bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic robustness of DNA microarrays in the classification of acute leukemia
Authors: Loh Marie , Mondry Adrian 
Published: July 2019

AbstractCountless statistical methods have been described for the analysis of DNA microarrays, and each yields distinct results. This raises the question whether DNA microarrays are robust diagnostic tools.In order to address this issue, we compared five formally similar statistical tests for gene selection on a single data set derived from acute leukemia patients. Inter-test agreement of gene selection, of sample classification and with standard clinical diagnosis was calculated using Cohen’s κ-score.The inter-test agreement scores were 0.15 < κ < 0.68 for gene selection, and 0.60 < κ < 0.89 for sample classification. Comparison to the clinical diagnosis showed agreement scores of 0.58< κ < 0.88. ’Marginal imbalance’ explains the low κ-scores at the level of gene selection. At the levels of sample classification and agreement with clinical diagnosis, κ-scores can be considered "substantial" to "excellent".For diagnostic purposes, the inter-test agreement of DNA microarrays is equivalent to that of experienced clinicians, as reported in the literature. The technique can thus be considered a useful and robust addendum to the available diagnostic tools.
Stomatin-like Protein 2 Links Mitochondria to T-Cell Receptor Signalosomes at the Immunological Synapse and Enhances T-Cell Activation
Authors: Kirchhof Mark , Chau Luan , Lemke Caitlin , Vardhana Santosh , Darlington Peter , Marquez Maria , Taylor Roy , Rizkalla Kamilia , Blaca Isaac , Dustin Michael , Madrenas Joaquin 
Published: July 2019

AbstractT cell activation through the antigen receptor (TCR) requires sustained signalling from microclusters in the peripheral region of the immunological synapse (IS). The bioenergetics of such prolonged signaling have been linked to the redistribution of mitochondria to the IS. Here, we report that stomatin-like protein-2 (SLP-2) plays an important role in this process by bridging polarized mitochondria to these signaling TCR microclusters or signalosomes in the IS in a polymerized actin-dependent manner. In this way, SLP-2 helps to sustain TCR-dependent signalling and enhances T cell activation.
Selective loss of GABAB receptors in orexin/hypocretin-producing neurons results in disrupted sleep/wakefulness architecture
Authors: Sakurai Takeshi , Matsuki Taizo , Takahira Hitomi , Hirashima Noriko , Kilduff Thomas , Kunita Satoshi , Takahashi Satoru , Yagami Ken-ichi , Bettler Bernard , Yanagisawa Masashi , Nomiyama Mika 
Published: July 2019

AbstractWe generated mice with a selective loss of GABAB receptors in orexin neurons. Orexin neurons in these GABAB1<sup>-/-(orexin)</sup> mice showed reduced responsiveness to GABA<sub>A</sub> receptor agonists due to a compensatory increase in GABAA receptor-mediated inhibition. This increased GABA<sub>A</sub> receptor-mediated inhibition of orexin neurons is due to orexin-1 receptor-mediated activation of local GABAergic interneurons. Surprisingly, orexin neurons were also less responsive to glutamate, apparently because the augmented GABA<sub>A</sub> receptor-mediated inhibition increases the membrane conductance and shunts excitatory currents. These observations indicate that absence of GABA<sub>B</sub> receptors decreases the sensitivity of orexin neurons to both excitatory and inhibitory inputs. GABAB1<sup>-/-(orexin)</sup>mice exhibited severe fragmentation of sleep/wake states during both the light and dark periods without affecting total sleep time or inducing cataplexy, indicating that GABA<sub>B</sub> receptors are crucial regulators of orexin neurons and that "fine tuning" of orexin neurons by inhibitory and excitatory inputs is important for the stability of sleep/waking states.
ACAT1, Cav-1, and PrP expression in brains and skin fibroblasts from Sarda breed sheep with scrapie-resistant and scrapie-susceptible genotype.
Authors: Pani Alessandra , Putzolu Marirosa , Mulas Claudia , Orrù Cristina D. , Abete Claudia , Norfo Claudia , Cannas M. Dolores , Laconi Sergio , La Colla Paolo , Dessì Sandra 
Published: July 2019

AbstractScrapie is an infective ovine neurodegenerative disease; the only identified component of the infectious agent being an aberrant isoform (PrPSc) of the cellular prion protein (PrPC). So far, no means for ante-mortem diagnosis are available for Scrapie as well as for any other mammal Transmissible Spongiform Encephalopaties. We recently found a strong relationship between cell susceptibility to scrapie-infection and intracellular cholesterol homeostasis alterations. In brain tissues as well as in ex vivo cultures of skin fibroblasts and PBMCs from healthy and scrapie-affected sheep carrying a scrapie-susceptible (ARQ/ARQ) genotype, the levels of cholesterol esters were consistently higher than in tissues and cultures derived from animals with a scrapie-resistant (ARR/ARR) genotype. Moreover, both uninfected and scrapie-affected ARQ/ARQ sheep showed abnormally low levels of high density lipoprotein-cholesterol (HDL-C) in their plasma, as compared to ARR/ARR animals. We now show that intracellular accumulation of cholesterol esters in fibroblasts derived from scrapie-susceptible sheep was accompanied by parallel alterations in the expression level of genes and gene products (ACAT1 and Cav-1) that are involved in the pathways leading to intracellular cholesterol esterification and trafficking. Comparative analysis of PrPc mRNA, showed an higher expression level in cells from animals carrying susceptible genotype, with or without Scrapie. Preliminary experiments also revealed the presence of PK-resistant PrP isoforms in the latter cultures. The data reported in the present paper suggest that accumulation of cholesterol esters in peripheral cells, together with the altered expression of some proteins implicated in intracellular cholesterol homeostasis, might serve to identify a distinctive lipid metabolic profile associated with increased susceptibility to develop prion disease following infection.
Internal ribosomal entry site lacks secondary structure
Authors: Xia Xuhua 
Published: July 2019

AbstractThe search for mechanisms of translational regulation has yielded many experimentally identified internal ribosome entry sites (IRES). Because of the lack of sequence similarity among the experimentally IRESs, it is widely assumed that IRESs posses stable secondary structure allowing them to interact with the components of the translation machinery. Contrary to this view, here we show that IRES activity in nine yeast IRESs, mapped to 60 nt immediately upstream of the initiation AUG, is strongly associated with the lack of secondary structure of IRESs. Furthermore, the reverse complements of these IRESs, with their secondary structure more stable than those of the IRESs, exhibit little IRES activity. The generality of this association is exemplified by the observation that, in the natural vpu-env bicistronic mRNA in HIV-1, the mRNA segment (60 nt) immediately upstream of the initiation AUG of env has the weakest secondary structure among all dominant HIV-1 mRNA species. These results suggest a unified model of alternative translation initiation.
Discovery of transcription factor binding sites through integration of generic motif finders
Authors: Wijaya Edward , Yiu Siu-Ming , Ngo Thanh Son , Kanagasabai Rajaraman , Sung Wing-Kin 
Published: July 2019

AbstractLocating transcription factor binding sites is a key step in understanding gene regulation. Due to its importance, many de novo motif-finding methods have been proposed. Individually, these motif finders perform unimpressively overall based on Tompa's benchmark datasets. Moreover, these motif finders vary in their definitions of what constitute a motif, and in their methods for finding statistically overrepresented motifs. There is no clear way for biologists to choose the motif finder that is most suitable for their task. The purpose of this work is to describe a method called MotifVoter to identify transcription factor binding sites by integrating the results found by motif finders of different models. Validation of our method on Tompa's benchmark, real metazoan and E. coli datasets show that it can improve the sensitivity significantly without sacrificing the precision. Our approach offers a practical alternative for biologists to study novel transcription factors.The MotifVoter software is available for public use at: http://www.comp.nus.edu.sg/~bioinfo/MotifVoter
Novel role of substance-p as a systemic wound messenger to mobilize mesenchymal stem cell from bone marrow and be engaged in the wound healing epithelial layer
Authors: Hong Hyun Sook , Lee Jung Sun , Kwon Young Sam , Lee Eun Kyung , Ahn Woosung , Kim Jae Chan , Son Youngsook 
Published: July 2019

AbstractTissue injury may bring up the systemic participation of bone marrow stem cells in the repair. In this study, we report that substance-p is a systemically acting messenger to mobilize mesenchymal stem cell (MSC) probably from the bone marrow and be engaged in the wound healing process. This was supported by the injury-inducible substance-p detection in the tissue and the peripheral blood and subsequent MSC mobilization in the alkali-burn rabbit eye model, whose kinetics were dependent on the wound size. Furthermore, i.v. injection of exogenous substance-p stimulated MSC mobilization in the uninjured rabbits and those mobilized cells showed multipotent differentiation capacity. We demonstrated that earlier substance-p elevation in the circulation by substance-p injection or transfusion of autologous PKH-labeled MSC mobilized by substance-p strongly accelerated the wound healing of the alkali-burned rabbit eye and the transfused MSCs were engrafted to the epithelial and stromal layer of the injured tissue, suggesting their epithelial transdifferentiation in the regenerating tissue. Finally, we showed that substance-p stimulated transmigration of human MSC with concomitant induction of MMPs and inhibition of their inhibitors, cell proliferation, ERK1/2 activation, and nuclear translocation of [beta]-catenin in vitro. In conclusion, substance-p plays a role as a systemic wound-messenger to promote the MSC mobilization from the marrow and their participation in the wound healing possibly through its stimulant effect on MSC repopulation as well.
A Case For Killing Humpback Whales?
Authors: Gales Nicholas , Clapham Phillip , Baker C. Scott 
Published: July 2019

AbstractDuring the austral summer of 2007/08, hunting of Southern Hemisphere (SH) humpback whales will recommence after almost half a century of protection. The stated rationale for this hunt, by the Government of Japan (GoJ), is to gather important scientific information for use in management. If the scientific need were defensible, and the proponents had accommodated reasonable conservation concerns, then criticisms of the hunt would be limited to philosophical issues. This is not the case. The program’s research objectives are unlikely to be achieved by lethal methods and do not address the principal research needs for SH humpback whales identified by the International Whaling Commission (IWC).
The Earliest Perfect Flower
Authors: Wang Xin , Zheng Shaolin 
Published: July 2019

AbstractDespite of angiosperms in the Yixian Formation (>125 Ma, early Cretaceous), there is no perfect flower typical of angiosperms to date. Here we report Euanthus dilaensis gen. et sp. nov as the earliest perfect flower known to date. The flower includes tepals, androecium and gynoecium. The anthers are globose in form, with bristles atop and in situ round-triangular pollen grains. The gynoecium is composed of probably two carpels with plumose stigmas and a carpel-enclosing receptacle. The discovery of Euanthus increases the diversity of early angiosperms, and indicates that perfect flowers occurred as early as 125 Ma ago.
Body-specific representations of action word meanings in right and left handers
Authors: Casasanto Daniel 
Published: July 2019

AbstractIf understanding action words involves mentally simulating our own actions, then the neurocognitive representation of word meanings must differ for people with different kinds of bodies, who perform actions in systematically different ways. In a test of the Body-Specificity Hypothesis, right- and left-handers were compared on two motor-meaning congruity tasks. Double dissociations in both action execution and recognition memory results showed that right and left handers form body-specific representations of words for manual actions.
Bioluminescence emission of the firefly
Authors: Gohain Barua Anurup , Hazarika Simanta , Saikia Nayanmoni , Baruah Gaurangadhar 
Published: July 2019

AbstractWe have recorded in vivo emission and time-resolved spectra of the firefly species Pyrophorus noctilucus. The emission spectrum shows the FWHM value for this particular species to be 55 nm, which is significantly smaller than the half widths reported till now. The time-resolved spectrum reveals that a flash, of duration about a hundred milliseconds, is in fact composed of a number of microsecond pulses. This result suggests that the speed of the enzyme-catalyzed chemiluminescence reaction in the firefly for the emission of light is much greater than is believed to be.
A visual sense of number
Authors: Burr David , Ross John 
Published: July 2019

AbstractEvidence exists for a non-verbal capacity to apprehend number, in humans^1^ (including infants^2,3^) and in other primates^4-6^. Here we show that perceived numerosity is susceptible to adaptation, along with primary visual properties of a scene like colour, contrast, size and speed. Apparent numerosity was decreased by adapting to large numbers of dots and increased by adapting to small numbers, the effect depended entirely on the numerosity of the adapter, not on contrast, size, orientation or pixel density, and occurred with very low adapter contrasts. We suggest that numerosity is also an independent primary visual property, not reducible to others like spatial frequency or density of texture^7^.
Prehistoric psychotropic consumption in Andean Chilean mummies
Authors: Ogalde Juan , Arriaza Bernardo , Soto Elia 
Published: July 2019

AbstractHallucinogenic plants are often regarded as the main source of psychoactive drugs in antiquity to reach deep altered states of consciousness^1,2^. Many researchers believe this was particularly true during the Tiwanaku empire expansion, circa (500-1000 A.D.), along the Atacama Desert of Chile. Highly decorated snuffing tablets and tubes are often found as grave goods during this period^3,4,5,6,7,8^. Until now the type of drugs consumed in this paraphernalia has been unclear. From the modern city of Arica, naturally mummified human bodies with abundant hair provided a unique opportunity to test for hallucinogenic plants consumed in Andean prehistory. Analysis by gas chromatography and mass spectrometry demonstrated the presence of harmine. The Banisteriopsis vine, commonly called Ayahuasca, was the probable source. This is the first confirmed evidence of psychoactive plant consumption in pre-Hispanic Andean populations along the Atacama coastal region. Of the 32 mummy hair samples analyzed 3 males tested positive for harmine. This alkaloid aids in the catalysis and synergic effects of powerful hallucinogenic drugs. The consumption of harmine was likely related to medicinal practices and not exclusively ingested by shamans. Another important aspect of this evidence is that Banisteriopsis is an Amazon plant. It does not grow in the Atacama coastal region. Thus, our findings reveal extensive plant trade networks in antiquity between the coast, desert, highlands, and Amazon basin. The excellent preservation of human organic specimens, the use of gas chromatography and mass spectrometry allowed us to map and demonstrate the consumption of psychoactive compound plants in Andean prehistory. In addition, our findings open the door for future studies to debate the consumption and social role of ancient psychoactive and hallucinogenic plants.
Evolution of the Protein Universe. Time Scales and Selection
Authors: Cosentino Lagomarsino Marco , Sellerio Alessandro , Heijning Philip , Bassetti Bruno 
Published: July 2019

AbstractThe availability of many genome sequences gives us abundant information, which is, however, very difficult to decode. As a consequence, in order to advance our understanding of biological processes at the whole-cell scale, it becomes very important to develop higher-level, synthetic descriptions of the contents of a genome. At the protein level, an effective scale of description is provided by protein domains. Domains are independent unit-shapes (or "folds") forming proteins. They are structurally stable and have thermodynamic origin. A domain determines a set of potential functions and interactions for the protein that carries it, for example DNA- or protein-binding capability or catalytic sites. Protein domains are found on genomes with notable statistical distributions, which bear a high degree of similarity. A stochastic growth model with two universal parameters, related to a minimal number of domains and to the relative time-scale of innovation to duplication reproduces two important features of these distributions: (i) the populations of domain classes (the sets, related to homology classes, containing realizations of the same domain in different proteins) follow common power-laws whose diversity is related to genome size measured by the total number of proteins or protein domains and (ii) the number of domain families is sublinear in genome size. In this evolutionary process, selective pressure can enter both as a global constraint on the innovation time-scale, and as a regulator of the population of specific domain classes, related to their modularity: some shapes are common to all genomes, some are contextual. These two features are sufficient to obtain general quantitative agreement with data from hundreds of genomes, and show that robust self-organizing phenomena encase specific selective pressures during evolution.
Chorionic Structures in Maternal Blood
Authors: Luz Nilo Pereira 
Published: July 2019

AbstractChorionic villi are the exchange structures of the placenta where human fetuses receive oxygen and nutrients from maternal blood, this article reports an improvement of a published method to recover them from the blood of pregnant, women, quotes their number and illustrates their size and trypsin impregnation. The reasons to explain the presence of chorionic structures and villi in the circulating maternal blood, the possible significance of their existence in maternal blood and the mechanisms to remove them are discussed. Their size and trypsin impregnation are illustrated. This paper discusses the significance of the presence of such allogeneic structures in the circulating blood of pregnant women and presents a brief discussion on the role of trypsin and its inhibitor in pregnancy homeostasis.
Abundance of intrinsic disorder in SV-IV, a multifunctional androgen-dependent protein secreted from rat seminal vesicle
Authors: Vilasi Silvia , Ragone Raffaele 
Published: July 2019

AbstractThe potent immunomodulatory, anti-inflammatory and procoagulant properties of theprotein no. 4 secreted from the rat seminal vesicle epithelium (SV-IV) have beenpreviously found to be modulated by a supramolecular monomer-trimer equilibrium.More structural details that integrate experimental data into a predictive frameworkhave recently been reported. Unfortunately, homology modelling and fold-recognitionstrategies were not successful in creating a theoretical model of the structuralorganization of SV-IV. It was inferred that the global structure of SV-IV is not similarto any protein of known three-dimensional structure. Reversing the classical approachto the sequence-structure-function paradigm, in this paper we report on novelinformation obtained by comparing physicochemical parameters of SV-IV with twodatasets made of intrinsically unfolded and ideally globular proteins. In addition, wehave analysed the SV-IV sequence by several publicly available disorder-orientedpredictors. Overall, disorder predictions and a re-examination of existing experimentaldata strongly suggest that SV-IV needs large plasticity to efficiently interact with thedifferent targets that characterize its multifaceted biological function and should betherefore better classified as an intrinsically disordered protein.
TMEPAI, a transmembrane TGF-β-inducible protein, sequesters Smad proteins in TGF-β signaling
Authors: Itoh Susumu , Watanabe Yukihide , Satoh Kiyotoshi , Inamitsu Masako , Shi Liang , Nakano Naoko , Tanaka Aya , Wiercinska Eliza , Shibuya Hiroshi , ten Dijke Peter , Kato Mitsuyasu 
Published: July 2019

AbstractTransforming growth factor-[beta] (TGF-[beta]) is a multifunctional cytokine of key importance for controlling embryogenesis and tissue homeostasis. How TGF-[beta] signals are attenuated and terminated is not well understood. Here, we show that TMEPAI, a direct target gene of TGF-[beta] signaling, antagonizes TGF-[beta] signaling by interfering with TGF-[beta] type I receptor (T[beta]RI)-induced R-Smad phosphorylation. TMEPAI can directly interact with R-Smads via a Smad interaction motif (SIM). TMEPAI competes with Smad anchor for receptor activation (SARA) for R-Smad binding, thereby sequestering R-Smads from T[beta]RI kinase activation. In mammalian cells, ectopic expression of TMEPAI inhibited TGF-[beta]-induced PAI-1 production, whereas specific siRNA-mediated knockdown of TMEPAI expression potentiated TGF-[beta]-induced Smad2 phosphorylation and cellular responsiveness by TGF-[beta]. Consistently, TMEPAI inhibits activin-mediated mesoderm formation in Xenopus embryos. Taken together, TMEPAI participates in a negative feedback loop to control the duration and intensity of TGF-[beta] signaling.
c-Myc induced changes in higher order rDNA structure accompany growth factor stimulation of quiescent cells
Authors: Shiue Chiou-Nan , Berkson Rachel , Wright Anthony 
Published: July 2019

AbstractHuman c-Myc is believed to be a high level coordinator of protein synthesis capacity and cell growth rate, capable of activating transcription by all three nuclear RNA Polymerases. Direct activation of rDNA transcription by c-Myc is functionally conserved in rat cells, despite high divergence in non-coding rDNA sequences, suggesting that this coordinating role is likely to be a general within mammals. Upon re-feeding of starved cells, c-Myc activity enhances the efficiency of RNA Polymerase I and SL1/TIF-1B recruitment to the rDNA and rapidly induces higher order gene loop structures in rDNA chromatin that juxtapose upstream and downstream rDNA sequences. Furthermore c-Myc induced gene-loop formation in rDNA genes occurs independently of rDNA transcription, implying that it may be an early step in the re-programming of quiescent cells as they enter the growth cycle.