bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of a Host Protein with Core Complexes of Bacteriophage Φ6 To Control Transcription
Authors: Qiao Xueying , Sun Yang , Qiao Jian , Mindich Leonard
Published: February 2010

Bacteriophages of the familyCystoviridaehave genomes consisting of three double-stranded RNA (dsRNA) segments, L, S, and M, packaged within a polyhedral capsid along with RNA polymerase. Transcription of genomic segment L is activated by the interaction of host protein YajQ with the capsid structure. Segment L codes for the proteins of the inner capsid, which are expressed early in infection. Green fluorescent protein (GFP) fusions with YajQ produce uniform fluorescence in uninfected cells and in cells infected with viruses not dependent on YajQ. Punctate fluorescence develops when cells are infected with YajQ-dependent viruses. It appears that the host protein binds to the infecting particles and remains with them during the entire infection period.
Reciprocal Regulation of AKT and MAP Kinase Dictates Virus-Host Cell Fusion
Authors: Sharma Nishi R. , Mani Prashant , Nandwani Neha , Mishra Rajakishore , Rana Ajay , Sarkar Debi P.
Published: February 2010

Viruses of the
Paramyxoviridae
family bind to their host cells by using hemagglutinin-neuraminidase (HN), which enhances fusion protein (F)-mediated membrane fusion. Although respiratory syncytial virus and parainfluenza virus 5 of this family are suggested to trigger host cell signaling during infection, the virus-induced intracellular signals dictating virus-cell fusion await elucidation. Using an F- or HN-F-containing reconstituted envelope of Sendai virus, another paramyxovirus, we revealed the role and regulation of AKT1 and Raf/MEK/ERK cascades during viral fusion with liver cells. Our observation that extracellular signal-regulated kinase (ERK) activation promotes viral fusion via ezrin-mediated cytoskeletal rearrangements, whereas AKT1 attenuates fusion by promoting phosphorylation of F protein, indicates a counteractive regulation of viral fusion by reciprocal activation of AKT1 and mitogen-activated protein kinase (MAPK) cascades, establishing a novel conceptual framework for a therapeutic strategy.
Familial Relationships in Hyperthermo- and Acidophilic Archaeal Viruses
Authors: Happonen Lotta Johanna , Redder Peter , Peng Xu , Reigstad Laila Johanne , Prangishvili David , Butcher Sarah Jane
Published: February 2010

Archaea often live in extreme, harsh environments such as acidic hot springs and hypersaline waters. To date, only two icosahedrally symmetric, membrane-containing archaeal viruses, SH1 and
Sulfolobus
turreted icosahedral virus (STIV), have been described in detail. We report the sequence and three-dimensional structure of a third such virus isolated from a hyperthermoacidophilic crenarchaeon,
Sulfolobus
strain G4ST-2. Characterization of this new isolate revealed it to be similar to STIV on the levels of genome and structural organization. The genome organization indicates that these two viruses have diverged from a common ancestor. Interestingly, the prominent surface turrets of the two viruses are strikingly different. By sequencing and mass spectrometry, we mapped several large insertions and deletions in the known structural proteins that could account for these differences and showed that both viruses can infect the same host. A combination of genomic and proteomic analyses revealed important new insights into the structural organization of these viruses and added to our limited knowledge of archaeal virus life cycles and host-cell interactions.
Mechanistic Consequences of hnRNP C Binding to Both RNA Termini of Poliovirus Negative-Strand RNA Intermediates
Authors: Ertel Kenneth J. , Brunner Jo Ellen , Semler Bert L.
Published: February 2010

The poliovirus 3′ noncoding region (3′ NCR) is necessary for efficient virus replication. A poliovirus mutant, PVΔ3′NCR, with a deletion of the entire 3′ NCR, yielded a virus that was capable of synthesizing viral RNA, albeit with a replication defect caused by deficient positive-strand RNA synthesis compared to wild-type virus. We detected multiple ribonucleoprotein (RNP) complexes in extracts from poliovirus-infected HeLa cells formed with a probe corresponding to the 5′ end of poliovirus negative-strand RNA (the complement of the genomic 3′ NCR), and the levels of these RNP complexes increased during the course of viral infection. Previous studies have identified RNP complexes formed with the 3′ end of poliovirus negative-strand RNA, including one that contains a 36-kDa protein later identified as heterogeneous nuclear ribonucleoprotein C (hnRNP C). We report here that the 5′ end of poliovirus negative-strand RNA is capable of interacting with endogenous hnRNP C, as well as with poliovirus nonstructural proteins. Further, we demonstrate that the addition of recombinant purified hnRNP C proteins can stimulate virus RNA synthesis
in vitro
and that depletion of hnRNP C proteins in cultured cells results in decreased virus yields and a correspondingly diminished accumulation of positive-strand RNAs. We propose that the association of hnRNP C with poliovirus negative-strand termini acts to stabilize or otherwise promote efficient positive-strand RNA synthesis.
Herpes Simplex Virus 1 Regulatory Protein ICP27 Undergoes a Head-to-Tail Intramolecular Interaction
Authors: Hernandez Felicia P. , Sandri-Goldin Rozanne M.
Published: February 2010

Herpes simplex virus type 1 (HSV-1) regulatory protein ICP27 is a multifunction functional protein that interacts with many cellular proteins. A number of the proteins with which ICP27 interacts require that both the N and C termini of ICP27 are intact. These include RNA polymerase II, TAP/NXF1, and Hsc70. We tested the possibility that the N and C termini of ICP27 could undergo a head-to-tail intramolecular interaction that exists in open and closed configurations for different binding partners. Here, we show by bimolecular fluorescence complementation (BiFC) assays and fluorescence resonance energy transfer (FRET) by acceptor photobleaching that ICP27 undergoes a head-to-tail intramolecular interaction but not head-to-tail or tail-to-tail intermolecular interactions. Substitution mutations in the N or C termini showed that the leucine-rich region (LRR) in the N terminus and the zinc finger-like region in the C terminus must be intact for intramolecular interactions. A recombinant virus, vNC-Venus-ICP27, was constructed, and this virus was severely impaired for virus replication. The expression of NC-Venus-ICP27 protein was delayed compared to ICP27 expression in wild-type HSV-1 infection, but NC-Venus-ICP27 was abundantly expressed at late times of infection. Because the renaturation of the Venus fluorescent protein results in a covalent bonding of the two halves of the Venus molecule, the head-to-tail interaction of NC-Venus-ICP27 locks ICP27 in a closed configuration. We suggest that the population of locked ICP27 molecules is not able to undergo further protein-protein interactions.
Inhibition of Human Natural Killer Cell Activity by Influenza Virions and Hemagglutinin
Authors: Mao Huawei , Tu Wenwei , Liu Yinping , Qin Gang , Zheng Jian , Chan Ping-Lung , Lam Kwok-Tai , Peiris J. S. Malik , Lau Yu-Lung
Published: February 2010

Natural killer (NK) cells keep viral infections under control at the early phase by directly killing infected cells. Influenza is an acute contagious respiratory viral disease transmitted from host-to-host in the first few days of infection. The evasion of host innate immune defenses including NK cells is important for its success as a viral pathogen of humans and animals. NK cells encounter influenza virus within the microenvironment of infected cells. It therefore is important to investigate the direct effects of influenza virus on NK cell activity. Recently we demonstrated that influenza virus directly infects human NK cells and induces cell apoptosis to counter their function (H. Mao, W. Tu, G. Qin, H. K. W. Law, S. F. Sia, P.-L. Chan, Y. Liu, K.-T. Lam, J. Zheng, M. Peiris, and Y.-L. Lau, J. Virol. 83:9215-9222, 2009). Here, we further demonstrated that both the intact influenza virion and free hemagglutinin protein inhibited the cytotoxicity of fresh and interleukin-2 (IL-2)-activated primary human NK cells. Hemagglutinin bound and internalized into NK cells via the sialic acids. This interaction did not decrease NKp46 expression but caused the downregulation of the ζ chain through the lysosomal pathway, which caused the decrease of NK cell cytotoxicity mediated by NKp46 and NKp30. The underlying dysregulation of the signaling pathway involved ζ chain downregulation, leading to decreased Syk and ERK activation and granule exocytosis upon target cell stimulation, finally causing reduced cytotoxicity. These findings suggest that influenza virus developed a novel strategy to evade NK cell innate immune defense that is likely to facilitate viral transmission and also contribute to virus pathogenesis.
Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by γ-Irradiated Influenza A Viruses
Authors: Furuya Yoichi , Chan Jennifer , Regner Matthias , Lobigs Mario , Koskinen Aulikki , Kok Tuckweng , Manavis Jim , Li Peng , Müllbacher Arno , Alsharifi Mohammed
Published: February 2010

We previously demonstrated that a single dose of nonadjuvanted intranasal γ-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed cross-protection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal heterosubtypic influenza virus challenge. Furthermore, γ-irradiated influenza viruses induced cross-reactive Tc-cell responses but not cross-neutralizing or cross-protective antibodies. In addition, histological analysis showed reduced lung inflammation in vaccinated mice compared to that in unvaccinated controls following heterosubtypic challenge. This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4+and CD8+, and with early influenza virus-specific cytotoxic T-cell responses. Therefore, cross-protective immunity induced by vaccination with γ-irradiated influenza A virus is mediated mainly by Tc-cell responses.
Dengue Virus Inhibits the Production of Type I Interferon in Primary Human Dendritic Cells
Authors: Rodriguez-Madoz Juan R. , Bernal-Rubio Dabeiba , Kaminski Dorota , Boyd Kelley , Fernandez-Sesma Ana
Published: February 2010

Dengue virus (DENV) infects human immune cellsin vitroand likely infects dendritic cells (DCs)in vivo. DENV-2 productive infection induces activation and release of high levels of chemokines and proinflammatory cytokines in monocyte-derived DCs (moDCs), with the notable exception of alpha/beta interferon (IFN-α/β). Interestingly, DENV-2-infected moDCs fail to prime T cells, most likely due to the lack of IFN-α/β released by moDCs, since this effect was reversed by addition of exogenous IFN-β. Together, our data show that inhibition of IFN-α/β production by DENV in primary human moDCs is a novel mechanism of immune evasion.
Rotavirus Differentially Infects and Polyclonally Stimulates Human B Cells Depending on Their Differentiation State and Tissue of Origin
Authors: Narváez Carlos F. , Franco Manuel A. , Angel Juana , Morton John M. , Greenberg Harry B.
Published: February 2010

We have shown previously that rotavirus (RV) can infect murine intestinal B220+cellsin vivo(M. Fenaux, M. A. Cuadras, N. Feng, M. Jaimes, and H. B. Greenberg, J. Virol. 80:5219-5232, 2006) and human blood B cellsin vitro(M. C. Mesa, L. S. Rodriguez, M. A. Franco, and J. Angel, Virology366:174-184, 2007). However, the effect of RV on B cells, especially those present in the human intestine, the primary site of RV infection, is unknown. Here, we compared the effects of thein vitroRV infection of human circulating (CBC) and intestinal B cells (IBC). RV infected four times more IBC than CBC, and in both types of B cells the viral replication was highly restricted to the memory subset. RV induced cell death in 30 and 3% of infected CBC and IBC, respectively. Moreover, RV induced activation and differentiation into antibody-secreting cells (ASC) of CBC but not IBC when the B cells were present with other mononuclear cells. However, RV did not induce these effects in purified CBC or IBC, suggesting the participation of other cells in activating and differentiating CBC. RV infection was associated with enhanced interleukin-6 (IL-6) production by CBC independent of viral replication. The infection of the anti-B-cell receptor, lipopolysaccharide, or CpG-stimulated CBC reduced the secretion of IL-6 and IL-8 and decreased the number of ASC. These inhibitory effects were associated with an increase in viral replication and cell death and were observed in polyclonally stimulated CBC but not in IBC. Thus, RV differentially interacts with primary human B cells depending on their tissue of origin and differentiation stage, and it affects their capacity to modulate the local and systemic immune responses.
Role of Herpes Simplex Virus ICP0 in the Transactivation of Genes Introduced by Infection or Transfection: a Reappraisal
Authors: Kalamvoki Maria , Roizman Bernard
Published: February 2010

ICP0, a promiscuous transactivator that enhances the expression of genes introduced by infection or transfection, functions in both nucleus and cytoplasm. The nuclear functions include degradation and dispersal of ND10 bodies and suppression of silencing of viral DNA. Subsequently, ICP0 shifts to the cytoplasm. Transfection of DNA prior to infection has no effect on the localization of ICP0 in cells that are efficient expressers of transgenes (e.g., Vero and HEK293) but results in delayed cytoplasmic localization of ICP0 in cells (e.g., HEp-2 and HEL) that are poor transgene expressers. Here, we examined by real-time PCR (qPCR) the accumulation of a transgene and of viral gI mRNAs in Vero or HEp-2 cells that were transfected and then infected with wild-type or ΔICP0 mutant viruses. The accumulation of transgene mRNA was unaffected by a ΔICP0 mutant, gradually increased in HEp-2 cells, but increased and then decreased in Vero cells infected with wild-type virus. In both cell lines, accumulation of gI mRNA increased with time and was less affected by the transfected DNA in Vero cells than in HEp-2 cells. The relative kinetics of mRNA accumulation reflected continued synthesis and degradation of the transgene and gI mRNAs. We conclude that the role of ICP0 is to render the DNA templates introduced by transfection or infection accessible by transcriptional factors, that the two cell lines differ with respect to the transcription-ready status of entering foreign DNA in the nucleus, and that ICP0 is not
per se
the recruiter of transcriptional factors to the accessible DNA templates.
FUZZY STRICT PREFERENCE RELATIONS COMPATIBLE WITH FUZZY ORDERINGS
Authors: LLAMAZARES BONIFACIO , DE BAETS BERNARD
Published: February 2010

One of the most important issues in the field of fuzzy preference modelling is the construction of a fuzzy strict preference relation and a fuzzy indifference relation from a fuzzy weak preference relation. Here, we focus on a particular class of fuzzy weak preference relations, the so-called fuzzy orderings. The definition of a fuzzy ordering involves a fuzzy equivalence relation and, in this paper, the latter will be considered as the corresponding fuzzy indifference relation. We search for fuzzy strict preference relations compatible with a given fuzzy ordering and its fuzzy indifference relation. In many situations, depending on the t-norm and t-conorm used, this quest results in a unique fuzzy strict preference relation. Our aim is to characterize these fuzzy strict preference relations and to study their transitivity.
LIPSCHITZ CONTINUITY OF DISCRETE UNIVERSAL INTEGRALS BASED ON COPULAS
Authors: KLEMENT ERICH PETER , KOLESÁROVÁ ANNA , MESIAR RADKO , STUPŇANOVÁ ANDREA
Published: February 2010

The stability of discrete universal integrals based on copulas is discussed and examined, both with respect to the norms L1 (Lipschitz stability) and L∞ (Chebyshev stability). Each of these integrals is shown to be 1-Lipschitz. Exactly the discrete universal integrals based on a copula which is stochastically increasing in its first coordinate turn out to be 1-Chebyshev. A new characterization of stochastically increasing Archimedean copulas is also given.
INTERVAL METHODS IN KNOWLEDGE REPRESENTATION
Authors: Kreinovich Vladik
Published: February 2010

This section is maintained by Vladik Kreinovich. Please send your abstracts (or copies of papers that you want to see reviewed here) to vladik@utep.edu, or by regular mail to: Vladik Kreinovich, Department of Computer Science, University of Texas at El Paso, El Paso, TX 79968, USA.
Blebbistatin, a myosin II inhibitor, suppresses contraction and disrupts contractile filaments organization of skinned taenia cecum from guinea pig
Authors: Watanabe Masaru , Yumoto Masatoshi , Tanaka Hideyuki , Wang Hon Hui , Katayama Takeshi , Yoshiyama Shinji , Black Jason , Thatcher Sean E. , Kohama Kazuhiro
Published: February 2010

To explore the precise mechanisms of the inhibitory effects of blebbistatin, a potent inhibitor of myosin II, on smooth muscle contraction, we studied the blebbistatin effects on the mechanical properties and the structure of contractile filaments of skinned (cell membrane permeabilized) preparations from guinea pig taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca2+-induced tension development at any given Ca2+ concentration but had little effects on the Ca2+-induced myosin light chain phosphorylation. Blebbistatin also suppressed the 10 and 2.75 mM Mg2+-induced, “myosin light chain phosphorylation-independent” tension development at more than 10 μM. Furthermore, blebbistatin induced conformational change of smooth muscle myosin (SMM) and disrupted arrangement of SMM and thin filaments, resulting in inhibition of actin-SMM interaction irrespective of activation with Ca2+. In addition, blebbistatin partially inhibited Mg2+-ATPase activity of native actomyosin from guinea pig taenia cecum at around 10 μM. These results suggested that blebbistatin suppressed skinned smooth muscle contraction through disruption of structure of SMM by the agent.
The switch of intestinal Slc26 exchangers from anion absorptive to HCO3− secretory mode is dependent on CFTR anion channel function
Authors: Singh Anurag Kumar , Riederer Brigitte , Chen Mingmin , Xiao Fang , Krabbenhöft Anja , Engelhardt Regina , Nylander Olof , Soleimani Manoocher , Seidler Ursula
Published: February 2010

CFTR has been recognized to function as both an anion channel and a key regulator of Slc26 anion transporters in heterologous expression systems. Whether this regulatory relationship between CFTR and Slc26 transporters is seen in native intestine, and whether this effect is coupled to CFTR transport function or other features of this protein, has not been studied. The duodena of anesthetized CFTR-, NHE3-, Slc26a6-, and Scl26a3-deficient mice and wild-type (WT) littermates were perfused, and duodenal bicarbonate (HCO3−) secretion (DBS) and fluid absorptive or secretory rates were measured. The selective NHE3 inhibitor S1611 or genetic ablation of NHE3 significantly reduced fluid absorptive rates and increased DBS. Slc26a6 (PAT1) or Slc26a3 (DRA) ablation reduced the S1611-induced DBS increase and reduced fluid absorptive rates, suggesting that the effect of S1611 or NHE3 ablation on HCO3− secretion may be an unmasking of Slc26a6- and Slc26a3-mediated Cl−/HCO3− exchange activity. In the absence of CFTR expression or after application of the CFTR(inh)-172, fluid absorptive rates were similar to those of WT, but S1611 induced virtually no increase in DBS, demonstrating that CFTR transport activity, and not just its presence, is required for Slc26-mediated duodenal HCO3− secretion. A functionally active CFTR is an absolute requirement for Slc26-mediated duodenal HCO3− secretion, but not for Slc26-mediated fluid absorption, in which these transporters operate in conjunction with the Na+/H+ exchanger NHE3. This suggests that Slc26a6 and Slc26a3 need proton recycling via NHE3 to operate in the Cl− absorptive mode and Cl− exit via CFTR to operate in the HCO3− secretory mode.
TRPC-mediated actin-myosin contraction is critical for BBB disruption following hypoxic stress
Authors: Hicks Kali , O'Neil Roger G. , Dubinsky William S. , Brown Rachel C.
Published: February 2010

Hypoxia-induced disruption of the blood-brain barrier (BBB) is the result of many different mechanisms, including alterations to the cytoskeleton. In this study, we identified actin-binding proteins involved in cytoskeletal dynamics with quantitative proteomics and assessed changes in subcellular localization of two proteins involved in actin polymerization [vasodilator-stimulated phosphoprotein (VASP)] and cytoskeleton-plasma membrane cross-linking (moesin). We found significant redistribution of both VASP and moesin to the cytoskeletal and membrane fractions of BBB endothelial cells after 1-h hypoxic stress. We also investigated activation of actin-myosin contraction through assessment of phosphorylated myosin light chain (pMLC) with confocal microscopy. Hypoxia caused a rapid and transient increase in pMLC. Blocking MLC phosphorylation through inhibition of myosin light chain kinase (MLCK) with ML-7 prevented hypoxia-induced BBB disruption and relocalization of the tight junction protein ZO-1. Finally, we implicate the transient receptor potential (TRP)C family of channels in mediating these events since blockade of TRPC channels and the associated calcium influx with SKF-96365 prevents hypoxia-induced permeability changes and the phosphorylation of MLC needed for actin-myosin contraction. These data suggest that hypoxic stress triggers alterations to cytoskeletal structure that contribute to BBB disruption and that calcium influx through TRPC channels contributes to these events.
Cigarette exposure induces changes in maternal vascular function in a pregnant mouse model
Authors: Gandley Robin E. , Jeyabalan Arun , Desai Ketaki , McGonigal Stacy , Rohland Jennifer , DeLoia Julie A.
Published: February 2010

Smoking is associated with multiple adverse pregnancy outcomes, including fetal growth restriction. The objective of this study was to determine whether cigarette smoke exposure during pregnancy in a mouse model affects the functional properties of maternal uterine, mesenteric, and renal arteries as a possible mechanism for growth restriction. C57Bl/CJ mice were exposed to whole body sidestream smoke for 4 h/day. Smoke particle exposure was increased from day 4 of gestation until late pregnancy ( day 16–19), with mean total suspended particle levels of 63 mg/m3, representative of moderate-to-heavy smoking in humans. Uterine, mesenteric, and renal arteries from late-pregnant and virgin mice were isolated and studied in a pressure-arteriograph system ( n = 23). Plasma cotinine was measured by ELISA. Fetal weights were significantly reduced in smoke-exposed compared with control fetuses (0.88 ± 0.1 vs. 1.0 ± 0.08 g, P < 0.02), while litter sizes were not different. Endothelium-mediated relaxation responses to methacholine were significantly impaired in both the uterine and mesenteric vasculature of pregnant mice exposed to cigarette smoke during gestation. This difference was not apparent in isolated renal arteries from pregnant mice exposed to cigarette smoke; however, relaxation was significantly reduced in renal arteries from smoke-exposed virgin mice. In conclusion, we found that passive cigarette smoke exposure is associated with impaired vascular relaxation of uterine and mesenteric arteries in pregnant mice. Functional maternal vascular perturbations during pregnancy, specifically impaired peripheral and uterine vasodilation, may contribute to a mechanism by which smoking results in fetal growth restriction.
Reduction in synaptic GABA release contributes to target-selective elevation of PVN neuronal activity in rats with myocardial infarction
Authors: Han Tae Hee , Lee Kiho , Park Jin Bong , Ahn Dongchoon , Park Jae-Hyeong , Kim Dae-Yong , Stern Javier E. , Lee So Yeong , Ryu Pan Dong
Published: February 2010

Neuronal activity in the paraventricular nucleus (PVN) is known to be elevated in rats with heart failure. However, the type of neurons involved and the underlying synaptic mechanisms remain unknown. Here we examined spontaneous firing activity and synaptic currents in presympathetic PVN neurons in rats with myocardial infarction (MI), using slice patch clamp combined with the retrograde labeling technique. In PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM), MI induced a significant increase in basal firing rate (1.79 to 3.02 Hz, P < 0.05) and a reduction in the frequency of spontaneous ( P < 0.05) and miniature ( P < 0.01) inhibitory postsynaptic currents (IPSCs). In addition, MI induced an increase in the paired-pulse ratio of evoked IPSCs ( P < 0.05). Bicuculline, a GABAA receptor antagonist, increased the firing rate of PVN-RVLM neurons in sham-operated (1.21 to 2.74 Hz, P < 0.05) but not MI ( P > 0.05) rats. In contrast, in PVN neurons projecting to the intermediolateral horn of the spinal cord (PVN-IML), MI did not induce any significant changes in the basal firing rate and the properties of spontaneous and miniature IPSCs. The properties of spontaneous excitatory postsynaptic currents (EPSCs) were not altered in either neuron group. In conclusion, our results indicate that MI induces an elevation of firing activity in PVN-RVLM but not in PVN-IML neurons and that the elevated firing rate is largely due to a decrease in GABA release. These results provide evidence for a novel target-selective synaptic plasticity in the PVN that is associated with the sympathetic hyperactivity commonly seen in heart failure.
Reactive oxygen species differently regulate renal tubular epithelial and interstitial cell proliferation after ischemia and reperfusion injury
Authors: Kim Jinu , Jung Kyong-Jin , Park Kwon Moo
Published: February 2010

Reactive oxygen species (ROS) function as an inducer of cell death and survival or proliferative factor, in a cell-type-specific and concentration-dependent manner. All of these roles are critical to ischemia-induced renal functional impairment and progressive fibrotic changes in the kidney. In an effort to define the role of ROS in the proliferation of tubular epithelial cells and of interstitial cells in kidneys recovering after ischemia and reperfusion (I/R) injury, experimental mice were subjected to 30 min of bilateral kidney ischemia and administered with manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP), a superoxide dismutase mimetic, from 2 to 15 days after I/R for 14 days daily (earlier and longer) and from 8 to 15 days after I/R for 8 days daily (later and shorter). Cell proliferation was assessed via 5′-bromo-2′-deoxyuridine (BrdU) incorporation assays for 20 h before the harvest of kidneys. After I/R, the numbers of BrdU-incorporating cells increased both in the tubules and interstitium. MnTMPyP administration was shown to accelerate the proliferation of tubular epithelial cells, presenting tubule-specific marker proteins along tubular segments, whereas it attenuated the proliferation of interstitial cells, evidencing α-smooth muscle actin, fibroblast-specific protein-1, F4/80, and NADPH oxidase-2 proteins; these results indicated that ROS attenuates tubular cell regeneration, but accelerates interstitial cell proliferation. Earlier and longer MnTMPyP treatment more effectively inhibited tissue superoxide formation, the increment of interstitial cells, and the decrement of epithelial cells compared with later and shorter treatment. After I/R, apoptotic cells appeared principally in the tubular epithelial cells, but not in the interstitial cells, thereby indicating that ROS is harmful in tubule cells, but is not in interstitial cells. In conclusion, ROS generated after I/R injury in cell proliferation and death performs a cell-type-specific and concentration-dependent role, even within the same tissues, and timely intervention of ROS is crucial for effective therapies.
Exercise and the metabolic syndrome with weight regain
Authors: Thomas Tom R. , Warner Shana O. , Dellsperger Kevin C. , Hinton Pamela S. , Whaley-Connell Adam T. , Rector R. Scott , Liu Ying , Linden Melissa A. , Chockalingam Anand , Thyfault John P. , Huyette David R. , Wang Ze , Cox Richard H.
Published: February 2010

Weight loss improves metabolic syndrome (MetS) factors, but risk may return with weight regain. This study was designed to determine if exercise training can maintain improvements in MetS risk factors during weight regain. In a randomized control trial,102 overweight or obese (body mass index 25.0–39.9 kg/m2) men and women (age 21–52 yr), with characteristics of the MetS, lost 10% of body weight with supervised walking/jogging at 60% of maximal oxygen consumption (V̇o2max) (−400 kcal/session), 5 days/wk, and caloric restriction (−600 kcal/day) over a 4- to 6-mo period. After weight loss, 77 remaining subjects underwent programmed weight regain (+50% of lost weight) for 4–6 mo with random assignment to two groups: no exercise (NoEX) or continued supervised exercise (EX). Blood pressure, regional fat, glucose homeostasis, lipids, and inflammatory markers were assessed at baseline, post-weight loss, and post-weight regain. Groups were compared by two-way repeated-measures ANOVA on the 67 subjects. After weight loss (9.7 ± 0.2% of body weight), significant ( P < 0.05) improvements were observed in almost all parameters assessed. Following weight regain (54.4 ± 1.6% of lost weight), the NoEX group exhibited deterioration in most metabolic markers, while the EX group maintained improvements in V̇o2max, blood pressures, glucose homeostasis, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), oxidized LDL, and other markers of inflammation, but did not maintain improvements in triglyceride and cholesterol concentrations or abdominal fat. Results of this design of controlled human weight regain suggest that aerobic exercise can counter the detrimental effects of partial weight regain on many markers of disease risk.
Roles of Narrow- and Broad-Spiking Dorsal Premotor Area Neurons in Reach Target Selection and Movement Production
Authors: Song Joo-Hyun , McPeek Robert M.
Published: February 2010

Most visual scenes are complex and crowded, with several different objects competing for attention and action. Thus a complete understanding of the production of goal-directed actions must incorporate the higher-level process of target selection. To examine the neural substrates of target selection for visually guided reaching, we recorded the activity of isolated neurons in the dorsal premotor area (PMd) of monkeys performing a reaction-time visual search task. In this task, monkeys reached to an odd-colored target presented with three distractors. We found that PMd neurons typically discriminate the target before movement onset, ∼150–200 ms after the appearance of the search array. In one subset of neurons, discrimination occurred at a consistent time after search array onset regardless of when the reaching movement occurred, suggesting that these neurons are involved in target selection. In a second group of neurons, discrimination time depended on reach reaction time, consistent with involvement in movement production but not in target selection. To look for physiological corroboration of these two functionally defined groups, we analyzed the extracellular spike waveforms of recorded neurons. This analysis showed a population of neurons with narrow action potentials that carried signals related to target selection. A second population with broader action potentials was more heterogeneous, with some neurons showing activity related to target selection and others showing only movement production activity. These results suggest that PMd contains signals related to target selection and movement execution and that different signals are carried by distinct neural subpopulations.
Differences in Movement Mechanics, Electromyographic, and Motor Cortex Activity Between Accurate and Nonaccurate Stepping
Authors: Beloozerova Irina N. , Farrell Bradley J. , Sirota Mikhail G. , Prilutsky Boris I.
Published: February 2010

What are the differences in mechanics, muscle, and motor cortex activity between accurate and nonaccurate movements? We addressed this question in relation to walking. We assessed full-body mechanics (229 variables), activity of 8 limb muscles, and activity of 63 neurons from the motor cortex forelimb representation during well-trained locomotion with different demands on the accuracy of paw placement in cats: during locomotion on a continuous surface and along horizontal ladders with crosspieces of different widths. We found that with increasing accuracy demands, cats assumed a more bent-forward posture (by lowering the center of mass, rotating the neck and head down, and by increasing flexion of the distal joints) and stepped on the support surface with less spatial variability. On the ladder, the wrist flexion moment was lower throughout stance, whereas ankle and knee extension moments were higher and hip moment was lower during early stance compared with unconstrained locomotion. The horizontal velocity time histories of paws were symmetric and smooth and did not differ among the tasks. Most of the other mechanical variables also did not depend on accuracy demands. Selected distal muscles slightly enhanced their activity with increasing accuracy demands. However, in a majority of motor cortex cells, discharge rate means, peaks, and depths of stride-related frequency modulation changed dramatically during accurate stepping as compared with simple walking. In addition, in 30% of neurons periods of stride-related elevation in firing became shorter and in 20–25% of neurons activity or depth of frequency modulation increased, albeit not linearly, with increasing accuracy demands. Considering the relatively small changes in locomotor mechanics and substantial changes in motor cortex activity with increasing accuracy demands, we conclude that during practiced accurate stepping the activity of motor cortex reflects other processes, likely those that involve integration of visual information with ongoing locomotion.
Mechanism for the Universal Pattern of Activity in Developing Neuronal Networks
Authors: Tabak Joël , Mascagni Michael , Bertram Richard
Published: February 2010

Spontaneous episodic activity is a fundamental mode of operation of developing networks. Surprisingly, the duration of an episode of activity correlates with the length of the silent interval that precedes it, but not with the interval that follows. Here we use a modeling approach to explain this characteristic, but thus far unexplained, feature of developing networks. Because the correlation pattern is observed in networks with different structures and components, a satisfactory model needs to generate the right pattern of activity regardless of the details of network architecture or individual cell properties. We thus developed simple models incorporating excitatory coupling between heterogeneous neurons and activity-dependent synaptic depression. These models robustly generated episodic activity with the correct correlation pattern. The correlation pattern resulted from episodes being triggered at random levels of recovery from depression while they terminated around the same level of depression. To explain this fundamental difference between episode onset and termination, we used a mean field model, where only average activity and average level of recovery from synaptic depression are considered. In this model, episode onset is highly sensitive to inputs. Thus noise resulting from random coincidences in the spike times of individual neurons led to the high variability at episode onset and to the observed correlation pattern. This work further shows that networks with widely different architectures, different cell types, and different functions all operate according to the same general mechanism early in their development.
Directional Coupling From the Olfactory Bulb to the Hippocampus During a Go/No-Go Odor Discrimination Task
Authors: Gourévitch Boris , Kay Leslie M. , Martin Claire
Published: February 2010

The hippocampus and olfactory regions are anatomically close, and both play a major role in memory formation. However, the way they interact during odor processing is still unclear. In both areas, strong oscillations of the local field potential (LFP) can be recorded, and are modulated by behavior. In particular, in the olfactory system, the beta rhythm (15–35 Hz) is associated with cognitive processing of an olfactory stimulus. Using LFP recordings in the olfactory bulb and dorsal and ventral hippocampus during performance of an olfactory go/no-go task in rats, we previously showed that beta oscillations are also present in the hippocampus, coherent with those in the olfactory bulb, during odor sampling. In this study, we provide further insight into information transfer in the olfacto-hippocampal network by using directional coherence (DCOH estimate), a method based on the temporal relation between two or more signals in the frequency domain. In the theta band (6–12 Hz), coherence between the olfactory bulb (OB) and the hippocampus (HPC) is weak and can be both in the feedback and feedforward directions. However, at this frequency, modulation of the coupling between the dorsal and ventral hippocampus is seen during stimulus expectation versus odor processing. In the beta frequency band (15–35 Hz), analysis showed a strong unidirectional coupling from the OB to dorsal and ventral HPC, indicating that, during odor processing, beta oscillations in the hippocampus are driven by the olfactory bulb.
Neurons in Area 5 of the Posterior Parietal Cortex in the Cat Contribute to Interlimb Coordination During Visually Guided Locomotion: A Role in Working Memory
Authors: Lajoie Kim , Andujar Jacques-Étienne , Pearson Keir , Drew Trevor
Published: February 2010

We tested the hypothesis that area 5 of the posterior parietal cortex (PPC) contributes to interlimb coordination in locomotor tasks requiring visual guidance by recording neuronal activity in this area in three cats in two locomotor paradigms. In the first paradigm, cats were required to step over obstacles attached to a moving treadmill belt. We recorded 47 neurons that discharged in relationship to the hindlimbs. Of these, 31/47 discharged between the passage of the fore- and hindlimbs (FL-HL cells) over the obstacle. The activity of most of these neurons (25/31) was related to the fore- and hindlimb contralateral to the recording site when the contralateral forelimb was the first to pass over the obstacle. In many cells, discharge activity was limb-independent in that it was better related to the ipsilateral limbs when they were the first to step over the obstacle. The other 16/47 neurons discharged only when the hindlimbs stepped over the obstacle with the majority of these (12/16) discharging between the passage of the two hindlimbs over the obstacle. We tested 15/47 cells, including 11/47 FL-HL cells, in a second paradigm in which cats stepped over an obstacle on a walkway. Discharge activity in all of these cells was significantly modulated when the cat stepped over the obstacle and remained modified for periods of ≤1 min when forward progress of the cat was delayed with either the fore- and hindlimbs, or the two hindlimbs, straddling the obstacle. We suggest that neurons in area 5 of the PPC contribute to interlimb coordination during locomotion by estimating the spatial and temporal attributes of the obstacle with respect to the body. We further suggest that the discharge observed both during the steps over the obstacle and in the delayed locomotor paradigm is a neuronal correlate of working memory.
Head-Free Gaze Shifts Provide Further Insights Into the Role of the Medial Cerebellum in the Control of Primate Saccadic Eye Movements
Authors: Fuchs Albert F. , Brettler Sandra , Ling Leo
Published: February 2010

This study examines how signals generated in the oculomotor cerebellum could be involved in the control of gaze shifts, which rapidly redirect the eyes from one object to another. Neurons in the caudal fastigial nucleus (cFN), the output of the oculomotor cerebellum, discharged when monkeys made horizontal head-unrestrained gaze shifts, composed of an eye saccade and a head movement. Eighty-seven percent of our neurons discharged a burst of spikes for both ipsiversive and contraversive gaze shifts. In both directions, burst end was much better timed with gaze end than was burst start with gaze start, was well correlated with eye end, and was poorly correlated with head end or the time of peak head velocity. Moreover, bursts accompanied all head-unrestrained gaze shifts whether the head moved or not. Therefore we conclude that the cFN is not part of the pathway that controls head movement. For contraversive gaze shifts, the early part of the burst was correlated with gaze acceleration. Thereafter, the burst of the neuronal population continued throughout the prolonged deceleration of large gaze shifts. For a majority of neurons, gaze duration was correlated with burst duration; for some, gaze amplitude was less well correlated with the number of spikes. Therefore we suggest that the population burst provides an acceleration boost for high acceleration (smaller) contraversive gaze shifts and helps maintain the drive required to extend the deceleration of large contraversive gaze shifts. In contrast, the ipsiversive population burst, which is less well correlated with gaze metrics but whose peak rate occurs before gaze end, seems responsible primarily for terminating the gaze shift.
A Unified Approach to High‐Gain Adaptive Controllers
Authors: Gravagne Ian A. , Davis John M. , DaCunha Jeffrey J.
Published: February 2010

It has been known for some time that proportional output feedback will stabilize MIMO, minimum‐phase, linear time‐invariant systems if the feedback gain is sufficiently large. High‐gain adaptive controllers achieve stability by automatically driving up the feedback gain monotonically. More recently, it was demonstrated that sample‐and‐hold implementations of the high‐gain adaptive controller also require adaptation of the sampling rate. In this paper, we use recent advances in the mathematical field of dynamic equations on time scales to unify and generalize the discrete and continuous versions of the high‐gain adaptive controller. We prove the stability of high‐gain adaptive controllers on a wide class of time scales.
Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women
Authors: Van Dyke Alison L. , Cote Michele L. , Wenzlaff Angela S. , Abrams Judith , Land Susan , Iyer Priyanka , Schwartz Ann G.
Published: February 2010

In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. TwoTERTregion SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, andTERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20GHRpolymorphisms andSEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance ofGHRamong Caucasians and identifiedAMACR, TERT, andGHRamong African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes inTERTandGHRassociated with NSCLC risk were identified. The roles ofTERT, GHR, AMACRandSEPP1genes in lung carcinogenesis warrant further exploration.
On Semicompact Sets and Associated Properties
Authors: Sarsak Mohammad S.
Published: February 2010

We continue the study of semicompact sets in a topological space. Several
properties, mapping properties of semicompact sets are studied.
A special interest to SCS spaces is given, where a space X is SCS if
every subset of X which is semicompact in X is semiclosed; we study
several properties of such spaces, it is mainly shown that a semi‐T2 semicompact space is SCS if and only if it is extremally disconnected.
It is also shown that in an os‐regular space X if every point has an SCS neighborhood, then X is SCS.
Synthesis of Carbon Nanotubes and Nanofibers on Silica and Cement Matrix Materials
Authors: Mudimela Prasantha R. , Nasibulina Larisa I. , Nasibulin Albert G. , Cwirzen Andrzej , Valkeapää Markus , Habermehl-Cwirzen Karin , Malm Jari E. M. , Karppinen Maarit J. , Penttala Vesa , Koltsova Tatiana S. , Tolochko Oleg V. , Kauppinen Esko I.
Published: February 2010

In order to create strong composite materials, a good dispersion of carbon nanotubes (CNTs) and nanofibers (CNFs) in a matrix material must be obtained. We proposed a simple method of growing the desirable carbon nanomaterial directly on the surface of matrix particles. CNTs and CNFs were synthesised on the surface of model object, silica fume particles impregnated by iron salt, and directly on pristine cement particles, naturally containing iron oxide. Acetylene was successfully utilised as a carbon source in the temperature range from 550 to 750∘C. 5–10 walled CNTs with diameters of 10–15 nm at 600∘C and 12–20 nm at 750∘C were synthesised on silica particles. In case of cement particles, mainly CNFs with a diameter of around 30 nm were grown. It was shown that high temperatures caused chemical and physical transformation of cement particles.
Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study
Authors: Antoniou Katerina M. , Soufla Giannoula , Proklou Athanasia , Margaritopoulos George , Choulaki Christiana , Lymbouridou Rena , Samara Katerina D. , Spandidos Demetrios A. , Siafakas Nikolaos M.
Published: February 2010

Background. We have previously shown a different local and systemic angiogenic profile of CXC chemokines in Idiopathic Pulmonary Fibrosis (IPF) patients compared to sarcoidosis. In particular, sarcoidosis showed an angiostatic microenvironment, as compared with the angiogenic cytokine milieu seen in IPF.Purpose of the Study. Our aim was to further investigate the aforementioned finding by measuring the expression of different chemokines in granulomatous and fibrotic diseases. We estimated the levels of vascular endothelial growth factor (VEGF) and its high-affinity receptor, Flt-1 (fms-like tyrosine kinase 1), in bronchoalveolar lavage fluid (BALF) of patients with IPF and pulmonary sarcoidosis. We have also investigated the mRNA expression of angiogenetic chemokines' receptors such as CXCR2 and CXCR3 and the biological axis of stromal derived factor-1 (SDF-1 or CXCL12/CXCL12) and receptor, CXCR4.Methods. We studied prospectively three groups of patients: (i) one group of 18 patients with IPF, (ii) one group of 16 patients with sarcoidosis, and (iii) 10 normal subjects.Results. A statistically significant increase has been detected in VEGF mRNA expression in IPF in comparison with pulmonary sarcoidosis . In addition, a significant increase has been measured in CXCL12 in sarcoidosis in comparison to IPF . Moreover, a statistically significant decrease has been found in Flt-1 protein levels in pulmonary sarcoidosis in comparison with IPF . A significant increase in VEGF and CXCR4 mRNA levels has been also detected in sarcoidosis' patients when compared with healthy controls.Conclusions. Our data suggest that increased expression of Flt-1 and downregulation of CXCL12 in IPF may further support the hypothesis of a different angiogenetic profile between fibrotic and granulomatous diseases. However, further studies are needed in order to better investigate these enigmatic diseases.