bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and Analysis of Functional Networks in the Gut Microbiome of Type 2 Diabetes Patients
Authors: Li Lianshuo , Wang Zicheng , He Peng , Ma Shining , Du Jie , Jiang Rui
Published: October 2016

Although networks of microbial species have been widely used in the analysis of 16S rRNA sequencing data of a microbiome, the construction and analysis of a complete microbial gene network are in general problematic because of the large number of microbial genes in metagenomics studies. To overcome this limitation, we propose to map microbial genes to functional units, including KEGG orthologous groups and the evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) orthologous groups, to enable the construction and analysis of a microbial functional network. We devised two statistical methods to infer pairwise relationships between microbial functional units based on a deep sequencing dataset of gut microbiome from type 2 diabetes (T2D) patients as well as healthy controls. Networks containing such functional units and their significant interactions were constructed subsequently. We conducted a variety of analyses of global properties, local properties, and functional modules in the resulting functional networks. Our data indicate that besides the observations consistent with the current knowledge, this study provides novel biological insights into the gut microbiome associated with T2D.
A pilot study exploring the molecular architecture of the tumor microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray
Authors: Pin Elisa , Stratton Steven , Belluco Claudio , Liotta Lance , Nagle Ray , Hodge K. Alex , Deng Jianghong , Dong Ting , Baldelli Elisa , Petricoin Emanuel , Pierobon Mariaelena
Published: October 2016

The cross‐talk between tumor epithelium and surrounding stromal/immune microenvironment is essential to sustain tumor growth and progression and provides new opportunities for the development of targeted treatments focused on disrupting the tumor ecology. Identification of novel approaches to study these interactions is of primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based protein signaling activation mapping we explored the molecular interconnection between tumor epithelium and surrounding stromal microenvironment in 18 prostate cancer (PCa) specimens. Four specimen‐matched cellular compartments (normal‐appearing epithelium and its adjacent stroma, and malignant epithelium and its adjacent stroma) were isolated for each case. The signaling network analysis of the four compartments unraveled a number of molecular mechanisms underlying the communication between tumor cells and stroma in the context of the tumor microenvironment. In particular, differential expression of inflammatory mediators like IL‐8 and IL‐10 by the stroma cells appeared to modulate specific cross‐talks between the tumor cells and surrounding microenvironment.
Relations de voyages et textes géographiques arabes, persans et turks relatifs a l'Extrême-Orient du VIIIe au XVIIIe siècles
Authors: Ferrand Gabriel
Published: October 2016

Gabriel Ferrand (1864–1935) travelled widely as a French diplomat and pursued scholarly passions as a polyglot orientalist. He served as consul to Madagascar and published several works about the island, noting the Arab influence that preceded the arrival of Europeans. A member of the Société Asiatique, and editor of its journal from 1920 until his death, Ferrand sought in particular to make Arabic geographical and nautical writings more accessible to fellow scholars and students. Forming part of that project, this work appeared in two volumes in 1913–14. It presents annotated French translations of mainly Arabic texts relating to the Far East. Brief biographical notes on the authors are given for the benefit of non-specialists. Volume 1 contains the preliminary matter explaining Ferrand's approach to transcription and translation. This is followed by texts up to the thirteenth century, including extracts from the ninth-century author Sulaiman al-Tajir.
Do neighbourhoods in Vancouver and surrounding areas demonstrate different rates of bystander CPR and survival for out-of-hospital cardiac arrest?
Authors: Barbic David , Klinkenberg Brian , Grunau Brian , Christenson Jim
Published: October 2016

Objective

No prior work exists examining the relation between the geographic distribution of out-of-hospital cardiac arrest (OHCA) in the city of Vancouver and surrounding areas that may exhibit a clustering of cases. The primary objective of this study was to describe the distribution of OHCA within the Vancouver Coastal Health region using a geographic information system (GIS) analysis and appropriate statistical analyses.

Methods

This study was a post-hoc GIS-based analysis of OHCA patients in the city of Vancouver and surrounding areas, using data collected by the Resuscitation Outcomes Consortium between September 2007 and December 2011. The kernel density techniques and regression tree analysis using binary recursive partitioning were used.

Results

We examined 1617 cases of OHCA with a mortality rate of 86.5% (95% CI 84.8-88.2). The mean age of OHCA cases was 66.6 years (95% CI 65.7-67.5), and 33.6% (95% CI 31.3-35.9) were female. The proportion with an initial shockable rhythm (VF or pulseless VT) was 22.2% (95% CI 20.2-24.2); 42.3% (95% CI 39.9-44.7) of all cases received bystander CPR, and 49.7% (95% CI 47.3-52.1) were transported to the hospital by paramedics. The rate of survival to hospital discharge with favourable neurological status (FNS) Cerebral Performance Category (CPC) 1 or 2 was 10.4% (8.9-11.9). Distance of transport to the hospital (less than 2.7 km) was a significant predictor of survival with FNS, but income did not predict survival with FNS. Areas with higher proportions of commuters by car demonstrated lower rates of survival with FNS.

Conclusion

This is the first GIS-based study to examine OHCA in a single large Canadian centre. Clustering of OHCA consistent with areas of high population density was observed. Distance of transport was a significant predictor of survival with FNS for patients with OHCA. This may have important implications for future emergency medical services deployment and dispatch decision-making, and public policy initiatives.
Hegel’s Subjective Logic as a Logic for (Hegel’s) Philosophy of Mind
Authors: Redding Paul
Published: October 2016

In the 1930s, C. I. Lewis, who was responsible for the revival of modal logic in the era of modern symbolic logic, characterized ‘intensional’ approaches to logic as typical of post-Leibnizian ‘continental philosophy’, in contrast to the ‘extensionalist’ approaches dominant in the British tradition. Indeed Lewis’s own work in this area had been inspired by the logic of his teacher, the American ‘Absolute Idealist’, Josiah Royce. Hegel’s ‘Subjective Logic’ in Book III of hisScience of Logic, can, I suggest, be considered as an intensional modal logic, and this paper explores parallels between it and a later variety of modal logic—tenselogic, as developed by Arthur Prior in the 1950s and 60s. Like Lewis, Prior too had been influenced in this area by a teacher with strong Hegelian leanings—John N. Findlay. Treated as anintensional(with an ‘s’) logic, Hegel’s subjective logic can be used as a framework for addressing issues ofintentionality(with a ‘t’)—the mind’s capacity to be intentionally directed to objects. In this way, I suggest that the structures of his subjective logic can clarify what is at issue in the ‘Psychology’ section of theEncyclopaediaPhilosophy of Subjective Spirit.
Imperfect Models: The Kingston Lunatic Asylum Scandal and the Problem of Postemancipation Imperialism
Authors: Fryar Christienna D.
Published: October 2016

This article examines an imperial scandal concerning the treatment of patients in the lunatic asylum of Kingston, Jamaica, that highlighted the inadequacies of the imperial government. A significant moment in the development of colonial public health policy, this scandal also spoke to broader questions of postemancipation imperial governance. At the heart of the scandal was a debate about whether standards of treatment developed in Britain—symbolized by the image of the ideal asylum and the ideology of moral management—could and should be implemented in colonies. This debate was all the more fraught because the designation of moral management as the official protocol was recent, its implementation incomplete, and its underlying ideas contested. Nevertheless, despite the instability of these ideas, during the scandal and its aftermath, actors treated them as a monolithic package of standards before making them the definitive model for all colonial institutions. Indeed, the scandal helped further bolster moral management in Britain.
The most elementary proof that ?
Authors: Lord Nick
Published: October 2016

Here we present a simplification of one of the standard proofs that . We then look at extensions of the new approach, and add comments on the nature of the simplification (which relates to Step 1 below) and finally on the literature.

As in most proofs of the result, we shall actually prove that ; because

this is equivalent to the result sought.
Hanoi revisited
Authors: Forbes Tamsin , Forbes Tony
Published: October 2016

We consider a simple extension of the familiar Tower of Hanoi puzzle. There are three vertical pegs lined up in a row and n discs. The discs have holes in their centres so that they can be threaded on to the pegs. Initially, all n discs are placed on the left-hand peg in non-increasing order of radius to form a tower, as in Figure 1. The object of the game is to transfer the entire tower to the right-hand peg by moving discs from peg to peg, one at a time according to the rules:

(1) only a disc at the top of a tower may be moved;

(2) a disc must never be placed on top of a smaller disc.
Unhinged Frames: Assessing Thought Experiments in Normative Political Theory
Authors: Thaler Mathias
Published: October 2016

This article develops a framework for assessing thought experiments in normative political theory. It argues that we should distinguish between relevant and irrelevant hypotheticals according to a criterion of modality. Relevant hypotheticals, while far-fetched, construct imaginary cases that are possible for us, here and now. Irrelevant hypotheticals conjure up imaginary cases that are barely conceivable at all. To establish this claim, the article interrogates, via a discussion of Susan Sontag and Judith Butler’s accounts of representations of violence, the frames through which hypotheticals construct possible worlds, and concludes that some frames are better than others at sustaining a link with the world as we know it. Frames that disrupt this link can be charged with failing to offer action-guidance.
A NOTE ON THE STYLE OF THE BELLVM HISPANIENSE. COLLOQUIALISMS AND ALLUSIVE SELF-FASHIONING?
Authors: Allendorf T.S.
Published: October 2016

The Bellum Hispaniense (= BHisp.), often considered alongside the two other pseudo-Caesarian commentarii, the Bellum Alexandrinum and the Bellum Africum, contains the account of Caesar's final battles with Pompey's forces in Spain during 46 and 45 b.c. In terms of its language and style, the BHisp. is certainly the most un-Caesarian of the pseudo-Caesarian Bella. The work abounds in phenomena belonging to different linguistic varieties, and is an important piece of evidence in the process of the standardization of written Latin.
TWO TEXTUAL PROBLEMS IN CICERO'S PHILOSOPHICA
Authors: Dyck Andrew R.
Published: October 2016

(1) deinde ibidem homo acutus, cum illud occurreret, si omnia deorsus e regione ferrentur et, ut dixi, ad lineam, numquam fore ut atomus altera alteram posset attingere †itaque† attulit rem commenticiam: declinare dixit atomum perpaulum …

(Fin. 1.19)
WATER FOR ALL? DEVELOPING A HUMAN RIGHT TO WATER IN NATIONAL AND INTERNATIONAL LAW
Authors: Arden The Rt Hon Lady Justice
Published: October 2016

Human rights are one of the great ideas of the twentieth century. After World War II, first Eleanor Roosevelt in relation to the Universal Declaration of Human Rights (‘the Universal Declaration’), and then later the drafters of the European Convention on Human Rights (‘the European Convention’) saw human rights as the way to make the world fairer and safer.
Changes in genetic variances and heritabilities in an early white maize population following S1 selection for grain yield, Striga resistance and drought tolerance
Authors: BADU-APRAKU B. , OYEKUNLE M. , TALABI A. O. , ANNOR B. , AKAOGU I. C.
Published: October 2016

Drought is a major constraint to maize production in West and Central Africa (WCA). Assessment of genetic gain from S1 recurrent selection under drought is crucial for the development of drought tolerance breeding strategies. In an early white population, 60 S1 families each derived from the base population and three cycles of selection were evaluated under drought and well-watered conditions at two locations in Nigeria for 2 years to determine genetic variability, gains from selection and predict response to selection for grain yield and other traits. Genetic variances generally decreased for yield and other traits in advanced cycles under drought and well-watered conditions except yield and ear height under well-watered conditions. Similarly, heritabilities for yield and other traits decreased in advanced cycles under drought but increased in advanced cycles under well-watered conditions. Realized gain for yield was 0·291 t/ha, corresponding to 30·5% per cycle under drought and 0·352 kg/ha with a corresponding gain of 16·7% per cycle under well-watered conditions. Predicted gain based on C3 was 0·282 and 0·583 t/ha under drought and well-watered conditions. Low genetic variances, heritabilities and predicted gain for yield and other traits suggested a need to introgress drought tolerance genes into the population.
Expression of sheep pathogenBabesiasp. Xinjiang rhoptry-associated protein 1 and evaluation of its diagnostic potential by enzyme-linked immunosorbent assay
Authors: NIU QINGLI , LIU ZHIJIE , YANG JIFEI , YU PEIFA , PAN YUPING , ZHAI BINTAO , LUO JIANXUN , GUAN GUIQUAN , YIN HONG
Published: October 2016

Ovine babesiosis is one of the most important tick-borne haemoparasitic diseases of small ruminants. The ovine parasiteBabesiasp. Xinjiang is widespread in China. In this study, recombinant full-length XJrRAP-1aα2 (rhoptry-associated protein 1aα2) and C-terminal XJrRAP-1aα2 CT ofBabesiasp. Xinjiang were expressed and used to evaluate their diagnostic potential forBabesiasp. Xinjiang infections by indirect enzyme-linked immunosorbent assay (ELISA). Purified XJrRAP-1aα2 was tested for reactivity with sera from animals experimentally infected withBabesiasp. Xinjiang and other haemoparasites using Western blotting and ELISA. The results showed no cross-reactivities between XJrRAP-1aα2 CT and sera from animals infected by other pathogens. High level of antibodies against RAP-1a usually lasted 10 weeks post-infection (wpi). A total of 3690 serum samples from small ruminants in 23 provinces located in 59 different regions of China were tested by ELISA. The results indicated that the average positive rate was 30·43%, and the infections were found in all of the investigated provinces. This is the first report on the expression and potential use of a recombinant XJrRAP-1aα2 CT antigen for the development of serological assays for the diagnosis of ovine babesiosis, caused byBabesiasp. Xinjiang.
Incident ion charge state dependence of the visible light emission of Xeq+ ions bombarding aluminum
Authors: Guo Y. , Yang Z. , Xu Q. , Ren J. , Zhao H. , Zhao Y.
Published: October 2016

In this work, we studied the photon emission in the visible light range for Xeq+ ions of different charge states (10 ≤ q ≤ 21) bombardment on an aluminum target at 410 keV. During the interactions, the spectra in wavelength range 300–500 nm are recorded, including the photons from Al atoms and neutralized Xe+ ions. The yield of the visible light strongly depends on the projectile charge states. Its variation tendency with the charge states is similar to that of the potential energy variation. In addition, the experimental results also indicate that when the incident charge state is less than the critical charge state, it obeys the staircase classical-over-barrier model.
Research of the anti-resonance pulse forming network and its application in the Marx generator
Authors: Pan Z.-L. , Yang J.-H. , Cheng X.-B.
Published: October 2016

An anti-resonance pulse forming network (PFN) has been designed, analyzed, and tested for its application in generating quasi-square pulses. According to the circuit simulations, a compact generator based on two/three-section network was constructed. Two-section network is applied in the generator due to its compact structure, while three-section network is employed for generating pulses with higher quality. When two-section network is applied in the generator, the full-width at half-maximum of the load pulse is 400 ns, at the same time, its rise time, flat top and fall time are 90, 180 and 217 ns, respectively. When the three-section network is applied with the same pulse width of the load pulse, the rise time of the output decreases to 60 ns, while the flat top increases to 240 ns and the fall time reduces to 109 ns. Meanwhile, this kind of network could be used to shape the output pulses of generators whose equivalent circuit is LC series discharge network, such as MARX generator, into quasi-square pulses. And the preliminary experiment demonstrates that anti-resonance network could work well on four-stage Marx generators. A sine pulse generated by the four-stage Marx generator is shaped into a quasi-square pulse with voltage of 11.8 kV and pulse width about 110 ns based on two-section anti-resonance network.
Cardiogenic unilateral pulmonary oedema in an infant with severe residual mitral regurgitation
Authors: Joong Anna , Lai Wyman W. , Ferris Anne
Published: October 2016

An infant with residual severe mitral regurgitation following mitral commissurotomy developed cardiogenic unilateral pulmonary oedema and subsegmental atelectasis that resolved with mechanical mitral valve replacement.
Structural priming within and across languages: a corpus-based perspective
Authors: GRIES STEFAN TH. , KOOTSTRA GERRIT JAN
Published: October 2016

Structural priming is the phenomenon that speakers tend to re-use structures they have recently comprehended or produced themselves. Most studies on this topic are experimental and looked at within-language priming. However, there are now also many observational studies, a development that is inextricably related to new/larger corpora, new statistical methodologies, and new theoretical ideas. Second, there is a growing body of research on cross-linguistic structural priming, though mostly experimental. These developments lead to a new potential research avenue: cross-linguistic priming on the basis of observational data. Here, we will first summarize some fundamental studies of cross-linguistic priming, and then trace the historical development of observational studies of structural priming to showcase how statistical and theoretical developments have shaped research on priming in general and discuss what such observational priming research has offered to within-language priming research. We end with a discussion of how this research can inform cross-linguistic priming.
Influence of sociodemographic characteristics on different dimensions of household food insecurity in Montevideo, Uruguay
Authors: Rossi Máximo , Ferre Zuleika , Curutchet María Rosa , Giménez Ana , Ares Gastón
Published: October 2016

Objective

To determine the factor structure of the Latin American & Caribbean Household Food Security Scale (ELCSA) and to study the influence of sociodemographic characteristics on each of the identified dimensions in Montevideo, Uruguay.

Design

Cross-sectional survey with a representative sample of urban households. Household food insecurity was measured using the ELCSA. The percentage of respondents who gave affirmative responses for each of the items of the ELCSA was determined. Exploratory factor analysis was carried out to determine the ELCSA’s factor structure. A probit model was used to determine the impact of some individual and household sociodemographic characteristics on the identified dimensions of food insecurity.

Setting

Metropolitan area centred on Montevideo, the capital city of Uruguay, April–September 2014.

Subjects

Adults aged between 18 and 93 years (n742).

Results

The percentage of affirmative responses to the items of the ELCSA ranged from 4·4 to 31·7 %. Two factors were identified in the exploratory factor analysis performed on data from households without children under 18 years old, whereas three factors were identified for households with children. The identified factors were associated with different severity levels of food insecurity. Likelihood of experiencing different levels of food insecurity was affected by individual characteristics of the respondent as well as characteristics of the household.

Conclusions

The influence of sociodemographic variables varied among the ELCSA dimensions. Household income had the largest influence on all dimensions, which indicates a strong relationship between income and food insecurity.
TRIAL AND ERROR MATHEMATICS II: DIALECTICAL SETS AND QUASIDIALECTICAL SETS, THEIR DEGREES, AND THEIR DISTRIBUTION WITHIN THE CLASS OF LIMIT SETS
Authors: AMIDEI JACOPO , PIANIGIANI DUCCIO , MAURO LUCA SAN , SORBI ANDREA
Published: October 2016

This paper is a continuation of Amidei, Pianigiani, San Mauro, Simi, & Sorbi (2016), where we have introduced the quasidialectical systems, which are abstract deductive systems designed to provide, in line with Lakatos’ views, a formalization of trial and error mathematics more adherent to the real mathematical practice of revision than Magari’s original dialectical systems. In this paper we prove that the two models of deductive systems (dialectical systems and quasidialectical systems) have in some sense the same information content, in that they represent two classes of sets (the dialectical sets and the quasidialectical sets, respectively), which have the same Turing degrees (namely, the computably enumerable Turing degrees), and the same enumeration degrees (namely, the ${\rm{\Pi }}_1^0$ enumeration degrees). Nonetheless, dialectical sets and quasidialectical sets do not coincide. Even restricting our attention to the so-called loopless quasidialectical sets, we show that the quasidialectical sets properly extend the dialectical sets. As both classes consist of ${\rm{\Delta }}_2^0$ sets, the extent to which the two classes differ is conveniently measured using the Ershov hierarchy: indeed, the dialectical sets are ω-computably enumerable (close inspection also shows that there are dialectical sets which do not lie in any finite level; and in every finite level n ≥ 2 of the Ershov hierarchy there is a dialectical set which does not lie in the previous level); on the other hand, the quasidialectical sets spread out throughout all classes of the hierarchy (close inspection shows that for every ordinal notation a of a nonzero computable ordinal, there is a quasidialectical set lying in ${\rm{\Sigma }}_a^{ - 1}$, but in none of the preceding levels).
Taxonomy of the archosaurOrnithosuchus: reassessingOrnithosuchus woodwardiNewton, 1894 andDasygnathoides longidens(Huxley 1877)
Authors: von Baczko M. Belén , Ezcurra Martín D.
Published: October 2016

The pseudosuchian archosaurOrnithosuchus, from the Lossiemouth Sandstone Formation (Late Triassic), Scotland, was the first ornithosuchid to be discovered, and the only one recorded, in the northern hemisphere. The fossil record of“Ornithosuchus longidens”is mainly based on natural moulds and, in a few cases, three-dimensional bony elements, complicating the interpretation of its anatomy. The taxonomy of this species has changed several times since the late 1800s and here we revisit its current status. The synonymy of“Dasygnathoides longidens”andOrnithosuchus woodwardiproposed by Walker (1964) is rejected, based on new interpretations of the holotype and referred specimens of“Dasygnathoides longidens”. The latter species is considered as anomen dubium, because it lacks diagnostic features and cannot be identified beyond Pseudosuchia. As a result,Ornithosuchus woodwardiis resurrected as a valid species and its diagnosis is emended. The body size range ofOrnithosuchus woodwardiis reduced to about a half, because ELGNM 1, previously considered the largest specimen of the genus, can no longer be referred to it.“Dasygnathoides longidens”cannot be assigned to any of the known archosauriforms from the Lossiemouth Sandstone Formation, but it still represents the largest predator currently known for its fauna.
Arsenic-induced instrumental genes of apoptotic signal amplification in death-survival interplay
Authors: Roy Sonali , Narzary Bardwi , Ray Atish , Bordoloi Manobjyoti
Published: October 2016

Arsenic is a global health concern at present and it is well reported for causing systemic toxicity. It is also well known for generation of free radical and inducing apoptosis in different cell types. Paradoxically arsenic is reported to be a susceptible carcinogen as well. There are several reports demonstrating diverse mechanism of apoptosis in different cell types. However, the universal scenario of instrumental genes and their interaction leading to amplification of apoptotic signal are yet to be completely uncovered, which is predicted here. Conventional studies on signaling pathway aided by time and concentration kinetics data are inadequate for prediction of anchored genes for apoptotic signal amplification. Therefore, expression profile-based approach is adopted. Core apoptosis related and glutathione metabolism genes in 1 and 10 μM of arsenic-treated HepG2 cells were analyzed after 12 h of incubation. An arsenic treatment of 1 μM exhibits no cell death at 12 h, whereas 10 μM arsenic treatment reveals around 50% cell death at 12 h. Results depict 28 and 44 affected genes in 1 and 10 μM arsenic-treated cells, respectively. Early initiation of apoptotic signaling is detected in no cell death regimens (at 1 μM), whereas amplified apoptotic signal is demonstrated at 50% cell death regimens (at 10 μM). Instrumental genes involved in progression of apoptosis in the concourse of cell death and survival is designated from the responsive genes common to both the condition. We predict the initiation process is fairly aided by the activation of intrinsic pathway, which is amplified via TNF signaling and extrinsic pathway. Furthermore, regulatory genes involved in interplay between apoptosis/anti-apoptosis and their interactions are demonstrated here.
Heterogeneity, functional specialization and differentiation of monocyte‐derived dendritic cells
Authors: Chow Kevin V , Sutherland Robyn M , Zhan Yifan , Lew Andrew M
Published: October 2016

Dendritic cells (DCs) are professional antigen‐presenting cells that consist of functionally and phenotypically heterogeneous populations. Monocyte‐derived DCs (moDCs) are a DC subset that have been attracting increasing interest owing to their potent influence on adaptive immune function and their rapid accumulation upon an inflammatory stimulus. Although early studies on moDCs mainly addressed infection, their emergence and function in other settings such as autoimmunity and allogeneic organ transplantation are now being increasingly appreciated. In this review, the relationship between murine monocyte subsets and the moDCs that arise from them is discussed. Their role in initiating and modulating innate and adaptive immune responses in various pathophysiological scenarios is also explored, including how they may separate their labour from conventional DCs. How these findings might relate to their human counterparts is also discussed. Overall, monocytes and moDCs exhibit complex and heterogeneous behaviours that are critical in responses against microbial invasion, autoimmunity and allograft rejection.
Stereotypic wheel running decreases cortical activity in mice
Authors: Fisher Simon P. , Cui Nanyi , McKillop Laura E. , Gemignani Jessica , Bannerman David M. , Oliver Peter L. , Peirson Stuart N. , Vyazovskiy Vladyslav V.
Published: October 2016

Prolonged wakefulness is thought to gradually increase ‘sleep need’ and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours.
Genome scans for divergent selection in natural populations of the widespread hardwood species Eucalyptus grandis (Myrtaceae) using microsatellites
Authors: Song Zhijiao , Zhang Miaomiao , Li Fagen , Weng Qijie , Zhou Chanpin , Li Mei , Li Jie , Huang Huanhua , Mo Xiaoyong , Gan Siming
Published: October 2016

Identification of loci or genes under natural selection is important for both understanding the genetic basis of local adaptation and practical applications, and genome scans provide a powerful means for such identification purposes. In this study, genome-wide simple sequence repeats markers (SSRs) were used to scan for molecular footprints of divergent selection in Eucalyptus grandis, a hardwood species occurring widely in costal areas from 32° S to 16° S in Australia. High population diversity levels and weak population structure were detected with putatively neutral genomic SSRs. Using three FST outlier detection methods, a total of 58 outlying SSRs were collectively identified as loci under divergent selection against three non-correlated climatic variables, namely, mean annual temperature, isothermality and annual precipitation. Using a spatial analysis method, nine significant associations were revealed between FST outlier allele frequencies and climatic variables, involving seven alleles from five SSR loci. Of the five significant SSRs, two (EUCeSSR1044 and Embra394) contained alleles of putative genes with known functional importance for response to climatic factors. Our study presents critical information on the population diversity and structure of the important woody species E. grandis and provides insight into the adaptive responses of perennial trees to climatic variations.
Fluorescence-based characterization of non-fluorescent transient states of tryptophan – prospects for protein conformation and interaction studies
Authors: Hevekerl Heike , Tornmalm Johan , Widengren Jerker
Published: October 2016

Tryptophan fluorescence is extensively used for label-free protein characterization. Here, we show that by analyzing how the average tryptophan fluorescence intensity varies with excitation modulation, kinetics of tryptophan dark transient states can be determined in a simple, robust and reliable manner. Thereby, highly environment-, protein conformation- and interaction-sensitive information can be recorded, inaccessible via traditional protein fluorescence readouts. For verification, tryptophan transient state kinetics were determined under different environmental conditions, and compared to literature data. Conformational changes in a spider silk protein were monitored via the triplet state kinetics of its tryptophan residues, reflecting their exposure to an air-saturated aqueous solution. Moreover, tryptophan fluorescence anti-bunching was discovered, reflecting local pH and buffer conditions, previously observed only by ultrasensitive measurements in highly fluorescent photo-acids. Taken together, the presented approach, broadly applicable under biologically relevant conditions, has the potential to become a standard biophysical approach for protein conformation, interaction and microenvironment studies.
Exocrine pancreatic function in children with Alagille syndrome
Authors: Gliwicz Dorota , Jankowska Irena , Wierzbicka Aldona , Miśkiewicz-Chotnicka Anna , Lisowska Aleksandra , Walkowiak Jarosław
Published: October 2016

Alagille syndrome (AGS) is often associated with symptoms of maldigestion, such as steatorrhea, hypotrophy and growth retardation. Exocrine pancreatic insufficiency was proposed as the underlying cause. We aimed to assess the exocrine pancreatic function with the use of different methods in AGS patients. Concentrations of fecal elastase-1 (FE1) and fecal lipase (FL) activities were measured in 33 children with AGS. The C-mixed triglyceride breath test (MTBT) in a subgroup comprising 15 patients. In all patients studied, FE1 concentrations and FL activities were normal. Abnormal MTBT results were documented in 4 (26.7%) patients. The FE1 and FL levels in MTBT-positive and MTBT-negative children did not differ. The results of this research do not confirm the presence of exocrine pancreatic dysfunction in AGS patients. Routine screening for exocrine pancreatic insufficiency of this group of patients is not necessary.
Dynamic Phosphoproteome Analysis of Seedling Leaves in Brachypodium distachyon L. Reveals Central Phosphorylated Proteins Involved in the Drought Stress Response
Authors: Yuan Lin-Lin , Zhang Ming , Yan Xing , Bian Yan-Wei , Zhen Shou-Min , Yan Yue-Ming
Published: October 2016

Drought stress is a major abiotic stress affecting plant growth and development. In this study, we performed the first dynamic phosphoproteome analysis ofBrachypodium distachyonL. seedling leaves under drought stress for different times. A total of 4924 phosphopeptides, contained 6362 phosphosites belonging to 2748 phosphoproteins. Rigorous standards were imposed to screen 484 phosphorylation sites, representing 442 unique phosphoproteins. Comparative analyses revealed significant changes in phosphorylation levels at 0, 6, and 24 h under drought stress. The most phosphorylated proteins and the highest phosphorylation level occurred at 6 h. Venn analysis showed that the up-regulated phosphopeptides at 6 h were almost two-fold those at 24 h. Motif-X analysis identified the six motifs: [sP], [Rxxs], [LxRxxs], [sxD], [sF], and [TP], among which [LxRxxs] was also previously identified inB. distachyon. Results from molecular function and protein-protein interaction analyses suggested that phosphoproteins mainly participate in signal transduction, gene expression, drought response and defense, photosynthesis and energy metabolism, and material transmembrane transport. These phosphoproteins, which showed significant changes in phosphorylation levels, play important roles in signal transduction and material transmembrane transport in response to drought conditions. Our results provide new insights into the molecular mechanism of this plant’s abiotic stress response through phosphorylation modification.
Prospective study of serum B vitamins levels and oesophageal and gastric cancers in China
Authors: Ren Jiansong , Murphy Gwen , Fan Jinhu , Dawsey Sanford M. , Taylor Philip R. , Selhub Jacob , Qiao Youlin , Abnet Christian C.
Published: October 2016

B vitamins play an essential role in DNA synthesis and methylation, and may protect against oesophageal and gastric cancers. In this case-cohort study, subjects were enrolled from the General Population Nutrition Intervention Trial in Linxian, China. Subjects included 498 oesophageal squamous cell carcinomas (OSCCs), 255 gastric cardia adenocarcinomas (GCAs), and an age- and sex-matched sub-cohort of 947 individuals. Baseline serum riboflavin, pyridoxal phosphate (PLP), folate, vitamin B12, and flavin mononucleotide (FMN) were measured for all subjects. We estimated the associations with Cox proportional hazard models, with adjustment for potential confounders. Compared to those in the lowest quartile of serum riboflavin, those in the highest had a 44% lower risk of OSCC (HR: 0.56, 95% CI: 0.41 to 0.75). Serum vitamin B12 as a continuous variable was observed to be significantly inversely associated with OSCC (HR: 0.95, 95% CI: 0.89 to 1.01, P for score test = 0.041). Higher serum FMN levels were significantly associated with increased risk of OSCC (HR: 1.08, 95% CI: 1.01 to 1.16) and GCA (HR: 1.09, 95% CI: 1.00 to 1.20). Our study prompted that B vitamins have the potential role as chemopreventive agents for upper gastrointestinal cancers.
Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus
Authors: Sheridan Kevin J. , Lechner Beatrix Elisabeth , Keeffe Grainne O’ , Keller Markus A. , Werner Ernst R. , Lindner Herbert , Jones Gary W. , Haas Hubertus , Doyle Sean
Published: October 2016

Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation. Quantitative proteomic analysis revealed substantial proteomic remodelling in ΔegtA compared to wild-type under both basal and ROS conditions, whereby the abundance of 290 proteins was altered. Specifically, the reciprocal differential abundance of cystathionine γ-synthase and β-lyase, respectively, influenced cystathionine availability to effect EGT biosynthesis. A combined deficiency in EGT biosynthesis and the oxidative stress response regulator Yap1, which led to extreme oxidative stress susceptibility, decreased resistance to heavy metals and production of the extracellular siderophore triacetylfusarinine C and increased accumulation of the intracellular siderophore ferricrocin. EGT dissipated H2O2in vitro, and elevated intracellular GSH levels accompanied abrogation of EGT biosynthesis. EGT deficiency only decreased resistance to high H2O2 levels which suggests functionality as an auxiliary antioxidant, required for growth at elevated oxidative stress conditions. Combined, these data reveal new interactions between cellular redox homeostasis, secondary metabolism and metal ion homeostasis.
The primary transcriptome of the Escherichia coli O104:H4 pAA plasmid and novel insights into its virulence gene expression and regulation
Authors: Berger Petya , Knödler Michael , Förstner Konrad U. , Berger Michael , Bertling Christian , Sharma Cynthia M. , Vogel Jörg , Karch Helge , Dobrindt Ulrich , Mellmann Alexander
Published: October 2016

Escherichia coli O104:H4 (E. coli O104:H4), which caused a massive outbreak of acute gastroenteritis and hemolytic uremic syndrome in 2011, carries an aggregative adherence fimbriae I (AAF/I) encoding virulence plasmid, pAA. The importance of pAA in host-pathogen interaction and disease severity has been demonstrated, however, not much is known about its transcriptional organization and gene regulation. Here, we analyzed the pAA primary transcriptome using differential RNA sequencing, which allows for the high-throughput mapping of transcription start site (TSS) and non-coding RNA candidates. We identified 248 TSS candidates in the 74-kb pAA and only 21% of them could be assigned as TSS of annotated genes. We detected TSS for the majority of pAA-encoded virulence factors. Interestingly, we mapped TSS, which could allow for the transcriptional uncoupling of the AAF/I operon, and potentially regulatory antisense RNA candidates against the genes encoding dispersin and the serine protease SepA. Moreover, a computational search for transcription factor binding sites suggested for AggR-mediated activation of SepA expression, which was additionally experimentally validated. This work advances our understanding of the molecular basis of E. coli O104:H4 pathogenicity and provides a valuable resource for further characterization of pAA virulence gene regulation.
Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies
Authors: Clement Mathew , Pearson James A. , Gras Stephanie , van den Berg Hugo A. , Lissina Anya , Llewellyn-Lacey Sian , Willis Mark D. , Dockree Tamsin , McLaren James E. , Ekeruche-Makinde Julia , Gostick Emma , Robertson Neil P. , Rossjohn Jamie , Burrows Scott R. , Price David A. , Wong F. Susan , Peakman Mark , Skowera Ania , Wooldridge Linda
Published: October 2016

CD8+ T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8+ T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8+ T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8+ T-cells are relatively CD8-independent. These generic differences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-specific TCRs according to the monomeric interaction affinity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, “blocking” anti-CD8 antibodies can suppress autoreactive CD8+ T-cell activation in a relatively selective manner. These findings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8+ T-cell compartment.
Binding of cellulose binding modules reveal differences between cellulose substrates
Authors: Arola Suvi , Linder Markus B.
Published: October 2016

The interaction between cellulase enzymes and their substrates is of central importance to several technological and scientific challenges. Here we report that the binding of cellulose binding modules (CBM) from Trichoderma reesei cellulases Cel6A and Cel7A show a major difference in how they interact with substrates originating from wood compared to bacterial cellulose. We found that the CBM from TrCel7A recognizes the two substrates differently and as a consequence shows an unexpected way of binding. We show that the substrate has a large impact on the exchange rate of the studied CBM, and moreover, CBM-TrCel7A seems to have an additional mode of binding on wood derived cellulose but not on cellulose originating from bacterial source. This mode is not seen in double CBM (DCBM) constructs comprising both CBM-TrCel7A and CBM-TrCel6A. The linker length of DCBMs affects the binding properties, and slows down the exchange rates of the proteins and thus, can be used to analyze the differences between the single CBM. These results have impact on the cellulase research and offer new understanding on how these industrially relevant enzymes act.
Prognosis of alcohol-associated lactic acidosis in critically ill patients: an 8-year study
Authors: Yang Chun-Chieh , Chan Khee-Siang , Tseng Kuei-Ling , Weng Shih-Feng
Published: October 2016

Lactic acidosis is common in critical care; by contrast, a subtype called alcohol-associated lactic acidosis (AALA) is rarely encountered. The primary purpose of this study was to determine the prognosis of AALA in critically ill patients and the second aim was to determine whether the survival was associated to the peak blood lactate concentration. An 8-year retrospective analysis of adult patients admitted to the intensive care unit (ICU) with AALA between January 2007 and December 2014 was considered in a tertiary care hospital. In total, 23 patients were analyzed and the median peak blood lactate level was 15.9 mmol/L. Only 2 patients (8.7%) presented peak blood lactate levels <10 mmol/L. In this study, 21 patients survived from ICU and hospital, the mortality rate was 8.7%. The result indicted the survival of AALA was not associated with peak blood lactate concentration although survivors still had a better lactate clearance rate per hour than non-survivors. Moreover, AALA patients with coexisting sepsis presenting higher lactate clearance rate and shorter lactate clearance time than those of AALA patients with solely sepsis-related lactic acidosis.
Cation/Anion Substitution in Cu2ZnSnS4 for Improved Photovoltaic Performance
Authors: Ananthoju Balakrishna , Mohapatra Jeotikanta , Jangid Manoj K. , Bahadur D. , Medhekar N. V. , Aslam M.
Published: October 2016

Cations and anions are replaced with Fe, Mn, and Se in CZTS in order to control the formations of the secondary phase, the band gap, and the micro structure of Cu2ZnSnS4. We demonstrate a simplified synthesis strategy for a range of quaternary chalcogenide nanoparticles such as Cu2ZnSnS4 (CZTS), Cu2FeSnS4 (CFTS), Cu2MnSnS4 (CMTS), Cu2ZnSnSe4 (CZTSe), and Cu2ZnSn(S0.5Se0.5)4 (CZTSSe) by thermolysis of metal chloride precursors using long chain amine molecules. It is observed that the crystal structure, band gap and micro structure of the CZTS thin films are affected by the substitution of anion/cations. Moreover, secondary phases are not observed and grain sizes are enhanced significantly with selenium doping (grain size ~1 μm). The earth-abundant Cu2MSnS4/Se4 (M = Zn, Mn and Fe) nanoparticles have band gaps in the range of 1.04–1.51 eV with high optical-absorption coefficients (~104 cm−1) in the visible region. The power conversion efficiency of a CZTS solar cell is enhanced significantly, from 0.4% to 7.4% with selenium doping, within an active area of 1.1 ± 0.1 cm2. The observed changes in the device performance parameters might be ascribed to the variation of optical band gap and microstructure of the thin films. The performance of the device is at par with sputtered fabricated films, at similar scales.
Accurate and stable equal-pressure measurements of water vapor transmission rate reaching the 10−6 g m−2 day−1 range
Authors: Nakano Yoichiro , Yanase Takashi , Nagahama Taro , Yoshida Hajime , Shimada Toshihiro
Published: October 2016

The water vapor transmission rate (WVTR) of a gas barrier coating is a critically important parameter for flexible organic device packaging, but its accurate measurement without mechanical stress to ultrathin films has been a significant challenge in instrumental analysis. At the current stage, no reliable results have been reported in the range of 10−6 g m−2 day−1 that is required for organic light emitting diodes (OLEDs). In this article, we describe a solution for this difficult, but important measurement, involving enhanced sensitivity by a cold trap, stabilized temperature system, pumped sealing and calibration by a standard conductance element.