bluuebunny/crossref_metadata_2025 huggingface dataset:
Systolic [Ca2+]i regulates diastolic levels in rat ventricular myocytes
Authors: Sankaranarayanan Rajiv , Kistamás Kornél , Greensmith David J. , Venetucci Luigi A. , Eisner David A.
Published: June 2017

Key points

For the heart to function as a pump, intracellular calcium concentration ([Ca2+]i) must increase during systole to activate contraction and then fall, during diastole, to allow the myofilaments to relax and the heart to refill with blood.

The present study investigates the control of diastolic [Ca2+]i in rat ventricular myocytes.

We show that diastolic [Ca2+]i is increased by manoeuvres that decrease sarcoplasmic reticulum function. This is accompanied by a decrease of systolic [Ca2+]i such that the time‐averaged [Ca2+]i remains constant.

We report that diastolic [Ca2+]i is controlled by the balance between Ca2+ entry and Ca2+ efflux during systole.

The results of the present study identify a novel mechanism by which changes of the amplitude of the systolic Ca transient control diastolic [Ca2+]i.

The intracellular Ca concentration ([Ca2+]i) must be sufficently low in diastole so that the ventricle is relaxed and can refill with blood. Interference with this will impair relaxation. The factors responsible for regulation of diastolic [Ca2+]i, in particular the relative roles of the sarcoplasmic reticulum (SR) and surface membrane, are unclear. We investigated the effects on diastolic [Ca2+]i that result from the changes of Ca cycling known to occur in heart failure. Experiments were performed using Fluo‐3 in voltage clamped rat ventricular myocytes. Increasing stimulation frequency increased diastolic [Ca2+]i. This increase of [Ca2+]i was larger when SR function was impaired either by making the ryanodine receptor leaky (with caffeine or ryanodine) or by decreasing sarco/endoplasmic reticulum Ca‐ATPase activity with thapsigargin. The increase of diastolic [Ca2+]i produced by interfering with the SR was accompanied by a decrease of the amplitude of the systolic Ca transient, such that there was no change of time‐averaged [Ca2+]i. Time‐averaged [Ca2+]i was increased by β‐adrenergic stimulation with isoprenaline and increased in a saturating manner with increased stimulation frequency; average [Ca2+]i was a linear function of Ca entry per unit time. Diastolic and time‐averaged [Ca2+]i were decreased by decreasing the L‐type Ca current (with 50 μm cadmium chloride). We conclude that diastolic [Ca2+]i is controlled by the balance between Ca entry and efflux during systole. Furthermore, manoeuvres that decrease the amplitude of the Ca transient (without decreasing Ca influx) will therefore increase diastolic [Ca2+]i. This identifies a novel mechanism by which changes of the amplitude of the systolic Ca transient control diastolic [Ca2+]i.
Validation of Single C-Arm Fluoroscopic Technique for Measuring In Vivo Abdominal Wall Deformation
Authors: Kahan Lindsey G. , Guertler Charlotte , Blatnik Jeffrey A. , Lake Spencer P.
Published: June 2017

Hernia meshes significantly reduce the recurrence rates in hernia repair. It is known that they affect the abdominal wall postimplantation, yet the understanding of in vivo mechanics in the mesh placement area is lacking. We established a single C-arm biplane fluoroscopic system to study strains at the interface between the mesh and repaired abdominal tissues. We aimed to validate this system for future porcine hernia repair studies. Custom matlab programs were written to correct for pincushion distortion, and direct linear transformation (DLT) reconstructed objects in 3D. Using a custom biplane-trough setup, image sets were acquired throughout the calibrated volume to evaluate a radio-opaque test piece with known distances between adjacent beads. Distances were measured postprocessing and compared to known measurements. Repeatability testing was conducted by taking image sets of the test piece in a fixed location to determine system movement. The error in areal stretch tracking was evaluated by imaging a square plate with fixed radio-opaque beads and using matlab programs to compare the measured areal stretch to known bead positions. Minor differences between measured and known distances in the test piece were not statistically different, and the system yielded a 0.01 mm bias in the XY plane and a precision of 0.61 mm. The measured areal stretch was 0.996, which was not significantly different than the expected value of 1. In addition, preliminary stretch data for a hernia mesh in a porcine model demonstrated technique feasibility to measure in vivo porcine abdominal mechanics.
Efficient Numerical Evaluation of Exact Solutions for One-Dimensional and Two-Dimensional Infinite Cylindrical Heat Conduction Problems
Authors: Pi Te , Cole Kevin , Beck James
Published: June 2017

Estimation of thermal properties or diffusion properties from transient data requires that a model is available that is physically meaningful and suitably precise. The model must also produce numerical values rapidly enough to accommodate iterative regression, inverse methods, or other estimation procedures during which the model is evaluated again and again. Bodies of infinite extent are a particular challenge from this perspective. Even for exact analytical solutions, because the solution often has the form of an improper integral that must be evaluated numerically, lengthy computer-evaluation time is a challenge. The subject of this paper is improving the computer evaluation time for exact solutions for infinite and semi-infinite bodies in the cylindrical coordinate system. The motivating applications for the present work include the line-source method for obtaining thermal properties, the estimation of thermal properties by the laser-flash method, and the estimation of aquifer properties or petroleum-field properties from well-test measurements. In this paper, the computer evaluation time is improved by replacing the integral-containing solution by a suitable finite-body series solution. The precision of the series solution may be controlled to a high level and the required computer time may be minimized, by a suitable choice of the extent of the finite body. The key finding of this paper is that the resulting series may be accurately evaluated with a fixed number of terms at any value of time, which removes a long-standing difficulty with series solution in general. The method is demonstrated for the one-dimensional case of a large body with a cylindrical hole and is extended to two-dimensional geometries of practical interest. The computer-evaluation time for the finite-body solutions are shown to be hundreds or thousands of time faster than the infinite-body solutions, depending on the geometry.
Influence of Si precursor type on the surface roughening of SiGe epitaxial layers deposited by ultrahigh vacuum chemical vapor deposition method
Authors: Kim Youngmo , Yoon Sungyeol , Ko Daehong , Sohn Hyunchul
Published: June 2017

Si1-xGex layers were deposited using Si2H6/GeH4 and Si3H8/GeH4 by ultrahigh vacuum chemical vapor deposition, and the effect of the Si precursor type on surface roughnening is investigated. The root mean square (RMS) of surface roughness of Si1-xGex layers that were deposited using either Si2H6 or Si3H8 was increased gradually with the increasing film thickness, resulting in an increase in the amplitude of the wavy surface below the critical thickness for the formation of threading dislocations. The residual strain in SiGe with Si2H6 was decreased significantly through the defect formation with an abrupt increase in RMS roughness for the thickness larger than the critical thickness. For the SiGe layer with Si3H8, RMS roughness of the SiGe layer was increased gradually and monotonically, while the residual strain was decreased gradually above the critical thickness. Therefore, the use of a Si3H8 precursor as a silicon source gas can be helpful to control the flat interface for heteroepitaxial growth.
A Conserved Leucine Zipper Motif in Gammaherpesvirus ORF52 Is Critical for Distinct Microtubule Rearrangements
Authors: Loftus Matthew S. , Verville Nancy , Kedes Dean H.
Published: June 2017

Productive viral infection often depends on the manipulation of the cytoskeleton. Herpesviruses, including rhesus monkey rhadinovirus (RRV) and its close homolog, the oncogenic human gammaherpesvirus Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8), exploit microtubule (MT)-based retrograde transport to deliver their genomes to the nucleus. Subsequently, during the lytic phase of the life cycle, the maturing viral particles undergo orchestrated translocation to specialized regions within the cytoplasm, leading to tegumentation, secondary envelopment, and then egress. As a result, we hypothesized that RRV might induce changes in the cytoskeleton at both early and late stages of infection. Using confocal imaging, we found that RRV infection led to the thickening and acetylation of MTs emanating from the MT-organizing center (MTOC) shortly after viral entry and more pronounced and diffuse MT reorganization during peak stages of lytic gene expression and virion production. We subsequently identified open reading frame 52 (ORF52), a multifunctional and abundant tegument protein, as being the only virally encoded component responsible for these cytoskeletal changes. Mutational and modeling analyses indicated that an evolutionarily conserved, truncated leucine zipper motif near the N terminus as well as a strictly conserved arginine residue toward the C terminus of ORF52 play critical roles in its ability to rearrange the architecture of the MT cytoskeleton. Taken together, our findings combined with data from previous studies describing diverse roles for ORF52 suggest that it likely binds to different cellular components, thereby allowing context-dependent modulation of function.

IMPORTANCE
A thorough understanding of the processes governing viral infection includes knowledge of how viruses manipulate their intracellular milieu, including the cytoskeleton. Altering the dynamics of actin or MT polymerization, for example, is a common strategy employed by viruses to ensure efficient entry, maturation, and egress as well as the avoidance of antiviral defenses through the sequestration of key cellular factors. We found that infection with RRV, a homolog of the human pathogen KSHV, led to perinuclear wrapping by acetylated MT bundles and identified ORF52 as the viral protein underlying these changes. Remarkably, incoming virions were able to supply sufficient ORF52 to induce MT thickening and acetylation near the MTOC, potentially aiding in the delivery viral genomes to the nucleus. Although the function of MT alterations during late stages of infection requires further study, ORF52 shares functional and structural similarities with alphaherpesvirus VP22, underscoring the evolutionary importance of MT cytoskeletal manipulations for this virus family.
Deficiency of the NOD-Like Receptor NLRC5 Results in Decreased CD8
+
T Cell Function and Impaired Viral Clearance
Authors: Lupfer Christopher R. , Stokes Kate L. , Kuriakose Teneema , Kanneganti Thirumala-Devi
Published: June 2017

Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied. Here we show that
Nlrc5
−/−
mice exhibit an altered CD8
+
T cell response during IAV infection compared to that of wild-type (WT) mice.
Nlrc5
−/−
mice have decreased MHC-I expression on hematopoietic cells and fewer CD8
+
T cells prior to infection. NLRC5 deficiency does not affect the generation of antigen-specific CD8
+
T cells following IAV infection; however, a change in epitope dominance is observed in
Nlrc5
−/−
mice. Moreover, IAV-specific CD8
+
T cells from
Nlrc5
−/−
mice have impaired effector functions. This change in the adaptive immune response is associated with impaired viral clearance in
Nlrc5
−/−
mice. Collectively, our results demonstrate an important role for NLRC5 in regulation of antiviral immune responses and viral clearance during IAV infection.

IMPORTANCE
The NOD-like receptor family member NLRC5 is known to regulate expression of MHC-I as well as other genes required for antigen processing. In addition, NLRC5 also regulates various immune signaling pathways. In this study, we investigated the role of NLRC5 during influenza virus infection and found a major role for NLRC5 in restricting virus replication and promoting viral clearance. The observed increases in viral titers in NLRC5-deficient mice correlated with impaired effector CD8
+
T cell responses. Although NLRC5-deficient mice were defective at clearing the virus, they did not show an increase in morbidity or mortality following influenza virus infection because of other compensatory immune mechanisms. Therefore, our study highlights how NLRC5 regulates multiple immune effector mechanisms to promote the host defense during influenza virus infection.
Plasticity and Epitope Exposure of the HIV-1 Envelope Trimer
Authors: Powell Rebecca L. R. , Totrov Maxim , Itri Vincenza , Liu Xiaomei , Fox Alisa , Zolla-Pazner Susan
Published: June 2017

We recently showed that mutations in the HIV-1 envelope (Env) destabilize the V3 loop, rendering neutralization-resistant viruses sensitive to V3-directed monoclonal antibodies (MAbs). Here, we investigated the propagation of this effect on other Env epitopes, with special emphasis on V2 loop exposure. Wild-type JR-FL and 19 mutant JR-FL pseudoviruses were tested for neutralization sensitivity to 21 MAbs specific for epitopes in V2, the CD4 binding site (CD4bs), and the CD4-induced (CD4i) region. Certain glycan mutants, mutations in the gp120 hydrophobic core, and mutations in residues involved in intraprotomer interactions exposed epitopes in the V2i region (which overlies the α4β7 integrin binding site) and the V3 crown, suggesting general destabilization of the distal region of the trimer apex. In contrast, other glycan mutants, mutations affecting interprotomer interactions, and mutations affecting the CD4bs exposed V3 but not V2i epitopes. These data indicate for the first time that V3 can move independently of V2, with V3 pivoting out from its “tucked” position in the trimer while apparently leaving the V2 apex intact. Notably, none of the mutations exposed V2 epitopes without also exposing V3, suggesting that movement of V2 releases V3. Most mutations increased sensitivity to CD4bs-directed MAbs without exposure of the CD4i epitope, implying these mutations facilitate the trimers' maintenance of an intermediate energy state between open and closed conformations. Taken together, these data indicate that several transient Env epitopes can be rendered more accessible to antibodies (Abs) via specific mutations, and this may facilitate the design of V1V2-targeting immunogens.

IMPORTANCE
Many epitopes of the HIV envelope (Env) spike are relatively inaccessible to antibodies (Abs) compared to their exposure in the open Env conformation induced by receptor binding. However, the reduced infection rate that resulted from the vaccine used in the RV144 HIV-1 vaccine trial was correlated with the elicitation of V2- and V3-directed antibodies. Previously, we identified various mechanisms responsible for destabilizing the V3 loop; here, we determined, via mutation of numerous Env residues, which of these elements maintain the V1V2 loop in an inaccessible state and which expose V1V2 and/or V3 epitopes. Notably, our data indicate that V3 can move independently of V2, but none of the mutations studied expose V2 epitopes without also exposing V3. Additionally, V1V2 can be rendered more accessible to Abs via specific mutations, facilitating the development of engineered V2 immunogens.
Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice
Authors: Lennemann Nicholas J. , Herbert Andrew S. , Brouillette Rachel , Rhein Bethany , Bakken Russell A. , Perschbacher Katherine J. , Cooney Ashley L. , Miller-Hunt Catherine L. , Ten Eyck Patrick , Biggins Julia , Olinger Gene , Dye John M. , Maury Wendy
Published: June 2017

The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.

IMPORTANCE
The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.
Fluconazole-Induced Ploidy Change in Cryptococcus neoformans Results from the Uncoupling of Cell Growth and Nuclear Division
Authors: Altamirano Sophie , Fang Diana , Simmons Charles , Sridhar Shreyas , Wu Peipei , Sanyal Kaustuv , Kozubowski Lukasz
Published: June 2017

Azoles are antifungals that are widely utilized due to relatively low toxicity and cost of treatment. One of their drawbacks, however, is that azoles are primarily cytostatic, leaving fungal cells capable of developing drug resistance. The human pathogen
Cryptococcus neoformans
acquires resistance to the azole drug fluconazole (FLC) through the development of aneuploidy, leading to elevated expression of key resistance genes, a mechanism that is also common for
Candida albicans
(K. J. Kwon-Chung and Y. C. Chang, PLoS Pathog 8:e1003022, 2012,
https://doi.org/10.1371/journal.ppat.1003022
; J. Morschhäuser, J Microbiol 54:192–201, 2016,
https://doi.org/10.1007/s12275-016-5628-4
). However, the exact ways in which FLC contributes to increased resistance in either of these important fungal pathogens remain unclear. Here we found that FLC treatment leads to an increase in DNA content in
C. neoformans
through multiple mechanisms, potentially increasing the size of a pool of cells from which aneuploids with increased resistance are selected. This study demonstrated the importance of FLC’s inhibitory effects on growth and cytokinesis in the generation of cell populations with decreased sensitivity to the drug.
Transient electro-osmotic flow of generalized second-grade fluids under slip boundary conditions
Authors: Wang Xiaoping , Qi Haitao , Xu Huanying
Published: June 2017

This work investigates the transient slip flow of viscoelastic fluids in a slit micro-channel under the combined influences of electro-osmotic and pressure gradient forcings. We adopt the generalized second-grade fluid model with fractional derivative as the constitutive equation and the Navier linear slip model as the boundary conditions. The analytical solution for velocity distribution of the electro-osmotic flow is determined by employing the Debye–Hückel approximation and the integral transform methods. The corresponding expressions of classical Newtonian and second-grade fluids are obtained as the limiting cases of our general results. These solutions are presented as a sum of steady-state and transient parts. The combined effects of slip boundary conditions, fluid rheology, electro-osmotic, and pressure gradient forcings on the fluid velocity distribution are also discussed graphically in terms of the pertinent dimensionless parameters. By comparison with the two cases corresponding to the Newtonian fluid and the classical second-grade fluid, it is found that the fractional derivative parameter β has a significant effect on the fluid velocity distribution and the time when the fluid flow reaches the steady state. Additionally, the slip velocity at the wall increases in a noticeable manner the flow rate in an electro-osmotic flow.
Finite commutative ring with genus two essential graph
Authors: Selvakumar K. , Subajini M. , Nikmehr M. J.
Published: June 2017

Let [Formula: see text] be a commutative ring with identity and let [Formula: see text] be the set of zero-divisors of [Formula: see text]. The essential graph of [Formula: see text] is defined as the graph [Formula: see text] with the vertex set [Formula: see text] and two distinct vertices [Formula: see text] and [Formula: see text] are adjacent if and only if [Formula: see text] is an essential ideal. In this paper, we classify all finite commutative rings with identity for which the genus of [Formula: see text] is two.
On the regular graph of ideals of total ring of fractions
Authors: Karimi Masoud
Published: June 2017

The regular graph of ideals of a commutative ring [Formula: see text], denoted by [Formula: see text], is a graph whose vertex-set is the set of all nontrivial ideals of [Formula: see text] and, for every two distinct vertices [Formula: see text] and [Formula: see text], there is an edge between [Formula: see text] and [Formula: see text], whenever [Formula: see text] contains a nonzero zero-divisor on [Formula: see text] or vice versa. In this paper, we will show that [Formula: see text] is isomorphic to an induced sub-graph of [Formula: see text] which nicely can describe [Formula: see text]. This approach enables us to find the independence number of [Formula: see text] when [Formula: see text] is a reduced ring. Among other things, some basic graph theoretic properties of [Formula: see text] and relevant ring theoretic properties of [Formula: see text] will be studied.
THE IMPORTANCE OF CULTURAL VALUES AND TRUST FOR INNOVATION — A EUROPEAN STUDY
Authors: ZHU BING , HABISCH ANDRÉ , THØGERSEN JOHN
Published: June 2017

Cultural values and social capital are important parts of the context that determines countries’ innovation performance (and, hence, economic development). This paper investigates the culture–innovation relationship in a European context, as well as the mediating role of the national-level trust in this connection. Data are used to test the hypotheses that a country’s innovation performance is influenced by its cultural value emphases and societal trust, and that the culture–innovation relationship is mediated by societal trust. Based on data from the Global Innovation Index and the European Social Survey covering 27 European countries, we find that innovation at the country level is positively correlated with the level of societal trust and with three cultural value dimensions: “Autonomy versus Embeddedness”, “Egalitarianism versus Hierarchy”, and “Harmony versus Mastery”. A multivariate SEM analysis reveals that when “Autonomy versus Embeddedness” is controlled, the two other cultural value dimensions are no longer significant. Further, a SEM path analysis confirms that the relationship between cultural values and innovation performances is completely mediated through the level of trust in a society. Overall, “Autonomy versus Embeddedness” has a stronger total effect than societal trust on a country’s innovation performance, but most of this effect is indirect, mediated through societal trust. Implications of our findings for the corporate level (i.e., entrepreneurs and managers) as well as for the institutional settings (i.e., policy makers) are discussed. It is suggested that for successful innovation to blossom, the actors on both levels should aim at strengthening the cultural emphasis on individual autonomy, institutional integrity and mutual trust.
Characterization of muscle ankyrin repeat proteins in human skeletal muscle
Authors: Wette Stefan G. , Smith Heather K. , Lamb Graham D. , Murphy Robyn M.
Published: June 2017

Muscle ankyrin repeat proteins (MARPs) are a family of titin-associated, stress-response molecules and putative transducers of stretch-induced signaling in skeletal muscle. In cardiac muscle, cardiac ankyrin repeat protein (CARP) and diabetes-related ankyrin repeat protein (DARP) reportedly redistribute from binding sites on titin to the nucleus following a prolonged stretch. However, it is unclear whether ankyrin repeat domain protein 2 (Ankrd 2) shows comparable stretch-induced redistribution to the nucleus. We measured the following in rested human skeletal muscle: 1) the absolute amount of MARPs and 2) the distribution of Ankrd 2 and DARP in both single fibers and whole muscle preparations. In absolute amounts, Ankrd 2 is the most abundant MARP in human skeletal muscle, there being ~3.1 µmol/kg, much greater than DARP and CARP (~0.11 and ~0.02 µmol/kg, respectively). All DARP was found to be tightly bound at cytoskeletal (or possibly nuclear) sites. In contrast, ~70% of the total Ankrd 2 is freely diffusible in the cytosol [including virtually all of the phosphorylated (p)Ankrd 2-Ser99 form], ~15% is bound to non-nuclear membranes, and ~15% is bound at cytoskeletal sites, likely at the N2A region of titin. These data are not consistent with the proposal that Ankrd 2, per se, or pAnkrd 2-Ser99 mediates stretch-induced signaling in skeletal muscle, dissociating from titin and translocating to the nucleus, because the majority of these forms of Ankrd 2 are already free in the cytosol. It will be necessary to show that the titin-associated Ankrd 2 is modified by stretch in some as-yet-unidentified way, distinct from the diffusible pool, if it is to act as a stretch-sensitive signaling molecule.
Wakefulness suppresses retinal wave-related neural activity in visual cortex
Authors: Mukherjee Didhiti , Yonk Alex J. , Sokoloff Greta , Blumberg Mark S.
Published: June 2017

By recording in visual cortex in unanesthetized infant rats, we show that neural activity attributable to retinal waves is specifically suppressed when pups spontaneously awaken or are experimentally aroused. These findings suggest that the relatively abundant sleep of early development plays a permissive functional role for the visual system. It follows, then, that biological or environmental factors that disrupt sleep may interfere with the development of these neural networks.
Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain
Authors: Liu Cui-Cui , Zhang Xin-Sheng , Ruan Yu-Ting , Huang Zhu-Xi , Zhang Su-Bo , Liu Meng , Luo Hai-Jie , Wu Shao-Ling , Ma Chao
Published: June 2017

Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain.
Hyperresponsiveness: Relating the Intact Airway to the Whole Lung
Authors: Lutchen Kenneth R. , Paré Peter D. , Seow Chun Y.
Published: June 2017

We relate changes of the airway wall to the response of the intact airway and the whole lung. We address how mechanical conditions and specific structural changes for an airway contribute to hyperresponsiveness resistant to deep inspiration. This review conveys that the origins of hyperresponsiveness do not devolve into an abnormality at single structural level but require examination of the complex interplay of all the parts.
Differentially Expressed MicroRNAs in the Development of Early Diabetic Retinopathy
Authors: Gong Qiaoyun , Xie Jia’nan , Liu Yang , Li Ying , Su Guanfang
Published: June 2017

The pathological mechanisms of diabetic retinopathy (DR), a leading cause of blindness in adults with diabetes mellitus, remain incompletely understood. Because microRNAs (miRNAs) represent effective DR therapeutic targets, we identified aberrantly expressed miRNAs associated with cellular dysfunction in early DR and detected their potential targets. We exposed human retinal endothelial cells (HRECs) and a cell line of retinal pigment epithelial (RPE) cells to high glucose (25 mmol/L, 1–7 days) to mimic DR progression and used streptozotocin-injected rats (4–8 weeks) for an in vivo diabetes model. HREC/RPE viability decreased after 24 h incubation and diminished further over 6 days, and Hoechst staining revealed hyperglycemia-induced HREC/RPE apoptosis. Although miR-124/-125b expression decreased with DR progression in vitro and in vivo, miR-135b/-199a levels decreased in retinal cells under hyperglycemia exposure, but increased in diabetic retinas. Moreover, miR-145/-146a expression decreased gradually in high-glucose-treated HRECs, but increased in hyperglycemia-exposed RPE cells and in diabetic rats. Our findings suggested that aberrant miRNA expression could be involved in hyperglycemia-induced retinal-cell dysfunction, and the identified miRNAs might vary in different retinal layers, with expression changes associated with DR development. Therefore, miRNA modulation and the targeting of miRNA effects on transcription factors could represent novel and effective DR-treatment strategies.
Solvent-Free Henry and Michael Reactions with Nitroalkanes Promoted by Potassium Carbonate as a Versatile Heterogeneous Catalyst
Authors: Bosica Giovanna , Polidano Kurt
Published: June 2017

The use of a simple weak inorganic base such as potassium carbonate facilitated the formation of carbon-carbon bonds through both the Henry and the Michael reactions with nitrocompounds. The application of this catalyst under environmentally friendly solventless heterogeneous conditions gave satisfactory to good yields of β-nitroalcohols, involving aliphatic and aromatic starting materials, as well as high to excellent yields in the formation of Michael adducts using several different Michael acceptors and nitroalkanes.
Membrane Fouling and Chemical Cleaning in Three Full-Scale Reverse Osmosis Plants Producing Demineralized Water
Authors: Beyer Florian , Laurinonyte Judita , Zwijnenburg Arie , Stams Alfons J. M. , Plugge Caroline M.
Published: June 2017

Membrane fouling and cleaning were studied in three reverse osmosis (RO) plants. Feed water was secondary wastewater effluent, river water, and surface water. Membrane autopsies were used for fouling characterization. Fouling layer measurements included total organic carbon (TOC), adenosine triphosphate, polysaccharides, proteins, and heterotrophic plate counts. In all locations, membrane and spacer fouling was (bio)organic. Plant chemical cleaning efficiencies were evaluated from full-scale operational data and cleaning trials in a laboratory setup. Standard cleaning procedures were compared to two cleaning procedures specifically adapted to treat (bio)organic fouling using commercial blend cleaners (mixtures of active substances). The three RO plants were impacted by irreversible foulants causing permanently decreased performance in normalized pressure drop and water permeability even after thorough chemical cleaning. The standard plant and adapted cleaning procedures reduced the TOC by 45% on average, with a maximum of ~80%. In general, around 20% higher biomass removal could be achieved with adapted procedure I compared to adapted procedure II. TOC measurements and SEM showed that none of cleaning procedures applied could remove foulants completely from the membrane elements. This study underlines the need for novel cleaning approaches targeting resistant foulants, as none of the procedures applied resulted in highly effective membrane regeneration.
The Role of Interleukin-17, Interleukin-23, and Transforming Growth Factor-β in Pregnancy Complicated by Placental Insufficiency
Authors: Darmochwal-Kolarz Dorota , Michalak Magdalena , Kolarz Bogdan , Przegalinska-Kalamucka Monika , Bojarska-Junak Agnieszka , Sliwa Dariusz , Oleszczuk Jan
Published: June 2017

Aim. The aim of the study was to evaluate the role of Interleukin-17 (IL-17), Interleukin-23 (IL-23), and transforming growth factor-β (TGF-β) in pregnancy complicated by placental insufficiency and in normal pregnancy. Material and Methods. The study comprised 34 patients with pregnancy complicated by fetal growth restriction (FGR) associated with preeclampsia (PE), as well as 35 healthy pregnant women. The concentrations of IL-17, IL-23, and TGF-β in sera from maternal peripheral blood were determined by an immunoenzymatic assay. Results. There were higher concentrations of IL-17 in the study group when compared to the controls. In the group of patients with placental insufficiency, the levels of IL-17 positively correlated with systolic blood pressure (R=0.42, p<0.01). The study obtained comparable concentrations of IL-23 in both studied groups. The concentrations of TGF-β were significantly lower in pregnancy complicated by the insufficiency of placenta when compared to the controls. Conclusions. It seems possible that the increased concentrations of IL-17 and the deficiency of TGF-β in pregnancy complicated by FGR and PE can be responsible for the activation of inflammatory response observed in PE cases.
Secure Screw Placement in Management of Acetabular Fractures Using the Suprapectineal Quadrilateral Buttress Plate
Authors: Egli R. J. , Keel M. J. B. , Cullmann J. L. , Bastian J. D.
Published: June 2017

Acetabular fractures involving predominantly the anterior column associated with a disruption of the quadrilateral surface can be treated with instrumentation implementing the stabilization of the quadrilateral surface. The recently introduced suprapectineal quadrilateral buttress plate is specifically designed to prevent secondary medial subluxation of the femoral head, especially in elderly patients with reduced ability for partial weight bearing. Whereas there are guidelines available for safe screw fixation for the anterior and posterior columns, there might be a concern for intra-articular placement of screws placed through the infrapectineal part of the quadrilateral buttress plate. Within this report we analyzed retrospectively screw placement in 30 plates in postoperative CT scans using algorithms for metal artifact reduction. None of the screws of the buttress plate penetrated the hip joint. We describe the placement, length, and spatial orientation of the screws used for fracture fixation and suggest that the use of intraoperative image intensifiers with a combined inlet-obturator view of 30–45° best projects the screws and the hip joint. Preoperative knowledge of approximate screw placement and information for accurate intraoperative imaging may contribute to safe acetabular fracture fixation and may reduce operating time and limit radiation exposure to the patient and the personnel. This trial is registered with KEK-BE: 266/2014.
Raman-Encoded Molecular Imaging with Topically Applied SERS Nanoparticles for Intraoperative Guidance of Lumpectomy
Authors: Wang Yu “Winston” , Reder Nicholas P. , Kang Soyoung , Glaser Adam K. , Yang Qian , Wall Matthew A. , Javid Sara H. , Dintzis Suzanne M. , Liu Jonathan T.C.
Published: June 2017

Intraoperative identification of carcinoma at lumpectomy margins would enable reduced re-excision rates, which are currently as high as 20% to 50%. Although imaging of disease-associated biomarkers can identify malignancies with high specificity, multiplexed imaging of such biomarkers is necessary to detect molecularly heterogeneous carcinomas with high sensitivity. We have developed a Raman-encoded molecular imaging (REMI) technique in which targeted nanoparticles are topically applied on excised tissues to enable rapid visualization of a multiplexed panel of cell surface biomarkers at surgical margin surfaces. A first-ever clinical study was performed in which 57 fresh specimens were imaged with REMI to simultaneously quantify the expression of four biomarkers HER2, ER, EGFR, and CD44. Combined detection of these biomarkers enabled REMI to achieve 89.3% sensitivity and 92.1% specificity for the detection of breast carcinoma. These results highlight the sensitivity and specificity of REMI to detect biomarkers in freshly resected tissue, which has the potential to reduce the rate of re-excision procedures in cancer patients. Cancer Res; 77(16); 4506–16. ©2017 AACR.
Successful Treatment of Richter Transformation with Ibrutinib in a Patient with Chronic Lymphocytic Leukemia following Allogeneic Hematopoietic Stem Cell Transplant
Authors: Master Samip , Leary Cheri , Takalkar Amol , Coltelingam James , Mansour Richard , Mills Glenn M. , Koshy Nebu
Published: June 2017

Patients with chronic lymphocytic leukemia (CLL) who progress to Richter transformation (RT) have a poor prognosis. Multi-agent chemotherapy regimens do not have good response rates. There are few case reports on the use of ibrutinib in RT. Here, we present a patient who was heavily pretreated for CLL, including allogeneic stem cell transplant, and progressed to RT. She had a mixed response to multi-agent chemotherapy and was started on ibrutinib. She had a complete response for 16 months on single-agent ibrutinib with minimal toxicity.
Progression from an Inflammatory to a Fibrostenotic Phenotype in Eosinophilic Esophagitis
Authors: Koutlas Nathaniel T. , Dellon Evan S.
Published: June 2017

Previous studies have suggested that eosinophilic esophagitis (EoE) progresses from chronic inflammation to fibrostenosis. However, natural history data illustrating this progression in individual patients are lacking. Here, we present 6 patients who progressed from an inflammatory to a fibrostenotic phenotype of EoE in the absence of treatment. At the time of diagnosis, none of the patients had significant evidence of fibrostenosis, but they did have other inflammatory findings of EoE such as edema, linear furrows, or exudates. After being lost to follow-up and treatment for an average of 7.8 ± 2.0 years, strictures (n = 5; 83%) or a small-caliber esophagus (n = 4; 67%) were present in a majority of the patients, and the majority required esophageal dilation. These cases confirm that EoE can progress from an inflammation-only phenotype to a fibrostenotic phenotype in certain patients.
Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients
Authors: Ouyang Qingqing , Wu Jing , Jiang Zhenlan , Zhao Jinjun , Wang Ran , Lou Aiju , Zhu Dingji , Shi Guo-Ping , Yang Min
Published: June 2017

Background/Aims: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening. Methods: We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value. Results: We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030). Conclusions: This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.
Liver Kinase B1/AMP-Activated Protein Kinase Pathway Activation Attenuated the Progression of Endotoxemia in the Diabetic Mice
Authors: Yang Yan , Dong Ruolan , Hu Danli , Chen Zhihui , Fu Menglu , Wang Dao Wen , Xu Xizhen , Tu Ling
Published: June 2017

Background/Aims: Sepsis is a common disease that continues to increase in prevalence worldwide, and diabetes mellitus may make the situation worse. This study was designed to determine the role of Liver Kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in diabetic mice complicated with systemic endotoxemia. Methods: The effects of LKB1/AMPK signaling pathway activation on endotoxemia were investigated in streptozotocin induced diabetic mice (STZ-mice) and db/db diabetic mice. Primary peritoneal macrophages and human umbilical vein endothelial cells (HUVECs) monolayers were simultaneously stimulated by both high glucose and LPS and used as a model to investigate the potential molecular mechanisms in vitro. Results: After treatment with LPS, high glucose or both LPS and high glucose, phosphor-AMPK expression was decreased, and moreover, AMPK activation by metformin treatment alleviated the decrease in phosphor-AMPK expression in HUVECs and macrophages as well as in lung tissue. Furthermore, both LPS and high glucose co-treatment decreased LKB1 and phosphor-AMPK expression via enhanced oxidative stress response, and importantly, LKB1 overexpression mediated by adenovirus inhibited the decrease in phosphor-AMPK expression in macrophages and HUVECs. AMPK activation by metformin administration improved the survival of STZ-induced diabetic mice and db/db diabetic mice, which was associated with reduced lung endothelial hyperpermeability and systemic inflammatory response. Furthermore, the permeability of HUVECs monolayers induced by both high glucose and LPS stimulation was also alleviated by AMPK activation, which was partly via suppression of VE-cadherin phosphorylation. Conclusion: These data demonstrated that LKB1/AMPK signaling pathway activation improved the survival of diabetic mice complicated with endotoxemia. Thus, LKB1/AMPK signaling pathway may serve as a potentially useful therapeutic target for severe infection in diabetic patients.
Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China
Authors: Jia Qiao-Wei , Chen Zhao-Hong , Ding Xiao-Qing , Liu Jie-Yin , Ge Peng-Cheng , An Feng-Hui , Li Li-Hua , Wang Lian-Sheng , Ma Wen-Zhu , Yang Zhi-Jian , Jia En-Zhi
Published: June 2017

Background: Differences in microRNA (miRNA) profiles between patients with and without coronary heart disease (CHD)have not been fully determined. The purpose of the study was to evaluate in a multi-ethnic population in China the predictive value of miRNAs previously suggested to have a role in CHD. Subject and method: 932 participants were included, and plasma samples obtained. A quantitative reverse-transcription PCR(RT-qPCR) assay was conducted to confirm the concentration of plasma miRNAs. Circulating levels of miRNAs were quantified using the 2-Δct method. The severity of coronary atherosclerosis was evaluated via Gensini Scores. Result: The circulating levels of the nine proposed miRNAs were not different among the five main ethnicities examined (all p > 0.05). The Spearman correlation analyses indicated that miR-221 and miR-130a were negatively associated with the severity of CHD as indicated by Gensini Scores (r = -0.106, p = 0.001;r = -0.073, p = 0.026). Results of the univariate analysis showed that lower circulating miR-221 (OR, 1.663; 95 % CI, 1.255-2.202, p = <0.001), miR-155 (OR, 1.520; 95 % CI, 1.132-2.042, p = 0.005), and miR-130a (OR, 1.943; 95% CI, 1.410-2.678, p = <0.001) were potential risk factors for CHD. Moreover, miR-130a (OR, 2.405; 95 % CI, 1.691-3.421, p = <0.001) remained independently associated with the risk of CHD after adjusting for potential confounding factors. The analysis of the possible positive/negative associations between miR-221, miR-155 and miR-130awere conducted. A positive association between miR-130a and miR-155 was found (SI = 1.60, SIM = 1.21 and AP = 0.22), and in these groups, the proportion of CHD attributable to the interaction between miR-130a and miR-155 was as high as 22 %. A negative interaction was found between miR-221 and miR-130a (SI = 0.68, SIM = 0.60 and AP = 0.27). Conclusion: Plasma levels of miR-221, miR-130a and miR-155 decreased in patients with CHD, and miR-130a may be an independent predictor for CHD.
ІМУНОЛОГІЧНИЙ МОНІТОРИНГ ДОРОСЛОГО НАСЕЛЕННЯ ЛЬВІВЩИНИ ЩОДО КАШЛЮКУ У 2016 РОЦІ
Authors: Ivanchenko N. O.
Published: June 2017

Мета – провести серологічний моніторинг серед дорослого населення щодо кількісного визначення імуноглобулінів класу G до кашлюку.Матеріали і методи. Дослідження проводились з використанням методу імуноферментного аналізу.Результати досліджень та їх обговорення. Серонегативний прошарок населення становить 50,0 %. Специфічні імуноглобуліни G у високих титрах (понад 50 BU/ml) були виявлені у 3,75 % осіб, що свідчить про період реконвалесценції після кашлюку.Висновки. Використання цього методу підтверджує наявність випадків захворювання на кашлюк серед дорослого населення при недостатній настороженості медичних працівників щодо захворюваності на кашлюк даної вікової групи. Підтверджено об’єктивність і інформативність методу та доцільність його широкого впровадження в практику громадського здоров’я з метою здійснення належного епідеміологічного нагляду.