bluuebunny/crossref_metadata_2025_split huggingface dataset:
A bacterial size law revealed by a coarse-grained model of cell physiology
Authors: Bertaux François , von Kügelgen Julius , Marguerat Samuel , Shahrezaei Vahid 
Published: October 2016

AbstractUniversal observations in Biology are sometimes described as “laws”. InE. coli, experimental studies performed over the past six decades have revealed major growth laws relating ribosomal mass fraction and cell size to the growth rate. Because they formalize complex emerging principles in biology, growth laws have been instrumental in shaping our understanding of bacterial physiology. Here, we discovered a novel size law that connects cell size to the inverse of the metabolic proteome mass fraction and the active fraction of ribosomes. We used a simple whole-cell coarse-grained model of cell physiology that combines the proteome allocation theory and the structural model of cell division. The model captures all available experimental data connecting the cell proteome composition, ribosome activity, division size and growth rate in response to nutrient quality, antibiotic treatment and increased protein burden. Finally, a stochastic extension of the model explains non-trivial correlations observed in single cell experiments including the adder principle. This work provides a simple and robust theoretical framework for studying the fundamental principles of cell size determination in unicellular organisms.
Evolving Notch polyQ tracts reveal possible solenoid interference elements
Authors: Erives Albert J. 
Published: October 2016

ABSTRACTPolyglutamine (polyQ) tracts in regulatory proteins are extremely polymorphic. As functional elements under selection for length, triplet repeats are prone to DNA replication slippage and indel mutations. Many polyQ tracts are also embedded within intrinsically disordered domains, which are less constrained, fast evolving, and difficult to characterize. To identify structural principles underlying polyQ tracts in disordered regulatory domains, here I analyze deep evolution of metazoan Notch polyQ tracts, which can generate alleles causing developmental and neurogenic defects. I show that Notch features polyQ tract turnover that is restricted to a discrete number of conserved “polyQ insertion slots”. Notch polyQ insertion slots are: (i) identifiable by an amphipathic “slot leader” motif; (ii) conserved as an intact C-terminal array in a 1-to-1 relationship with the N-terminal solenoid-forming ankyrin repeats (ARs); and (iii) enriched in carboxamide residues (Q/N), whose sidechains feature dual hydrogen bond donor and acceptor atoms. Correspondingly, the terminal loop and β-strand of each AR feature conserved carboxamide residues, which would be susceptible to folding interference by hydrogen bonding with residues outside the ARs. I thus suggest that Notch polyQ insertion slots constitute an array of AR interference elements (ARIEs). Notch ARIEs would dynamically compete with the delicate serial folding induced by adjacent ARs. Huntingtin, which harbors solenoid-forming HEAT repeats, also possesses a similar number of polyQ insertion slots. These results strongly suggest that intrinsically disordered interference arrays featuring carboxamide and polyQ enrichment are coupled proteodynamic modulators of solenoids.SIGNIFICANCENeurodegenerative disorders are often caused by expanded polyglutamine (polyQ) tracts embedded in the disordered regions of regulatory proteins, which are difficult to characterize structurally. To identify functional principles underlying polyQ tracts in disordered regulatory domains, I analyze evolution of the Notch protein, which can generate polyQ-related alleles causing neurodevelopmental defects. I show that Notch evolves polyQ tracts that come and go in a few conserved “polyQ insertion slots”. Several features suggest these slots are ankyrin repeat (AR) interference elements, which dynamically compete with the delicate solenoid formed by Notch. Huntingtin, whose polyQ expansions causes Huntington’s Disease in humans, also has solenoid-forming modules and polyQ insertion slots, suggesting a common architectural principle underlies solenoid-forming polyQ-rich proteins.
Analysis of semilocal convergence for ameliorated super-Halley methods with less computation for inversion
Authors: Wang Xiuhua , Kou Jisheng 
Published: October 2016

In this paper, the semilocal convergence for ameliorated super-Halley methods in Banach spaces is considered. Different from the results in [J. M. Gutiérrez and M. A. Hernández, Comput. Math. Appl. 36 (1998) 1–8], these ameliorated methods do not need to compute a second derivative, the computation for inversion is reduced and the $R$-order is also heightened. Under a weaker condition, an existence–uniqueness theorem for the solution is proved.
Risk Factors, Outcomes, and Mechanisms of Tigecycline-Nonsusceptible Klebsiella pneumoniae Bacteremia
Authors: Juan Chih-Han , Huang Yi-Wei , Lin Yi-Tsung , Yang Tsuey-Ching , Wang Fu-Der 
Published: October 2016

ABSTRACT

A rise in tigecycline resistance in
Klebsiella pneumoniae
has been reported recently worldwide. We sought to identify risk factors, outcomes, and mechanisms for adult patients with tigecycline-nonsusceptible
K. pneumoniae
bacteremia in Taiwan. We conducted a matched case-control study (ratio of 1:1) in a medical center in Taiwan from January 2011 through June 2015. The cases were patients with tigecycline-nonsusceptible
K. pneumoniae
bacteremia, and the controls were patients with tigecycline-susceptible
K. pneumoniae
bacteremia. Logistic regression was performed to evaluate the potential risk factors for tigecycline-nonsusceptible
K. pneumoniae
bacteremia. Quantitative reverse transcription-PCR was performed to analyze
acrA
,
oqxA
,
ramA
,
rarA
, and
kpgA
expression among these isolates. A total of 43 cases were matched with 43 controls. The 14-day mortality of patients with tigecycline-nonsusceptible
K. pneumoniae
bacteremia was 30.2%, and the 28-day mortality was 41.9%. The attributable mortalities of tigecycline-nonsusceptible
K. pneumoniae
at 14 and 28 days were 9.3 and 18.6%, respectively. Fluoroquinolone use within 30 days prior to bacteremia was the only independent risk factor for tigecycline-nonsusceptible
K. pneumoniae
bacteremia. The tigecycline-nonsusceptible
K. pneumoniae
bacteremia was mostly caused by overexpression of AcrAB and/or OqxAB efflux pumps, together with the upregulation of RamA and/or RarA, respectively. One isolate demonstrated isolated overexpression of
kpgA
. In conclusion, tigecycline-nonsusceptible
K. pneumoniae
bacteremia was associated with high mortality, and prior fluoroquinolone use was the independent risk factor for the acquisition of tigecycline-nonsusceptible
K. pneumoniae
. The overexpression of AcrAB and/or OqxAB contributes to tigecycline nonsusceptibility in
K. pneumoniae
.
Breaking the Permeability Barrier of Escherichia coli by Controlled Hyperporination of the Outer Membrane
Authors: Krishnamoorthy Ganesh , Wolloscheck David , Weeks Jon W. , Croft Cameron , Rybenkov Valentin V. , Zgurskaya Helen I. 
Published: October 2016

ABSTRACT

In Gram-negative bacteria, a synergistic relationship between slow passive uptake of antibiotics across the outer membrane and active efflux transporters creates a permeability barrier, which efficiently reduces the effective concentrations of antibiotics in cells and, hence, their activities. To analyze the relative contributions of active efflux and the passive barrier to the activities of antibiotics, we constructed
Escherichia coli
strains with controllable permeability of the outer membrane. The strains expressed a large pore that does not discriminate between compounds on the basis of their hydrophilicity and sensitizes cells to a variety of antibacterial agents. We found that the efficacies of antibiotics in these strains were specifically affected by either active efflux or slow uptake, or both, and reflect differences in the properties of the outer membrane barrier, the repertoire of efflux pumps, and the inhibitory activities of antibiotics. Our results identify antibiotics which are the best candidates for the potentiation of activities through efflux inhibition and permeabilization of the outer membrane.
Pharmacokinetics of the Antischistosomal Lead Ozonide OZ418 in Uninfected Mice Determined by Liquid Chromatography-Tandem Mass Spectrometry
Authors: Leonidova Anna , Vargas Mireille , Huwyler Jörg , Keiser Jennifer 
Published: October 2016

ABSTRACT

One of the major neglected tropical diseases, schistosomiasis, is currently treated and controlled with a single drug, praziquantel. The quest for an alternative drug is fueled by the lack of activity of praziquantel against juvenile
Schistosoma
worms and the fear of emerging resistance. The synthetic ozonide OZ418 has shown high activity against
Schistosoma mansoni
,
S. haematobium
, and
S. japonicum
in vivo
, but its drug disposition remains unknown. To bridge this gap, our study determined the basic pharmacokinetic (PK) parameters of a single oral dose (400 mg/kg of body weight) of OZ418 in uninfected mice. First, a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify OZ418 concentrations in mouse plasma was successfully developed and validated according to U.S. FDA guidelines. This method proved to be selective, accurate (93 to 103%), precise (5 to 16%), and devoid of significant matrix effects (90 to 102%) and provided excellent recovery (101 to 102%). A median peak concentration of 190 (range, 185 to 231) μg/ml was reached at 2 h (2 to 3 h) posttreatment. A naive pooled noncompartmental PK analysis estimated a mean area under the plasma concentration-versus-time curve (AUC) of 9,303 μg h/ml (7,039.2 to 11,908.5 μg h/ml) and a half-life of 38.7 h (20 to 64.6 h). Thus, the OZ418 level in plasma remained well above its
in vitro
50% inhibitory concentrations (IC
50
s) of 27.4 μg/ml (adult
S. mansoni
worms at 72 h) for at least 75 h. Consistently, OZ418 degraded little in plasma at 37°C (<20% in 121 h) and weakly inhibited cytochrome P450 (CYP450) metabolism (IC
50
of 37 to 144 μM). Our results provide a first insight into the disposition of OZ418, paving the way for further studies of its biological fate and effect.
Aag Hypoxanthine-DNA Glycosylase Is Synthesized in the Forespore Compartment and Involved in Counteracting the Genotoxic and Mutagenic Effects of Hypoxanthine and Alkylated Bases in DNA during Bacillus subtilis Sporulation
Authors: Ayala-García Víctor M. , Valenzuela-García Luz I. , Setlow Peter , Pedraza-Reyes Mario 
Published: October 2016

ABSTRACT

Aag from
Bacillus subtilis
has been implicated in
in vitro
removal of hypoxanthine and alkylated bases from DNA. The regulation of expression of
aag
in
B. subtilis
and the resistance to genotoxic agents and mutagenic properties of an Aag-deficient strain were studied here. A strain with a transcriptional
aag-lacZ
fusion expressed low levels of β-galactosidase during growth and early sporulation but exhibited increased transcription during late stages of this developmental process. Notably,
aag-lacZ
expression was higher inside the forespore than in the mother cell compartment, and this expression was abolished in a
sigG
-deficient background, suggesting a forespore-specific mechanism of
aag
transcription. Two additional findings supported this suggestion: (i) expression of an
aag-yfp
fusion was observed in the forespore, and (ii)
in vivo
mapping of the
aag
transcription start site revealed the existence of upstream regulatory sequences possessing homology to σ
G
-dependent promoters. In comparison with the wild-type strain, disruption of
aag
significantly reduced survival of sporulating
B. subtilis
cells following nitrous acid or methyl methanesulfonate treatments, and the Rif
r
mutation frequency was significantly increased in an
aag
strain. These results suggest that Aag protects the genome of developing
B. subtilis
sporangia from the cytotoxic and genotoxic effects of base deamination and alkylation.

IMPORTANCE
In this study, evidence is presented revealing that
aag
, encoding a DNA glycosylase implicated in processing of hypoxanthine and alkylated DNA bases, exhibits a forespore-specific pattern of gene expression during
B. subtilis
sporulation. Consistent with this spatiotemporal mode of expression, Aag was found to protect the sporulating cells of this microorganism from the noxious and mutagenic effects of base deamination and alkylation.
Interactions between the Cytoplasmic Domains of PspB and PspC Silence the Yersinia enterocolitica Phage Shock Protein Response
Authors: Flores-Kim Josué , Darwin Andrew J. 
Published: October 2016

ABSTRACT

The phage shock protein (Psp) system is a widely conserved cell envelope stress response that is essential for the virulence of some bacteria, including
Yersinia enterocolitica
. Recruitment of PspA by the inner membrane PspB-PspC complex characterizes the activated state of this response. The PspB-PspC complex has been proposed to be a stress-responsive switch, changing from an OFF to an ON state in response to an inducing stimulus. In the OFF state, PspA cannot access its binding site in the C-terminal cytoplasmic domain of PspC (PspC
CT
), because this site is bound to PspB. PspC has another cytoplasmic domain at its N-terminal end (PspC
NT
), which has been thought to play a role in maintaining the OFF state, because its removal causes constitutive activation. However, until now, this role has proved recalcitrant to experimental investigation. Here, we developed a combination of approaches to investigate the role of PspC
NT
in
Y. enterocolitica
. Pulldown assays provided evidence that PspC
NT
mediates the interaction of PspC with the C-terminal cytoplasmic domain of PspB (PspB
CT
)
in vitro
. Furthermore, site-specific oxidative cross-linking suggested that a PspC
NT
-PspB
CT
interaction occurs only under noninducing conditions
in vivo
. Additional experiments indicated that mutations in
pspC
might cause constitutive activation by compromising this PspC
NT
binding site or by causing a conformational disturbance that repositions PspC
NT
in vivo
. These findings have provided the first insight into the regulatory function of the N-terminal cytoplasmic domain of PspC, revealing that its ability to participate in an inhibitory complex is essential to silencing the Psp response.

IMPORTANCE
The phage shock protein (Psp) response has generated widespread interest because it is linked to important phenotypes, including antibiotic resistance, biofilm formation, and virulence in a diverse group of bacteria. Therefore, achieving a comprehensive understanding of how this response is controlled at the molecular level has obvious significance. An integral inner membrane protein complex is believed to be a critical regulatory component that acts as a stress-responsive switch, but some essential characteristics of the switch states are poorly understood. This study provides an important advance by uncovering a new protein interaction domain within this membrane protein complex that is essential to silencing the Psp response in the absence of an inducing stimulus.
Therapeutic Effects of Dry Needling in Patients with Upper Trapezius Myofascial Trigger Points
Authors: Abbaszadeh-Amirdehi Maryam , Ansari Noureddin Nakhostin , Naghdi Soofia , Olyaei Gholamreza , Nourbakhsh Mohammad Reza 
Published: October 2016

Background Active myofascial trigger points (MTrPs) are major pain generators in myofascial pain syndrome. Dry needling (DN) is an effective method for the treatment of MTrPs. Objective To assess the immediate neurophysiological and clinical effects of DN in patients with upper trapezius MTrPs. Methods This was a prospective, clinical trial study of 20 patients with upper trapezius MTrPs and 20 healthy volunteers (matched for height, weight, body mass index and age), all of whom received one session of DN. Primary outcome measures were neuromuscular junction response (NMJR) and sympathetic skin response (SSR). Secondary outcomes were pain intensity (PI) and pressure pain threshold (PPT). Data were collected at baseline and immediately post-intervention. Results At baseline, SSR amplitude was higher in patients versus healthy volunteers (p<0.003). With respect to NMJR, a clinically abnormal increment and normal reduction was observed in patients and healthy volunteers, respectively. Moreover, PPT of patients was less than healthy volunteers (p<0.0001). After DN, SSR amplitude decreased significantly in patients (p<0.01), but did not change in healthy volunteers. A clinically important reduction in the NMJR of patients and increment in healthy volunteers was demonstrated after DN. PPT increased after DN in patients, but decreased in healthy volunteers (p<0.0001). PI improved after DN in patients (p<0.001). Conclusions The results of this study showed that one session of DN targeting active MTrPs appears to reduce hyperactivity of the sympathetic nervous system and irritability of the motor endplate. DN seems effective at improving symptoms and deactivating active MTrPs, although further research is needed. Trial registration number IRCT20130316128.
Geology and geochemistry of Late Quaternary volcanism in northern Harrat Rahat, Kingdom of Saudi Arabia: implications for eruption dynamics, regional stratigraphy and magma evolution
Authors: Murcia H. , Lindsay J. M. , Németh K. , Smith I. E. M. , Cronin S. J. , Moufti M. R. H. , El-Masry N. N. , Niedermann S. 
Published: October 2016

Abstract

Harrat Rahat (<10 Ma) is one of the largest volcanic fields on western Arabia. In the north of the field, some of the youngest volcanic centres evolved through either point-like, complex or multiple aligned vents (i.e. along fissures), and have pyroclastic cones, lapilli fall deposits and/or lava flows associated with them. The products reflect dominantly Hawaiian eruptions, and only one centre experienced phreatomagmatism. Results from new
3
He surface-exposure dating provide constraints on stratigraphy of the youngest (<0.3 Ma) products.

The rocks are compositionally alkali-basalt and hawaiite, with intra-plate basalt (prevalent mantle (PREMA)) affinity. Each eruption displays a distinct whole-rock composition in an overall linear trend. We suggest that the magma source for each centre is similar, and that composition of the products is different due to different degrees of fractionation. In a single eruption, the magma that reaches the surface first is the least evolved, with the most evolved magma erupting last. We also found that the most primitive magmas erupt less explosively. We think that the degree of magma evolution might correlate with ascent times, assuming that the more evolved magma spent more time en route. We suggest that magma ascent time is likely to be longer than that of other more primitive intra-plate basalts.

Supplementary material:
Whole-rock chemistry results, mineral chemistry results and fractional crystallization modeling data are available at
https://doi.org/10.6084/m9.figshare.c.3488988
Conceptual and Aesthetic Dimensions of an ECG/RESP Sensor
Artwork
Authors: Chen Yi-Huei , Lai Wen-Shu 
Published: October 2016

Abstract
This article aims to explore an innovative application pairing optical fibers with an electrocardiography (ECG)/respiration (RESP) sensor in art. The constructed interactive work Clock Inside Out not only reflects multifaceted human life but also coexists with the body in the world. Thus, the body is extended to take on a technological character and portrayed as a heteromerous embodiment. Following an analysis of the artwork, the article elaborates on the aesthetic and corporeal phenomena arising from it and concludes with the new meanings and implications carried by the artwork.
Structuralizing the Fluxus Way of Life: The Social Network of
Fluxus
Authors: Lee Rooni , Sohn Yunkyu , Lee Wonjae 
Published: October 2016

Abstract
Fluxus is often understood as an avant-garde art movement led by George Maciunas in the 1960s. Such a narrative, however, is limiting as it overlooks the contribution of other prominent Fluxus artists. This article aims to challenge what is referred to as the Maciunas-based paradigm in its temporal scope and ideological homogeneity through the adoption of social network analysis.
Molding the Signifier: Codesculpting the Possible Shapes of a Future Consciousness
Authors: Diosi Ivor “ID” 
Published: October 2016

Abstract
This article introduces the art/science/transmedia project Molding the Signifier and maps out its wider cultural and societal connotations, reach and significance, with specific reference to its staging within the Trust Me, I’m an Artist event (an EU Creative Europe-funded project) that took place in Prague in 2015. As the work itself strives to artistically bridge and synthesize recent—in the opinion of the authoring artist group—existentially highly relevant results in science, so the article provides an overview and synthesis of their art/science fusion approach and methods.
A Coupled-Mode Shallow-Water Model for Tidal Analysis: Internal Tide Reflection and Refraction by the Gulf Stream
Authors: Kelly Samuel M. , Lermusiaux Pierre F. J. , Duda Timothy F. , Haley Patrick J. 
Published: October 2016

AbstractA hydrostatic, coupled-mode, shallow-water model (CSW) is described and used to diagnose and simulate tidal dynamics in the greater Mid-Atlantic Bight region. The reduced-physics model incorporates realistic stratification and topography, internal tide forcing from a priori estimates of the surface tide, and advection terms that describe first-order interactions of internal tides with slowly varying mean flow and mean buoyancy fields and their respective shear. The model is validated via comparisons with semianalytic models and nonlinear primitive equation models in several idealized and realistic simulations that include internal tide interactions with topography and mean flows. Then, 24 simulations of internal tide generation and propagation in the greater Mid-Atlantic Bight region are used to diagnose significant internal tide interactions with the Gulf Stream. The simulations indicate that locally generated mode-one internal tides refract and/or reflect at the Gulf Stream. The redirected internal tides often reappear at the shelf break, where their onshore energy fluxes are intermittent (i.e., noncoherent with surface tide) because meanders in the Gulf Stream alter their precise location, phase, and amplitude. These results provide an explanation for anomalous onshore energy fluxes that were previously observed at the New Jersey shelf break and linked to the irregular generation of nonlinear internal waves.