bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct excitation of parvalbumin‐positive interneurons by M1 muscarinic acetylcholine receptors: roles in cellular excitability, inhibitory transmission and cognition
Authors: Yi Feng , Ball Jackson , Stoll Kurt E. , Satpute Vaishali C. , Mitchell Samantha M. , Pauli Jordan L. , Holloway Benjamin B. , Johnston April D. , Nathanson Neil M. , Deisseroth Karl , Gerber David J. , Tonegawa Susumu , Lawrence J. Josh
Published: May 2014

Key points

Parvalbumin‐containing (PV) neurons from mouse CA1 hippocampus (HC) and prefrontal cortex exhibit a fast spiking phenotype in vitro. Within CA1, HC PV cells are mainly comprised of basket and bistratified cell types.

Direct activation of muscarinic acetylcholine receptors (mAChRs) enhances excitability more in CA1 HC than in prefrontal cortex PV cells.

mAChR‐induced excitation of CA1 PV cells occurs through direct activation of M1 mAChRs.

Transgenetic deletion of M1 mAChRs from PV cells diminishes M1 mAChR expression and cholinergic excitation of CA1 PV cells.

mAChR‐induced excitation exclusively in PV cells enhances GABAergic transmission in CA1 pyramidal cells.

In vivo activation of M1 mAChRs in PV cells is important in recognition and working memory but not spatial memory.

Parvalbumin‐containing (PV) neurons, a major class of GABAergic interneurons, are essential circuit elements of learning networks. As levels of acetylcholine rise during active learning tasks, PV neurons become increasingly engaged in network dynamics. Conversely, impairment of either cholinergic or PV interneuron function induces learning deficits. Here, we examined PV interneurons in hippocampus (HC) and prefrontal cortex (PFC) and their modulation by muscarinic acetylcholine receptors (mAChRs). HC PV cells, visualized by crossing PV‐CRE mice with Rosa26YFP mice, were anatomically identified as basket cells and PV bistratified cells in the stratum pyramidale; in stratum oriens, HC PV cells were electrophysiologically distinct from somatostatin‐containing cells. With glutamatergic transmission pharmacologically blocked, mAChR activation enhanced PV cell excitability in both CA1 HC and PFC; however, CA1 HC PV cells exhibited a stronger postsynaptic depolarization than PFC PV cells. To delete M1 mAChRs genetically from PV interneurons, we created PV‐M1 knockout mice by crossing PV‐CRE and floxed M1 mice. The elimination of M1 mAChRs from PV cells diminished M1 mAChR immunoreactivity and muscarinic excitation of HC PV cells. Selective cholinergic activation of HC PV interneurons using Designer Receptors Exclusively Activated by Designer Drugs technology enhanced the frequency and amplitude of inhibitory synaptic currents in CA1 pyramidal cells. Finally, relative to wild‐type controls, PV‐M1 knockout mice exhibited impaired novel object recognition and, to a lesser extent, impaired spatial working memory, but reference memory remained intact. Therefore, the direct activation of M1 mAChRs on PV cells contributes to some forms of learning and memory.
Shape Optimization With Isoperimetric Constraints for Isothermal Pipes Embedded in an Insulated Slab
Authors: Leontiou Theodoros , Fyrillas Marios M.
Published: May 2014

In this paper, we consider the heat transfer from a periodic array of isothermal pipes embedded in a rectangular slab. The upper surface of the slab is sustained at a constant temperature while the lower surface is insulated. The particular configuration is a classical heat conduction problem with a wide range of practical applications. We consider both the classical problem, i.e., estimating the shape factor of a given configuration, and the inverse problem, i.e., calculating the optimum shape that maximizes the heat transfer rate associated with a set of geometrical constraints. The way the present formulation differs from previous formulations is that: (i) the array of pipes does not have to be placed at the midsection of the slab and (ii) we have included an isoperimetric constraint (not changing in perimeter) through which we can control the deviation of the optimum shape from that of a circle. This is very important considering that most of the applications deal with buried pipes and a realistic shape is a practical necessity. The isoperimetric constraint is included through the isoperimetric quotient (IQ), which is the ratio between the area and the perimeter of a closed curve.
Design of a Magnetic Resonance Imaging-Compatible Cable-Driven Manipulator With New Instrumentation and Synthesis Methods
Authors: Abdelaziz S. , Esteveny L. , Barbé L. , Renaud P. , Bayle B. , de Mathelin M.
Published: May 2014

This paper deals with the design of a cable-driven manipulator (CDM) with instrumented structure for magnetic resonance imaging (MRI)-guided interventions. The strong magnetic field and the limited space inside the scanner constitute two severe design constraints. To handle them, a new synthesis approach for CDM is proposed in order to optimize the device compactness. This approach is based on the use of the zonotope properties to optimize the robot geometry, and the interval analysis tools for its validation. Remote actuation with Bowden cables is considered for MRI-compatibility. High friction along the line transmissions can then be expected which leads to a new instrumentation for cable tension evaluation. A prototype is manufactured and assessed. The principle of the instrumentation is validated as well as the user requirements in terms of workspace and ability to resist to external forces applied by the physician.
Computation of Motion and Added Wave Resistance With the Panel-Free Method
Authors: Peng Hongxuan (Heather) , Qiu Wei
Published: May 2014

Computations have been performed to predict motions and added wave resistances for ships at forward speeds. The radiation and diffraction problems of a ship with forward speed are solved with the panel-free method in the frequency domain. In this paper, the effect of the m-terms and forward-speed/zero-speed Green functions (GFs) on the solutions are investigated using two Wigley hull ships. Computed motions, hydrodynamic coefficients, and added wave resistances were compared with the experimental data.
Determination of Johnson–Cook Parameters for Cast Aluminum Alloys
Authors: Gupta Sachin , Abotula Sandeep , Shukla Arun
Published: May 2014

A series of experiments were conducted to determine the Johnson–Cook parameters for three different cast aluminum alloys, namely, A356, A357, and F357. Room temperature compression experiments were performed under varying rates of loading ranging from 10−3 s−1 to 5000 s−1. High temperature compression (235 °C and 435 °C) experiments were performed at an average strain rate of 5000 s−1. A split Hopkinson pressure bar (SHPB) apparatus was utilized in conjunction with an induction coil heating system for applying dynamic loading at elevated temperatures. In addition, experiments were performed under high strain rate tensile loading using tensile SHPB apparatus, and the fractured specimens were examined under scanning electron microscope (SEM) to understand the failure modes in these alloys. High-speed photography was used to capture the chronological progression of the deformation under dynamic tensile loading. The results indicated that all the three cast aluminum alloys were sensitive to strain rate and temperature. A356 exhibited the least value of flow stress under both static and dynamic loading conditions, and the highest elongation before break under dynamic tensile loading. The SEM images of the fractured specimens under dynamic tensile loading showed characteristics of transcrystalline ductile fracture in these cast aluminum alloys.
Transient Pressure Measurements on a High Head Model Francis Turbine During Emergency Shutdown, Total Load Rejection, and Runaway
Authors: Trivedi Chirag , Cervantes Michel J. , Gandhi B. K. , Dahlhaug Ole G.
Published: May 2014

The penetration of intermittent wind and solar power to the grid network above manageable limits disrupts electrical power grids. Consequently, hydraulic turbines synchronized to the grid experience total load rejection and are forced to shut down immediately. The turbine runner accelerates to runaway speeds in a few seconds, inducing high-amplitude, unsteady pressure loading on the blades. This sometimes results in a failure of the turbine components. Moreover, the unsteady pressure loading significantly affects the operating life of the turbine runner. Transient measurements were carried out on a scale model of a Francis turbine prototype (specific speed = 0.27) during an emergency shutdown with a transition into total load rejection. A detailed analysis of variables such as the head, discharge, pressure at different locations including the runner blades, shaft torque, and the guide vane angular movements are performed. The maximum amplitudes of the unsteady pressure fluctuations in the turbine were observed under a runaway condition. The amplitudes were 2.1 and 2.6 times that of the pressure loading at the best efficiency point in the vaneless space and runner, respectively. Such high-amplitude, unsteady pressure pulsations can affect the operating life of the turbine.
Efficacy of coral-hydroxyapatite and biphasic calcium phosphate for early bacterial detection
Authors: Lobaina Tamara , Zhurbenko Raisa , Alfonso Ivonne , Rodríguez Claudio , Gala-García Alfonso , Gontijo Sávio Lacerda , Cortés Maria E. , Gomes Alinne , Sinisterra Ruben Dario
Published: May 2014

Nano- or microhydroxyapatites with microbiological properties are being used to detect pathogens in clinical samples and industrial environments. In this study, the calcium phosphates coral–hydroxyapatite and biphasic calcium phosphate were characterized physicochemically using x-ray diffraction, thermogravimetric, and differential thermal analysis. The morphology, texture, and chemical composition of the ceramics were also investigated using scanning electron microscopy with energy dispersive spectroscopy. The biocompatibility of the ceramics was evaluated using Escherichia coli and Enterococcus faecalis. Microorganisms were detected by incorporating the enzyme markers 4-metilumbelliferil-β-d-glucoside and 4-metilumbelliferil-β-d-glucuronide in the ceramic powders and evaluating fluorescence. The characterization of the ceramics revealed typical characteristics, such as crystallinity, thermal stability, and chemical composition, consistent with other calcium phosphates. The calcium phosphates coral-hydroxyapatite and biphasic calcium phosphate ceramics differed from one another in morphology, structural topography, particle size distribution, and the capacity to absorb water. These properties can influence the rates of microbiological responses and bacterial detection. Although both materials are suitable for use as structural supports in microbial diagnostic systems, BCP was more efficient and detected E. coli and E. faecalis more rapidly than CHA.
Silicon etch using SF6/C4F8/Ar gas mixtures
Authors: Bates Robert L. , Stephan Thamban P. L. , Goeckner Matthew J. , Overzet Lawrence. J.
Published: May 2014

While plasmas using mixtures of SF6, C4F8, and Ar are widely used in deep silicon etching, very few studies have linked the discharge parameters to etching results. The authors form such linkages in this report. The authors measured the optical emission intensities of lines from Ar, F, S, SFx, CF2, C2, C3, and CS as a function of the percentage C4F8 in the gas flow, the total gas flow rate, and the bias power. In addition, the ion current density and electron temperature were measured using a floating Langmuir probe. For comparison, trenches were etched of various widths and the trench profiles (etch depth, undercut) were measured. The addition of C4F8 to an SF6/Ar plasma acts to reduce the availability of F as well as increase the deposition of passivation film. Sulfur combines with carbon in the plasma efficiently to create a large optical emission of CS and suppress optical emissions from C2 and C3. At low fractional flows of C4F8, the etch process appears to be controlled by the ion flux more so than by the F density. At large C4F8 fractional flows, the etch process appears to be controlled more by the F density than by the ion flux or deposition rate of passivation film. CF2 and C2 do not appear to cause deposition from the plasma, but CS and other carbon containing molecules as well as ions do.
Effect of Al concentration on Al-doped ZnO channels fabricated by atomic-layer deposition for top-gate oxide thin-film transistor applications
Authors: Kim Eom-Ji , Bak Jun-Yong , Choi Jeong-Seon , Yoon Sung-Min
Published: May 2014

Al-doped ZnO (AZO) thin films were prepared by atomic layer deposition, in order to optimize their characteristics as active channel materials for oxide thin-film transistors (TFTs). The crystalline phases of the AZO films deposited at 100 °C appeared as mainly (100) planes, and their surface morphologies were homogeneous and smooth. The electrical conductivities of AZO films with varying Al concentrations were measured in-situ with a temperature sweep from 50 to 250 °C. From the conductivities, the activation energies for the carrier transport of each composition were calculated at some specified temperature ranges. A critical value of incorporated Al increased electrical conductivity by means of the donor doping effect: beyond that value, additional Al was found to act as a typical carrier suppressor. Top-gate-structured AZO TFTs were fabricated and characterized. The maximum field-effect mobility at the saturation region was found to be 0.64 cm2 V−1 s−1 when 1-at. %-Al was incorporated into the ZnO channel. Mobility showed a decreasing trend with increasing Al concentration. Negative and positive bias-stress (NBS and PBS) stabilities of the AZO-TFTs were also evaluated. The threshold voltage shifts during the NBS and PBS for 104 s were as low as −1.8 and −0.9 V, respectively. Raising the Al concentration increased the NBS instabilities, whereas the PBS stabilities were improved by higher Al concentrations.
Ni2.36Mn0.72Ga0.92 nanowires with high martensite transition temperature
Authors: Gyawali Parshu , Sapkota Keshab , Pegg Ian , Philip John
Published: May 2014

Nanowires of ferromagnetic shape memory alloy Ni2.36Mn0.72Ga0.92 are grown and their structural and magnetic properties are investigated. Single phase nanowires are obtained only after they were quenched to 77 K from high temperature annealing at 873 K. The nanowires are in martensitic orthorhombic phase and they retain the martensitic nature to low temperature. The martensite phase of the nanowires is supported by magnetic measurements, which showed no anomaly in magnetization versus temperature plot below 400 K. The ferromagnetic transition temperature of the nanowires is observed to be greater than 400 K.
Biodegradation performance of a chitosan coated magnesium-zinc-tricalcium phosphate composite as an implant
Authors: Zhao Jun , Chen Liangjian , Yu Kun , Chen Chang , Dai Yilong , Qiao Xueyan , Yan Yang
Published: May 2014

A Mg-Zn-tricalcium phosphate composite with a chitosan coating was prepared in this investigation to study its biodegradation performance both in vitro and in vivo conditions. The in vitro test results show that the immersion corrosion rate, the pH values of the simulated body fluids and the released metal ion concentration of the chitosan coated composite are all lower than those of the uncoated composite. The in vitro cytotoxicity test shows that the chitosan coated specimens is safe for cellular applications. When the chitosan coated composite is tested in vivo, the concentration of metal ions from the composite observed in the venous blood of Zelanian rabbits is less than the uncoated composite specimens. The chitosan coating slows down the in vivo degradation of the composite after surgery. In vivo testing also indicates that the chitosan coated composite is harmless to important visceral organs, including the heart, kidneys, and liver of the rabbits. The new bone formation surrounding the chitosan coated composite implant shows that the composite improves the concrescence of the bone tissues. The chitosan coating is an effective corrosion resistant layer that reduces the hydrogen release of the implant composite, thereby decreasing the subcutaneous gas bubbles formed.
Passive ultrasonics using sub-Nyquist sampling of high-frequency thermal-mechanical noise
Authors: Sabra Karim G. , Romberg Justin , Lani Shane , Levent Degertekin F.
Published: May 2014

Monolithic integration of capacitive micromachined ultrasonic transducer arrays with low noise complementary metal oxide semiconductor electronics minimizes interconnect parasitics thus allowing the measurement of thermal-mechanical (TM) noise. This enables passive ultrasonics based on cross-correlations of diffuse TM noise to extract coherent ultrasonic waves propagating between receivers. However, synchronous recording of high-frequency TM noise puts stringent requirements on the analog to digital converter's sampling rate. To alleviate this restriction, high-frequency TM noise cross-correlations (12–25 MHz) were estimated instead using compressed measurements of TM noise which could be digitized at a sampling frequency lower than the Nyquist frequency.
Indoor-Biofilter Growth and Exposure to Airborne Chemicals Drive Similar Changes in Plant Root Bacterial Communities
Authors: Russell Jacob A. , Hu Yi , Chau Linh , Pauliushchyk Margarita , Anastopoulos Ioannis , Anandan Shivanthi , Waring Michael S.
Published: May 2014

Due to the long durations spent inside by many humans, indoor air quality has become a growing concern. Biofiltration has emerged as a potential mechanism to clean indoor air of harmful volatile organic compounds (VOCs), which are typically found at concentrations higher indoors than outdoors. Root-associated microbes are thought to drive the functioning of plant-based biofilters, or biowalls, converting VOCs into biomass, energy, and carbon dioxide, but little is known about the root microbial communities of such artificially grown plants, how or whether they differ from those of plants grown in soil, and whether any changes in composition are driven by VOCs. In this study, we investigated how bacterial communities on biofilter plant roots change over time and in response to VOC exposure. Through 16S rRNA amplicon sequencing, we compared root bacterial communities from soil-grown plants with those from two biowalls, while also comparing communities from roots exposed to clean versus VOC-laden air in a laboratory biofiltration system. The results showed differences in bacterial communities between soil-grown and biowall-grown plants and between bacterial communities from plant roots exposed to clean air and those from VOC-exposed plant roots. Both biowall-grown and VOC-exposed roots harbored enriched levels of bacteria from the genus
Hyphomicrobium
. Given their known capacities to break down aromatic and halogenated compounds, we hypothesize that these bacteria are important VOC degraders. While different strains of
Hyphomicrobium
proliferated in the two studied biowalls and our lab experiment, strains were shared across plant species, suggesting that a wide range of ornamental houseplants harbor similar microbes of potential use in living biofilters.
Biomineralization of Uranium by PhoY Phosphatase Activity Aids Cell Survival in Caulobacter crescentus
Authors: Yung Mimi C. , Jiao Yongqin
Published: May 2014

Caulobacter crescentus
is known to tolerate high levels of uranium [U(VI)], but its detoxification mechanism is poorly understood. Here we show that
C. crescentus
is able to facilitate U(VI) biomineralization through the formation of U-P
i
precipitates via its native alkaline phosphatase activity. The U-P
i
precipitates, deposited on the cell surface in the form of meta-autunite structures, have a lower U/P
i
ratio than do chemically produced precipitates. The enzyme that is responsible for the phosphatase activity and thus the biomineralization process is identified as PhoY, a periplasmic alkaline phosphatase with broad substrate specificity. Furthermore, PhoY is shown to confer a survival advantage on
C. crescentus
toward U(VI) under both growth and nongrowth conditions. Results obtained in this study thus highlight U(VI) biomineralization as a resistance mechanism in microbes, which not only improves our understanding of bacterium-mineral interactions but also aids in defining potential ecological niches for metal-resistant bacteria.
Tagging Frogs with Passive Integrated Transponders Causes Disruption of the Cutaneous Bacterial Community and Proliferation of Opportunistic Fungi
Authors: Antwis Rachael E. , Garcia Gerardo , Fidgett Andrea L. , Preziosi Richard F.
Published: May 2014

Symbiotic bacterial communities play a key role in protecting amphibians from infectious diseases including chytridiomycosis, caused by the pathogenic fungus
Batrachochytrium dendrobatidis
. Events that lead to the disruption of the bacterial community may have implications for the susceptibility of amphibians to such diseases. Amphibians are often marked both in the wild and in captivity for a variety of reasons, and although existing literature indicates that marking techniques have few negative effects, the response of cutaneous microbial communities has not yet been investigated. Here we determine the effects of passive integrated transponder (PIT) tagging on culturable cutaneous microbial communities of captive Morelet's tree frogs (
Agalychnis moreletii
) and assess the isolated bacterial strains for anti-
B. dendrobatidis
activity
in vitro
. We find that PIT tagging causes a major disruption to the bacterial community associated with the skin of frogs (∼12-fold increase in abundance), as well as a concurrent proliferation in resident fungi (up to ∼200-fold increase). Handling also caused a disruption the bacterial community, although to a lesser extent than PIT tagging. However, the effects of both tagging and handling were temporary, and after 2 weeks, the bacterial communities were similar to their original compositions. We also identify two bacterial strains that inhibit
B. dendrobatidis
, one of which increased in abundance on PIT-tagged frogs at 1 day postmarking, while the other was unaffected. These results show that PIT tagging has previously unobserved consequences for cutaneous microbial communities of frogs and may be particularly relevant for studies that intend to use PIT tagging to identify individuals involved in trials to develop probiotic treatments.
Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane
Authors: Saada Edwin A. , Kabututu Z. Pius , Lopez Miguel , Shimogawa Michelle M. , Langousis Gerasimos , Oberholzer Michael , Riestra Angelica , Jonsson Zophonias O. , Wohlschlegel James A. , Hill Kent L.
Published: May 2014

Increasing evidence indicates that the
Trypanosoma brucei
flagellum (synonymous with cilium) plays important roles in host-parasite interactions. Several studies have identified virulence factors and signaling proteins in the flagellar membrane of bloodstream-stage
T. brucei
, but less is known about flagellar membrane proteins in procyclic, insect-stage parasites. Here we report on the identification of several receptor-type flagellar adenylate cyclases (ACs) that are specifically upregulated in procyclic
T. brucei
parasites. Identification of insect stage-specific ACs is novel, as previously studied ACs were constitutively expressed or confined to bloodstream-stage parasites. We show that procyclic stage-specific ACs are glycosylated, surface-exposed proteins that dimerize and possess catalytic activity. We used gene-specific tags to examine the distribution of individual AC isoforms. All ACs examined localized to the flagellum. Notably, however, while some ACs were distributed along the length of the flagellum, others specifically localized to the flagellum tip. These are the first transmembrane domain proteins to be localized specifically at the flagellum tip in
T. brucei
, emphasizing that the flagellum membrane is organized into specific subdomains. Deletion analysis reveals that C-terminal sequences are critical for targeting ACs to the flagellum, and sequence comparisons suggest that differential subflagellar localization might be specified by isoform-specific C termini. Our combined results suggest insect stage-specific roles for a subset of flagellar adenylate cyclases and support a microdomain model for flagellar cyclic AMP (cAMP) signaling in
T. brucei
. In this model, cAMP production is compartmentalized through differential localization of individual ACs, thereby allowing diverse cellular responses to be controlled by a common signaling molecule.
Distinct Innate Immune Phagocyte Responses to Aspergillus fumigatus Conidia and Hyphae in Zebrafish Larvae
Authors: Knox Benjamin P. , Deng Qing , Rood Mary , Eickhoff Jens C. , Keller Nancy P. , Huttenlocher Anna
Published: May 2014

Aspergillus fumigatus
is the most common filamentous fungal pathogen of immunocompromised hosts, resulting in invasive aspergillosis (IA) and high mortality rates. Innate immunity is known to be the predominant host defense against
A. fumigatus
; however, innate phagocyte responses to
A. fumigatus
in an intact host and their contributions to host survival remain unclear. Here, we describe a larval zebrafish
A. fumigatus
infection model amenable to real-time imaging of host-fungal interactions in live animals. Following infection with
A. fumigatus
, innate phagocyte populations exhibit clear preferences for different fungal morphologies: macrophages rapidly phagocytose conidia and form aggregates around hyphae, while the neutrophil response is dependent upon the presence of hyphae. Depletion of macrophages rendered host larvae susceptible to invasive disease. Moreover, a zebrafish model of human leukocyte adhesion deficiency with impaired neutrophil function also resulted in invasive disease and impaired host survival. In contrast, macrophage-deficient but not neutrophil-deficient larvae exhibited attenuated disease following challenge with a less virulent (Δ
laeA
) strain of
A. fumigatus
, which has defects in secondary metabolite production. Taking these results together, we have established a new vertebrate model for studying innate immune responses to
A. fumigatus
that reveals distinct roles for neutrophils and macrophages in mediating host defense against IA.
Intracellular β-Glucosidases CEL1a and CEL1b Are Essential for Cellulase Induction on Lactose in Trichoderma reesei
Authors: Xu Jintao , Zhao Guolei , Kou Yanbo , Zhang Weixin , Zhou Qingxin , Chen Guanjun , Liu Weifeng
Published: May 2014

Lactose (1,4-
O
-β-
d
-galacto-pyranosyl-
d
-glucose) induces cellulolytic enzymes in
Trichoderma reesei
and is in fact one of the most important soluble carbon sources used to produce cellulases on an industrial level. The mechanism underlying the induction is, however, not fully understood. In this study, we investigated the cellular functions of the intracellular β-glucosidases CEL1a and CEL1b in the induction of cellulase genes by lactose in
T. reesei
. We demonstrated that while CEL1a and CEL1b were functionally equivalent in mediating the induction, the simultaneous absence of these intracellular β-glucosidases abolished
cbh1
gene expression on lactose.
d
-Galactose restored the efficient cellulase gene induction in the Δ
cel1a
strain independently of its reductive metabolism, but not in the Δ
cel1a
Δ
cel1b
strain. A further comparison of the transcriptional responses of the Δ
cel1a
Δ
cel1b
strain complemented with wild-type CEL1a or a catalytically inactive CEL1a version and the Δ
cel1a
strain constitutively expressing CEL1a or the
Kluyveromyces lactis
β-galactosidase LAC4 showed that both the CEL1a protein and its glycoside hydrolytic activity were indispensable for cellulase induction by lactose. We also present evidence that intracellular β-glucosidase-mediated lactose induction is further conveyed to XYR1 to ensure the efficiently induced expression of cellulase genes.
Heterochromatin Controls γH2A Localization in Neurospora crassa
Authors: Sasaki Takahiko , Lynch Kelsey L. , Mueller Caitlin V. , Friedman Steven , Freitag Michael , Lewis Zachary A.
Published: May 2014

In response to genotoxic stress, ATR and ATM kinases phosphorylate H2A in fungi and H2AX in animals on a C-terminal serine. The resulting modified histone, called γH2A, recruits chromatin-binding proteins that stabilize stalled replication forks or promote DNA double-strand-break repair. To identify genomic loci that might be prone to replication fork stalling or DNA breakage inNeurospora crassa, we performed chromatin immunoprecipitation (ChIP) of γH2A followed by next-generation sequencing (ChIP-seq). γH2A-containing nucleosomes are enriched inNeurosporaheterochromatin domains. These domains are comprised of A·T-rich repetitive DNA sequences associated with histone H3 methylated at lysine-9 (H3K9me), the H3K9me-binding protein heterochromatin protein 1 (HP1), and DNA cytosine methylation. H3K9 methylation, catalyzed by DIM-5, is required for normal γH2A localization. In contrast, γH2A is not required for H3K9 methylation or DNA methylation. Normal γH2A localization also depends on HP1 and a histone deacetylase, HDA-1, but is independent of the DNA methyltransferase DIM-2. γH2A is globally induced indim-5mutants under normal growth conditions, suggesting that the DNA damage response is activated in these mutants in the absence of exogenous DNA damage. Together, these data suggest that heterochromatin formation is essential for normal DNA replication or repair.
TbKAP6, a Mitochondrial HMG Box-Containing Protein in Trypanosoma brucei, Is the First Trypanosomatid Kinetoplast-Associated Protein Essential for Kinetoplast DNA Replication and Maintenance
Authors: Wang Jianyang , Pappas-Brown Valeria , Englund Paul T. , Jensen Robert E.
Published: May 2014

Kinetoplast DNA (kDNA), the mitochondrial genome of trypanosomatids, is a giant planar network of catenated minicircles and maxicircles.
In vivo
kDNA is organized as a highly condensed nucleoprotein disk. So far, in
Trypanosoma brucei
, proteins involved in the maintenance of the kDNA condensed structure remain poorly characterized. In
Crithidia fasciculata
, some small basic histone H1-like
k
inetoplast-
a
ssociated
p
roteins (CfKAP) have been shown to condense isolated kDNA networks
in vitro
. High-mobility group (HMG) box-containing proteins, such as mitochondrial transcription factor A (TFAM) in mammalian cells and Abf2 in the budding yeast, have been shown essential for the packaging of mitochondrial DNA (mtDNA) into mitochondrial nucleoids, remodeling of mitochondrial nucleoids, gene expression, and maintenance of mtDNA. Here, we report that TbKAP6, a mitochondrial HMG box-containing protein, is essential for parasite cell viability and involved in kDNA replication and maintenance. The RNA interference (RNAi) depletion of TbKAP6 stopped cell growth. Replication of both minicircles and maxicircles was inhibited. RNAi or overexpression of TbKAP6 resulted in the disorganization, shrinkage, and loss of kDNA. Minicircle release, the first step in kDNA replication, was inhibited immediately after induction of RNAi, but it quickly increased 3-fold upon overexpression of TbKAP6. Since the release of covalently closed minicircles is mediated by a type II topoisomerase (topo II), we examined the potential interactions between TbKAP6 and topo II. Recombinant TbKAP6 (rTbKAP6) promotes the topo II-mediated decatenation of kDNA. rTbKAP6 can condense isolated kDNA networks
in vitro
. These results indicate that TbKAP6 is involved in the replication and maintenance of kDNA.
An overview and methodological assessment of systematic reviews and meta-analyses of enhanced recovery programmes in colorectal surgery
Authors: Chambers Duncan , Paton Fiona , Wilson Paul , Eastwood Alison , Craig Dawn , Fox Dave , Jayne David , McGinnes Erika
Published: May 2014

Objectives

To identify and critically assess the extent to which systematic reviews of enhanced recovery programmes for patients undergoing colorectal surgery differ in their methodology and reported estimates of effect.

Design

Review of published systematic reviews. We searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) Database from 1990 to March 2013. Systematic reviews of enhanced recovery programmes for patients undergoing colorectal surgery were eligible for inclusion.

Primary and secondary outcome measures

The primary outcome was length of hospital stay. We assessed changes in pooled estimates of treatment effect over time and how these might have been influenced by decisions taken by researchers as well as by the availability of new trials. The quality of systematic reviews was assessed using the Centre for Reviews and Dissemination (CRD) DARE critical appraisal process.

Results

10 systematic reviews were included. Systematic reviews of randomised controlled trials have consistently shown a reduction in length of hospital stay with enhanced recovery compared with traditional care. The estimated effect tended to increase from 2006 to 2010 as more trials were published but has not altered significantly in the most recent review, despite the inclusion of several unique trials. The best estimate appears to be an average reduction of around 2.5 days in primary postoperative length of stay. Differences between reviews reflected differences in interpretation of inclusion criteria, searching and analytical methods or software.

Conclusions

Systematic reviews of enhanced recovery programmes show a high level of research waste, with multiple reviews covering identical or very similar groups of trials. Where multiple reviews exist on a topic, interpretation may require careful attention to apparently minor differences between reviews. Researchers can help readers by acknowledging existing reviews and through clear reporting of key decisions, especially on inclusion/exclusion and on statistical pooling.
Identifying hopelessness in population research: a validation study of two brief measures of hopelessness
Authors: Fraser Lindsay , Burnell Matthew , Salter Laura Currin , Fourkala Evangelia-Ourania , Kalsi Jatinderpal , Ryan Andy , Gessler Sue , Gidron Yori , Steptoe Andrew , Menon Usha
Published: May 2014

Objective

Hopelessness is an important construct in psychosocial epidemiology, but there is great pressure on the length of questionnaire measures in large-scale population and clinical studies. We examined the validity and test–retest reliability of two brief measures of hopelessness, an existing negatively worded two-item measure of hopelessness (Brief-H-Neg) and a positively worded version of the same instrument (Brief-H-Pos).

Design

Cohort study.

Setting

Control arm of the UK Collaborative Trial of Ovarian Cancer Screening.

Participants

A non-clinical research-based sample of 5000 postmenopausal women selected from 56 512 participants.

Primary and secondary outcome measures

Spearman's rank correlation of brief measures of hopelessness with the Beck Hopelessness Scale (BHS). Spearman's rank correlation with the Centre for Epidemiological Studies Depression Scale (CES-D) and change in mean score on repeat testing.

Methods

Two short hopelessness measures, a negatively worded brief measure of hopelessness (Brief-H-Neg) and a positively worded brief measure of hopelessness (Brief-H-Pos), were administered by postal questionnaire to 5000 women together with the 20-item BHS and 20-item CES-D. The Brief-H-Neg and Brief-H-Pos were readministered to 500 women after a 2-week interval.

Results

2413 postmenopausal women (mean age 68.9 years) completed the questionnaire. The Brief-H-Neg and Brief-H-Pos correlated 0.93 and 0.87 with the BHS after correction for attenuation and their association with the CES-D mirrored that seen with the BHS (Spearman's rank correlation 0.88 and 0.68, respectively). There was no change in mean scores on the two measures with repeat testing in the 433 women who completed them and test–retest reliability was good (intraclass correlations Brief-H-Neg 0.67 and Brief-H-Pos 0.72).

Conclusions

These findings provide support for the validity of the Brief-H-Neg and Brief-H-Pos. These brief measures are likely to be useful in large population studies assessing hopelessness.

Trial registration number

NCT00058032.
Improving skills and care standards in the support workforce for older people: a realist review
Authors: Rycroft-Malone Jo , Burton Christopher , Hall Beth , McCormack Brendan , Nutley Sandra , Seddon Diane , Williams Lynne
Published: May 2014

Introduction

In the context of a population that is growing older, and a number of high-profile scandals about care standards in hospital and community settings, having a skilled and knowledgeable workforce caring for older people is an ethical and policy imperative. Support workers make up the majority of the workforce in health and social care services for older people (aged 65 years and over), and yet little is known about the best way to facilitate their development. Given this gap, this review will draw on evidence to address the question: how can workforce development interventions improve the skills and the care standards of support workers within older people's health and social care services?

Methods and analysis

As we are interested in how and why workforce development interventions might work, in what circumstances and with whom, we will conduct a realist review, sourcing evidence from health, social care, policing and education. The review will be conducted in four steps over 18 months to (1) construct a theoretical framework, that is, the review’s programme theories; (2) retrieve, review and synthesise evidence relating to interventions designed to develop the support workforce guided by the programme theories; (3) ‘test out’ our synthesis findings and refine the programme theories, establish their practical relevance/potential for implementation and (4) formulate recommendations about improvements to current workforce development interventions to contribute to the improvement of care standards in older people's health and social care services, potentially transferrable to other services.

Ethics and dissemination

Ethical approval is not required to undertake this review. Knowledge exchange activities through stakeholder engagement and online postings are embedded throughout the lifetime of the project. The main output from this review will be a new theory driven framework for skill development for the support workforce in health and social care for older people.

Trial registration number

CRD42013006283.
Spatial, demographic and clinical patterns of Angiostrongylus vasorum infection in the dog population of Southern England
Authors: Blehaut T. R. W. , Hardstaff J. L. , Chapman P. S. , Pfeiffer D. U. , Boag A. K. , Guitian F. J.
Published: May 2014

A retrospective study was carried out to provide updated knowledge of the spatial pattern of Angiostrongylus vasorum infection in Southern England and to investigate associations between selected host characteristics (age, breed, sex), risk of infection and clinical presentation (cardiorespiratory signs v haemorrhagic diathesis). One hundred and forty‐one cases diagnosed between April 1999 and July 2012 were compared with a control population of dogs referred to the same hospital. A significant association was found between haemorrhagic diathesis and breed but not for other host characteristics and clinical presentations. Younger dogs and certain breeds of dog (Jack Russell terriers, Cocker Spaniels, Springer Spaniels, Cavalier King Charles spaniels and Staffordshire Bull Terriers) had significantly higher odds of angiostrongylosis than other breeds in the study. A significant cluster of cases was found in Southern England. Animals presenting with cardiorespiratory signs or haemorrhagic diathesis in Southern England, especially if they are young or of a breed associated with angiostrongylosis, should be given special consideration with regards to possible A. vasorum infestation. Our results should be interpreted bearing in mind that they are based on the retrospective exploration of dogs seen at a referral centre.
Interplay of rheology and entrainment in debris avalanches: a numerical study
Authors: Cuomo Sabatino , Pastor Manuel , Cascini Leonardo , Castorino Giuseppe Claudio
Published: May 2014

Flow-type landslides are a major global hazard. They occur worldwide, and are responsible for a large number of casualties, significant structural damage to property and infrastructure, and economic losses. The features of debris avalanches are particularly important, as they involve open slopes and affect triangular source areas when initial slides turn into avalanches through further failures or eventual soil entrainment. In this paper, the propagation stage of debris avalanches is numerically modelled to provide information such as the propagation pattern of the mobilized material and its velocity, thickness, and run-out distance. The use of a “depth-integrated” model has the following advantages: (i) it adequately accommodates the irregular topography of real slopes, which greatly affects the evolution of the propagation stage; and (ii) it is less time consuming than full three-dimensional approaches. The model is named “GeoFlow_SPH” and has previously been applied to theoretical, experimental, and real case histories. The behaviour of debris avalanches is analysed with particular attention to the apical angle, one of the main features of this type of landslide, in relation to soil rheology, hillslope geometry, and the geometric aspect ratio of the triggering area. The role of bed entrainment is also investigated with reference to differences in steepness of the uppermost parts of open slopes. First, simplified benchmark slopes are analysed using both water-like materials (with negligible shear strength) and debris-type materials (saturated frictional soil). Next, the paper addresses three important case studies from the Campania region of southern Italy (Cervinara, Nocera Inferiore, and Sarno), where debris avalanches occur in pyroclastic soils that originated from the eruptive products of the Mount Vesuvius volcano. In all of the cases analysed, the effects of erosion rate are compared with those of simulated soil propagation height, run-out distance, and velocity. In a novel contribution to the existing research, the results obtained from analysis of both the benchmark slopes and the real case histories indicate that landslide propagation depends on the interplay of rheology and bed entrainment. In particular, increased erosion growth rates correspond to shorter run-out distances, lower velocities, and larger propagation depths. It is further shown that erosion depth increases with either friction angle or the consolidation coefficient of pore-water pressure; the latter reduces bed entrainment but does not significantly affect the apical angle of debris avalanches. Globally, the results are particularly satisfactory because they indicate that the GeoFlow_SPH model is a suitable tool for the analysis and forecasting of debris avalanches.
Cyclostratigraphy: data filtering as a source of spurious spectral peaks
Authors: Vaughan Simon , Bailey Robin J. , Smith David G.
Published: May 2014

Searches for periodic signals (candidate Milankovitch cycles) in stratigraphic data often make use of methods of spectral analysis, some of which have come to be regarded as standard and therefore reliable. In this paper we highlight a problem with the application of filtering, or smoothing, to the data
prior
to spectral analysis. Such preprocessing is frequently used to amplify the signal-to-noise ratio at the expected wavelength. Using synthetic random data, we demonstrate how filtering generates artificial spectral peaks close to the characteristic wavelength of the filter. When applying the same preprocessing methods to actual stratigraphic data, we find that it is possible to replicate some recently published results claiming to show cyclicity. We recommend that filtering and other preprocessing techniques be used with great care: spectral peaks occurring close to the characteristic scale of the applied filter are likely to be artefacts of preprocessing.
Carbonate petrophysical rock typing: integrating geological attributes and petrophysical properties while linking with dynamic behaviour
Authors: Skalinski Mark , Kenter Jeroen A. M.
Published: May 2014

Carbonate rock typing provides a vehicle to propagate petrophysical properties through association with geological attributes and, therefore, is critical for distributing reservoir properties, such as permeability and water saturation, in the reservoir model. The conventional approaches to rock typing have significant gaps in incorporating diagenetic processes, transferring rock types from core to log domain, accounting for fractures and using appropriate methodology to realistically distribute rock types in the static reservoir model. The workflow proposed in this paper addresses these issues in a comprehensive way by determination of petrophysical rock types (PRTs), which control static properties and dynamic behaviour of the reservoir, while optimally linking to geological attributes (depositional and diagenetic) and their spatial interrelationships and trends. This approach is novel for the fact that it: (1) integrates geological processes, petrophysics and Earth modelling aspects of rock typing; (2) integrates core and log scales; and (3) provides a flexible ‘road map’ from core to 3D model for variable data scenarios that can be updated with progressive changes in data quality and quantity during the life cycle of an asset. This paper introduces the rationale behind this workflow, and demonstrates its workings and agility through deployment in two large carbonate fields.
Blunted cerebral blood flow velocity in response to a nitric oxide donor in postural tachycardia syndrome
Authors: Del Pozzi Andrew T. , Pandey Akash , Medow Marvin S. , Messer Zachary R. , Stewart Julian M.
Published: May 2014

Cognitive deficits are characteristic of postural tachycardia syndrome (POTS). Intact nitrergic nitric oxide (NO) is important to cerebral blood flow (CBF) regulation, neurovascular coupling, and cognitive efficacy. POTS patients often experience defective NO-mediated vasodilation caused by oxidative stress. We have previously shown dilation of the middle cerebral artery in response to a bolus administration of the NO donor sodium nitroprusside (SNP) in healthy volunteers. In the present study, we hypothesized a blunted middle cerebral artery response to SNP in POTS. We used combined transcranial Doppler-ultrasound to measure CBF velocity and near-infrared spectroscopy to measure cerebral hemoglobin oxygenation while subjects were in the supine position. The responses of 17 POTS patients were compared with 12 healthy control subjects (age: 14–28 yr). CBF velocity in POTS patients and control subjects were not different at baseline (75 ± 3 vs. 71 ± 2 cm/s, P = 0.31) and decreased to a lesser degree with SNP in POTS patients (to 71 ± 3 vs. 62 ± 2 cm/s, P = 0.02). Changes in total and oxygenated hemoglobin (8.83 ± 0.45 and 8.13 ± 0.48 μmol/kg tissue) were markedly reduced in POTS patients compared with control subjects (14.2 ± 1.4 and 13.6 ± 1.6 μmol/kg tissue), primarily due to increased venous efflux. The data indicate reduced cerebral oxygenation, blunting of cerebral arterial vasodilation, and heightened cerebral venodilation. We conclude, based on the present study outcomes, that decreased bioavailability of NO is apparent in the vascular beds, resulting in a downregulation of NO receptor sites, ultimately leading to blunted responses to exogenous NO.