bluuebunny/crossref_metadata_2025_split huggingface dataset:
A calcium‐dependent pathway underlies activity‐dependent plasticity of electrical synapses in the thalamic reticular nucleus
Authors: Sevetson Jessica , Fittro Sarah , Heckman Emily , Haas Julie S. 
Published: March 2017

Key points
Electrical synapses are modified by various forms of activity, including paired activity in coupled neurons and tetanization of the input to coupled neurons.
We show that plasticity of electrical synapses that results from paired spiking activity in coupled neurons depends on calcium influx and calcium‐initiated signalling pathways.
Plasticity that results from tetanization of input fibres does not depend on calcium influx or dynamics.
These results imply that electrically coupled neurons have distinct sets of mechanisms for adjusting coupling according to the specific type of activity they experience.
AbstractRecent results have demonstrated modification of electrical synapse strength by varied forms of neuronal activity. However, the mechanisms underlying plasticity induction in central mammalian neurons are unclear. Here we show that the two established inductors of plasticity at electrical synapses in the thalamic reticular nucleus – paired burst spiking in coupled neurons, and mGluR‐dependent tetanization of synaptic input – are separate pathways that converge at a common downstream endpoint. Using occlusion experiments and pharmacology in patched pairs of coupled neurons in vitro, we show that burst‐induced depression depends on calcium entry via voltage‐gated channels, is blocked by BAPTA chelation, and recruits intracellular calcium release on its way to activation of phosphatase activity. In contrast, mGluR‐dependent plasticity is independent of calcium entry or calcium dynamics. Together, these results show that the spiking‐initiated mechanisms underlying electrical synapse plasticity are similar to those that induce plasticity at chemical synapses, and offer the possibility that calcium‐regulated mechanisms may also lead to alternate outcomes, such as potentiation. Because these mechanistic elements are widely found in mature neurons, we expect them to apply broadly to electrical synapses across the brain, acting as the crucial link between neuronal activity and electrical synapse strength.
Identification of MupP as a New Peptidoglycan Recycling Factor and Antibiotic Resistance Determinant in
Pseudomonas aeruginosa
Authors: Fumeaux Coralie , Bernhardt Thomas G. 
Published: March 2017

ABSTRACT

Peptidoglycan (PG) is an essential cross-linked polymer that surrounds most bacterial cells to prevent osmotic rupture of the cytoplasmic membrane. Its synthesis relies on penicillin-binding proteins, the targets of beta-lactam antibiotics. Many Gram-negative bacteria, including the opportunistic pathogen
Pseudomonas aeruginosa
, are resistant to beta-lactams because of a chromosomally encoded beta-lactamase called AmpC. In
P. aeruginosa
, expression of the
ampC
gene is tightly regulated and its induction is linked to cell wall stress. We reasoned that a reporter gene fusion to the
ampC
promoter would allow us to identify mutants defective in maintaining cell wall homeostasis and thereby uncover new factors involved in the process. A library of transposon-mutagenized
P. aeruginosa
was therefore screened for mutants with elevated
ampC
promoter activity. As an indication that the screen was working as expected, mutants with transposons disrupting the
dacB
gene were isolated. Defects in DacB have previously been implicated in
ampC
induction and clinical resistance to beta-lactam antibiotics. The screen also uncovered
murU
and
PA3172
mutants that, upon further characterization, displayed nearly identical drug resistance and sensitivity profiles. We present genetic evidence that
PA3172
, renamed
mupP
, encodes the missing phosphatase predicted to function in the MurU PG recycling pathway that is widely distributed among Gram-negative bacteria.

IMPORTANCE
The cell wall biogenesis pathway is the target of many of our best antibiotics, including penicillin and related beta-lactam drugs. Resistance to these therapies is on the rise, particularly among Gram-negative species like
Pseudomonas aeruginosa
, a problematic opportunistic pathogen. To better understand how these organisms resist cell wall-targeting antibiotics, we screened for
P. aeruginosa
mutants defective in maintaining cell wall homeostasis. The screen identified a new factor, called MupP, involved in the recycling of cell wall turnover products. Characterization of MupP and other components of the pathway revealed that cell wall recycling plays important roles in both the resistance and the sensitivity of
P. aeruginosa
to cell wall-targeting antibiotics.
A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins
Authors: Tejeda-Dominguez Farid , Huerta-Cantillo Jazmin , Chavez-Dueñas Lucia , Navarro-Garcia Fernando 
Published: March 2017

ABSTRACT

The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic
Escherichia coli
(EPEC) autotransporter, and YopH, a protein detected on the surface of
Yersinia
, require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore. Interestingly, this novel mechanism does not exclude the injection model (i.e., EspF) operating through the T3SS conduit; therefore, T3SS can be functioning as an internal conduit or as an external railway, which can be used to reach the translocator pore, and this mechanism appears to be conserved among different T3SS-dependent pathogens.

IMPORTANCE
The type 3 secretion system is essential for injection of virulence factors, which are delivered directly into the cytosol of the host cells for usurping and subverting host processes. Recent studies have shown that these effectors proteins indeed travel inside an “injectisome” conduit through a single step of translocation by connecting the bacterium and host cell cytoplasms. However, all findings are not compatible with this model. For example, both YopH, a protein detected on the surface of
Yersinia
, and EspC, an autotransporter protein secreted by enteropathogenic
E. coli
, require a functional T3SS for host cell translocation. Both proteins have an intermediate extracellular step before their T3SS-dependent translocation. Here, we show an alternative delivery mechanism for these extracellularly secreted virulence factors that are then incorporated into the T3SS to enter the cells; this novel mechanism coexists with but diverges from the canonical injection model that involves the passage of the protein inside the injectisome.
Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection
Authors: Leyva-Grado Victor H. , Ermler Megan E. , Schotsaert Michael , Gonzalez Ma G. , Gillespie Virginia , Lim Jean K. , García-Sastre Adolfo 
Published: March 2017

ABSTRACT

An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain. Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice. This effect was not virus strain specific. Overall lung pathology and apoptosis were reduced in virus-infected KO mice. Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-γ), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice. Infiltration of neutrophils and depletion of CD11b
+
macrophages, characteristic of severe influenza virus infection in mice, were lower in the KO animals. Together, these results demonstrate that activation of the P2X7 receptor is involved in the exacerbated immune response observed during influenza virus infection.

IMPORTANCE
A hallmark of influenza virus infection is the development of lung pathology induced by an exacerbated immune response. The mechanisms shared by the antiviral host defense required for viral clearance and those required for development of immunopathology are not clearly understood. Purinergic receptors, and in particular the purinergic receptor P2X7 (P2X7r), are involved in activation of the immune response. We used mice lacking the P2X7r (P2X7r KO mice) to better understand the mechanisms that lead to development of lung pathology during influenza virus infection. In our studies, we observed that P2X7r KO mice developed less lung immunopathology and had better survival than the wild-type mice. These results implicate P2X7r in the induction of an exacerbated local immune response to influenza virus and help us to better understand the mechanisms leading to the lung immunopathology observed during severe viral infections.
CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria
Authors: Ruhe Zachary C. , Nguyen Josephine Y. , Xiong Jing , Koskiniemi Sanna , Beck Christina M. , Perkins Basil R. , Low David A. , Hayes Christopher S. 
Published: March 2017

ABSTRACT

Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified, but the molecular basis of receptor specificity is not understood. Alignment of BamA-specific CdiA
EC93
from
Escherichia coli
EC93 and OmpC-specific CdiA
EC536
from
E. coli
536 suggests that the receptor-binding domain resides within a central region that varies between the two effectors. In support of this hypothesis, we find that CdiA
EC93
fragments containing residues Arg1358 to Phe1646 bind specifically to purified BamA. Moreover, chimeric CdiA
EC93
that carries the corresponding sequence from CdiA
EC536
is endowed with OmpC-binding activity, demonstrating that this region dictates receptor specificity. A survey of
E. coli
CdiA proteins reveals two additional effector classes, which presumably recognize distinct receptors. Using a genetic approach, we identify the outer membrane nucleoside transporter Tsx as the receptor for a third class of CdiA effectors. Thus, CDI systems exploit multiple outer membrane proteins to identify and engage target cells. These results underscore the modularity of CdiA proteins and suggest that novel effectors can be constructed through genetic recombination to interchange different receptor-binding domains and toxic payloads.

IMPORTANCE
CdiB/CdiA two-partner secretion proteins mediate interbacterial competition through the delivery of polymorphic toxin domains. This process, known as contact-dependent growth inhibition (CDI), requires stable interactions between the CdiA effector protein and specific receptors on the surface of target bacteria. Here, we localize the receptor-binding domain to the central region of
E. coli
CdiA. Receptor-binding domains vary between CdiA proteins, and
E. coli
strains collectively encode at least four distinct effector classes. Further, we show that receptor specificity can be altered by exchanging receptor-binding regions, demonstrating the modularity of this domain. We propose that novel CdiA effectors are naturally generated through genetic recombination to interchange different receptor-binding domains and toxin payloads.
Protocol for a scoping review of existing policies on the prevention and control of obesity across countries in Africa
Authors: Adom Theodosia , Puoane Thandi , De Villiers Anniza , Kengne André Pascal 
Published: March 2017

IntroductionThe obesity epidemic is a public health challenge for all, including low-income countries. The behavioural patterns known to contribute to the rise in obesity prevalence occur in an environmental context which is not conducive for healthy choices. A policy approach to obesity prevention constitutes a form of public intervention in that it extends beyond individuals to influence entire populations and is a mechanism for creating healthier environments. Little is known about obesity prevention policies in Africa. This scoping review seeks to examine the nature, extent and range of policies covering obesity prevention in Africa in order to assess how they align with international efforts in creating less obesogenic environments. This will help identify gaps in the approaches that are adopted in Africa.Methods and analysisUsing the Arksey and O'Malley's scoping methodological framework as a guide, a comprehensive search of MEDLINE (PubMed), MEDLINE (EbscoHost) CINAHL (EbscoHost), Academic Search Complete (EbscoHost) and ISI Web of Science (Science Citation Index) databases will be carried out for peer reviewed journal articles related to obesity prevention policies using the African search filter. A grey literature search for policy documents and reports will also be conducted. There will be no language and date restrictions. Eligible policy documents and reports will be obtained and screened using the inclusion criteria. Data will be extracted and results analysed using descriptive numerical summary analysis and qualitative thematic analysis.Ethics and disseminationNo primary data will be collected since all data that will be presented in this review are based on published articles and publicly available documents, and therefore ethics committee approval is not a requirement. The findings of this systematic review will be presented at workshops and conferences; and will be submitted for publication in peer-reviewed journal. This will also form a chapter of a PhD thesis.
Influencing Factors of Inductance for 3D Micro-PCB Rectangular Coil
Authors: Chi Haokun , Cong Yanping , Wei Zhiqiang , Yin Bo , Gong Feixiang 
Published: March 2017

The main constraint that restricts wireless charging technology successfully applied in miniature medical electronic equipment is that the volume of the transmission coil is difficult to reduce. The printed circuit board (PCB) coil can take advantage of multi-layer wiring space to achieve the coil stack, achieving the purpose of increasing the relative magnetic flux, so that it could replace the traditional spiral coil to become the medium of wireless power transmission in the mini-medical electronic device. In this paper, we analyzed several electrical parameters that could affect the 3D PCB rectangular coil inductance value based on the 3D PCB rectangular coil inductance computing method. Then we sort these influencing factors so that these results can help designers to design the 3D PCB coil. The conclusions are as follows: (1) number of layers, total number of turns have positive correlation with the self-inductance; metal width, substrate thickness, the pitch between adjacent turns have negative correlation with the self-inductance. (2) The sorting of influencing factors of the inductance is as follows: total number of turns[Formula: see text]number of layers, the pitch between adjacent turns[Formula: see text]substrate thickness[Formula: see text]metal width.
Structural Process Pattern Matching Based on Graph Morphism Detection
Authors: Gacitua-Decar Veronica , Pahl Claus 
Published: March 2017

Context: Processes are central to the operation of many systems or organizations. Process-centric systems, ranging from enterprise workflow systems to open distributed service compositions, have significantly increased in number and complexity. Objective: Designers of process-centric systems can benefit from process abstractions (including patterns) capturing and allowing the reuse of designs for frequent operational problems. Existing process patterns detection techniques have efficiency problems and difficulties to identify partial and inexact pattern instances. Method: We propose a process pattern detection technique based on a family of subgraph matching algorithms. The algorithms implement surjective graph morphism detection and a mechanism to incorporate semantic similarity computation for types and attributes of process graph elements. Results: Efficiency is addressed using simplified data structures, reducing the search space and its exploration. Match accuracy and time-complexity are demonstrated in an experimental study. Conclusions: Using process patterns allows business and technical processes to be provided as sharable service resources. Patterns can help to manage processes as configurable resources where a pattern can define a family of concrete customizable processes.
A User eXperience Evaluation Framework for Mobile Usability
Authors: Lee Hee-Jin , Lee Joon-Sang , Jee Eunkyoung , Bae Doo-Hwan 
Published: March 2017

The worldwide mobile software market has grown dramatically since feature phones became popular in the early 1990s. In practice, mobile usability — which can be defined for a resource-constrained device in two ways, namely, User eXperience (UX) and User Interface (UI) — has been regarded as the key to gaining superiority in terms of both market share and customer loyalty. Unfortunately, de facto standards for software design and the development process, such as Unified Modeling Language (UML) and Rational Unified Process (RUP), do not seem to promote mobile usability in a systematic manner in practice. This paper proposes a systematic and generalizable approach to modeling and evaluating the properties of mobile usability, herein treating it as a first-class software quality from the perspective of software engineering. We devise a UX evaluation framework for mobile usability, which we call UX Evaluation Framework (UEF) throughout this paper. A UX is specified by inter-scene interactions between users and terminals of software products using Extended Menu Navigation Viewpoints (EMNVs); then, a model checker, NuSMV, is adopted to observe whether the EMNV model meets a set of given UX properties. Importantly, the analysis and design of RUP is extended to support the co-design of UX and UI so that major roles, activities and artifacts in the UX and UI can be explicitly monitored and controlled by stakeholders. Through case studies, we demonstrate that UEF works properly to treat software products that prioritize mobile usability. Consequently, UEF plays a key role in filling the gap between two research disciplines to address usability: software engineering and human–computer interactions.
Thucydides on Aetiology and Methodology and Some Links with the Philosophy of Heraclitus
Authors: Parmeggiani Giovanni 
Published: March 2017

AbstractAn analysis of Thucydides’ most famous statements on the origins of the war between Athens and Sparta (1.23.4-6) and on the methodology of research of the facts (1.22.2. Cf. 1.20-21) shows a philosophical approach to history and historical research. A critically assessed comparison with some of Heraclitus of Ephesus’ statements also suggests that Thucydides’ own knowledge of early ancient philosophy helped him to shape his view on fundamental issues of historical research.Thucydides appears to have introduced himself in a similar way as one might expect a philosopher would have done. Besides the rhetoric of self-presentation and self-definition, Thucydides was indeed a philosopher: he conceived his own political science as a hiddensophiawhich showed the invisible forces that, by reciprocal interaction, shaped historical development.
Impact of Assimilating Underwater Glider Data on Hurricane Gonzalo (2014) Forecasts
Authors: Dong Jili , Domingues Ricardo , Goni Gustavo , Halliwell George , Kim Hyun-Sook , Lee Sang-Ki , Mehari Michael , Bringas Francis , Morell Julio , Pomales Luis 
Published: March 2017

Abstract
The initialization of ocean conditions is essential to coupled tropical cyclone (TC) forecasts. This study investigates the impact of ocean observation assimilation, particularly underwater glider data, on high-resolution coupled TC forecasts. Using the coupled Hurricane Weather Research and Forecasting (HWRF) Model–Hybrid Coordinate Ocean Model (HYCOM) system, numerical experiments are performed by assimilating underwater glider observations alone and with other standard ocean observations for the forecast of Hurricane Gonzalo (2014). The glider observations are able to provide valuable information on subsurface ocean thermal and saline structure, even with their limited spatial coverage along the storm track and the relatively small amount of data assimilated. Through the assimilation of underwater glider observations, the prestorm thermal and saline structures of initial upper-ocean conditions are significantly improved near the location of glider observations, though the impact is localized because of the limited coverage of glider data. The ocean initial conditions are best represented when both the standard ocean observations and the underwater glider data are assimilated together. The barrier layer and the associated sharp density gradient in the upper ocean are successfully represented in the ocean initial conditions only with the use of underwater glider observations. The upper-ocean temperature and salinity forecasts in the first 48 h are improved by assimilating both underwater glider and standard ocean observations. The assimilation of glider observations alone does not make a large impact on the intensity forecast due to their limited coverage along the storm track. The 126-h intensity forecast of Hurricane Gonzalo is improved moderately through assimilating both underwater glider data and standard ocean observations.