bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and Characterization of an Air-Liquid Canine Corneal Organ Culture Model To Study Acute Herpes Keratitis
Authors: Harman Rebecca M. , Bussche Leen , Ledbetter Eric C. , Van de Walle Gerlinde R.
Published: September 2014

Despite the clinical importance of herpes simplex virus (HSV)-induced ocular disease, the underlying pathophysiology of the disease remains poorly understood, in part due to the lack of adequate virus–natural-host models in which to study the cellular and viral factors involved in acute corneal infection. We developed an air-liquid canine corneal organ culture model and evaluated its susceptibility to canine herpesvirus type 1 (CHV-1) in order to study ocular herpes in a physiologically relevant natural host model. Canine corneas were maintained in culture at an air-liquid interface for up to 25 days, and no degenerative changes were observed in the corneal epithelium during cultivation using histology for morphometric analyses, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays, and transmission electron microscopy (TEM). Next, canine corneas were inoculated with CHV-1 for 48 h, and at that time point postinfection, viral plaques could be visualized in the corneal epithelium and viral DNA copies were detected in both the infected corneas and culture supernatants. In addition, we found that canine corneas produced proinflammatory cytokines in response to CHV-1 infection similarly to what has been described for HSV-1. This emphasizes the value of our model as a virus–natural-host model to study ocular herpesvirus infections.

IMPORTANCEThis study is the first to describe the establishment of an air-liquid canine corneal organ culture model as a useful model to study ocular herpesvirus infections. The advantages of this physiologically relevant model include the fact that (i) it provides a system in which ocular herpes can be studied in a virus–natural-host setting and (ii) it reduces the number of experimental animals needed. In addition, this long-term explant culture model may also facilitate research in other fields where noninfectious and infectious ocular diseases of dogs and humans are being studied.
Molecular Mimicry between Dengue Virus and Coagulation Factors Induces Antibodies To Inhibit Thrombin Activity and Enhance Fibrinolysis
Authors: Chuang Yung-Chun , Lin Yee-Shin , Liu Hsiao-Sheng , Yeh Trai-Ming
Published: September 2014

Dengue virus (DENV) is the most common cause of viral hemorrhagic fever, and it may lead to life-threating dengue hemorrhagic fever and shock syndrome (DHF/DSS). Because most cases of DHF/DSS occur in patients with secondary DENV infection, anti-DENV antibodies are generally considered to play a role in the pathogenesis of DHF/DSS. Previously, we have found that antithrombin antibodies (ATAs) with both antithrombotic and profibrinolytic activities are present in the sera of dengue patients. However, the mechanism by which these autoantibodies are induced is unclear. In this study, we demonstrated that antibodies induced by DENV immunization in mice and rabbits could bind to DENV antigens as well as to human thrombin and plasminogen (Plg). The binding of anti-DENV antibodies to thrombin and Plg was inhibited by preadsorption with DENV nonstructural protein 1. In addition, affinity-purified ATAs from DENV-immunized rabbit sera could inhibit thrombin activity and enhance Plg activation both
in vitro
and
in vivo
. Taken together, our results suggest that molecular mimicry between DENV and coagulation factors can induce the production of autoantibodies with biological effects similar to those of ATAs found in dengue patients. These coagulation-factor cross-reactive anti-DENV antibodies can interfere with the balance of coagulation and fibrinolysis, which may lead to the tendency of DHF/DSS patients to bleed.

IMPORTANCE
Dengue virus (DENV) infection is the most common mosquito-borne viral disease in tropical and subtropical areas. Over 50 million DENV infection cases develop each year, and more than 2.5 billion people are at risk of dengue-induced hemorrhagic fever and shock syndrome. Currently, there is no vaccine or drug treatment for DENV. In the present study, we demonstrated that DENV immunization could induce thrombin and plasminogen (Plg) cross-reactive antibodies, which were able to inhibit thrombin activity and enhance Plg activation. These results suggest that molecular mimicry between DENV antigens, thrombin, and Plg may elicit antibodies that disturb hemostasis. The selection of appropriate candidate antigens for use in DENV vaccines should prevent these potentially dangerous autoimmune responses.
HIV-1 Uncoating Is Facilitated by Dynein and Kinesin 1
Authors: Lukic Zana , Dharan Adarsh , Fricke Thomas , Diaz-Griffero Felipe , Campbell Edward M.
Published: September 2014

Following entry into the target cell, human immunodeficiency virus type 1 (HIV-1) must reverse transcribe its RNA genome to DNA and traffic to the nuclear envelope, where the viral genome is translocated into the nucleus for subsequent integration into the host cell chromosome. During this time, the viral core, which houses the genome, undergoes a poorly understood process of disassembly, known as uncoating. Collectively, many studies suggest that uncoating is tightly regulated to allow nuclear import of the genome while minimizing the exposure of the newly synthesized DNA to cytosolic DNA sensors. However, whether host cellular proteins facilitate this process remains poorly understood. Here we report that intact microtubules facilitate HIV-1 uncoating in target cells. Disruption of microtubules with nocodazole substantially delays HIV-1 uncoating, as revealed with three different assay systems. This defect in uncoating did not correlate with defective reverse transcription at early times postinfection, demonstrating that microtubule-facilitated uncoating is distinct from the previously reported role of viral reverse transcription in the uncoating process. We also find that pharmacological or small interfering RNA (siRNA)-mediated inhibition of cytoplasmic dynein or the kinesin 1 heavy chain KIF5B delays uncoating, providing detailed insight into how microtubules facilitate the uncoating process. These studies reveal a previously unappreciated role for microtubules and microtubule motor function in HIV-1 uncoating, establishing a functional link between viral trafficking and uncoating. Targeted disruption of the capsid motor interaction may reveal novel mechanisms of inhibition of viral infection or provide opportunities to activate cytoplasmic antiviral responses directed against capsid or viral DNA.

IMPORTANCE
During HIV-1 infection, fusion of viral and target cell membranes dispenses the viral ribonucleoprotein complex into the cytoplasm of target cells. During this time, the virus must reverse transcribe its RNA genome, traffic from the location of fusion to the nuclear membrane, and undergo the process of uncoating, whereby the viral capsid core disassembles to allow the subsequent nuclear import of the viral genome. Numerous cellular restriction factors target the viral capsid, suggesting that perturbation of the uncoating process represents an excellent antiviral target. However, this uncoating process, and the cellular factors that facilitate uncoating, remains poorly understood. The main observation of this study is that normal uncoating requires intact microtubules and is facilitated by dynein and kinesin motors. Targeting these factors may either directly inhibit infection or delay it enough to trigger mediators of intrinsic immunity that recognize cytoplasmic capsid or DNA and subsequently induce an antiviral state in these cells.
Vaginal Memory T Cells Induced by Intranasal Vaccination Are Critical for Protective T Cell Recruitment and Prevention of Genital HSV-2 Disease
Authors: Sato Ayuko , Suwanto Aldina , Okabe Manami , Sato Shintaro , Nochi Tomonori , Imai Takahiko , Koyanagi Naoto , Kunisawa Jun , Kawaguchi Yasushi , Kiyono Hiroshi
Published: September 2014

Protective immunity against genital pathogens causing chronic infections, such as herpes simplex virus 2 (HSV-2) or human immunodeficiency virus, requires the induction of cell-mediated immune responses locally in the genital tract. Intranasal immunization with a thymidine kinase-deficient (TK−) mutant of HSV-2 effectively induces HSV-2-specific gamma interferon (IFN-γ)-secreting memory T cell production and protective immunity against intravaginal challenge with wild-type HSV-2. However, the precise mechanism by which intranasal immunization induces protective immunity in the distant genital mucosa more effectively than does systemic immunization is unknown. Here, we showed that intranasal immunization with live HSV-2 TK−induced the production of effector T cells and their migration to, and retention in, the vaginal mucosa, whereas systemic vaccination barely established a local effector T cell pool, even when it induced the production of circulating memory T cells in the systemic compartment. The long-lasting HSV-2-specific local effector T cells induced by intranasal vaccination provided superior protection against intravaginal wild-type HSV-2 challenge by starting viral clearance at the entry site earlier than with intraperitoneal immunization. Intranasal immunization is an effective strategy for eliciting high levels of cell-mediated protection of the genital tract by providing long-lasting antigen (Ag)-specific local effector T cells without introducing topical infection or inflammation.

IMPORTANCEIntranasal (i.n.) vaccines against sexually transmitted diseases that are caused by viruses such as herpes simplex virus 2 (HSV-2) have long been in development, but no vaccine candidate is currently available. Understanding the cellular mechanisms of immune responses in a distant vaginal mucosa induced by i.n. immunization with HSV-2 will contribute to designing such a vaccine. Our study demonstrated that i.n. immunization with an attenuated strain of HSV-2 generated long-lasting IFN-γ-secreting T cells in vaginal mucosa more effectively than systemic immunization. We found that these vaginal effector memory T cells are critical for the early stage of viral clearance at natural infection sites and prevent severe vaginal inflammation and herpes encephalitis.
Acute haemolytic anaemia and myolysis due to G6PD deficiency
Authors: Mangat Chetna , Inoue Susumu , Saah Elna , Sharman Mahesh
Published: September 2014

A 2-year-old African-American male patient with sickle cell trait developed cough, red coloured urine, pallor and fatigue. The patient was hospitalised. Diagnostic workup showed that he was glucose 6 phosphate dehydrogenase (G6PD) deficient in erythrocytes. He also had chest X-ray findings of pneumonia. His urine examination showed the presence of haemoglobin and myoglobin. On repeated questioning it was found that he had a moth ball in his mouth a few days prior to this medical episode. This case illustrates a rarely described complication of myolysis in G6PD deficient persons on exposure to a strong oxidant. A review of the literature showed that most people with G6PD deficiency tolerate exercise well without untoward effect in muscles. However, assay of myoglobin in urine has not been routinely performed in these patients during acute haemolytic episode, and thus it is uncertain how frequent myoglobulinaemia occurs in a similar stress situation.
Utilization of Pipeline embolization device for treatment of ruptured intracranial aneurysms: US multicenter experience
Authors: Lin Ning , Brouillard Adam M , Keigher Kiffon M , Lopes Demetrius K , Binning Mandy J , Liebman Kenneth M , Veznedaroglu Erol , Magarik Jordan A , Mocco J , Duckworth Edward A , Arthur Adam S , Ringer Andrew J , Snyder Kenneth V , Levy Elad I , Siddiqui Adnan H
Published: September 2014

Objective

Utilization of the Pipeline embolization device (PED) in complex ruptured aneurysms has not been well studied. We evaluated the safety and effectiveness data from five participating US centers.

Methods

Records of patients with ruptured cerebral aneurysms who underwent PED treatment between 2011 and 2013 were retrospectively reviewed.

Results

26 patients with ruptured aneurysms underwent PED treatment (mean age 51.4±13.2 years;16 women). At presentation, 8 patients (30.8%) had a Hunt–Hess grade of IV or above; 11 required extraventricular drain placement. Aneurysm morphologies were: 8 dissecting, 8 blister-like, 6 fusiform, and 4 saccular. There were 22 anterior circulation and 4 posterior circulation aneurysms. PED deployment was successful in all patients, with adjunctive coiling utilized in 12. Periprocedural complications occurred in 5 (19.2%), including 3 inhospital deaths. 23 patients (88.5%) had postoperative angiography at a mean of 5.9 months: 18 aneurysms (78.3%) were completely occluded, 3 (13.0%) had residual neck filling, and 2 (8.7%) had residual dome filling. All blister-type aneurysms were completely occluded at follow-up. Clinical follow-up was available for an average of 10.1 months (range 2–21 months), with one asymptomatic in-stent stenosis and one asymptomatic thromboembolic stroke noted. Good outcome (modified Rankin Scale (mRS) score of 0–2) was achieved in 20 patients (76.9%), fair (mRS 3–4) in 3 (11.5%), and 3 died (11.5%).

Conclusions

The PED can be utilized for ruptured aneurysms and is a good option for blister-type aneurysms. However, due to periprocedural complications, it should be reserved for lesions that are difficult to treat by conventional clipping or coiling.
Cerebral vasospasm patterns following aneurysmal subarachnoid hemorrhage: an angiographic study comparing coils with clips
Authors: Jones J , Sayre J , Chang R , Tian J , Szeder V , Gonzalez N , Jahan R , Vinuela F , Duckwiler G , Tateshima S
Published: September 2014

Background and purpose

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in significant morbidity due to ischemia. Subarachnoid hematoma evacuation during aneurysm clipping reduces the incidence of vasospasm. However, studies comparing endovascular coiling with open clipping have reported similar rates of spasm. We addressed the question of how coiling produces similar (if not less) vasospasm without the benefit of clot evacuation by evaluating vasospasm patterns among patients with aSAH. We hypothesize that cerebrospinal fluid (CSF) circulation plays a major role in clearing blood breakdown products, and that coiling may preserve CSF flow in the subarachnoid space.

Methods

A retrospective chart review identified 36 (18 coiled/18 clipped) patients with aSAH who developed angiographic vasospasm. The degree of spasm was quantified using an ordinal scale from 0 (none) to 5 (severe) for 26 anatomic vessel segments evaluated on 164 successive angiograms. Statistical analysis was performed using the Fisher exact test for proportions and the Wilcoxon and Student t tests on ordinal/continuous measures. Quadratic regression was also used as a model for spasm activity versus post-bleed days.

Results

In both the coiling and clipping groups the most severely spastic vessels were located adjacent to aneurysm rupture. Perianeurysmal spasm affected all subjects. However, whereas spasm remained largely confined in patients treated by clipping, those who underwent coiling developed stepwise progression distally over time. The distal vasospasm severity scores were higher among subjects treated by coiling, particularly in the most dependent regions of the subarachnoid space.

Conclusions

Patients with aSAH treated by endovascular coiling and surgical clipping demonstrate distinct vasospasm patterns. While both initially exhibit perianeurysmal spasm, patients treated by coiling go on to develop stepwise progression distally over time. This finding may reflect dispersion of blood breakdown products along preserved CSF egress pathways in patients treated by endovascular coiling.
Equine disease surveillance
Authors: Slater Josh
Published: September 2014

The National Equine Health Survey (NEHS) was introduced in 2010 by the Blue Cross and British Equine Veterinary Association in response to a perceived need for some form of syndromic endemic disease surveillance in horses in the UK. Data are now collected on an annual ‘snapshot’ basis directly from horse owners. Here, Josh Slater discusses some of the findings from the survey carried out in 2013
Discovery of novel membrane binding structures and functions
Authors: Kufareva Irina , Lenoir Marc , Dancea Felician , Sridhar Pooja , Raush Eugene , Bissig Christin , Gruenberg Jean , Abagyan Ruben , Overduin Michael
Published: September 2014

The function of a protein is determined by its intrinsic activity in the context of its subcellular distribution. Membranes localize proteins within cellular compartments and govern their specific activities. Discovering such membrane-protein interactions is important for understanding biological mechanisms and could uncover novel sites for therapeutic intervention. We present a method for detecting membrane interactive proteins and their exposed residues that insert into lipid bilayers. Although the development process involved analysis of how C1b, C2, ENTH, FYVE, Gla, pleckstrin homology (PH), and PX domains bind membranes, the resulting membrane optimal docking area (MODA) method yields predictions for a given protein of known three-dimensional structures without referring to canonical membrane-targeting modules. This approach was tested on the Arf1 GTPase, ATF2 acetyltransferase, von Willebrand factor A3 domain, and Neisseria gonorrhoeae MsrB protein and further refined with membrane interactive and non-interactive FAPP1 and PKD1 pleckstrin homology domains, respectively. Furthermore we demonstrate how this tool can be used to discover unprecedented membrane binding functions as illustrated by the Bro1 domain of Alix, which was revealed to recognize lysobisphosphatidic acid (LBPA). Validation of novel membrane-protein interactions relies on other techniques such as nuclear magnetic resonance spectroscopy (NMR), which was used here to map the sites of micelle interaction. Together this indicates that genome-wide identification of known and novel membrane interactive proteins and sites is now feasible and provides a new tool for functional annotation of the proteome.
Accounting for marine reserves using spatial stock assessments
Authors: McGilliard Carey R. , Punt André E. , Methot Richard D. , Hilborn Ray
Published: September 2014

Some fish stock assessments are conducted in regions that contain no-take marine reserves (NTMRs). NTMRs are expected to lead to spatial heterogeneity in fish biomass by allowing a buildup of biomass inside their borders while fishing pressure occurs outside. Stock assessments do not typically account for spatial heterogeneity caused by NTMRs, which may lead to biased estimates of biomass. Simulation modeling is used to analyze the ability of several stock assessment configurations to estimate current biomass after the implementation of a single, large NTMR. Age-structured spatial operating models with three patterns of ontogenetic movement are used to represent the “true” population dynamics. Results show that assessing populations as a single stock with use of fishery catch-rate data and without accounting for the NTMR results in severe underestimation of biomass for two of the movement patterns. Omitting fishery catch-rate data or allowing time-varying dome-shaped selectivity after NTMR implementation leads to improved estimates of current biomass, but severe bias in estimated trends in biomass over time. Performing separate assessments for fished areas and NTMRs leads to improved estimation performance in the absence of movement among assessment areas, but can severely overestimate biomass otherwise. Performing a spatial assessment with estimation of movement parameters among areas was found to be the best way to assess a species, even when movement patterns were unknown. However, future work should explore the performance of spatial assessments when catchability varies among areas.
Identification of best indicators of peptide-spectrum match using a permutation resampling approach
Authors: Akhtar Malik N. , Southey Bruce R. , Andrén Per E. , Sweedler Jonathan V. , Rodriguez-Zas Sandra L.
Published: September 2014

Various indicators of observed-theoretical spectrum matches were compared and the resulting statistical significance was characterized using permutation resampling. Novel decoy databases built by resampling the terminal positions of peptide sequences were evaluated to identify the conditions for accurate computation of peptide match significance levels. The methodology was tested on real and manually curated tandem mass spectra from peptides across a wide range of sizes. Spectra match indicators from complementary database search programs were profiled and optimal indicators were identified. The combination of the optimal indicator and permuted decoy databases improved the calculation of the peptide match significance compared to the approaches currently implemented in the database search programs that rely on distributional assumptions. Permutation tests using p-values obtained from software-dependent matching scores and E-values outperformed permutation tests using all other indicators. The higher overlap in matches between the database search programs when using end permutation compared to existing approaches confirmed the superiority of the end permutation method to identify peptides. The combination of effective match indicators and the end permutation method is recommended for accurate detection of peptides.
Realized Volatility, Liquidity, and Corporate Yield Spreads
Authors: Rossi Marco
Published: September 2014

I propose a friction measure of bond round-trip liquidity costs that is robust to outliers and accounts for the idiosyncratic information behind trading decisions. Particularly effective with investment-grade bonds, the proposed measure displays properties consistent with the credit risk puzzle. Using transactions from January 2004 to December 2011, I find that liquidity costs display a strong correlation with credit conditions and peaked during the sub-prime crisis. After controlling for equity volatility with high-frequency measures, liquidity costs explain a substantial fraction of the variation in the yield spreads of highly rated bonds, but become less important for speculative-grade bonds.
The Miocene of Pianosa Island: key to understanding the opening of the Northern Tyrrhenian back-arc basin (Central Mediterranean)
Authors: Cornamusini Gianluca , Foresi Luca Maria , Dall’antonia Barbara , Bossio Alessandro , Mazzei Roberto , Salvatorini Gianfranco
Published: September 2014

The only place where Neogene–Quaternary rocks crop out for the entire Tuscan Archipelago in the Northern Tyrrhenian Sea is the island of Pianosa. In particular, the Miocene deposits record the depositional and tectonic evolution of the Northern Tyrrhenian region during this time period. These deposits are subdivided into two successions separated by a low-angle unconformity. The older, middle Burdigalian succession represents a calciturbidite shallow marine system, whereas the younger late Tortonian–early Messinian succession comprises a continental alluvial system that evolves upwards into a lagoonal–marginal marine environment. Here we present sedimentological, palaeontological and petrographical data that support a new stratigraphic and palaeogeographical framework for reconstructing the opening of the Northern Tyrrhenian back-arc basin. The early Miocene succession records a pre-rift marine depositional phase followed by a late Burdigalian–Langhian erosional phase. This was followed by a period of synrift continental-marginal deposition, as recorded by the late Miocene succession, terminated by an important phase of uplift, probably induced by the start of magmatic activity in the Tuscan Archipelago area.
Alpine Tethys closure as revealed by amphibole-rich mafic and ultramafic rocks from the Adamello and the Bergell intrusions (Central Alps)
Authors: Tiepolo Massimo , Tribuzio Riccardo , Ji Wei-Qiang , Wu Fu-Yuan , Lustrino Michele
Published: September 2014

U–Pb ages and Hf isotope data were obtained for zircon from amphibole-rich mafic to ultramafic rocks from the Adamello batholith and the Bergell pluton, the largest Palaeogene intrusions of the Alpine Orogen. The
206
Pb/
238
U age pattern of U–Pb concordant dates from the Adamello mafic rock shows a major crystallization event at
c
. 41 Ma and older age peaks at
c
. 50 and
c
. 45 Ma. Hornblendite and amphibole gabbro samples of the Adamello batholith have zircon with initial ϵHf of
c
. +9.0 and
c
. +7.0, respectively. Amphibole gabbro and diorite samples of the Bergell pluton yield a younger age of
c
. 31 Ma and have zircon with lower initial ϵHf (
c
. +4.0). We propose that the amphibole-rich rocks from the Adamello batholith originated from a depleted mantle source activated by the subduction of the Ligurian–Piedmontese Basin. The amphibole-rich rocks from the Bergell pluton formed 10–15 Ma later than the Adamello counterparts by melts derived from a mantle sector metasomatized by the subduction of the Valais Basin. The enriched Hf isotopic signature of the amphibole-rich rocks from the Bergell pluton is therefore interpreted to reflect the peculiar lithostratigraphy of the Valais Basin or a primary feature of the newly activated mantle source.

Supplementary material:

(1) A map showing the location of analysed samples and table with GPS coordinates of the samples, (2) data tables for U–Pb in zircon determined by LA-ICP-MS, (3) data tables for Hf isotopes in zircon, (4) U–Pb and Hf isotope analytical methods, (5) cathodoluminescence images of analysed zircon from the amphibole-rich mafic rocks of the Adamello and Bergell intrusions, and (6) a U–Pb concordia diagram for zircon of the Adamello amphibole gabbro are available at
www.geolsoc.org.uk/SUP18763
.
The thermal history of the western Irish onshore
Authors: Cogné Nathan , Chew David , Stuart Finlay M.
Published: September 2014

We present here a low-temperature thermochronological study that combines the apatite fission-track and (U + Th)/He dating methods with a pseudo-vertical sampling approach to generate continuous and well-constrained temperature–time histories from the onshore Irish Atlantic margin. The apatite fission-track and (U + Th)/He ages range from the Late Jurassic to Early Cretaceous and the mean track lengths are relatively short. Thermal histories derived from inverse modelling show that following post-orogenic exhumation the sample profiles cooled to
c
. 75 °C. A rapid cooling event to surface temperatures occurred during the Late Jurassic to Early Cretaceous and was diachronous from north to south. It was most probably caused by
c
. 2.5 km of rift-shoulder related exhumation and can be temporally linked to the main stage of Mesozoic rifting in the offshore basins. A slow phase of reheating during the Late Cretaceous and Early Cenozoic is attributed to the deposition of a thick sedimentary sequence that resulted in
c
. 1.5 km of burial. Our data imply a final pulse of exhumation in Neogene times, probably related to compression of the margin. However, it is possible that an Early Cenozoic cooling event, compatible with our data but not seen in our inverse models, accounts for part of the Cenozoic exhumation.

Supplementary material:

Details on the apatite fission-track and (U + Th)/He methods are available at
www.geolsoc.org.uk/SUP18765
.
Volcanism and tectonism across the inner solar system: an overview
Authors: Platz T. , Byrne P. K. , Massironi M. , Hiesinger H.
Published: September 2014

Volcanism and tectonism are the dominant endogenic means by which planetary surfaces change. This book, in general, and this overview, in particular, aim to encompass the broad range in character of volcanism, tectonism, faulting and associated interactions observed on planetary bodies across the inner solar system – a region that includes Mercury, Venus, Earth, the Moon, Mars and asteroids. The diversity and breadth of landforms produced by volcanic and tectonic processes are enormous, and vary across the inventory of inner solar system bodies. As a result, the selection of prevailing landforms and their underlying formational processes that are described and highlighted in this review are but a primer to the expansive field of planetary volcanism and tectonism. In addition to this extended introductory contribution, this Special Publication features 21 dedicated research articles about volcanic and tectonic processes manifest across the inner solar system. Those articles are summarized at the end of this review.
AQP4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at COOH-terminal serine residues
Authors: Assentoft Mette , Larsen Brian R. , Olesen Emma T. B. , Fenton Robert A. , MacAulay Nanna
Published: September 2014

Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. AQP4 serves as a water entry site during brain edema formation, and regulation of AQP4 may therefore be of therapeutic interest. Phosphorylation of aquaporins can regulate plasma membrane localization and, possibly, the unit water permeability via gating of the AQP channel itself. In vivo phosphorylation of six serine residues in the COOH terminus of AQP4 has been detected by mass spectrometry: Ser276, Ser285, Ser315, Ser316, Ser321, and Ser322. To address the role of these phosphorylation sites for AQP4 function, serine-to-alanine mutants were created to abolish the phosphorylation sites. All mutants were detected at the plasma membrane of transfected C6 cells, with the fraction of the total cellular AQP4 expressed at the plasma membrane of transfected C6 cells being similar between the wild-type (WT) and mutant forms of AQP4. Activation of protein kinases A, C, and G in primary astrocytic cultures did not affect the plasma membrane abundance of AQP4. The unit water permeability was determined for the mutant AQP4s upon heterologous expression in Xenopus laevis oocytes (along with serine-to-aspartate mutants of the same residues to mimic a phosphorylation). None of the mutant AQP4 constructs displayed alterations in the unit water permeability. Thus phosphorylation of six different serine residues in the COOH terminus of AQP4 appears not to be required for proper plasma membrane localization of AQP4 or to act as a molecular switch to gate the water channel.
Effects of dipeptidyl peptidase IV inhibition on glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to fat in healthy males
Authors: Heruc Gabriella A. , Horowitz Michael , Deacon Carolyn F. , Feinle-Bisset Christine , Rayner Christopher K. , Luscombe-Marsh Natalie , Little Tanya J.
Published: September 2014

Fat is the most potent stimulus for glucagon-like peptide-1 (GLP-1) secretion. The aims of this study were to determine whether dipeptidyl peptidase IV (DPP-IV) inhibition would enhance plasma active incretin [glucose-dependent insulinotropic polypeptide (GIP), GLP-1] concentrations and modulate the glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to intraduodenal fat infusion. In a double-blind, randomized, placebo-controlled crossover design, 16 healthy lean males received 50 mg vildagliptin (V), or matched placebo (P), before intraduodenal fat infusion (2 kcal/min, 120 min). Blood glucose, plasma insulin, glucagon, active GLP-1, and GIP and peptide YY (PYY)-(3–36) concentrations; resting energy expenditure; and energy intake at a subsequent buffet meal (time = 120–150 min) were quantified. Data are presented as areas under the curve (0–120 min, means ± SE). Vildagliptin decreased glycemia (P: 598 ± 8 vs. V: 573 ± 9 mmol·l−1·min−1, P < 0.05) during intraduodenal lipid. This was associated with increased insulin (P: 15,964 ± 1,193 vs. V: 18,243 ± 1,257 pmol·l−1·min−1, P < 0.05), reduced glucagon (P: 1,008 ± 52 vs. V: 902 ± 46 pmol·l−1·min−1, P < 0.05), enhanced active GLP-1 (P: 294 ± 40 vs. V: 694 ± 78 pmol·l−1·min−1) and GIP (P: 2,748 ± 77 vs. V: 4,256 ± 157 pmol·l−1·min−1), and reduced PYY-(3–36) (P: 9,527 ± 754 vs. V: 4,469 ± 431 pM/min) concentrations compared with placebo ( P < 0.05, for all). Vildagliptin increased resting energy expenditure (P: 1,821 ± 54 vs. V: 1,896 ± 65 kcal/day, P < 0.05) without effecting energy intake. Vildagliptin 1) modulates the effects of intraduodenal fat to enhance active GLP-1 and GIP, stimulate insulin, and suppress glucagon, thereby reducing glycemia and 2) increases energy expenditure. These observations suggest that the fat content of a meal, by enhancing GLP-1 and GIP secretion, may contribute to the response to DPP-IV inhibition.
Nicotine increases GABAergic input on rat dorsal raphe serotonergic neurons through alpha7 nicotinic acetylcholine receptor
Authors: Hernández-Vázquez F. , Chavarría K. , Garduño J. , Hernández-López S. , Mihailescu S. P.
Published: September 2014

The dorsal raphe nucleus (DRN) contains large populations of serotonergic (5-HT) neurons. This nucleus receives GABAergic inhibitory afferents from many brain areas and from DRN interneurons. Both GABAergic and 5-HT DRN neurons express functional nicotinic acetylcholine receptors (nAChRs). Previous studies have demonstrated that nicotine increases 5-HT release and 5-HT DRN neuron discharge rate by stimulating postsynaptic nAChRs and by increasing glutamate and norepinephrine release inside DRN. However, the influence of nicotine on the GABAergic input to 5-HT DRN neurons was poorly investigated. Therefore, the aim of this work was to determine the effect of nicotine on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of 5-HT DRN neurons and the subtype of nAChR(s) involved in this response. Experiments were performed in coronal slices obtained from young Wistar rats. GABAergic sIPSCs were recorded from post hoc-identified 5-HT DRN neurons with the whole cell voltage patch-clamp technique. Administration of nicotine (1 μM) increased sIPSC frequency in 72% of identified 5-HT DRN neurons. This effect was not reproduced by the α4β2 nAChR agonist RJR-2403 and was not influenced by TTX (1 μM). It was mimicked by the selective agonist for α7 nAChR, PNU-282987, and exacerbated by the positive allosteric modulator of the same receptor, PNU-120596. The nicotine-induced increase in sIPSC frequency was independent on voltage-gated calcium channels and dependent on Ca2+-induced Ca2+ release (CICR). These results demonstrate that nicotine increases the GABAergic input to most 5-HT DRN neurons, by activating α7 nAChRs and producing CICR in DRN GABAergic terminals.
Adeno-associated virus-RNAi of GlyRα1 and characterization of its synapse-specific inhibition in OFF alpha transient retinal ganglion cells
Authors: Zhang C. , Rompani S. B. , Roska B. , McCall M. A.
Published: September 2014

In the central nervous system, inhibition shapes neuronal excitation. In spinal cord glycinergic inhibition predominates, whereas GABAergic inhibition predominates in the brain. The retina uses GABA and glycine in approximately equal proportions. Glycinergic crossover inhibition, initiated in the On retinal pathway, controls glutamate release from presynaptic OFF cone bipolar cells (CBCs) and directly shapes temporal response properties of OFF retinal ganglion cells (RGCs). In the retina, four glycine receptor (GlyR) α-subunit isoforms are expressed in different sublaminae and their synaptic currents differ in decay kinetics. GlyRα1, expressed in both On and Off sublaminae of the inner plexiform layer, could be the glycinergic isoform that mediates On-to-Off crossover inhibition. However, subunit-selective glycine contributions remain unknown because we lack selective antagonists or cell class-specific subunit knockouts. To examine the role of GlyRα1 in direct inhibition in mature RGCs, we used retrogradely transported adeno-associated virus (AAV) that performed RNAi and eliminated almost all glycinergic spontaneous and visually evoked responses in PV5 (OFFαTransient) RGCs. Comparisons of responses in PV5 RGCs infected with AAV-scrambled-short hairpin RNA (shRNA) or AAV- Glra1-shRNA confirm a role for GlyRα1 in crossover inhibition in cone-driven circuits. Our results also define a role for direct GlyRα1 inhibition in setting the resting membrane potential of PV5 RGCs. The absence of GlyRα1 input unmasked a serial and a direct feedforward GABAAergic modulation in PV5 RGCs, reflecting a complex interaction between glycinergic and GABAAergic inhibition.
Alteration of the mu opioid receptor: Ca2+channel signaling pathway in a subset of rat sensory neurons following chronic femoral artery occlusion
Authors: Hassan Bassil , Kim Joyce S. , Farrag Mohamed , Kaufman Marc P. , Ruiz-Velasco Victor
Published: September 2014

The exercise pressor reflex, a crucial component of the cardiovascular response under physiological and pathophysiological states, is activated via metabolic and mechanical mediators that originate from contracting muscles and stimulate group III and IV afferents. We reported previously that stimulation of mu opioid receptors (MOR), expressed in both afferents, led to a significant attenuation of the reflex in rats whose femoral arteries had been occluded for 72 h. The present study examined the effect of arterial occlusion on the signaling components involved in the opioid-mediated modulation of Ca2+channels in rat dorsal root ganglion neurons innervating the triceps surae muscles. We focused on neurons that were transfected with cDNA coding for enhanced green fluorescent protein whose expression is driven by the voltage-gated Na+channel 1.8 (NaV1.8) promoter region, a channel expressed primarily in nociceptive neurons. With the use of a small interference RNA approach, our results show that the pertussis toxin-sensitive Gαi3subunit couples MOR with Ca2+channels. We observed a significant leftward shift of the MOR agonist [d-Ala2-N-Me-Phe4-Glycol5]-enkephalin concentration-response relationship in neurons isolated from rats with occluded arteries compared with those that were perfused freely. Femoral occlusion did not affect Ca2+channel density or the fraction of the main Ca2+channel subtype. Furthermore, Western blotting analysis indicated that the leftward shift did not result from either increased Gαi3or MOR expression. Finally, all neurons from both groups exhibited an inward current following exposure of the transient potential receptor vanilloid 1 (TRPV1) agonist, 8-methyl-N-vanillyl-6-nonenamide. These findings suggest that sensory neurons mediating the exercise pressor reflex express NaV1.8 and TRPV1 channels, and femoral occlusion alters the MOR pharmacological profile.
Congenital Insensitivity to Pain: A Case Report and Review of the Literature
Authors: Peddareddygari Leema Reddy , Oberoi Kinsi , Grewal Raji P.
Published: September 2014

Congenital insensitivity to pain (CIP) is a rare autosomal recessive genetic disease caused by mutations in theSCN9Agene. We report a patient with the clinical features consistent with CIP in whom we detected a novel homozygous G2755T mutation in exon 15 of this gene. Routine electrophysiological studies are typically normal in patients with CIP. In our patient, these studies were abnormal and could represent the consequences of secondary complications of cervical and lumbosacral spine disease and associated severe Charcot’s joints.
Epigenetic Dynamics: Role of Epimarks and Underlying Machinery in Plants Exposed to Abiotic Stress
Authors: Dhar Manoj Kumar , Vishal Parivartan , Sharma Rahul , Kaul Sanjana
Published: September 2014

Abiotic stress induces several changes in plants at physiological and molecular level. Plants have evolved regulatory mechanisms guided towards establishment of stress tolerance in which epigenetic modifications play a pivotal role. We provide examples of gene expression changes that are brought about by conversion of active chromatin to silent heterochromatin and vice versa. Methylation of CG sites and specific modification of histone tail determine whether a particular locus is transcriptionally active or silent. We present a lucid review of epigenetic machinery and epigenetic alterations involving DNA methylation, histone tail modifications, chromatin remodeling, and RNA directed epigenetic changes.
A New Iterative Procedure for Deconvolution of Seismic Ground Motion in Dam-Reservoir-Foundation Systems
Authors: Sooch Gurinderbir S. , Bagchi Ashutosh
Published: September 2014

The concrete gravity dams are designed to perform satisfactorily during an earthquake since the consequence of failure is catastrophic to the downstream communities. The foundation in a dam is usually modeled by a substructuring approach for the purpose of seismic response analysis. However, the substructuring cannot be used for solving nonlinear dynamic problems that may be encountered in dam-reservoir-foundation systems. For that reason, the time domain approach is preferred for such systems. The deconvolved earthquake input model is preferred as it can remove the seismic scattering effects due to artificial boundaries of the semi-infinite foundation domain. Deconvolution is a mathematical process that allows the adjustment of the amplitude and frequency contents of a seismic ground motion applied at the base of the foundation in order to get the desired output at the dam-foundation interface. It is observed that the existing procedures of deconvolution are not effective for all types of earthquake records. A modified procedure has been proposed here for efficient deconvolution of all types of earthquake records including high-frequency and low-frequency ground motions.
Sound Scattering and Its Reduction by a Janus Sphere Type
Authors: Kim Deliya , Avital Eldad Jitzhak , Miloh Touvia
Published: September 2014

Sound scattering by a Janus sphere type is considered. The sphere has two surface zones: a soft surface of zero acoustic impedance and a hard surface of infinite acoustic impedance. The zones are arranged such that axisymmetry of the sound field is preserved. The equivalent source method is used to compute the sound field. It is shown that, by varying the sizes of the soft and hard zones on the sphere, a significant reduction can be achieved in the scattered acoustic power and upstream directivity when the sphere is near a free surface and its soft zone faces the incoming wave and vice versa for a hard ground. In both cases the size of the sphere’s hard zone is much larger than that of its soft zone. The boundary location between the two zones coincides with the location of a zero pressure line of the incoming standing sound wave, thus masking the sphere within the sound field reflected by the free surface or the hard ground. The reduction in the scattered acoustic power diminishes when the sphere is placed in free space. Variations of the scattered acoustic power and directivity with the sound frequency are also given and discussed.
Cooperation-Controlled Learning for Explicit Class Structure in Self-Organizing Maps
Authors: Kamimura Ryotaro
Published: September 2014

We attempt to demonstrate the effectiveness of multiple points of view toward neural networks. By restricting ourselves to two points of view of a neuron, we propose a new type of information-theoretic method called “cooperation-controlled learning.” In this method, individual and collective neurons are distinguished from one another, and we suppose that the characteristics of individual and collective neurons are different. To implement individual and collective neurons, we prepare two networks, namely, cooperative and uncooperative networks. The roles of these networks and the roles of individual and collective neurons are controlled by the cooperation parameter. As the parameter is increased, the role of cooperative networks becomes more important in learning, and the characteristics of collective neurons become more dominant. On the other hand, when the parameter is small, individual neurons play a more important role. We applied the method to the automobile and housing data from the machine learning database and examined whether explicit class boundaries could be obtained. Experimental results showed that cooperation-controlled learning, in particular taking into account information on input units, could be used to produce clearer class structure than conventional self-organizing maps.
EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia
Authors: Morales-Sánchez A. , Pompa-Mera E. N. , Fajardo-Gutiérrez A. , Alvarez-Rodríguez F. J. , Bekker-Méndez V. C. , Flores-Chapa J. de Diego , Flores-Lujano J. , Jiménez-Hernández E. , Peñaloza-González J. G. , Rodríguez-Zepeda M. C. , Torres-Nava J. R. , Velázquez-Aviña M. M. , Amador-Sánchez R. , Alvarado-Ibarra M. , Reyes-Zepeda N. , Espinosa-Elizondo R. M. , Pérez-Saldivar M. L. , Núñez-Enríquez J. C. , Mejía-Aranguré J. M. , Fuentes-Pananá E. M.
Published: September 2014

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.
Computational Insights into Substrate and Site Specificities, Catalytic Mechanism, and Protonation States of the Catalytic Asp Dyad ofβ-Secretase
Authors: Barman Arghya , Prabhakar Rajeev
Published: September 2014

In this review, information regarding substrate and site specificities, catalytic mechanism, and protonation states of the catalytic Asp dyad ofβ-secretase (BACE1) derived from computational studies has been discussed. BACE1 catalyzes the rate-limiting step in the generation of Alzheimer amyloid beta peptide through the proteolytic cleavage of the amyloid precursor protein. Due to its biological functioning, this enzyme has been considered as one of the most important targets for finding the cure for Alzheimer’s disease. Molecular dynamics (MD) simulations suggested that structural differences in the key regions (inserts A, D, and F and the 10s loop) of the enzyme are responsible for the observed difference in its activities towards the WT- and SW-substrates. The modifications in the flap, third strand, and insert F regions were found to be involved in the alteration in the site specificity of the glycosylphosphatidylinositol bound form of BACE1. Our QM and QM/MM calculations suggested that BACE1 hydrolyzed the SW-substrate more efficiently than the WT-substrate and that cleavage of the peptide bond occurred in the rate-determining step. The results from molecular docking studies showed that the information concerning a single protonation state of the Asp dyad is not enough to run an in silico screening campaign.