bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fabrication of fibrillosomes from droplets stabilized by protein nanofibrils at all-aqueous interfaces
Authors: Song Yang , Shimanovich Ulyana , Michaels Thomas C. T. , Ma Qingming , Li Jingmei , Knowles Tuomas P. J. , Shum Ho Cheung 
Published: October 2016

AbstractAll-aqueous emulsions exploit spontaneous liquid–liquid separation and due to their water-based nature are particular advantageous for the biocompatible storage and processing of biomacromolecules. However, the ultralow interfacial tensions characteristic of all-aqueous interfaces represent an inherent limitation to the use of thermally adsorbed particles to achieve emulsion stability. Here, we use protein nanofibrils to generate colloidosome-like two-dimensional crosslinked networks of nanostructures templated by all-aqueous emulsions, which we term fibrillosomes. We show that this approach not only allows us to operate below the thermal limit at ultra-low surface tensions but also yields structures that are stable even in the complete absence of an interface. Moreover, we show that the growth and multilayer deposition of fibrils allows us to control the thickness of the capsule shells. These results open up the possibility of stabilizing aqueous two-phase systems using natural proteins, and creating self-standing protein capsules without the requirement for three-phase emulsions or water/oil interfaces.
Large-scale microfluidics providing high-resolution and high-throughput screening of Caenorhabditis elegans poly-glutamine aggregation model
Authors: Mondal Sudip , Hegarty Evan , Martin Chris , Gökçe Sertan Kutal , Ghorashian Navid , Ben-Yakar Adela 
Published: October 2016

AbstractNext generation drug screening could benefit greatly from in vivo studies, using small animal models such as Caenorhabditis elegans for hit identification and lead optimization. Current in vivo assays can operate either at low throughput with high resolution or with low resolution at high throughput. To enable both high-throughput and high-resolution imaging of C. elegans, we developed an automated microfluidic platform. This platform can image 15 z-stacks of ∼4,000 C. elegans from 96 different populations using a large-scale chip with a micron resolution in 16 min. Using this platform, we screened ∼100,000 animals of the poly-glutamine aggregation model on 25 chips. We tested the efficacy of ∼1,000 FDA-approved drugs in improving the aggregation phenotype of the model and identified four confirmed hits. This robust platform now enables high-content screening of various C. elegans disease models at the speed and cost of in vitro cell-based assays.
Nop9 is a PUF-like protein that prevents premature cleavage to correctly process pre-18S rRNA
Authors: Zhang Jun , McCann Kathleen L. , Qiu Chen , Gonzalez Lauren E. , Baserga Susan J. , Hall Traci M. Tanaka 
Published: October 2016

AbstractNumerous factors direct eukaryotic ribosome biogenesis, and defects in a single ribosome assembly factor may be lethal or produce tissue-specific human ribosomopathies. Pre-ribosomal RNAs (pre-rRNAs) must be processed stepwise and at the correct subcellular locations to produce the mature rRNAs. Nop9 is a conserved small ribosomal subunit biogenesis factor, essential in yeast. Here we report a 2.1-Å crystal structure of Nop9 and a small-angle X-ray-scattering model of a Nop9:RNA complex that reveals a ‘C’-shaped fold formed from 11 Pumilio repeats. We show that Nop9 recognizes sequence and structural features of the 20S pre-rRNA near the cleavage site of the nuclease, Nob1. We further demonstrate that Nop9 inhibits Nob1 cleavage, the final processing step to produce mature small ribosomal subunit 18S rRNA. Together, our results suggest that Nop9 is critical for timely cleavage of the 20S pre-rRNA. Moreover, the Nop9 structure exemplifies a new class of Pumilio repeat proteins.
Increased global transcription activity as a mechanism of replication stress in cancer
Authors: Kotsantis Panagiotis , Silva Lara Marques , Irmscher Sarah , Jones Rebecca M. , Folkes Lisa , Gromak Natalia , Petermann Eva 
Published: October 2016

AbstractCancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRASV12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRASV12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.
Gate-tunable negative longitudinal magnetoresistance in the predicted type-II Weyl semimetal WTe2
Authors: Wang Yaojia , Liu Erfu , Liu Huimei , Pan Yiming , Zhang Longqiang , Zeng Junwen , Fu Yajun , Wang Miao , Xu Kang , Huang Zhong , Wang Zhenlin , Lu Hai-Zhou , Xing Dingyu , Wang Baigeng , Wan Xiangang , Miao Feng 
Published: October 2016

AbstractThe progress in exploiting new electronic materials has been a major driving force in solid-state physics. As a new state of matter, a Weyl semimetal (WSM), in particular a type-II WSM, hosts Weyl fermions as emergent quasiparticles and may harbour novel electrical transport properties. Nevertheless, such a type-II WSM material has not been experimentally observed. In this work, by performing systematic magneto-transport studies on thin films of a predicted material candidate WTe2, we observe notable negative longitudinal magnetoresistance, which can be attributed to the chiral anomaly in WSM. This phenomenon also exhibits strong planar orientation dependence with the absence along the tungsten chains, consistent with the distinctive feature of a type-II WSM. By applying a gate voltage, we demonstrate that the Fermi energy can be in-situ tuned through the Weyl points via the electric field effect. Our results may open opportunities for implementing new electronic applications, such as field-effect chiral devices.
Theory of highly efficient multiexciton generation in type-II nanorods
Authors: Eshet Hagai , Baer Roi , Neuhauser Daniel , Rabani Eran 
Published: October 2016

AbstractMultiexciton generation, by which more than a single electron–hole pair is generated on optical excitation, is a promising paradigm for pushing the efficiency of solar cells beyond the Shockley–Queisser limit of 31%. Utilizing this paradigm, however, requires the onset energy of multiexciton generation to be close to twice the band gap energy and the efficiency to increase rapidly above this onset. This challenge remains unattainable even using confined nanocrystals, nanorods or nanowires. Here, we show how both goals can be achieved in a nanorod heterostructure with type-II band offsets. Using pseudopotential atomistic calculation on a model type-II semiconductor heterostructure we predict the optimal conditions for controlling multiexciton generation efficiencies at twice the band gap energy. For a finite band offset, this requires a sharp interface along with a reduction of the exciton cooling and may enable a route for breaking the Shockley–Queisser limit.
Embrained drives to perform extraordinary roles predict schizotypal traits in the general population
Authors: Fernandez-Cruz Ana L , Ali Ola Mohamed , Asare Gifty , Whyte Morgan S , Walpola Ishan , Segal Julia , Debruille J Bruno 
Published: October 2016

AbstractSome personal drives correspond to extraordinary social roles. Given that behavioral strategies associated with such drives may conflict with those associated with ordinary roles, they could cause behavioral disorganization. To test whether they do so independent of the factors responsible for full-blown schizotypy and schizophrenia, these drives were assessed in the general population. Two hundred and nine healthy volunteers were individually presented with hundreds of names of social roles in experimental psychology conditions. The task of the participant was to decide whether or not (s)he would consider performing the role at any moment of his/her life. Schizotypal traits were measured with the schizotypal personality questionnaire (SPQ), and delusion-like ideations were assessed by the Peters et al. Delusion Inventory. Demographics and social desirability were controlled for. Participants accepting a greater percentage of extraordinary roles had higher SPQ scores. Among the three factors of the SPQ, disorganization was the one best predicted by those percentages. This correlation (r=0.40, P=7.2E−09) was significantly greater (Fisher Z-transform, P=0.003) than the correlation between the percentages of ordinary roles accepted and the SPQ scores (r=0.145, P=0.044). Reaction times revealed no suboptimal cognitive functioning in high accepters of extraordinary roles and further strengthened the drive hypothesis. Their acceptances of roles were done faster and their rejections took longer than those of low accepters (P=5E−12). Culturally embrained drives to do extraordinary roles could thus be an independent factor of the symptoms measured in the normality to schizophrenia continuum.
Effect of methyl salicylate (MeSA), an elicitor on growth, physiology and pathology of resistant and susceptible rice varieties
Authors: Kalaivani Kandaswamy , Kalaiselvi Marimuthu Maruthi , Senthil-Nathan Sengottayan 
Published: October 2016

AbstractMethyl salicylate (MeSA) is a volatile organic compound synthesized from salicylic acid (SA) a plant hormone that helps to fight against plant disease. Seed treatment with MeSA, is an encouraging method to the seed industry to produce more growth and yield. The aim of our study is to find out the growth, development and disease tolerance of rice seed treated with different concentrations of MeSA. Also the seed treatments were studied to determine whether they directly influenced seedling emergence and growth in rice (Oryza sativa L) cultivars ‘IR 20, IR 50, IR 64, ASD 16, ASD 19 and ADT 46’ under greenhouse condition. MeSA seed treatments at 25, 50, 75 and 100 mg/L significantly increased seedling emergence. Effects were stronger in IR 50, and IR 64 and the effects were dose dependent, although the relationship between dose and effect was not always linear. MeSA seed treated rice plant against bacterial blight were analyzed. Bacterial blight was more effectively controlled by the seed treated with 100 mg/L than others. These results suggest that seed treatment with MeSA alters plant physiology in ways that may be useful for crop production as well as protection.
Uterus-targeted liposomes for preterm labor management: studies in pregnant mice
Authors: Refuerzo Jerrie S. , Leonard Fransisca , Bulayeva Nataliya , Gorenstein David , Chiossi Giuseppe , Ontiveros Alejandra , Longo Monica , Godin Biana 
Published: October 2016

AbstractPreterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug development in obstetrics that could greatly impact preterm birth, which currently has no successful treatments.
Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips
Authors: Homan Kimberly A. , Kolesky David B. , Skylar-Scott Mark A. , Herrmann Jessica , Obuobi Humphrey , Moisan Annie , Lewis Jennifer A. 
Published: October 2016

AbstractThree-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.
Hepatocellular Carcinoma-propagating Cells are Detectable by Side Population Analysis and Possess an Expression Profile Reflective of a Primitive Origin
Authors: Xia Honghai , Cao Jun , Li Qing , Lv Yang , Jia Weidong , Ren Weihua , Cheng Qingyu , Song Xiaoyuan , Xu Geliang 
Published: October 2016

AbstractThe recent identification of “Side Population” (SP) cells in a number of unrelated human cancers has renewed interests in the hypothesis of cancer stem cells. Here we isolated SP cells from HepG2 cells and 18 of the 21 fresh hepatocellular carcinoma (HCC) tissue samples. These SP cells have higher abilities of forming spheroids, invasion and migration. Tumors could generate only from SP, not non-SP (NSP), cells in a low dose of subcutaneous injection to the NOD/SCID mice (5 × 102 cells/mouse). The mRNA microarray analysis of the SP vs. NSP cells isolated from HepG2 cells revealed that the SP cells express higher levels of pluripotency- and stem cell-associated transcription factors including Klf4, NF-Ya, SALL4 and HMGA2. Some of the known hepatobiliary progenitor/stem cell markers, such as Sox9 was also up-regulated. RT-qPCR analysis of the gene expression between SP cells and NSP cells isolated from both HepG2 cells and HCC tissue samples showed that most of the tested mRNAs’ changes were in consistent with the microarray data, including the general progenitor/stem cells markers such as Klf4, NF-Ya, SALL4 and HMGA2, which were up-regulated in SP cells. Our data indicates that HCC cancer stem cells exist in HepG2 and HCC fresh tissue samples and can be isolated by SP assay.
A network approach to discerning the identities of C. elegans in a free moving population
Authors: Winter Peter B. , Brielmann Renee M. , Timkovich Nicholas P. , Navarro Helio T. , Teixeira-Castro Andreia , Morimoto Richard I. , Amaral Luis A. N. 
Published: October 2016

AbstractThe study of C. elegans has led to ground-breaking discoveries in gene-function, neuronal circuits, and physiological responses. Subtle behavioral phenotypes, however, are often difficult to measure reproducibly. We have developed an experimental and computational infrastructure to simultaneously record and analyze the physical characteristics, movement, and social behaviors of dozens of interacting free-moving nematodes. Our algorithm implements a directed acyclic network that reconstructs the complex behavioral trajectories generated by individual C. elegans in a free moving population by chaining hundreds to thousands of short tracks into long contiguous trails. This technique allows for the high-throughput quantification of behavioral characteristics that require long-term observation of individual animals. The graphical interface we developed will enable researchers to uncover, in a reproducible manner, subtle time-dependent behavioral phenotypes that will allow dissection of the molecular mechanisms that give rise to organism-level behavior.
Time-course of coherence in the human basal ganglia during voluntary movements
Authors: Talakoub Omid , Neagu Bogdan , Udupa Kaviraja , Tsang Eric , Chen Robert , Popovic Milos R. , Wong Willy 
Published: October 2016

AbstractWe are interested in characterizing how brain networks interact and communicate with each other during voluntary movements. We recorded electrical activities from the globus pallidus pars interna (GPi), subthalamic nucleus (STN) and the motor cortex during voluntary wrist movements. Seven patients with dystonia and six patients with Parkinson’s disease underwent bilateral deep brain stimulation (DBS) electrode placement. Local field potentials from the DBS electrodes and scalp EEG from the electrodes placed over the motor cortices were recorded while the patients performed externally triggered and self-initiated movements. The coherence calculated between the motor cortex and STN or GPi was found to be coupled to its power in both the beta and the gamma bands. The association of coherence with power suggests that a coupling in neural activity between the basal ganglia and the motor cortex is required for the execution of voluntary movements. Finally, we propose a mathematical model involving coupled neural oscillators which provides a possible explanation for how inter-regional coupling takes place.
Generation of transgenic marmosets expressing genetically encoded calcium indicators
Authors: Park Jung Eun , Zhang Xian Feng , Choi Sang-Ho , Okahara Junko , Sasaki Erika , Silva Afonso C. 
Published: October 2016

AbstractChronic monitoring of neuronal activity in the living brain with optical imaging techniques became feasible owing to the continued development of genetically encoded calcium indicators (GECIs). Here we report for the first time the successful generation of transgenic marmosets (Callithrix jacchus), an important nonhuman primate model in neurophysiological research, which were engineered to express the green fluorescent protein (GFP)-based family of GECIs, GCaMP, under control of either the CMV or the hSyn promoter. High titer lentiviral vectors were produced, and injected into embryos collected from donor females. The infected embryos were then transferred to recipient females. Eight transgenic animals were born and shown to have stable and functional GCaMP expression in several different tissues. Germline transmission of the transgene was confirmed in embryos generated from two of the founder transgenic marmosets that reached sexual maturity. These embryos were implanted into six recipient females, three of which became pregnant and are in advanced stages of gestation. We believe these transgenic marmosets will be invaluable non-human primate models in neuroscience, allowing chronic in vivo monitoring of neural activity with functional confocal and multi-photon optical microscopy imaging of intracellular calcium dynamics.
Single neuron transcriptomics identify SRSF/SR protein B52 as a regulator of axon growth and Choline acetyltransferase splicing
Authors: Liu Boyin , Bossing Torsten 
Published: October 2016

AbstractWe removed single identified neurons from living Drosophila embryos to gain insight into the transcriptional control of developing neuronal networks. The microarray analysis of the transcriptome of two sibling neurons revealed seven differentially expressed transcripts between both neurons (threshold: log21.4). One transcript encodes the RNA splicing factor B52. Loss of B52 increases growth of axon branches. B52 function is also required for Choline acetyltransferase (ChAT ) splicing. At the end of embryogenesis, loss of B52 function impedes splicing of ChAT, reduces acetylcholine synthesis, and extends the period of uncoordinated muscle twitches during larval hatching. ChAT regulation by SRSF proteins may be a conserved feature since changes in SRSF5 expression and increased acetylcholine levels in brains of bipolar disease patients have been reported recently.
Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles
Authors: Yamano Emi , Sugimoto Masahiro , Hirayama Akiyoshi , Kume Satoshi , Yamato Masanori , Jin Guanghua , Tajima Seiki , Goda Nobuhito , Iwai Kazuhiro , Fukuda Sanae , Yamaguti Kouzi , Kuratsune Hirohiko , Soga Tomoyoshi , Watanabe Yasuyoshi , Kataoka Yosky 
Published: October 2016

AbstractChronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma.
Functional visualization and disruption of targeted genes using CRISPR/Cas9-mediated eGFP reporter integration in zebrafish
Authors: Ota Satoshi , Taimatsu Kiyohito , Yanagi Kanoko , Namiki Tomohiro , Ohga Rie , Higashijima Shin-ichi , Kawahara Atsuo 
Published: October 2016

AbstractThe CRISPR/Cas9 complex, which is composed of a guide RNA (gRNA) and the Cas9 nuclease, is useful for carrying out genome modifications in various organisms. Recently, the CRISPR/Cas9-mediated locus-specific integration of a reporter, which contains the Mbait sequence targeted using Mbait-gRNA, the hsp70 promoter and the eGFP gene, has allowed the visualization of the target gene expression. However, it has not been ascertained whether the reporter integrations at both targeted alleles cause loss-of-function phenotypes in zebrafish. In this study, we have inserted the Mbait-hs-eGFP reporter into the pax2a gene because the disruption of pax2a causes the loss of the midbrain-hindbrain boundary (MHB) in zebrafish. In the heterozygous Tg[pax2a-hs:eGFP] embryos, MHB formed normally and the eGFP expression recapitulated the endogenous pax2a expression, including the MHB. We observed the loss of the MHB in homozygous Tg[pax2a-hs:eGFP] embryos. Furthermore, we succeeded in integrating the Mbait-hs-eGFP reporter into an uncharacterized gene epdr1. The eGFP expression in heterozygous Tg[epdr1-hs:eGFP] embryos overlapped the epdr1 expression, whereas the distribution of eGFP-positive cells was disorganized in the MHB of homozygous Tg[epdr1-hs:eGFP] embryos. We propose that the locus-specific integration of the Mbait-hs-eGFP reporter is a powerful method to investigate both gene expression profiles and loss-of-function phenotypes.