bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Alternatively Activated Macrophages Enhances Pathogenesis during Severe Acute Respiratory Syndrome Coronavirus Infection
Authors: Page Carly , Goicochea Lindsay , Matthews Krystal , Zhang Yong , Klover Peter , Holtzman Michael J. , Hennighausen Lothar , Frieman Matthew
Published: September 2012

Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1−/−mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6−/−double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA macrophages by STAT1 is critical to regulating immune pathologies and for protection from long-term progression to fibrotic lung disease in a mouse model of SARS-CoV infection.
Functional Analysis of a Crustacean MicroRNA in Host-Virus Interactions
Authors: Huang Tianzhi , Zhang Xiaobo
Published: September 2012

Growing evidence from mammals suggests that host microRNAs (miRNAs) play important roles in the antiviral immune response. However, the roles of invertebrate miRNAs in response to virus infection remain to be investigated. Based on our previous studies, the shrimp miR-7 was found to be upregulated in response to white spot syndrome virus (WSSV) infection. In this study, the results showed that shrimp miR-7 could target the 3′-untranslated region (3′UTR) of the WSSV early gene wsv477, implying that miR-7 was involved in viral DNA replication. In insect High Five cells, the synthesized miR-7 significantly decreased the expression level of the fluorescent construct bearing the 3′UTR of wsv477 compared with the expression of the control constructs. When the activity of transfected miR-7 was blocked by locked-nucleic-acid (LNA)-modified anti-miR-7 oligonucleotide (AMO-miR-7), the repression of luciferase gene expression by miR-7 was relieved.
In vivo
, when the synthesized miR-7 was injected into shrimp, the numbers of WSSV genome copies/mg gills were 1,000-fold lower than those of WSSV only at 72 and 96 h postinfection. The results indicated that the blocking of endogenous miR-7 by AMO-miR-7 led to about a 10-fold increase of WSSV genome copies/mg gills in WSSV-infected shrimp compared with the control WSSV only. Further, it was revealed that the host Dicer1 was an important component for the biogenesis of miR-7, which had a large effect on virus infection. Therefore, our study revealed a novel regulatory function for an invertebrate miRNA in host-virus interactions by targeting the viral early gene.
Longitudinal Analysis of the Human Antibody Response to Chikungunya Virus Infection: Implications for Serodiagnosis and Vaccine Development
Authors: Kam Yiu-Wing , Lee Wendy W. L. , Simarmata Diane , Harjanto Sumitro , Teng Terk-Shin , Tolou Hugues , Chow Angela , Lin Raymond T. P. , Leo Yee-Sin , Rénia Laurent , Ng Lisa F. P.
Published: September 2012

Chikungunya virus (CHIKV) is an alphavirus which causes chronic and incapacitating arthralgia in humans. Although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against CHIKV is not known. Here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. We have shown that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response. Moreover, we have identified the different regions in these proteins which contain the linear epitopes recognized by the anti-CHIKV antibodies and determined their structural localization. Data also illustrated the effect of a single K252Q amino acid change at the E2 glycoprotein that was able to influence antibody binding and interaction between the antibodies and epitope because of the changes of epitope-antibody binding capacity. This study provides important knowledge that will not only aid in the understanding of the immune response to CHIKV infection but also provide new knowledge in the design of modern vaccine development. Furthermore, these pathogen-specific epitopes could be used for future seroepidemiological studies that will unravel the molecular mechanisms of human immunity and protection from CHIKV disease.
Pseudotyped Influenza A Virus as a Vaccine for the Induction of Heterotypic Immunity
Authors: Powell Timothy J. , Silk Jonathan D. , Sharps Jane , Fodor Ervin , Townsend Alain R. M.
Published: September 2012

There is a need for vaccines that can protect broadly across all influenza A strains. We have produced a pseudotyped influenza virus based on suppression of the A/PR/8/34 hemagglutinin signal sequence (S-FLU) that can infect cells and express the viral core proteins and neuraminidase but cannot replicate. We show that when given by inhalation to mice, S-FLU is nonpathogenic but generates a vigorous T cell response in the lung associated with markedly reduced viral titers and weight loss after challenge with H1 and H3 influenza viruses. These properties of S-FLU suggest that it may have potential as a broadly protective A virus vaccine, particularly in the setting of a threatened pandemic before matched subunit vaccines become available.
Cell-Specific Regulation of Nucleic Acid Sensor Cascades: a Controlling Interest in the Antiviral Response
Authors: Stein Saskia C. , Lam Eric , Falck-Pedersen Erik
Published: September 2012

In this study, we examined the capacities of non-antigen-presenting cell types to propagate antiviral signals following infection with recombinant adenovirus or by direct nucleic acid transfection. Three murine cell lines (RAW264.7 macrophages as a positive control, FL83B hepatocytes, and MS1 endothelial cells) were assessed following exposure to adenovirus, DNA, or RNA ligands. Based on primary (interferon response factor 3 [IRF3] phosphorylation) and secondary (STAT1/2 phosphorylation) response markers, we found each cell line presented a unique response profile: RAW cells were highly responsive, MS1 cells were modified in their response, and FL83B cells were essentially nonresponsive. Comparative reverse transcription-quantitative PCR (RT-qPCR) of nucleic acid sensing components revealed major differences between the three cell types. A prominent difference was at the level of adaptor molecules; TRIF, MyD88, MAVS, and STING. TRIF was absent in MS1 and FL83B cells, whereas MyD88 levels were diminished in FL83B hepatocytes. These differences resulted in compromised TLR-mediated activation. While the cytosolic adaptor MAVS was well represented in all cell lines, the DNA adaptor STING was deficient in FL83B hepatocytes (down by nearly 3 log units). The absence of STING provides an explanation for the lack of DNA responsiveness in these cells. This hypothesis was confirmed by acquisition of IRF3 activation in Flag-STING FL83B cells following DNA transfection. To consolidate the central role of adaptors in MS1 endothelial cells, short hairpin RNA (shRNA) knockdown of STING and MAVS resulted in a ligand-specific loss of IRF3 responsiveness. In contrast to the requirement for specific adaptor proteins, a requirement for a specific DNA sensor (AIM2, DDx41, or p204) in the IRF3 activation response was not detected by shRNA knockdown in MS1 cells. The data reveal that cell-specific regulation of nucleic acid sensing cascade components influences antiviral recognition responses, that controlling levels of adaptor molecules is a recurring strategy in regulating antiviral recognition response functions, and that comparative RT-qPCR has predictive value for antiviral/innate response functions in these cells.
Elevated HIV prevalence and risk behaviours among men who have sex with men (MSM) in Vietnam: a systematic review
Authors: García Macarena C , Meyer Samantha B , Ward Paul
Published: September 2012

Objectives

To review and analyse original studies on HIV prevalence and risk behaviours among men who have sex with men (MSM) in Vietnam.

Design

Systematic literature review. Comprehensive identification of material was conducted by systematic electronic searches of selected databases. Inclusion criteria included studies conducted from 2002 onwards, following a systematic review concluding in 2001 conducted by Colby, Nghia Huu and Doussantousse. Data analysis was undertaken through the application of both the Cochrane Collaboration and ePPI Centre approaches to the synthesis of qualitative and quantitative studies.

Setting

Vietnam.

Results

Sixteen studies, undertaken during 2005–2011, were identified that met the inclusion criteria. The analysis showed that HIV prevalence among MSM in Vietnam has increased significantly (eg, from 9.4% in 2006 to 20% in 2010 in Hanoi) and that protective behaviours, such as condom use and HIV testing and counselling, continue at inadequately low levels.

Conclusions

Increasing HIV prevalence and the lack of effective protective behaviours such as consistent condom use during anal sex among MSM in Vietnam indicate a potential for a more severe HIV epidemic in the future unless targeted and segmented comprehensive HIV prevention strategies for MSM in Vietnam are designed and programmes implemented.
Is admission blood glucose concentration a more powerful predictor of mortality after myocardial infarction than diabetes diagnosis? A retrospective cohort study
Authors: Gholap Nitin Narayan , Mehta Rajnikant Laxmishanker , Ng Leong , Davies Melanie J , Khunti Kamlesh , Squire Iain B
Published: September 2012

Objective

To explore the relative association of admission blood glucose levels and antecedent diabetes on early and long-term survival in a contemporary UK population of patients with ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI).

Design

Retrospective cohort study based on the Myocardial Ischaemia National Audit Project dataset.

Setting

Tertiary care centre.

Participants

4111 (20.3% known diabetes) consecutive patients admitted with acute myocardial infarction (58.3% STEMI) between October 2002 and September 2008.

Primary and secondary outcome measures

All-cause mortality at 30 days and 1 year. The relative association of admission blood glucose and of antecedent diabetes with mortality was assessed using multivariate Cox regression analysis. Furthermore, we compared these relationships in patients with STEMI to those with NSTEMI.

Results

By 30 days and 1 year, 409 (9.9%) and 677 (16.5%) of patients died. After adjusting for covariates, diabetes did not show independent association with mortality at any time point, in the entire cohort (HR 30 days 0.93 (95% CI 0.63 to 1.38); 1 year 1.00 (0.77 to 1.30)) or in subgroups of STEMI (HR 30 days 1.03 (0.65 to 1.64); 1 year 1.08 (0.77 to 1.51)) and NSTEMI (HR 30 days 0.62 (0.26 to 1.50); 1 year 0.87 (0.56 to 1.36)). In contrast, after adjusting for covariates, admission glucose showed robust and independent association with mortality in the entire cohort (HR: 30 days 1.07 (1.04 to 1.10); 1 year 1.05 (1.03 to 1.08)), and in the subgroup of STEMI (30 days 1.07 (1.03 to 1.10); 1 year 1.07 (1.04 to 1.10)), and NSTEMI (HR 30 days 1.07 (1.00 to 1.14); 1 year 1.02 (0.97 to 1.06)).

Conclusions

Admission glucose is strongly associated with mortality in all presentations of acute myocardial infarction (AMI), irrespective of established diabetes diagnosis. The increased risk is maintained up to 1 year. Future studies are required to assess the impact of active management of elevated blood glucose in improving mortality in individuals admitted with AMI.
GRAVITATIONAL FIELD OF A ROTATING GLOBAL MONOPOLE IN f(R) THEORY
Authors: MORAIS GRAÇA J. P. , BEZERRA V. B.
Published: September 2012

In the framework of f(R) theory, we obtain the solution which corresponds to a rotating global monopole from its static counterpart by applying the method of complex coordinate transformation.
EXCLUSIVE WEAK B DECAYS INVOLVING τ LEPTON IN THE RELATIVISTIC QUARK MODEL
Authors: FAUSTOV R. N. , GALKIN V. O.
Published: September 2012

Semileptonic and leptonic B decays are analyzed in the framework of the relativistic quark model. Special attention is paid to the decays involving τ lepton. It is found that the calculated particular decay branching fractions are consistent with available experimental data within error bars. However, the predicted and recently measured ratios R(D(*)) of the B→D(*)τντ and B→D(*)lνl branching fractions differ by 1.75σ for R(D) and by 2.4σ for R(D*).
FADDEEV–JACKIW FORMALISM FOR CONSTRAINED SYSTEMS WITH GRASSMANN DYNAMICAL FIELD VARIABLES
Authors: MANAVELLA EDMUNDO C.
Published: September 2012

The Faddeev–Jackiw canonical quantization formalism for constrained systems with Grassmann dynamical variables within the framework of the field theory is reviewed. First, by means of a iterative process, the symplectic supermatrix is constructed and their associated constraints are found. Next, by taking into account the phase space of the system, the constraint structure is considered. It is found that, if there are no auxiliary dynamical field variables, the supermatrix whose elements are the Bose–Fermi brackets between the constraints associated with the independent dynamical field variables coincides with the symplectic supermatrix corresponding to these independent variables. An alternative procedure to obtain the first-class constraints is given. It is shown that for systems with gauge symmetries, by means of suitable gauge-fixing conditions, a nonsingular final symplectic supermatrix can be found. Then, two possible ways of calculating the Faddeev–Jackiw brackets are pointed out. The relation between the Faddeev–Jackiw and Dirac brackets is discussed. Throughout the previous developments, the Faddeev–Jackiw and Dirac algorithms are compared. Finally, the Faddeev–Jackiw canonical quantization method is applied to a simple model and the obtained results are compared with the ones corresponding to the use of the Dirac procedure on this model.
SURFACE SUBGROUPS OF GRAPH PRODUCTS OF GROUPS
Authors: KIM SANG-HYUN
Published: September 2012

Let G be a graph product of a collection of groups and H be the direct product of the same collection of groups, so that there is a natural surjection p : G → H. The kernel of this map p is called a graph product kernel. We prove that a graph product kernel of countable groups is special, and a graph product of finite or cyclic groups is virtually cocompact special in the sense of Haglund and Wise. The proof of this yields conditions for a graph over which the graph product of arbitrary nontrivial groups (or some cyclic groups, or some finite groups) contains a hyperbolic surface group. In particular, the graph product of arbitrary nontrivial groups over a cycle of length at least five, or over its opposite graph, contains a hyperbolic surface group. For the case when the defining graphs have at most seven vertices, we completely characterize right-angled Coxeter groups with hyperbolic surface subgroups.
A WHITEHEAD ALGORITHM FOR TORAL RELATIVELY HYPERBOLIC GROUPS
Authors: KHARLAMPOVICH OLGA , VENTURA ENRIC
Published: September 2012

The Whitehead problem is solved in the class of toral relatively hyperbolic groups G (i.e. torsion-free relatively hyperbolic groups with abelian parabolic subgroups): there is an algorithm which, given two finite tuples (u1,…,un) and (v1,…,vn) of elements of G, decides whether there is an automorphism of G taking ui to vi for all i.
THE MAGNUS EMBEDDING IS A QUASI-ISOMETRY
Authors: VASSILEVA SVETLA
Published: September 2012

We show that the Magnus embedding, which embeds the free solvable group Sd, r of rank r and degree d into the wreath product ℤr ≀ Sd-1, r, is a quasi-isometry.
Basolateral targeting and microtubule-dependent transcytosis of the aquaporin-2 water channel
Authors: Yui Naofumi , Lu Hua A. J. , Chen Ying , Nomura Naohiro , Bouley Richard , Brown Dennis
Published: September 2012

The aquaporin-2 (AQP2) water channel relocates mainly to the apical plasma membrane of collecting duct principal cells after vasopressin (VP) stimulation. AQP2 transport to this membrane domain is assumed to be a direct route involving recycling of intracellular vesicles. However, basolateral plasma membrane expression of AQP2 is observed in vivo in principal cells. Here, we asked whether there is a transcytotic pathway of AQP2 trafficking between apical and basolateral membranes. We used MDCK cells in which AQP2 normally accumulates apically after VP exposure. In contrast, both site-specific biotinylation and immunofluorescence showed that AQP2 is strongly accumulated in the basolateral membrane, along with the endocytic protein clathrin, after a brief cold shock (4°C). This suggests that AQP2 may be constitutively targeted to basolateral membranes and then retrieved by clathrin-mediated endocytosis at physiological temperatures. Rab11 does not accumulate in basolateral membranes after cold shock, suggesting that the AQP2 in this location is not associated with Rab11-positive vesicles. After rewarming (37°C), basolateral AQP2 staining is diminished and it subsequently accumulates at the apical membrane in the presence of VP/forskolin, suggesting that transcytosis can be followed by apical insertion of AQP2. This process is inhibited by treatment with colchicine. Our data suggest that the cold shock procedure reveals the presence of microtubule-dependent AQP2 transcytosis, which represents an indirect pathway of apical AQP2 delivery in these cells. Furthermore, our data indicate that protein polarity data obtained from biotinylation assays, which require cells to be cooled to 4°C during the labeling procedure, should be interpreted with caution.
Single fiber analyses of glycogen-related proteins reveal their differential association with glycogen in rat skeletal muscle
Authors: Murphy Robyn M. , Xu Hongyang , Latchman Heidy , Larkins Noni T. , Gooley Paul R. , Stapleton David I.
Published: September 2012

To understand how glycogen affects skeletal muscle physiology, we examined enzymes essential for muscle glycogen synthesis and degradation using single fibers from quiescent and stimulated rat skeletal muscle. Presenting a shift in paradigm, we show these proteins are differentially associated with glycogen granules. Protein diffusibility and/or abundance of glycogenin, glycogen branching enzyme (GBE), debranching enzyme (GDE), phosphorylase (GP), and synthase (GS) were examined in fibers isolated from rat fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscle. GDE and GP proteins were more abundant (∼10- to 100-fold) in fibers from EDL compared with SOL muscle. GS and glycogenin proteins were similar between muscles while GBE had an approximately fourfold greater abundance in SOL muscle. Mechanically skinned fibers exposed to physiological buffer for 10 min showed ∼70% total pools of GBE and GP were diffusible (nonbound), whereas GDE and GS were considerably less diffusible. Intense in vitro stimulation, sufficient to elicit a ∼50% decrease in intracellular glycogen, increased diffusibility of GDE, GP, and GS (∼15–60%) and decreased GBE diffusibility (∼20%). Amylase treatment, which breaks α-1,4 linkages of glycogen, indicated differential diffusibilities and hence glycogen associations of GDE and GS. Membrane solubilization (1% Triton-X-100) allowed a small additional amount of GDE and GS to diffuse from fibers, suggesting the majority of nonglycogen-associated GDE/GS is associated with myofibrillar/contractile network of muscle rather than membranes. Given differences in enzymes required for glycogen metabolism, the current findings suggest glycogen particles have fiber-type-dependent structures. The greater catabolic potential of glycogen breakdown in fast-twitch fibers may account for different contraction induced rates of glycogen utilization.
Blockade of orexin receptors with Almorexant reduces cardiorespiratory responses evoked from the hypothalamus but not baro- or chemoreceptor reflex responses
Authors: Iigaya Kamon , Horiuchi Jouji , McDowall Lachlan M. , Lam Alex C. B. , Sediqi Yusuf , Polson Jaimie W. , Carrive Pascal , Dampney Roger A. L.
Published: September 2012

Orexin neurons form a restricted group in the dorsal hypothalamus. The group is centered on the perifornical area within the classic hypothalamic defense area, an area which when activated produces marked cardiovascular and respiratory effects. Central administration of orexin can produce cardiorespiratory effects, but the extent to which orexin contributes to such responses evoked from the perifornical hypothalamus is not clear. To determine this, we used the dual orexin receptor antagonist Almorexant to challenge the cardiorespiratory effects evoked by disinhibition of the perifornical hypothalamus. Bicuculline (10 and 20 pmol) was microinjected in the perifornical area before and after administration of Almorexant (15 mg/kg iv) or vehicle in urethane-anesthetized rats. Almorexant significantly reduced the pressor, tachycardic, renal sympathoexcitatory, and tachypneic responses to bicuculline (10 pmol, by 55%, 53%, 28%, 77%; 20 pmol, by 54%, 27%, 51%, 72%, respectively). Reductions of similar magnitude were observed with bicuculline microinjections centered on more caudal sites just peripheral to the orexin neuron group, which would likely have activated fewer orexin neurons. In contrast, Almorexant had no effect on the cardiorespiratory response of the chemoreflex (sodium cyanide injection) or the sympathetic component of the baroreflex. Thus orexin makes a major contribution to the cardiorespiratory response evoked from the perifornical area even though orexin neurons represent only a fraction of the output of this area. Orexin neurons may also mediate cardiorespiratory responses from non-orexin neurons in the caudal hypothalamus. However, under resting conditions, blockade of orexin receptors does not affect the chemo- and baroreflexes.
CYP-epoxygenases contribute to A2A receptor-mediated aortic relaxation via sarcolemmal KATP channels
Authors: Ponnoth Dovenia S. , Nayeem Mohammed A. , Tilley Stephen L. , Ledent Catherine , Jamal Mustafa S.
Published: September 2012

Previously, we have shown that A2A adenosine receptor (A2AAR) mediates aortic relaxation via cytochrome P-450 (CYP)-epoxygenases. However, the signaling mechanism is not understood properly. We hypothesized that ATP-sensitive K+ (KATP) channels play an important role in A2AAR-mediated relaxation. Organ bath and Western blot experiments were done using isolated aorta from A2AKO and corresponding wild-type (WT) mice. Aortic rings from WT and A2A knockout (KO) mice were precontracted with submaximal dose of phenylephrine (PE, 10−6 M), and concentration-response curves for pinacidil, cromakalim (nonselective KATP openers), and diazoxide (mitochondrial KATP opener) were obtained. Diazoxide did not have any relaxation effect on PE-precontracted tissues, whereas relaxation to pinacidil (48.09 ± 5.23% in WT vs. 25.41 ± 2.73% in A2AKO; P < 0.05) and cromakalim (51.19 ± 2.05% in WT vs. 38.50 ± 2.26% in A2AKO; P < 0.05) was higher in WT than A2AKO aorta. This suggested the involvement of sarcolemmal rather than mitochondrial KATP channels. Endothelium removal, treatment with SCH 58651 (A2AAR antagonist; 10−6 M), NG-nitro-l-arginine methyl ester (l-NAME, nitric oxide synthase inhibitor) and methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH, CYP-epoxygenases inhibitor; 10−5 M) significantly reduced pinacidil-induced relaxation in WT compared with controls, whereas these treatments did not have any effect in A2AKO aorta. Glibenclamide (KATP channel inhibitor, 10−5 M) blocked 2- p-(2-carboxyethyl)phenethylamino-5′ N-ethylcarboxamido adenosine hydrochloride (CGS 21680, A2AAR agonist)-induced relaxation in WT and changed 5′- N-ethylcarboxamide (NECA) (nonselective adenosine analog)-induced response to higher contraction in WT and A2AKO. 5-Hydroxydecanoate (5-HD, mitochondrial KATP channel inhibitor, 10−4 M) had no effect on CGS 21680-mediated response in WT aorta. Our data suggest that A2AAR-mediated vasorelaxation occurs through opening of sarcolemmal KATP channels via CYP-epoxygenases and possibly, nitric oxide, contributing to pinacidil-induced responses.
Loss of muscle strength during sepsis is in part regulated by glucocorticoids and is associated with reduced muscle fiber stiffness
Authors: Alamdari Nima , Toraldo Gianluca , Aversa Zaira , Smith Ira , Castillero Estibaliz , Renaud Guillaume , Qaisar Rizwan , Larsson Lars , Jasuja Ravi , Hasselgren Per-Olof
Published: September 2012

Sepsis is associated with impaired muscle function but the role of glucocorticoids in sepsis-induced muscle weakness is not known. We tested the role of glucocorticoids in sepsis-induced muscle weakness by treating septic rats with the glucocorticoid receptor antagonist RU38486. In addition, normal rats were treated with dexamethasone to further examine the role of glucocorticoids in the regulation of muscle strength. Sepsis was induced in rats by cecal ligation and puncture, and muscle force generation (peak twitch and tetanic tension) was determined in lower extremity muscles. In other experiments, absolute and specific force as well as stiffness (reflecting the function of actomyosin cross bridges) were determined in isolated skinned muscle fibers from control and septic rats. Sepsis and treatment with dexamethasone resulted in reduced maximal twitch and tetanic force in intact isolated extensor digitorum longus muscles. The absolute and specific maximal force in isolated muscle fibers was reduced during sepsis together with decreased fiber stiffness. These effects of sepsis were blunted (but not abolished) by RU38486. The results suggest that muscle weakness during sepsis is at least in part regulated by glucocorticoids and reflects loss of contractility at the cellular (individual muscle fiber) level. In addition, the results suggest that reduced function of the cross bridges between actin and myosin (documented as reduced muscle fiber stiffness) may be involved in sepsis-induced muscle weakness. An increased understanding of mechanisms involved in loss of muscle strength will be important for the development of new treatment strategies in patients with this debilitating consequence of sepsis.
Concurrent binding and modifications of AUF1 and HuR mediate the pH-responsive stabilization of phosphoenolpyruvate carboxykinase mRNA in kidney cells
Authors: Gummadi Lakshmi , Taylor Lynn , Curthoys Norman P.
Published: September 2012

Onset of metabolic acidosis leads to a pronounced increase in renal expression of phosphoenolpyruvate carboxykinase (PEPCK). This response, which is mediated in part by stabilization of PEPCK mRNA, is effectively modeled by treating LLC-PK1-F+-9C cells with an acidic medium. siRNA knockdown of HuR prevented the pH-responsive increase in PEPCK mRNA half-life suggesting that HuR is necessary for this response. A recruitment assay, using a reporter mRNA in which the pH response elements of the PEPCK 3′-UTR were replaced with six MS2 stem-loop sequences, was developed to test this hypothesis. The individual recruitment of a chimeric protein containing the MS2 coat protein and either HuR or p40AUF1 failed to produce a pH-responsive stabilization. However, the concurrent expression of both chimeric proteins was sufficient to produce a pH-responsive increase in the half-life of the reporter mRNA. siRNA knockdown of AUF1 produced slight increases in basal levels of PEPCK mRNA and protein, but partially inhibited the pH-responsive increases. Complete inhibition of the latter response was achieved by knockdown of both RNA-binding proteins. The results suggest that binding of HuR and AUF1 has opposite effects on basal expression, but may interact to mediate the pH-responsive increase in PEPCK mRNA. Two-dimensional gel electrophoresis indicated that treatment with acidic medium caused a decrease in phosphorylation of HuR, but may increase phosphorylation of the multiple AUF1 isoforms. Thus, the pH-responsive stabilization of PEPCK mRNA requires the concurrent binding of HuR and AUF1 and may be mediated by changes in their extent of covalent modification.
The impact of peptidase activity on clear cell renal cell carcinoma survival
Authors: Larrinaga Gorka , Blanco Lorena , Sanz Begoña , Perez Itxaro , Gil Javier , Unda Miguel , Andrés Leire , Casis Luis , López José I.
Published: September 2012

Several studies have proposed that protease expression and activity may have a predictive value in the survival of clear cell renal cell carcinoma (CCRCC). Most efforts on this issue have been focused on the analysis of matrix metalloproteinases (MMP) and very little on the role of other proteases, such as peptidases. The catalytic activity of 9 peptidases (APN, APB, ASP, CAP, DPP-IV, NEP/CD10, PEP, PGI, and PSA) was quantified by fluorometric methods in a series of 79 CCRCC patients, and the results obtained were analyzed for survival (Kaplan-Meier curves, log-rank test, and Cox multivariate analysis). CCRCC patients with higher activity levels of membrane-bound APN and soluble APN, DPP-IV, and CAP had significantly shorter 5-yr survival rates than those with lower levels. By contrast, higher soluble APB activity significantly correlated with longer survival. Our data suggest the involvement of peptidases in the biological aggressiveness of CCRCC and support the usefulness of measuring these proteases to assess the prognosis of patients with CCRCC.
The Experience of Being Born: A Natural Context for Learning to Suckle
Authors: Alberts Jeffrey R. , Ronca April E.
Published: September 2012

Understanding the developmental origins of congenital capabilities such as sucking is fundamental knowledge that can contribute to improving the clinical management of early feeding and facilitate the onset of oral ingestion. We describe analyses in rats showing that sensory stimulationin uteroand during birth establishes the newborn’s sucking responses to maternal cues. We mimicked elements of labor and delivery (viz., compressions simulating labor contractions, stroking simulating postnatal maternal licking of the newborn, and postnatal thermal flux), and used them to induce postnatal respiration and nipple attachment in caesarian-delivered pups. We report herein new data showing that, by simulating a fetal rat’s experience of being born, specific components of vaginal birth provide sufficient conditions for the odor learning that guides newborn’s sucking responses. In contrast, the absence ofin uterocompressions was associated with poor sucking onset. Knowing how birth stimuli contribute to the first nipple attachment and constitute a context for learning to suckle is an important step toward better management of some early feeding problems. It can serve also as a foundation for understanding the challenges of facilitating sucking by babies born prematurely so that they do not experience the typical contingencies mediating onset of oral ingestion.
Viscosity Approximation Methods for Equilibrium Problems, Variational Inequality Problems of Infinitely Strict Pseudocontractions in Hilbert Spaces
Authors: Wang Aihong
Published: September 2012

We introduce an iterative scheme by the viscosity approximation method for finding a common element of the set of the solutions of the equilibrium problem and the set of fixed points of infinitely strict pseudocontractive mappings. Strong convergence theorems are established in Hilbert spaces. Our results improve and extend the corresponding results announced by many others recently.
Comparative Analysis of Mathematical Models for Blood Flow in Tapered Constricted Arteries
Authors: Sankar D. S. , Yatim Yazariah
Published: September 2012

Pulsatile flow of blood in narrow tapered arteries with mild overlapping stenosis in the presence of periodic body acceleration is analyzed mathematically, treating it as two‐fluid model with the suspension of all the erythrocytes in the core region as non‐Newtonian fluid with yield stress and the plasma in the peripheral layer region as Newtonian. The non‐Newtonian fluid with yield stress in the core region is assumed as (i) Herschel‐Bulkley fluid and (ii) Casson fluid. The expressions for the shear stress, velocity, flow rate, wall shear stress, plug core radius, and longitudinal impedance to flow obtained by Sankar (2010) for two‐fluid Herschel‐Bulkley model and Sankar and Lee (2011) for two‐fluid Casson model are used to compute the data for comparing these fluid models. It is observed that the plug core radius, wall shear stress, and longitudinal impedance to flow are lower for the two‐fluid H‐B model compared to the corresponding flow quantities of the two‐fluid Casson model. It is noted that the plug core radius and longitudinal impedance to flow increases with the increase of the maximum depth of the stenosis. The mean velocity and mean flow rate of two‐fluid H‐B model are higher than those of the two‐fluid Casson model.
Analysis of User Requirements in Interactive 3D Video Systems
Authors: Yuan Haiyue , Ćalić Janko , Kondoz Ahmet
Published: September 2012

The recent development of three dimensional (3D) display technologies has resulted in a proliferation of 3D video production and broadcasting, attracting a lot of research into capture, compression and delivery of stereoscopic content. However, the predominant design practice of interactions with 3D video content has failed to address its differences and possibilities in comparison to the existing 2D video interactions. This paper presents a study of user requirements related to interaction with the stereoscopic 3D video. The study suggests that the change of view, zoom in/out, dynamic video browsing, and textual information are the most relevant interactions with stereoscopic 3D video. In addition, we identified a strong demand for object selection that resulted in a follow-up study of user preferences in 3D selection using virtual-hand and ray-casting metaphors. These results indicate that interaction modality affects users’ decision of object selection in terms of chosen location in 3D, while user attitudes do not have significant impact. Furthermore, the ray-casting-based interaction modality using Wiimote can outperform the volume-based interaction modality using mouse and keyboard for object positioning accuracy.
Stability and Existence of Periodic Solutions for Cellular Neural Networks with State Dependent Delays on Time Scales
Authors: Ren Yaping , Li Yongkun
Published: September 2012

We study delayed cellular neural networks on time scales. Without assuming the boundedness of the activation functions, we establish the exponential stability and existence of periodic solutions. The results in this paper are completely new even in case of the time scale 𝕋 = ℝ or ℤ and improve some of the previously known results.
Temporal Variation of N Isotopic Composition of Decomposing Legume Roots and Its Implications to N Cycling Estimates inN15Tracer Studies in Agroforestry Systems
Authors: Jalonen Riina , Sierra Jorge
Published: September 2012

Below-ground residue of agroforestry trees is an important N source for associated crops. Several studies have shown that its isotopic signature (δ15N) may change after tree pruning, which makes it difficult to study below-ground N inputs from pruned trees by isotopic techniques. We studied how temporal variation of legume root residueδ15N could be explained by considering differential decomposition kinetics and15N content of residue fractions. A mathematical model on the isotopic patterns of soil and a N recipient plant during root decomposition was developed and applied for testing assumptions about residue characteristics against two experimental datasets. Observed15N patterns of the recipient plants could be satisfactorily simulated only when the residue was assumed to consist of at least two fractions with distinctδ15N and decomposition rates depending on their C : N ratio. Assumingδ15N of residue constant over time resulted in substantial underestimates of N derived from low-quality residue (%Ndfr) by the recipient plant when compared with experimental data. Results of this study suggest that residue fractionation can help improve estimation of %Ndfr in isotopic studies, as an alternative or complementary method to assuming or aiming at homogenous isotopic composition of N sources.
Multiple Intestinal Intussusceptions as a Complication of Severe Hyperglycemia in a Patient with Diabetic Ketoacidosis
Authors: Raghavan Pooja , Salon Jeffrey , Rajan Dhyan
Published: September 2012

Intussusception in adults is a rare phenomenon, occurring in approximately 1 in 30,000 hospital admissions annually. When it does occur, the majority of cases involve an organic lesion serving as a lead point for intussusception, such as tumors or postoperative adhesions. In a small percentage of cases, a lead point is not found, and intussusception is thought to be idiopathic or secondary to a disease process contributing to dysrhythmic peristalsis of the gastrointestinal tract. A few cases of functional intussusception have been reported as being secondary to severe hyperglycemia and metabolic derangements, including metabolic acidosis and hyperkalemia, by causing impaired gastrointestinal motility. We present a case of a 23-year-old Caucasian male who presented with severe hyperglycemia and diabetic ketoacidosis. Imaging of the abdomen revealed three intussusceptions involving the small intestine, which were easily reduced manually during exploratory laparotomy.
Case Report: Ductal CarcinomaIn Situin the Male Breast
Authors: Chern Joshua , Liao Lydia , Baraldi Raymond , Tinney Elizabeth , Hendershott Karen , Germaine Pauline
Published: September 2012

High-grade ductal carcinoma in situ is incredibly rare in male patients. The prognosis for ductal carcinoma in situ (DCIS) in a male patient is the same as it would be for a female with the same stage disease; therefore, early recognition and diagnosis are of the utmost importance. We present a case of a male with unilateral invasive ductal carcinoma who was diagnosed with DCIS in the contralateral breast. The DCIS presented as microcalcifications on mammography and was found to be biopsy proven grade 3 papillary DCIS. This case also illustrates the importance of family history and risk factors, all of which need to be evaluated in any male presenting with a breast mass or nipple discharge.
Characteristics of Hemodynamic Disorders in Patients with Severe Traumatic Brain Injury
Authors: Rzheutskaya Ryta E.
Published: September 2012

Purpose. To define specific features of central hemodynamic parameter changes in patients with isolated severe traumatic brain injury (STBI) and in patients with clinically established brain death and to determine the required course of treatment for their correction.Data and Research Methods. A close study of central hemodynamic parameters was undertaken. The study involved 13 patients with isolated STBI (group STBI) and 15 patients with isolated STBI and clinically established brain death (group STBI-BD). The parameters of central hemodynamics were researched applying transpulmonary thermodilution.Results. In the present study, various types of hemodynamic reaction (normodynamic, hyperdynamic, and hypodynamic) were identified in patients with isolated STBI in an acute period of traumatic disease. Hyperdynamic type of blood circulation was not observed in patients with isolated STBI and clinically established brain death. Detected hemodynamic disorders led to the correction of the ongoing therapy under the control of central hemodynamic parameters.Conclusions. Monitoring of parameters of central hemodynamics allows to detect the cause of disorders, to timely carry out the required correction, and to coordinate infusion, inotropic, and vasopressor therapy.
Excised Abdominoplasty Material as a Systematic Plastic Surgical Training Model
Authors: Demirseren M. Erol , Ceran Candemir , Duman Yakup , Sarici Murat
Published: September 2012

Achieving a level of technical skill and confidence in surgical operations is the main goal of plastic surgical training. Operating rooms were accepted as the practical teaching venues of the traditional apprenticeship model. However, increased patient population, time, and ethical and legal considerations made preoperation room practical work a must for plastic surgical training. There are several plastic surgical teaching models and simulators which are very useful in preoperation room practical training and the evaluation of plastic surgery residents. The full thickness skin with its vascular network excised in abdominoplasty procedures is an easily obtainable real human tissue which could be used as a training model in plastic surgery.
Relations between Stochastic and Partial Differential Equations in Hilbert Spaces
Authors: Melnikova I. V. , Parfenenkova V. S.
Published: September 2012

The aim of the paper is to introduce a generalization of the Feynman-Kac theorem in Hilbert spaces. Connection between solutions to the abstract stochastic differential equation and solutions to the deterministic partial differential (with derivatives in Hilbert spaces) equation for the probability characteristic is proved. Interpretation of objects in the equations is given.
Landfill Leachates Treatment by /UV, /, Modified Fenton, and Modified Photo-Fenton Methods
Authors: Naumczyk Jeremi , Prokurat Izabela , Marcinowski Piotr
Published: September 2012

Advanced oxidation processes (AOPs) such as H2O2/UV, O3/H2O2, modified Fenton, and modified photo-Fenton processes have been investigated in terms of the treatment of landfill leachate with ratio of BOD5/COD in the range of 0.22 to 0.24. The modification of Fenton and photo-Fenton processes consisted in the inclusion of precipitation and separation of humic substances at pH 3. Due to the precipitation, the value of COD decreased by 39% and BOD5by 7.1%. The modification of the processes allowed us to improve the efficiency and to decrease the doses of reagents necessary to continue the process. Modified photo-Fenton process proved to be the most effective (92.7% COD removal) of all processes investigated. Additionally, modified-Fenton process was much more effective than the other two processes when compared up to 120 min, while after longer times it gave the least satisfactory results. After 30 min of modified-Fenton process BOD5/COD ratio increased to 0.43. The parameter referred to as “efficiency of oxidants” was used to estimate the efficiency of all the processes—its value varied from 178 to 239%. Various substances including phthalates, hydrocarbons, silanes, and siloxanes were identified in raw and treated leachate.
Newborn with Dilated Cardiomyopathy Secondary to Vitamin D Deficiency
Authors: Al Azkawi Hanan , Al Mutair Angham
Published: September 2012

Hypocalcemia is a rare but reversible cause of dilated cardiomyopathy with limited cases being reported in the literature. Vitamin D deficiency is the main cause of hypocalcemia in almost all reported cases. We report a newborn presented with hypocalcemia-induced dilated cardiomyopathy secondary to vitamin D deficiency. After calcium and vitamin D therapy, the baby showed a rapid recovery of the cardiac function.
Positive Periodic Solutions for Second-Order Ordinary Differential Equations with Derivative Terms and Singularity in Nonlinearities
Authors: Li Yongxiang , Jiang Xiaoyu
Published: September 2012

The existence results of positiveω-periodic solutions are obtained for the second-order ordinary differential equationu′′(t)=f(t,u(t),u'(t)),t∈ℝwhere,f:ℝ×(0,∞)×ℝ→ℝis a continuous function, which isω-periodic intandf(t,u,v)may be singular atu=0. The discussion is based on the fixed point index theory in cones.
Imaging mRNA Expression in Live Cells via PNA·DNA Strand Displacement-Activated Probes
Authors: Wang Zhenghui , Zhang Ke , Wooley Karen L. , Taylor John-Stephen
Published: September 2012

Probes for monitoring mRNA expressionin vivoare of great interest for the study of biological and biomedical problems, but progress has been hampered by poor signal to noise and effective means for delivering the probes into live cells. Herein we report a PNA·DNA strand displacement-activated fluorescent probe that can image the expression of iNOS (inducible nitric oxide synthase) mRNA, a marker of inflammation. The probe consists of a fluorescein labeled antisense PNA annealed to a shorterDABCYLplus-labeled DNA which quenches the fluorescence, but when the quencher strand is displaced by the target mRNA the fluorescence is restored. DNA was used for the quencher strand to facilitate electrostatic binding of the otherwise netural PNA strand to a cationic shell crosslinked knedel-like (cSCK) nanoparticle which can deliver the PNA·DNA duplex probe into cells with less toxicity and greater efficiency than other transfection agents. RAW 264.7 mouse macrophage cells transfected with the iNOS PNA·DNA probe via the cSCK showed a 16 to 54-fold increase in average fluorescence per cell upon iNOS stimulation. The increase was 4 to 7-fold higher than that for a non-complementary probe, thereby validating the ability of a PNA·DNA strand displacement-activated probe to image mRNA expressionin vivo.
Diarylmethyl Ethers for the Protection of Polyols
Authors: Petursson Sigthor
Published: September 2012

The paper discusses the use of diarylmethyl ethers for the protection of hydroxyl groups, in particular, carbohydrate hydroxyl groups. The formation of these ethers can be done nonselectively by the thermal reactions of diryldiazomethanes via a carbene mechanism or by tin(II) halide catalysis of the diazo compounds with diols. The catalyzed reactions give useful regioselectivities.