bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of operating condition on the denitrifying bacterial community structure in a 3DBER-SAD reactor
Authors: Hao Ruixia , Meng Chengcheng , Li Jianbing
Published: October 2016

Two main operating parameters (influent C/N ratio and electric current intensity) were examined for their impacts on the denitrifying bacterial community structure in an integrated system of three-dimensional biofilm-electrode reactor and sulfur autotrophic denitrification (3DBER-SAD). It was found that genus β-proteobacteria played a leading role under different operating conditions. The influent C/N ratio illustrated a great impact on denitrifying bacteria diversity. When the C/N ratio decreased from 1.07 to 0.36, the Shannon–Wiener index and Simpson index increased from 2.44 to 2.71 and from 0.89 to 0.92, respectively, while the proportion of heterotrophic denitrifying bacteria Thauera decreased from 61.4 to 21.1%, and the sulfur autotrophic denitrifying bacteria (e.g., genus Sulfuricella and Thiobacillus denitrificans) increased from 3.5 to 19.3%. In terms of the impact of electric current intensity, the Shannon–Wiener index and Simpson index decreased from 2.71 to 2.63 and from 0.92 to 0.90, respectively, as the current intensity increased from 60 to 400 mA.
Complex fractionated atrial electrograms, high dominant frequency regions, and left atrial voltages during sinus rhythm and atrial fibrillation
Authors: Sasaki Naoko , Watanabe Ichiro , Okumura Yasuo , Nagashima Koichi , Kogawa Rikitake , Sonoda Kazumasa , Iso Kazuki , Takahashi Keiko , Arai Masaru , Watanabe Ryuta , Kurokawa Sayaka , Ohkubo Kimie , Nakai Toshiko , Hirayama Atsushi , Nikaido Mizuki
Published: October 2016

Background

Ablation targeting complex fractionated atrial electrograms (CFAEs) or high dominant frequency (DF) sites is generally effective for persistent atrial fibrillation (AF). CFAEs and/or high DF sites may exist in low‐voltage regions, which theoretically represent abnormal substrates. However, whether CFAEs or high DF sites reflect low voltage substrates during sinus rhythm (SR) is unknown.

Methods

Sixteen patients with AF (8 with paroxysmal AF; 8, persistent AF) underwent high‐density mapping of the left atrium (LA) with a 3‐dimensional electroanatomic mapping system before ablation. The LA was divided into 7 segments and the mean bipolar voltage recorded during AF and SR, CFAEs (cycle lengths of 50–120 ms), and DF sites were assessed in each segment with either a duo‐decapolar ring catheter (n=10) or a 64‐pole basket catheter (n=6). Low‐voltage areas were defined as those of <0.5 mV during AF and <1.0 mV during SR.

Results

Regional mean voltage recorded from the basket catheter showed good correlation between AF and SR (r=0.60, p<0.01); however, the % low‐voltage area in the LA recorded from the ring catheter showed weak correlation (r=0.34, p=0.05). Mean voltage was lower during AF than during SR (1.0 mV [IQR, 0.5–1.4] vs. 2.6 mV [IQR, 1.8–3.6], p<0.01). The regional and overall % low‐voltage area of the LA was greater during AF than during SR (20% vs. 11%, p=0.05). CFAEs and high DF sites (>8 Hz) did not correlate with % low‐voltage sites during SR; however, CFAEs sites were located in high‐voltage regions during AF and high DF sites were located in low voltage regions during AF.

Conclusions

CFAEs and high DF areas during AF do not reflect damaged atrial myocardium as shown by the SR voltage. However, CFAEs and high DF sites may demonstrate different electrophysiologic properties because of different voltage amplitude during AF.
A multicenter, randomized, placebo‐controlled trial for cilostazol in patients with mild cognitive impairment: The COMCID study protocol
Authors: Saito Satoshi , Kojima Shinsuke , Oishi Naoya , Kakuta Ryosuke , Maki Takakuni , Yasuno Fumihiko , Nagatsuka Kazuyuki , Yamamoto Haruko , Fukuyama Hidenao , Fukushima Masanori , Ihara Masafumi
Published: October 2016

Introduction

There are currently no effective treatments preventing conversion from mild cognitive impairment (MCI) to Alzheimer's disease. Cilostazol is a selective type‐3 phosphodiesterase inhibitor that ameliorates accumulation of amyloid‐β and has prevented cognitive decline in rodent models. Furthermore, cilostazol is known to suppress platelet aggregation, protect vascular endothelia, dilate vessels, and increase cerebral blood flow. Beneficial effects have also been shown in observational cohort studies, demonstrating the need for a prospective clinical trial.

Methods

The Cilostazol for prevention of COnversion from MCI to Dementia (COMCID) study is a double‐blind, randomized phase II study of patients with MCI. Participants will receive cilostazol or placebo for 96 weeks. The primary objective is to evaluate whether cilostazol slows down cognitive decline measured by the Mini‐Mental State Examination. Secondary objectives are assessing time to conversion from MCI to dementia and assessing incremental changes in several psychological assessment scales.

Discussion

The COMCID trial will identify the therapeutic potential of cilostazol. This trial, which is based on a drug repositioning strategy, may aid the development of a neurovascular treatment for neurocognitive disorders.
Management of Burn Injuries in the Wilderness: Lessons from Low-Resource Settings
Authors: Bitter Cindy C. , Erickson Timothy B.
Published: October 2016

Burns are a common source of injuries worldwide, with a high burden of disease in low- and middle-income countries. Burns also account for 2%−8% of wilderness injuries. Although many are minor, the potential for serious morbidity and mortality exists, and standard treatments used in high-resource settings are not readily available in the backcountry. A literature review was performed to find evidence from low-resource settings that supports alternative or improvised therapies that may be adapted to care of burns in the wilderness. There is good evidence for use of oral rehydration to support volume status in burn patients. There is moderate evidence to support cold therapy as first aid and adjunct for pain control. Some evidence supports use of alternative dressings such as boiled potato peel, banana leaf, aloe vera, honey, sugar paste, and papaya when standard therapies are not available.
A pilot study examining the speed and accuracy of triage for simulated disaster patients in an emergency department setting: Comparison of a computerized version of Canadian Triage Acuity Scale (CTAS) and Simple Triage and Rapid Treatment (START) methods
Authors: Curran-Sills Gwynn , Franc Jeffrey M.
Published: October 2016

Objective

To compare emergency department triage nurses’ time to triage and accuracy of a simulated mass casualty incident (MCI) population using a computerized version of CTAS or START systems.

Methods

This pilot study was a prospective trial using a convenience sample. A total of 20 ED triage nurses, 10 in each arm of the study, were recruited. The paper-based questionnaire contained nine simulated MCI vignettes. An expert panel arrived at consensuses on the wording of the vignettes and created a standard triage score from which to compare the study participants. Linear regression and chi-squared test were used to examine the time to triage and accuracy of triage, respectively.

Results

The mean triage time for computerized CTAS (cCTAS) and START were 138 seconds/patient and 33 seconds/patient, respectively. The effect size due to triage method was 108 seconds/patient (95% CI 83-134 seconds/patient). The cumulative triage accuracy for the cCTAS and START tools were 70/90 (77.8%) and 65/90 (72.2%), respectively. The percent difference between cumulative triage was 6% (95% CI −19-8%).

Conclusions

Triage nurses completed START triage 105 seconds/patient faster when compared to cCTAS triage and a similar level of accuracy between the two methods was achieved. However, when the typing time is taken into consideration cCTAS took 45 seconds/patient longer. The use of either CTAS or START in the ED during a MCI may be reasonable but choosing one method over another is not justified from this investigation.
Increased IgG antibody responses to excretory/secretory antigens in neonates born from mothers infected with filarial nematodes
Authors: Achary K.G. , Bal M.S. , Mandal N.N. , Satapathy A.K.
Published: October 2016

The present investigation aimed to evaluate the extent to which maternal filarial infection influences IgG subclass immune responses in the cord blood of neonates. Prevalence of antigenaemia was detected using an Og4C3 assay. Filaria-specific IgG subclasses against excretory/secretory antigens were measured by ELISA. Transplacental transfer of circulating filarial antigen (CFA) was observed from 34.8% of CFA-positive mothers to their respective cord bloods. Filaria-specific IgG1, IgG2 and IgG4 responses were significantly higher among cord bloods of infected mothers compared to cord bloods of uninfected mothers. In contrast, the IgG3 response was significantly higher among cord bloods of uninfected mothers. The study shows that transplacental transfer of filarial antigens and filaria-specific IgG4 occurs more in mothers having high worm burdens, and transfer of filaria-specific IgG3 occurs more in the cord blood of uninfected mothers. The findings of the study provide evidence for the development of prenatal sensitization to filarial antigens in utero, and high filaria-specific IgG4 in cord blood may serve as a marker for in-utero sensitization.
Effects of anatomical variation on trainee performance in a virtual reality temporal bone surgery simulator
Authors: Piromchai P , Ioannou I , Wijewickrema S , Kasemsiri P , Lodge J , Kennedy G , O'Leary S
Published: October 2016

Objective:

To investigate the importance of anatomical variation in acquiring skills in virtual reality cochlear implant surgery.

Methods:

Eleven otolaryngology residents participated in this study. They were randomly allocated to practice cochlear implant surgery on the same specimen or on different specimens for four weeks. They were then tested on two new specimens, one standard and one challenging. Videos of their performance were de-identified and reviewed independently, by two blinded consultant otolaryngologists, using a validated assessment scale. The scores were compared between groups.

Results:

On the standard specimen, the round window preparation score was 2.7 ± 0.4 for the experimental group and 1.7 ± 0.6 for the control group (p = 0.01). On the challenging specimen, instrument handling and facial nerve preservation scores of the experimental group were 3.0 ± 0.4 and 3.5 ± 0.7 respectively, while the control group received scores of 2.1 ± 0.8 and 2.4 ± 0.9 respectively (p < 0.05).

Conclusion:

Training on temporal bones with differing anatomies is beneficial in the development of expertise.
An archaeological analysis of a battlefield of the Second Punic War: the camps of the battle of Baecula
Authors: Bellón Juan Pedro , Rueda Carmen , Lechuga Miguel Ángel , Moreno María Isabel
Published: October 2016

Since 2002, our team at the University of Jaén's Research Institute for Iberian Archaeology has been undertaking an archaeological research project focusing on the analysis of the site of a conflict that can indisputably be dated to the final phase of the Second Punic War. Based on the topography, descriptions in the ancient sources, and archaeological data, we present the hypothesis that the site we have located corresponds to that of the battle of Baecula. In that confrontation in 208 B.C., Scipio the Younger faced Hasdrubal Barca. It was a momentous battle, at least in terms of its subsequent outcome, given that it could be considered the event that triggered Hasdrubal's withdrawal to Italy.

Our research project has yielded information which we believe to be paradigmatic in two respects. First, we have been able to ascertain the size of the area over which an armed confrontation of this type would have taken place, thanks to the identification of determining elements such as the different camps set up for the battle and their sizes. It covers the area where the armies clashed, where they were positioned and deployed, their movements on the battlefield, and so forth. Second, thanks to intensive sampling, we have recovered a corpus of finds that may be used in the future as a reference for the allocation of other sites to the period of the Second Punic War.
On Giacomo Boni, the origins of the Forum, and where we stand today
Authors: Ammerman Albert J.
Published: October 2016

The pioneer in excavating early sites in the Roman Forum was Giacomo Boni (b. Venice 1859; d. Rome 1925). He lived through the turbulent years when the new nation of Italy was starting to find its stride. A number of puzzles associated with his life and work, in particular the origins of the Forum, are starting to be better understood; by digging more deeply into archives in Milan, Rome and Venice, it has been possible to make gains. A conference held recently in Venice gave the opportunity to bring together the two sides of his life in Venice and Rome. In a moment, something will be said about the new perspectives that were discussed at the Convegno. Then I will turn to Boni's work in the Forum and his ideas about its origins. In the final section I will discuss briefly where the study of the origins of the Forum now stands. Returning to this question gives an opportunity to update the gains (e.g., the discovery of clay beds in the Velabrum) that have been made over the last 25 years, specific questions that remain open (the dating of the first gravel pavement of the Forum), and the work that needs to be done.
Early Roman copper-alloy brooch production: a compositional analysis of 400 brooches from Germania Inferior
Authors: Roxburgh Marcus , Heeren Stijn , Huisman Hans , Van Os Bertil
Published: October 2016

We present here a compositional study of a large number of copper-alloy brooches, undertaken in 2014 using Handheld X-ray Fluorescence Spectrometry (HHpXRF). The brooches, which come from the area of Nijmegen, date from the Late Iron Age until the 2nd c. A.D. Our aim is to explore the ways in which artefact production was organized both in the context of Roman centres and in the countryside. The link between alloys and workshop organization will be elucidated before the methodology and results are presented. The results will then be discussed, leading to the formation of several hypotheses regarding the organization of workshops that produced metal artefacts.

Scientific interest in the composition of ancient artefacts has existed for well over two centuries. Roman brooches in particular have been in the forefront of this research both because of their ease of categorization and because they are found in large numbers on archaeological sites. Much work has been done on how they were made and on the technical choices available to the craftsmen. In particular, the choice of alloying agents (tin, lead, zinc) added to copper demonstrated a complex relationship between composition and typology, especially in the debate over Roman or local production. The technological restraints imposed on these artefacts by different alloy ratios have been studied in some detail, especially in terms of casting in liquid form, into a mould, or being wrought through beating with a hammer.
Tire choices in Roman chariot racing
Authors: Sandor Bela I.
Published: October 2016

Formal chariot racing was a sophisticated and popular sport for over 1800 years, from Etruria in the 6th c. B.C. down to the fall of Constantinople, and the races held in a large number of circuses and hippodromes imply that huge numbers of racing chariots were made over the course of those centuries. It may therefore be thought surprising that no racing machine has been found, but the dearth of such hardware is plausible given the perishable wood and leather components of the lightweight vehicles and the desirability of recycling the metal parts. In this situation a particular artifact must be accorded special significance. It is a hand-sized bronze model of a Roman racing biga, known as the Tiber model because found in the river. Dated to the 1st-2nd c. A.D., it is now on display in the British Museum (GR 1894.10-30.1, Bronze 2694). With this model as our guide, all the major dimensions of Roman racing chariots have been reasonably well determined; further, several technical aspects (some obvious, others quite subtle) of actual racing chariots can be established from it. Among the subtle details of the model, one feature is especially intriguing in view of the remarkably realistic work of its maker, who was clearly knowledgeable in matters large and small of vehicular racing. As first mentioned to me by J. Swaddling of the British Museum during our latest study of the model (November 2014), an unusual tire configuration is apparently represented on this all-bronze model: the right wheel has a slightly raised rim, as if to indicate a thin iron tire, but the left wheel lacks this feature (fig. 1). This asymmetrical arrangement is not only curious, it also implies extra work and expense. What, then, could be the reason for it?

One possibility for having apparently only one tire on the Tiber model — which was probably a toy for a rich individual; the emperor Nero, an avid racer, was said to play with toy chariots — is that two different castings were used in the toy's production, and either one could have been used in the assembly, in random selection from a box.
An amulet from London and events surrounding the Antonine Plague
Authors: Jones Christopher P.
Published: October 2016

R. S. O. Tomlin has recently provided an excellent publication of an amulet found in the City of London in 1989. It is a long, narrow strip cut from a sheet of pewter, with 30 lines of Greek text, and the bearer was a certain Demetri(o)s. By a curious coincidence, two of the Greek inscriptions of Britain also involve a Demetrios, though a different one. They are inscribed on two bronze plates found in York about 1840. One reads , the other , and the bearer is presumably identical with a grammaticus from Tarsus of the same name, described as having come from Britain to Delphi in one of Plutarch's dialogues. This note mainly treats the second of two hexameter oracles incorporated in the text of the London amulet, but I begin by discussing the text as a whole.
A value-based assessment of alternative US state pension plans
Authors: LEKNIŪTĖ ZINA , BEETSMA ROEL , PONDS EDUARD
Published: October 2016

We explore how the contract values of the various stakeholders of a typical US state civil servants pension fund are affected under the continuation of current policies and under alternative policies, such as changes in contribution, indexation and investment allocation policies. We find that all participant cohorts derive a substantial net benefit from the current pension contract, while all tax-paying cohorts make substantial contributions. The shift in value from tax payers to participants can be reduced substantially by having the latter make larger contributions or making indexation less generous. Under our baseline calibration, and continuation of existing policies, the chances are high that the fund's assets get depleted in the coming decades.
‘CHASING’ THE DIAGRAM—THE USE OF VISUALIZATIONS IN ALGEBRAIC REASONING
Authors: DE TOFFOLI SILVIA
Published: October 2016

The aim of this article is to investigate the roles of commutative diagrams (CDs) in a specific mathematical domain, and to unveil the reasons underlying their effectiveness as a mathematical notation; this will be done through a case study. It will be shown that CDs do not depict spatial relations, but represent mathematical structures. CDs will be interpreted as a hybrid notation that goes beyond the traditional bipartition of mathematical representations into diagrammatic and linguistic. It will be argued that one of the reasons why CDs form a good notation is that they are highly mathematically tractable: experts can obtain valid results by ‘calculating’ with CDs. These calculations, take the form of ‘diagram chases’. In order to draw inferences, experts move algebraic elements around the diagrams. It will be argued that these diagrams are dynamic. It is thanks to their dynamicity that CDs can externalize the relevant reasoning and allow experts to draw conclusions directly by manipulating them. Lastly, it will be shown that CDs play essential roles in the context of proof as well as in other phases of the mathematical enterprise, such as discovery and conjecture formation.
Prosocial Consequences of Interpersonal Synchrony
Authors: Rennung Miriam , Göritz Anja S.
Published: October 2016

Abstract. The capacity to establish interpersonal synchrony is fundamental to human beings because it constitutes the basis for social connection and understanding. Interpersonal synchrony refers to instances when the movements or sensations of two or more people overlap in time and form. Recently, the causal influence of interpersonal synchrony on prosociality has been established through experiments. The current meta-analysis is the first to synthesize these isolated and sometimes contradictory experiments. We meta-analyzed 60 published and unpublished experiments that compared an interpersonal synchrony condition with at least one control condition. The results reveal a medium effect of interpersonal synchrony on prosociality with regard to both attitudes and behaviors. Furthermore, experimenter effects and intentionality moderate these effects. We discuss the strengths and limitations of our analysis, as well as its practical implications, and we suggest avenues for future research.
How Effective are Behavior Change Interventions Based on the Theory	of Planned Behavior?
Authors: Steinmetz Holger , Knappstein Michael , Ajzen Icek , Schmidt Peter , Kabst Rüdiger
Published: October 2016

Abstract. The theory of planned behavior (TPB) is a prominent framework for predicting and explaining behavior in a variety of domains. The theory is also increasingly being used as a framework for conducting behavior change interventions. In this meta-analysis, we identified 82 papers reporting results of 123 interventions in a variety of disciplines. Our analysis confirmed the effectiveness of TPB-based interventions, with a mean effect size of .50 for changes in behavior and effect sizes ranging from .14 to .68 for changes in antecedent variables (behavioral, normative, and control beliefs, attitude, subjective norm, perceived behavioral control, and intention). Further analyses revealed that the interventions’ effectiveness varied for the diverse behavior change methods. In addition, interventions conducted in public and with groups were more successful than interventions in private locations or focusing on individuals. Finally, we identified gender and education as well as behavioral domain as moderators of the interventions’ effectiveness.
Cognitive Factors Mediate the Relation Between Age and Flight Path	Maintenance in General Aviation
Authors: Van Benthem Kathleen , Herdman Chris M.
Published: October 2016

Abstract. Identifying pilot attributes associated with risk is important, especially in general aviation where pilot error is implicated in most accidents. This research examined the relationship of pilot age, expertise, and cognitive functioning to deviations from an ideal circuit trajectory. In all, 54 pilots, of varying age, flew a Cessna 172 simulator. Cognitive measures were obtained using the CogScreen-AE ( Kay, 1995 ). Older age and lower levels of expertise and cognitive functioning were associated with significantly greater flight path deviations. The relationship between age and performance was fully mediated by a cluster of cognitive factors: speed and working memory, visual attention, and cognitive flexibility. These findings add to the literature showing that age-related changes in cognition may impact pilot performance.
Space Weather from a Southern Point of View
Authors: Hartinger Michael , Clauer C. , Xu Zhonghua
Published: October 2016

A recently completed instrument array in Antarctica provides a more complete understanding of the near-Earth space environment.
Corals Reveal Ancient Ocean Temperatures in Great Barrier Reef
Authors: Stanley Sarah
Published: October 2016

Old coral colonies suggest that a prehistoric warming event called the mid-Holocene Thermal Maximum may have occurred earlier than previously thought.
Hypoxic modulation of hepatocyte responses to the cytokine interleukin‐22
Authors: Budda Scott A , Bhattarai Krishna , Alexander Justine L , Zenewicz Lauren A
Published: October 2016

The cytokine interleukin‐22 (IL‐22) is a potent regulator of tissue responses during inflammation. Depending on the context of inflammation, IL‐22 can have protective or inflammatory effects on epithelial cells. This dual nature of IL‐22 leads us to hypothesize that its activity must be exquisitely regulated to prevent host tissue damage. Environmental factors may act as a cellular cue as to how cells respond to IL‐22. Inflammatory environments are characterized by low oxygen and thus we examined whether cells respond differently to IL‐22 hypoxia compared with normoxia. In this study, we show that hepatocyte responses to IL‐22 stimulation are reduced in hypoxic environments. IL‐22 stimulation of hepatocytes incubated in low oxygen led to reduced levels of activated signal transducer and activator of transcription 3 and further downstream effects such as reduced induction of the anti‐microbial protein, lipocalin‐2. This modulation appears to be independent of the hypoxia‐inducible factor‐1α signaling pathway. Thus, hypoxia that accompanies chronic inflammation may be a mechanism to regulate the bioactivity of the dual‐natured IL‐22 cytokine.
Evolution of heterogeneous genome differentiation across multiple contact zones in a crow species complex
Authors: Vijay Nagarjun , Bossu Christen M. , Poelstra Jelmer W. , Weissensteiner Matthias H. , Suh Alexander , Kryukov Alexey P. , Wolf Jochen B. W.
Published: October 2016

Uncovering the genetic basis of species diversification is a central goal in evolutionary biology. Yet, the link between the accumulation of genomic changes during population divergence and the evolutionary forces promoting reproductive isolation is poorly understood. Here, we analysed 124 genomes of crow populations with various degrees of genome-wide differentiation, with parallelism of a sexually selected plumage phenotype, and ongoing hybridization. Overall, heterogeneity in genetic differentiation along the genome was best explained by linked selection exposed on a shared genome architecture. Superimposed on this common background, we identified genomic regions with signatures of selection specific to independent phenotypic contact zones. Candidate pigmentation genes with evidence for divergent selection were only partly shared, suggesting context-dependent selection on a multigenic trait architecture and parallelism by pathway rather than by repeated single-gene effects. This study provides insight into how various forms of selection shape genome-wide patterns of genomic differentiation as populations diverge.
KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification
Authors: Fournier Marjorie , Orpinell Meritxell , Grauffel Cédric , Scheer Elisabeth , Garnier Jean-Marie , Ye Tao , Chavant Virginie , Joint Mathilde , Esashi Fumiko , Dejaegere Annick , Gönczy Pierre , Tora László
Published: October 2016

Lysine acetylation is a widespread post-translational modification regulating various biological processes. To characterize cellular functions of the human lysine acetyltransferases KAT2A (GCN5) and KAT2B (PCAF), we determined their acetylome by shotgun proteomics. One of the newly identified KAT2A/2B substrate is polo-like kinase 4 (PLK4), a key regulator of centrosome duplication. We demonstrate that KAT2A/2B acetylate the PLK4 kinase domain on residues K45 and K46. Molecular dynamics modelling suggests that K45/K46 acetylation impairs kinase activity by shifting the kinase to an inactive conformation. Accordingly, PLK4 activity is reduced uponin vitroacetylation of its kinase domain. Moreover, the overexpression of the PLK4 K45R/K46R mutant in cells does not lead to centrosome overamplification, as observed with wild-type PLK4. We also find that impairing KAT2A/2B-acetyltransferase activity results in diminished phosphorylation of PLK4 and in excess centrosome numbers in cells. Overall, our study identifies the global human KAT2A/2B acetylome and uncovers that KAT2A/2B acetylation of PLK4 prevents centrosome amplification.
Structure of the bacterial plant-ferredoxin receptor FusA
Authors: Grinter Rhys , Josts Inokentijs , Mosbahi Khedidja , Roszak Aleksander W. , Cogdell Richard J. , Bonvin Alexandre M. J. J. , Milner Joel J. , Kelly Sharon M. , Byron Olwyn , Smith Brian O. , Walker Daniel
Published: October 2016

Iron is a limiting nutrient in bacterial infection putting it at the centre of an evolutionary arms race between host and pathogen. Gram-negative bacteria utilize TonB-dependent outer membrane receptors to obtain iron during infection. These receptors acquire iron either in concert with soluble iron-scavenging siderophores or through direct interaction and extraction from host proteins. Characterization of these receptors provides invaluable insight into pathogenesis. However, only a subset of virulence-related TonB-dependent receptors have been currently described. Here we report the discovery of FusA, a new class of TonB-dependent receptor, which is utilized by phytopathogenic Pectobacterium spp. to obtain iron from plant ferredoxin. Through the crystal structure of FusA we show that binding of ferredoxin occurs through specialized extracellular loops that form extensive interactions with ferredoxin. The function of FusA and the presence of homologues in clinically important pathogens suggests that small iron-containing proteins represent an iron source for bacterial pathogens.
How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome
Authors: Noel Jeffrey K. , Whitford Paul C.
Published: October 2016

It has long been recognized that the thermodynamics of mRNA–tRNA base pairing is insufficient to explain the high fidelity and efficiency of aminoacyl-tRNA (aa-tRNA) selection by the ribosome. To rationalize this apparent inconsistency, Hopfield proposed that the ribosome may improve accuracy by utilizing a multi-step kinetic proofreading mechanism. While biochemical, structural and single-molecule studies have provided a detailed characterization of aa-tRNA selection, there is a limited understanding of how the physical–chemical properties of the ribosome enable proofreading. To this end, we probe the role of EF-Tu during aa-tRNA accommodation (the proofreading step) through the use of energy landscape principles, molecular dynamics simulations and kinetic models. We find that the steric composition of EF-Tu can reduce the free-energy barrier associated with the first step of accommodation: elbow accommodation. We interpret this effect within an extended kinetic model of accommodation and show how EF-Tu can contribute to efficient and accurate proofreading.
Ubc13 haploinsufficiency protects against age-related insulin resistance and high-fat diet-induced obesity
Authors: Joo Erina , Fukushima Toru , Harada Norio , Reed John C. , Matsuzawa Shu-ichi , Inagaki Nobuya
Published: October 2016

Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity. We compared wild-type (WT) and Ubc13 haploinsufficient (ubc13+/−) mice under normal diet (ND) and HFD, since homozygous knockout mice (ubc13−/−) are embryonic lethal. Male and female ubc13+/− mice were protected against age-related insulin resistance under ND and HFD compared to WT mice. Interestingly, only female ubc13+/− mice were protected against HFD-induced obesity and hepatic steatosis. Moreover, only female HFD-fed ubc13+/− mice showed lower expression of inflammatory cytokines that was secondary to reduction in weight gain not present in the other groups. In summary, our results indicate that suppression of Ubc13 activity may play a metabolic role independent of its inflammatory function. Thus, Ubc13 could represent a therapeutic target for insulin resistance, diet-induced obesity, and associated metabolic dysfunctions.
Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution
Authors: Yoshitomi Munetake , Ohta Keisuke , Kanazawa Tomonoshin , Togo Akinobu , Hirashima Shingo , Uemura Kei-ichiro , Okayama Satoko , Morioka Motohiro , Nakamura Kei-ichiro
Published: October 2016

Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.
Thermophysical properties and oxygen transport in (Thx,Pu1−x)O2
Authors: Galvin C. O. T. , Cooper M. W. D. , Rushton M. J. D. , Grimes R. W.
Published: October 2016

Using Molecular Dynamics, this paper investigates the thermophysical properties and oxygen transport of (Thx,Pu1−x)O2 (0 ≤ x ≤ 1) between 300–3500 K. In particular, the superionic transition is investigated and viewed via the thermal dependence of lattice parameter, linear thermal expansion coefficient, enthalpy and specific heat at constant pressure. Oxygen diffusivity and activation enthalpy are also investigated. Below the superionic temperature an increase of oxygen diffusivity for certain compositions of (Thx,Pu1−x)O2 compared to the pure end members is predicted. Oxygen defect formation enthalpies are also examined, as they underpin the superionic transition temperature and the increase in oxygen diffusivity. The increase in oxygen diffusivity for (Thx,Pu1−x)O2 is explained in terms of lower oxygen defect formation enthalpies for (Thx,Pu1−x)O2 than PuO2 and ThO2, while links are drawn between the superionic transition temperature and oxygen Frenkel disorder.
microRNAs Involved in the Control of Innate Immunity in Candida Infected Caenorhabditis elegans
Authors: Sun Lingmei , Zhi Lingtong , Shakoor Shumaila , Liao Kai , Wang Dayong
Published: October 2016

The role of microRNAs (miRNAs) in regulating innate immune response to Candida albicans infection in Caenorhabditis elegans is still largely unclear. Using small RNA SOLiD deep sequencing technique, we profiled the miRNAs that were dysregulated by C. albicans infection. We identified 16 miRNAs that were up-regulated and 4 miRNAs that were down-regulated in nematodes infected with C. albicans. Bioinformatics analysis implied that these dysregulated miRNAs may be involved in the control of many important biological processes. Using available mutants, we observed that mir-251 and mir-252 loss-of-function mutants were resistant to C. albicans infection, whereas mir-360 mutants were hypersensitive to C. albicans infection. The expression pattern of antimicrobial genes suggested that mir-251, mir-252, and mir-360 played crucial roles in regulating the innate immune response to C. albicans infection. Fungal burden might be closely associated with altered lifespan and innate immune response in mir-251, mir-252, and mir-360 mutants. Moreover, mir-251 and mir-252 might function downstream of p38 mitogen activated protein kinase (MAPK) or IGF-1/insulin-like pathway to regulate the innate immune response to C. albicans infection. Our results provide an important molecular basis for further elucidating how miRNA-mRNA networks may control the innate immune response to C. albicans infection.
Evolutionary study of Yersinia genomes deciphers emergence of human pathogenic species
Authors: Tan Shi Yang , Tan Irene Kit Ping , Tan Mui Fern , Dutta Avirup , Choo Siew Woh
Published: October 2016

On record, there are 17 species in the Yersinia genus, of which three are known to be pathogenic to human. While the chromosomal and pYV (or pCD1) plasmid-borne virulence genes as well as pathogenesis of these three species are well studied, their genomic evolution is poorly understood. Our study aims to predict the key evolutionary events that led to the emergence of pathogenic Yersinia species by analyzing gene gain-and-loss, virulence genes, and “Clustered regularly-interspaced short palindromic repeats”. Our results suggest that the most recent ancestor shared by the human pathogenic Yersinia was most probably an environmental species that had adapted to the human body. This might have led to ecological specialization that diverged Yersinia into ecotypes and distinct lineages based on differential gene gain-and-loss in different niches. Our data also suggest that Y. pseudotuberculosis group might be the donor of the ail virulence gene to Y. enterocolitica. Hence, we postulate that evolution of human pathogenic Yersinia might not be totally in parallel, but instead, there were lateral gene transfer events. Furthermore, the presence of virulence genes seems to be important for the positive selection of virulence plasmid. Our studies provide better insights into the evolutionary biology of these bacteria.
Smooth deuterated cellulose films for the visualisation of adsorbed bio-macromolecules
Authors: Su Jielong , Raghuwanshi Vikram S. , Raverty Warwick , Garvey Christopher J. , Holden Peter J. , Gillon Marie , Holt Stephen A. , Tabor Rico , Batchelor Warren , Garnier Gil
Published: October 2016

Novel thin and smooth deuterated cellulose films were synthesised to visualize adsorbed bio-macromolecules using contrast variation neutron reflectivity (NR) measurements. Incorporation of varying degrees of deuteration into cellulose was achieved by growing Gluconacetobacter xylinus in deuterated glycerol as carbon source dissolved in growth media containing D2O. The derivative of deuterated cellulose was prepared by trimethylsilylation(TMS) in ionic liquid(1-butyl-3-methylimidazolium chloride). The TMS derivative was dissolved in toluene for thin film preparation by spin-coating. The resulting film was regenerated into deuterated cellulose by exposure to acidic vapour. A common enzyme, horseradish peroxidase (HRP), was adsorbed from solution onto the deuterated cellulose films and visualized by NR. The scattering length density contrast of the deuterated cellulose enabled accurate visualization and quantification of the adsorbed HRP, which would have been impossible to achieve with non-deuterated cellulose. The procedure described enables preparing deuterated cellulose films that allows differentiation of cellulose and non-deuterated bio-macromolecules using NR.
Opportunistic brood theft in the context of colony relocation in an Indian queenless ant
Authors: Paul Bishwarup , Paul Manabi , Annagiri Sumana
Published: October 2016

Brood is a very valuable part of an ant colony and behaviours increasing its number with minimum investment is expected to be favoured by natural selection. Brood theft has been well documented in ants belonging to the subfamilies Myrmicinae and Formicinae. In this study we report opportunistic brood theft in the context of nest relocation in Diacamma indicum, belonging to the primitively eusocial subfamily Ponerinae. Pupae was the preferred stolen item both in laboratory conditions and in natural habitat and a small percentage of the members of a colony acting as thieves stole about 12% of the brood of the victim colony. Stolen brood were not consumed but became slaves. We propose a new dimension to the risks of relocation in the form of brood theft by conspecific neighbours and speculate that examination of this phenomenon in other primitively eusocial species will help understand the origin of brood theft in ants.
Phenotype-genotype correlation in multiple primary lung cancer patients in China
Authors: Yang Yang , Yin Wei , He Wenxin , Jiang Chao , Zhou Xiao , Song Xiao , Zhu Junjie , Fei Ke , Cao Weijun , Jiang Gening
Published: October 2016

Due to recent advances in high-resolution detection technology, multiple primary lung cancer (MPLC) is becoming an increasingly common diagnosis. However, the genotype-phenotype correlations in MPLC patients have not yet been assessed. In this study, we analyzed the clinical and pathological data for 129 consecutive MPLC patients who received curative surgery at the Tongji University Shanghai Pulmonary Hospital, China. We have screened 129 patients in the present study and found mutations in EGFR, BRAF, ROS1 and KRAS genes, as well as the rearrangement of the EML4-ALK gene in 113 patients. The mean patient age was 59.9 (25–78) years old and 41 patients were males (31.8%). Among the total patients, 123 (95.4%) had two primary lesions, 5 (3.9%) had three primary lesions, and 1 (0.8%) had four primary lesions. In 38.8% of the patients, all lesions were located on only one side of the body. Most of the detected mutations (98 patients) were in the EGFR gene. The patients exhibited significant differences in the EGFR mutation, age at diagnosis, and foci location.
Calculation of exchange integrals and Curie temperature for La-substituted barium hexaferrites
Authors: Wu Chuanjian , Yu Zhong , Sun Ke , Nie Jinlan , Guo Rongdi , Liu Hai , Jiang Xiaona , Lan Zhongwen
Published: October 2016

As the macro behavior of the strength of exchange interaction, state of the art of Curie temperature Tc, which is directly proportional to the exchange integrals, makes sense to the high-frequency and high-reliability microwave devices. Challenge remains as finding a quantitative way to reveal the relationship between the Curie temperature and the exchange integrals for doped barium hexaferrites. Here in this report, for La-substituted barium hexaferrites, the electronic structure has been determined by the density functional theory (DFT) and generalized gradient approximation (GGA). By means of the comparison between the ground and relative state, thirteen exchange integrals have been calculated as a function of the effective value Ueff. Furthermore, based on the Heisenberg model, the molecular field approximation (MFA) and random phase approximation (RPA), which provide an upper and lower bound of the Curie temperature Tc, have been adopted to deduce the Curie temperature Tc. In addition, the Curie temperature Tc derived from the MFA are coincided well with the experimental data. Finally, the strength of superexchange interaction mainly depends on 2b-4f1, 4f2-12k, 2a-4f1, and 4f1-12k interactions.
Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis
Authors: Chung I-Che , OuYang Chun-Nan , Yuan Sheng-Ning , Li Hsin-Pai , Chen Jeng-Ting , Shieh Hui-Ru , Chen Yu-Jen , Ojcius David M. , Chu Ching-Liang , Yu Jau-Song , Chang Yu-Sun , Chen Lih-Chyang
Published: October 2016

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, and only the phosphorylated ASC could participate in speck formation and trigger IL-1β secretion. Moreover, the clinical-trial-tested Pyk2/FAK dual inhibitor PF-562271 reduced monosodium urate-mediated peritonitis, a disease model used for studying the consequences of NLRP3 activation. Our results suggest that although Pyk2 and FAK are involved in inflammasome activation, only Pyk2 directly phosphorylates ASC and brings ASC into an oligomerization-competent state by allowing Tyr146 phosphorylation to participate ASC speck formation and subsequent NLRP3 inflammation.
Identifying reproducible cancer-associated highly expressed genes with important functional significances using multiple datasets
Authors: Huang Haiyan , Li Xiangyu , Guo You , Zhang Yuncong , Deng Xusheng , Chen Lufei , Zhang Jiahui , Guo Zheng , Ao Lu
Published: October 2016

Identifying differentially expressed (DE) genes between cancer and normal tissues is of basic importance for studying cancer mechanisms. However, current methods, such as the commonly used Significance Analysis of Microarrays (SAM), are biased to genes with low expression levels. Recently, we proposed an algorithm, named the pairwise difference (PD) algorithm, to identify highly expressed DE genes based on reproducibility evaluation of top-ranked expression differences between paired technical replicates of cells under two experimental conditions. In this study, we extended the application of the algorithm to the identification of DE genes between two types of tissue samples (biological replicates) based on several independent datasets or sub-datasets of a dataset, by constructing multiple paired average gene expression profiles for the two types of samples. Using multiple datasets for lung and esophageal cancers, we demonstrated that PD could identify many DE genes highly expressed in both cancer and normal tissues that tended to be missed by the commonly used SAM. These highly expressed DE genes, including many housekeeping genes, were significantly enriched in many conservative pathways, such as ribosome, proteasome, phagosome and TNF signaling pathways with important functional significances in oncogenesis.