Published: September 2017

SummaryVariability in neuronal responses to identical stimuli is frequently correlated across a population. Attention is thought to reduce these correlations by suppressing noisy inputs shared by the population. However, even with precise control of the visual stimulus, the subject’s attentional state varies across trials. While these state fluctuations are bound to induce some degree of correlated variability, it is currently unknown how strong their effect is, as previous studies generally do not dissociate changes in attentional strength from changes in attentional state variability. We designed a novel paradigm that does so and find both a pronounced effect of attentional fluctuations on correlated variability at long timescales and attention-dependent reductions in correlations at short timescales. These effects predominate in layers 2/3, as expected from a feedback signal such as attention. Thus, significant portions of correlated variability can be attributed to fluctuations in internally generated signals, like attention, rather than noise.
Atomic structure of the mitochondrial inner membrane AAA+ protease YME1 reveals the mechanism of substrate processing
Authors: Puchades Cristina , Rampello Anthony J. , Shin Mia , Giuliano Christopher J. , Wiseman R. Luke , Glynn Steven E. , Lander Gabriel C. 
Published: September 2017

AbstractWe present the first atomic model of a substrate-bound inner mitochondrial membrane AAA+ quality control protease, YME1. Our ~3.4 Å cryo-EM structure reveals how the ATPases form a closed spiral staircase encircling an unfolded substrate, directing it toward the flat, symmetric protease ring. Importantly, the structure reveals how three coexisting nucleotide states allosterically induce distinct positioning of tyrosines in the central channel, resulting in substrate engagement and translocation to the negatively charged proteolytic chamber. This tight coordination by a network of conserved residues defines a sequential, around-the-ring ATP hydrolysis cycle that results in step-wise substrate translocation. Furthermore, we identify a hinge-like linker that accommodates the large-scale nucleotide-driven motions of the ATPase spiral independently of the contiguous planar proteolytic base. These results define the first molecular mechanism for a mitochondrial inner membrane AAA+ protease and reveal a translocation mechanism likely conserved for other AAA+ ATPases.
SCGN Administration prevents Insulin Resistance and Diabetic Complications in High-Fat Diet Fed Animals
Authors: Sharma Anand Kumar , Khandelwal Radhika , Chadalawada Swathi , Ram N Sai , Raj T Avinash , Mahesh Kumar M Jerald , Sharma Yogendra 
Published: September 2017

AbstractSecretagogin (SCGN) is poorly-studied secretory/cytosolic CaBP enriched in pancreaticβ-cells. Recent studies implicated SCGN in diabetes; however, its function and therapeutic prospect remain uncharted. Based on the apparent synchrony of SCGN and insulin secretion (and its disruption in HFD-fed animals) and consideringSCGNdownregulation in Type 2 diabetes, we hypothesized that SCGN is a key regulator of insulin response. To test this, we administered rSCGN to HFD-fed animals. We here report that a novel SCGN-insulin interaction stabilizes insulin and potentiates insulin action. Moreover, a chronic rSCGN administration improves insulin response and alleviates obesity associated risk factors such as weight gain, liver steatosis and cholesterol imbalance in DIO animals. Beside the anti-diabetic effects, prolonged rSCGN treatment also induces β-cell regeneration. These effects seem to originate from SCGN mediated regulation of insulin concentration & function as validated in insulin-deficient STZ animals. Our results demonstrate the prospects of the therapeutic potential of SCGN against diabetes.
Genome-wide Variants of Eurasian Facial Shape Differentiation and a prospective model of DNA based Face Prediction
Authors: Qiao Lu , Yang Yajun , Fu Pengcheng , Hu Sile , Zhou Hang , Peng Shouneng , Tan Jingze , Lu Yan , Lou Haiyi , Lu Dongsheng , Wu Sijie , Guo Jing , Jin Li , Guan Yaqun , Wang Sijia , Xu Shuhua , Tang Kun 
Published: September 2017

AbstractIt is a long standing question as to which genes define the characteristic facial features among different ethnic groups. In this study, we use Uyghurs, an ancient admixed population to query the genetic bases why Europeans and Han Chinese look different. Facial traits were analyzed based on high-dense 3D facial images; numerous biometric spaces were examined for divergent facial features between European and Han Chinese, ranging from inter-landmark distances to dense shape geometrics. Genome-wide association analyses were conducted on a discovery panel of Uyghurs. Six significant loci were identified four of which, rs1868752, rs118078182, rs60159418 at or near UBASH3B, COL23A1, PCDH7 and rs17868256 were replicated in independent cohorts of Uyghurs or Southern Han Chinese. A prospective model was also developed to predict 3D faces based on top GWAS signals, and tested in hypothetic forensic scenarios.
The Early Diagnosis in Lung Cancer by the Detection of Circulating Tumor DNA
Authors: Tian Geng , Li Xiaohua , Xie Yuancai , Xu Feiyue , Yu Dan , Cao Fengjun , Wang Xuanbin , Yu Fenglei , Zhong Weiquan , Lu Shixin , Tu Xiaonian , Yao Xumei , He Jiankui , Liu Chaoyu 
Published: September 2017

BackgroundRemarkable advances for clinical diagnosis and treatment in cancers including lung cancer involve cell-free circulating tumor DNA (ctDNA) detection through next generation sequencing. However, before the sensitivity and specificity of ctDNA detection can be widely recognized, the consistency of mutations in tumor tissue and ctDNA should be evaluated. The urgency of this consistency is extremely obvious in lung cancer to which great attention has been paid to in liquid biopsy field.MethodsWe have developed an approach named systematic error correction sequencing (Sec-Seq) to improve the evaluation of sequence alterations in circulating cell-free DNA. Averagely 10 ml preoperative blood samples were collected from 30 patients containing pulmonary space occupying pathological changes by traditional clinic diagnosis. cfDNA from plasma, genomic DNA from white blood cells, and genomic DNA from solid tumor of above patients were extracted and constructed as libraries for each sample before subjected to sequencing by a panel contains 50 cancer-associated genes encompassing 29 kb by custom probe hybridization capture with average depth >40000, 7000, or 6300 folds respectively.ResultsDetection limit for mutant allele frequency in our study was 0.1%. The sequencing results were analyzed by bioinformatic expertise based on our previous studies on the baseline mutation profiling of circulating cell-free DNA and the clinicopathological data of these patients. Among all the lung cancer patients, 78% patients were predicted as positive by ctDNA sequencing when the shreshold was defined as at least one of the hotspot mutations detected in the blood (ctDNA) was also detected in tumor tissue. Pneumonia and pulmonary tuberculosis were detected as negative according to the above standard. When evaluating all hotspots in driver genes in the panel, 24% mutations detected in tumor tissue (tDNA) were also detected in patients blood (ctDNA). When evaluating all genetic variations in the panel, including all the driver genes and passenger genes, 28% detected in tumor tissue (tDNA) were also detected in patients blood (ctDNA). Positive detection rates of plasma ctDNA in stage I lung cancer patients is 85%, compared with 17% of tumor biomarkers.ConclusionWe demonstrated the importance of sequencing both circulating cell-free DNA and genomic DNA in tumor tissue for ctDNA detection in lung cancer currently. We also determined and confirmed the consistency of ctDNA and tumor tissue through NGS according to the criteria explored in our studies. Our strategy can initially distinguish the lung cancer from benign lesions of lung. Our work shows that the consistency will be benefited from the optimization in sensitivity and specificity in ctDNA detection.
PartsGenie: an integrated tool for optimising and sharing synthetic biology parts
Authors: Swainston Neil , Dunstan Mark , Jervis Adrian J. , Robinson Christopher J. , Carbonell Pablo , Williams Alan R. , Faulon Jean-Loup , Scrutton Nigel S. , Kell Douglas B. 
Published: September 2017

AbstractSynthetic biology is typified by developing novel genetic constructs from the assembly of reusable synthetic DNA parts, which contain one or more features such as promoters, ribosome binding sites, coding sequences and terminators. While repositories of such parts exist to promote their reuse, there is still a need to design novel parts from scratch.PartsGenie, freely available athttp://parts.synbiochem.co.uk, is introduced to facilitate the computational design of such synthetic biology parts. PartsGenie has been designed to bridge the gap between optimisation tools for the design of novel parts, the representation of such parts in community-developed data standards such as Synthetic Biology Open Language (SBOL), and their sharing in journal-recommended data repositories.Consisting of a drag-and-drop web interface, a number of DNA optimisation algorithms, and an interface to the well-used data repository JBEI ICE, PartsGenie facilitates the design, optimisation and dissemination of reusable synthetic biology parts through a single, integrated application. PartsGenie can therefore be used as a single, stand-alone tool, or integrated into larger synthetic biology pipelines that are being developed in the SYNBIOCHEM centre and elsewhere.
Sensory noise increases metacognitive efficiency
Authors: Bang Ji Won , Shekhar Medha , Rahnev Dobromir 
Published: September 2017

AbstractVisual metacognition is the ability to employ confidence ratings in order to predict the accuracy of ones decisions about visual stimuli. Despite years of research, it is still unclear how visual metacognitive efficiency can be manipulated. Here we show that a hierarchical model of confidence generation makes a counterintuitive prediction: Higher sensory noise should increase metacognitive efficiency. The reason is that sensory noise has a large negative influence on the decision (where it is the only corrupting influence) but a smaller negative influence on confidence (where it is one of two corrupting influences; the other one being metacognitive noise). To test this prediction, we used a perceptual learning paradigm to decrease the amount of sensory noise. In Experiment 1, seven days of training led to significant decrease in noise as well as a corresponding decrease in metacognitive efficiency. Experiment 2 showed the same effect in a brief 97-trial learning for each of two different tasks. Finally, in Experiment 3, we experimentally manipulated stimulus contrast to increase sensory noise and observed a corresponding increase in metacognitive efficiency. Our findings demonstrate the existence of a robust positive relationship between sensory noise and metacognitive efficiency. These results could not be captured by a standard model in which decision and confidence judgments are made based on the same underlying information. Thus, our study provides a novel way to directly manipulate metacognitive efficiency and suggests the existence of metacognitive noise that corrupts confidence but not the perceptual decision.
Pre-post synaptic alignment through neuroligin tunes synaptic transmission efficiency
Authors: Haas Kalina T. , Compans Benjamin , Letellier Mathieu , Bartol Thomas M , Grillo-Bosch Dolors , Sejnowski Terrence J , Sainlos Matthieu , Choquet Daniel , Thoumine Olivier , Hosy Eric 
Published: September 2017

SummaryThe nanoscale organization of neurotransmitter receptors relative to pre-synaptic release sites is a fundamental determinant of both the amplitude and reliability of synaptic transmission. How modifications in the alignment between pre- and post-synaptic machineries affect synaptic current properties has only been addressed with computer modeling, and therefore remains hypothetical. Using dual-color single molecule based super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a C-terminal truncated form of NLG1 disrupted this correlation without affecting the intrinsic organization of AMPAR nanodomains. Moreover, this NLG1 dominant-negative mutant significantly shifted the pre-synaptic release machinery from AMPAR synaptic clusters. Electrophysiology and computer modeling show that this physical shift is sufficient to induce a significant decrease in synaptic transmission. Thus, our results suggest the necessity for synapses to release glutamate in front of AMPAR nanodomains, to maintain a high efficiency of synaptic responses.
redkmer: an assembly-free pipeline for the identification of abundant and specific X-chromosome target sequences for X-shredding by CRISPR endonucleases
Authors: Papathanos Philippos Aris , Windbichler Nikolai 
Published: September 2017

AbstractCRISPR-based synthetic sex ratio distorters, that operate by shredding the X-chromosome during male meiosis, are promising tools for the area-wide control of harmful insect pest or disease vector species. However, the selection of gRNA targets, in the form of high-copy sequence repeats on the X chromosome of a given species, is difficult since such repeats are not accurately resolved in genome assemblies and can’t be assigned to chromosomes with confidence. We have therefore developed the redkmer computational pipeline, designed to identify short and highly-abundant sequence elements occurring uniquely on the X-chromosome. Redkmer was designed to use as input exclusively raw WGS data from males and females. We tested redkmer with suitable short and long read WGS data ofAn. gambiae, the major vector of human malaria, in which the X-shredding paradigm was originally developed. Redkmer establishes long reads as chromosomal proxies with excellent correlation to the genome assembly and uses them to rank X-candidate kmers for their level of X-specificity and abundance. Redkmer identified a high-confidence set of 25-mers, many of which belong to previously known X-chromosome specific repeats ofAn. gambiae, including the ribosomal gene array and the selfish genetics elements harbored within it. WGS data from a control strain in which these repeats are also present on the Y chromosome confirmed the elimination of these kmers in the filtering steps. Finally, we show that redkmer output can be linked directly to gRNA selection and can also inform gRNA off-target prediction. The redkmer pipeline is designed to enable the generation of synthetic sex ratio distorters for the control of harmful insect species of medical or agricultural importance. It proceeds from WGS input data to deliver candidate X-specific CRISPR gRNA candidate target sequences. In addition the output of redkmer, including the prediction of chromosomal origin of single-molecule long reads and chromosome specific kmers, could also be used for the characterization of other biologically relevant sex chromosome sequences, a task that is frequently hampered by the repetitiveness of sex chromosome sequence content.
plot2DO: a tool to assess the quality and distribution of genomic data
Authors: Chereji Răzvan V. 
Published: September 2017

AbstractSummaryMicrococcal nuclease digestion followed by deep sequencing (MNase-seq) is the most used method to investigate nucleosome organization on a genome-wide scale. We presentplot2DO, a software package for creating 2D occupancy plots, which allows biologists to evaluate the quality of MNase-seq data and to visualize the distribution of nucleosomes near the functional regions of the genome (e.g. gene promoters, origins of replication, etc.).Availability And ImplementationTheplot2DOopen source package is freely available on GitHub athttps://github.com/rchereji/plot2DOunder the MIT license.Contactrazvan.chereji@nih.govSupplementary InformationSupplementary data are available atBioinformaticsonline.
CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo
Authors: Aughey Gabriel N. , Estacio Gomez Alicia , Thomson Jamie , Yin Hang , Southall Tony D. 
Published: September 2017

AbstractRegulation of eukaryotic gene expression is coordinated by dynamic changes to chromatin states throughout development. Measurements of accessible chromatin are used extensively to identify genomic regulatory elements. Whilst the chromatin landscapes of pluripotent stem cells are well characterised, chromatin accessibility changes in the development of somatic stem cell lineages are not well defined. Here we show that tissue specific chromatin accessibility data can be produced via ectopic expression ofE. coliDam methylasein vivo, without the requirement for cell-sorting. We have profiled chromatin accessibility in individual cell types of theDrosophilaneural and midgut stem cell lineages. Functional cell-type specific enhancers were identified, as well as novel motifs enriched at diferent stages of development. Finally, we show global changes in the accessibility of chromatin between stem-cells and their diferentiated progeny. Our results demonstrate the dynamic nature of chromatin accessibility in somatic tissues during stem cell diferentiation and provide a novel approach to understanding the gene regulatory mechanisms underlying development.
The brain compass: a perspective on how self-motion updates the head direction cell attractor
Authors: Laurens Jean , Angelaki Dora E. 
Published: September 2017

ABSTRACTHead Direction cells form an internal compass that signals head azimuth orientation even in the absence of visual landmarks. It is well accepted that head direction properties are generated through a ring attractor that is updated using rotation self-motion cues. The properties and origin of this self-motion velocity drive remain, however, unknown. We propose a unified, quantitative framework whereby the attractor velocity input represents a multisensory self-motion estimate computed through an internal model that uses sensory prediction error based on vestibular, visual, and somatosensory cues to improve on-line motor drive. We show how context-dependent strength of recurrent connections within the attractor itself, rather than the self-motion input, explain differences in head direction cell firing between free foraging and restrained movements. We also summarize recent findings on how head tilt relative to gravity influences the azimuth coding of head direction cells, and explain why and how these effects reflect an updating self-motion velocity drive that is not purely egocentric. Finally, we highlight recent findings that the internal compass may be three-dimensional and hypothesize that the additional vertical degrees of freedom are defined based on global allocentric gravity cues.
The separation of auditory experience and the temporal structure of MEG recorded brain activity
Authors: Allen Chris 
Published: September 2017

AbstractDo brain oscillations limit the temporal dynamics of experience? This pre-registered study used the separation of auditory stimuli to track perceptual experience and related this to oscillatory activity using magnetoencephalography. The rates at which auditory stimuli could be individuated matched the rates of oscillatory brain activity. Stimuli also entrained brain activity at the frequencies at which they were presented and a progression of high frequency gamma band events appeared to predict successful separation. These findings support a generalised function for brain oscillations, across frequency bands, in the alignment of activity to delineate representations.