Altered Purkinje cell responses and calmodulin expression in the spontaneously ataxic mouse, Pogo

Lee, Kwan Young,Kim, Jin Seong,Kim, Se Hoon,Park, Hyung Seo,Jeong, Young‐,Gil,Lee, Nam‐,Seob,Kim, Dong Kwan Blackwell Publishing Ltd 2011 The European journal of neuroscience Vol.33 No.8

<P><B>Abstract</B></P><P>Ataxia is often associated with altered cerebellar motor control, a process in which Purkinje cells (PCs) play a principal role. Pogo mice display severe motor deficits characterized by an ataxic gait accompanying hindlimb hyperextension. Here, using whole‐cell patch‐clamp recordings, we show that parallel fiber (PF)‐excitatory post‐synaptic currents (PF‐EPSCs) are reduced, paired‐pulse facilitation (PPF) is increased and PF‐PC long‐term depression (LTD) is impaired in Pogo mice; in contrast, climbing‐fiber EPSCs are preserved. In control mice, treatment with the calmodulin antagonist calmidazolium (5 μ<SMALL>m</SMALL>) impaired PPF and LTD. Notably, cerebellar calmodulin expression was significantly reduced in Pogo mice compared with control mice. Control PCs predominantly exhibited a tonic firing pattern, whereas the firing pattern in Pogo PCs was mainly a complex burst type. These results implicate alterations in PC responses and calmodulin content in the abnormal cerebellar function of Pogo mice.</P>

Probing the nature of high‐<i>z</i> short GRB 090426 with its early optical and X‐ray afterglows

Xin, Li‐,Ping,Liang, En‐,Wei,Wei, Jian‐,Yan,Zhang, Bing,Lv, Hou‐,Jun,Zheng, Wei‐,Kang,Urata, Yuji,Im, Myungshin,Wang, Jing,Qiu, Yu‐,Lei,Deng, Jin‐,Song,Huang, Blackwell Publishing Ltd 2011 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.410 No.1

<P><B>ABSTRACT</B></P><P>GRB 090426 is a short‐duration burst detected by <I>Swift</I> (<IMG src='/wiley-blackwell_img/equation/MNR_17419_mu1.gif' alt ='inline image'/> s in the observer frame and <IMG src='/wiley-blackwell_img/equation/MNR_17419_mu2.gif' alt ='inline image'/> s in the burst frame at <I>z</I>= 2.609). Its host galaxy properties and some gamma‐ray‐related correlations are analogous to those seen in long‐duration gamma‐ray bursts (GRBs), which are believed to be of a massive star origin (so‐called Type II GRBs). We present the results of its early optical observations with the 0.8‐m Tsinghua University–National Astronomical Observatory of China Telescope (TNT) at Xinglong Observatory and the 1‐m LOAO telescope at Mt Lemmon Optical Astronomy Observatory in Arizona. Our well‐sampled optical afterglow light curve covers from <IMG src='/wiley-blackwell_img/equation/MNR_17419_mu3.gif' alt ='inline image'/> to 10<SUP>4</SUP> s after the GRB trigger. It shows two shallow decay episodes that are likely due to energy injection, which end at <IMG src='/wiley-blackwell_img/equation/MNR_17419_mu4.gif' alt ='inline image'/> and 7100 s, respectively. The decay slopes after the injection phases are consistent with each other (<IMG src='/wiley-blackwell_img/equation/MNR_17419_mu5.gif' alt ='inline image'/>). The X‐ray afterglow light curve appears to trace the optical, although the second energy‐injection phase was missed due to visibility constraints introduced by the <I>Swift</I> orbit. The X‐ray spectral index is <IMG src='/wiley-blackwell_img/equation/MNR_17419_mu6.gif' alt ='inline image'/> without temporal evolution. Its decay slope is consistent with the prediction of the forward shock model. Both X‐ray and optical emission are consistent with being in the same spectral regime above the cooling frequency (<IMG src='/wiley-blackwell_img/equation/MNR_17419_mu7.gif' alt ='inline image'/>). The fact that <IMG src='/wiley-blackwell_img/equation/MNR_17419_mu8.gif' alt ='inline image'/> is below the optical band from the very early epoch of the observation provides a constraint on the burst environment, which is similar to that seen in classical long‐duration GRBs. We therefore suggest that death of a massive star is the possible progenitor of this short burst.</P>

Rescue of epithelial HCO₃⁻ secretion in murine intestine by apical membrane expression of the cystic fibrosis transmembrane conductance regulator mutant F508del

Xiao, Fang,Li, Junhua,Singh, Anurag Kumar,Riederer, Brigitte,Wang, Jiang,Sultan, Ayesha,Park, Henry,Lee, Min Goo,Lamprecht, Georg,Scholte, Bob J.,De Jonge, Hugo R.,Seidler, Ursula Blackwell Publishing Ltd 2012 The Journal of physiology Vol.590 No.21

<P><B>Key points</B></P><P><P>Cystic fibrosis (CF) is a lethal disease characterized by low rates of epithelial Cl<SUP>−</SUP> and HCO<SUB>3</SUB><SUP>−</SUP> secretion and obstruction of the airways and gastrointestinal and reproductive organs by sticky mucus. HCO<SUB>3</SUB><SUP>−</SUP> secretion has recently been demonstrated to be necessary for mucus hydration.</P><P>The most frequent CF mutation is F508del. This mutant protein is usually degraded in the proteasome. New therapeutic strategies have been developed which deliver F508del to the plasma membrane.</P><P>Utilizing transgenic F508del mutant and cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice, apical membrane expression of F508del protein was found to be associated with enhanced stimulation of intestinal HCO<SUB>3</SUB><SUP>−</SUP> secretion.</P><P>The predominant molecular mechanism for enhanced F508del HCO<SUB>3</SUB><SUP>−</SUP> stimulation appeared to be the activation of a Cl<SUP>−</SUP> recycling pathway, with Cl<SUP>−</SUP> exit via membrane‐resident F508del protein and Cl<SUP>−</SUP> entry in exchange for HCO<SUB>3</SUB><SUP>−</SUP> by apical Cl<SUP>−</SUP>/HCO<SUB>3</SUB><SUP>−</SUP> exchange. In contrast, the predominant molecular mechanism for cAMP‐activated HCO<SUB>3</SUB><SUP>−</SUP> secretion in WT intestine appears to be HCO<SUB>3</SUB><SUP>−</SUP> exit via CFTR itself.</P></P><P><B>Abstract </B> This study investigated whether expression of the common cystic fibrosis transmembrane conductance regulator (CFTR) mutant F508del in the apical membrane of enterocytes confers increased bicarbonate secretory capacity on the intestinal epithelium of F508del mutant mice compared to that of CFTR knockout (KO) mice. CFTR KO mice, F508del mutant mice (F508del) and wild‐type (WT) littermates were bred on the FVB/N background. F508del isolated brush border membrane (BBM) contained approximately 5–10% fully glycosylated band C protein compared to WT BBM. Similarly, the forskolin (FSK)‐induced, CFTR‐dependent short‐circuit current (Δ<I>I</I><SUB>sc</SUB>) of F508del mucosa was approximately 5–10% of WT, whereas the HCO<SUB>3</SUB><SUP>−</SUP> secretory response (<IMG src='/wiley-blackwell_img/equation/TJP_5291_mu1.gif' alt ='inline image'/>) was almost half that of WT in both duodenum and mid‐colon studied <I>in vitro</I> and <I>in vivo.</I> While WT intestine retained full FSK‐induced <IMG src='/wiley-blackwell_img/equation/TJP_5291_mu2.gif' alt ='inline image'/> in the absence of luminal Cl<SUP>−</SUP>, the markedly higher <IMG src='/wiley-blackwell_img/equation/TJP_5291_mu3.gif' alt ='inline image'/> than Δ<I>I</I><SUB>sc</SUB> in F508del intestine was dependent on the presence of luminal Cl<SUP>−</SUP>, and was blocked by CFTR inhibitors. The Ste20‐related proline–alanine‐rich kinases (SPAK/OSR1), which are downstream of the with‐no‐lysine (K) protein kinases (WNK), were rapidly phosphorylated by FSK in WT and F508del, but significantly more slowly in CFTR KO intestine. In conclusion, the data demonstrate that low levels of F508del membrane expression in the intestine of F508del mice significantly increased FSK‐induced HCO<SUB>3</SUB><SUP>−</SUP> secretion mediated by Cl<SUP>−</SUP>/HCO<SUB>3</SUB><SUP>−</SUP> exchange. However, in WT mucosa FSK elicited strong SPAK/OSR1 phosphorylation and Cl<SUP>−</SUP>‐independent HCO<SUB>3</SUB><SUP>−</SUP> efflux. This suggests that therapeutic strategies which deliver F508del to the apical membrane have the potential to significantly enhance epithelial HCO<SUB>3</SUB><SUP>−</SUP> secretion.</P>

CaFe interstellar clouds^★

Bondar, A.,Kozak, M.,Gnaciń,ski, P.,Galazutdinov, G. A.,Beletsky, Y.,Krełowski, J. Blackwell Publishing Ltd 2007 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.378 No.3

<P>ABSTRACT</P><P>A new kind of interstellar cloud is proposed. These are rare (just a few examples among ∼300 lines of sight) objects with the Ca <SMALL>I</SMALL> 4227-Å, Fe <SMALL>I</SMALL> 3720-Å and 3860-Å lines stronger than those of K <SMALL>I</SMALL> (near 7699 Å) and Na <SMALL>I</SMALL> (near 3302 Å). We propose the name ‘CaFe’ for these clouds. Apparently they occupy different volumes from the well-known interstellar H <SMALL>I</SMALL> clouds where the K <SMALL>I</SMALL> and ultraviolet Na <SMALL>I</SMALL> lines are dominant features. In the CaFe clouds we have not found either detectable molecular features (CH, CN) or diffuse interstellar bands which, as commonly believed, are carried by some complex, organic molecules. We have found the CaFe clouds only along sightlines toward hot, luminous (and thus distant) objects with high rates of mass loss. In principle, the observed gas-phase interstellar abundances reflect the combined effects of the nucleosynthetic history of the material, the depletion of heavy elements into dust grains and the ionization state of these elements which may depend on irradiation by neighbouring stars.</P>

Nerve growth factor and expression of its receptors in patients with diabetic neuropathy

Kim, H. C.,Cho, Y. J.,Ahn, C. W.,Park, K. S.,Kim, J. C.,Nam, J. S.,Im, Y. S.,Lee, J. E.,Lee, S. C.,Lee, H. K. Blackwell Publishing Ltd 2009 Diabetic medicine Vol.26 No.12

<P><B>Abstract</B></P><P><B>Aims </B> Low serum nerve growth factor (NGF) levels have been reported in patients with diabetic peripheral neuropathy (DPN), but the role of NGF in the development of neuropathy is unclear. Thus, we investigated the associations of serum NGF level and NGF receptor activity with the presence and severity of DPN.</P><P><B>Methods </B> One hundred and thirty‐six patients with Type 2 diabetes were included in this cross‐sectional study. Serum NGF levels were measured by ELISA. Expressions of NGF receptors (TrkA and p75<SUP>NTR</SUP>) were measured by immunohistochemical staining. The presence and severity of DPN were assessed by neuropathy disability score (NDS) and by corneal nerve fibre length (cNFL) and nerve branch density (cNBD) using <I>in vivo</I> confocal microscopy.</P><P><B>Results </B> Patients with DPN had higher serum NGF levels (56–451 pg/ml) than patients without DPN (4–54 pg/ml). However, in DPN patients, serum NGF was negatively associated with neuropathy severity (mild 222 ± 64 pg/ml; moderate 114 ± 17 pg/ml; severe 89 ± 20 pg/ml). This negative association was consistent in all severity indices (NDS, <I>P</I> < 0.001; cNFL, <I>P</I> < 0.001; cNBD <I>P</I> = 0.010) even after adjustment for age, sex, diabetes duration, insulin use, fasting glucose and glycated haemoglobin. Although NGF receptor activities had significantly (<I>P</I> < 0.05) negative associations with the presence and severity of neuropathy, these associations were not significant when adjusted for other factors.</P><P><B>Conclusions </B> Serum NGF level was positively associated with the presence of DPN but negatively associated with neuropathy severity in DPN patients. The change in serum NGF might be a consequence of, rather than a contributor to, the early development of DPN.</P><!--<abstractinfo format='display'>Diabet. Med. 26, 1228–1234 (2009)</abstractinfo>-->

Enumeration, isolation and identification of diazotrophs from Korean wetland rice varieties grown with long-term application of N and compost and their short-term inoculation effect on rice plants

Muthukumarasamy, R.,Kang, U.G.,Park, K.D.,Jeon, W.-T.,Park, C.Y.,Cho, Y.S.,Kwon, S.-W.,Song, J.,Roh, D.-H.,Revathi, G. Blackwell Publishing Ltd 2007 Journal of applied microbiology Vol.102 No.4

<P>Abstract</P><P>Aim: </P><P>This study has been aimed (i) to isolate and identify diazotrophs from Korean rice varieties; (ii) to examine the long-term effect of N and compost on the population dynamics of diazotrophs and (iii) to realize the shot-term inoculation effect of these diazotrophs on rice seedlings.</P><P>Methods and Results: </P><P>Diazotrophic and heterotrophic bacterial numbers were enumerated by most probable number method and the isolates were identified based on morphological, physiological, biochemical and 16s rDNA sequence analysis. Long-term application of fertilizer N with compost enhanced both these numbers in rice plants and its environment. Bacteria were high in numbers when malate and azelaic acids were used as carbon source, but less when sucrose was used as a carbon substrate. The combined application promoted the association of diazotrophic bacteria like <I>Azospirillum</I> spp., <I>Herbaspirillum</I> spp., <I>Burkholderia</I> spp., <I>Gluconacetobacter diazotrophicus</I> and <I>Pseudomonas</I> spp. in wetland rice plants. Detection of <I>nif</I>D genes from different diazotrophic isolates indicated their nitrogen fixing ability. Inoculation of a representative isolate from each group onto rice seedlings of the variety IR 36 grown in test tubes indicated the positive effect of these diazotrophs on the growth of rice seedlings though the percentage of N present in the plants did not differ much.</P><P>Conclusions: </P><P>Application of compost with fertilizer N promoted the diazotrophic and heterotrophic bacterial numbers and their association with wetland rice and its environment. Compost application in high N fertilized fields would avert the reduction of N<SUB>2</SUB>-fixing bacterial numbers and their association was beneficial to the growth of rice plants.</P><P>Significance and Impact of the Study: </P><P>The inhibitory effect of high N fertilization on diazotrophic bacterial numbers could be reduced by the application of compost and this observation would encourage more usage of organic manure. This study has also thrown light on the wider geographic distribution of <I>G. diazotrophicus</I> with wetland rice in temperate region where sugarcane (from which this bacterium was first reported to be associating and thereon from other plant species) is not cultivated.</P>

Perianal Crohn's disease with a clenched fist–like appearance

Kim, B-S,Kim, H-S,Kim, M-B,Oh, C-K,Kwon, K-S Blackwell Publishing Ltd 2009 Journal of the European Academy of Dermatology and Vol.23 No.10

Phosphodiesterase inhibition by naloxone augments the inotropic actions of β-adrenergic stimulation

PARK, W. K.,CHANG, C. H.,CHAE, J. E.,KIM, M. H.,CHO, Y. L.,AHN, D. S. Blackwell Publishing Ltd 2009 Acta anaesthesiologica Scandinavica Vol.53 No.8

<P>Background</P><P>In a shock state, naloxone generates the cardiovascular pressor effect by displacing the endogenous opiate-like peptide β-endorphin, resulting in restoration of the normal response to catecholamines. In addition to this opioid antagonistic effect, the non-opiate receptor-mediated effect has also been proposed. The aim of this study was to define the mechanism of non-opiate receptor-mediated action of naloxone.</P><P>Methods</P><P>In guinea-pig ventricular tissues, cumulative concentration–response curves for isoproterenol as well as for forskolin and 3-isobutylmethylxanthine (IBMX) were obtained by increasing the concentration stepwise. To assess the effect on the phosphodiesterase (PDE), the effects of naloxone on contractile forces induced by isoproterenol (0.05 μM) in the presence of IBMX, cilostamide (a PDE III inhibitor), or rolipram (a PDE IV inhibitor) were observed. Naloxone-induced changes in cAMP production by isoproterenol both in the absence and in the presence of IBMX were measured. Naloxone-induced changes in cAMP production by forskolin in the presence of IBMX were also measured.</P><P>Results</P><P>Naloxone (30 μM) produced a leftward shift of the isoproterenol concentration–response curve (0.01–2 μM) without changing the maximal response. Forskolin (0.5–10 μM) produced a concentration-dependent increase in contractile forces. Naloxone increased the maximal inotropic response of forskolin. Naloxone showed no effect on the IBMX concentration–response curve. In the presence of IBMX (200 μM), naloxone did not alter the contractions evoked by isoproterenol or forskolin. Whereas naloxone increased contractile forces significantly (approximately 25%) more than that of isoproterenol in the presence of rolipram, no alteration of contractile forces in the cilostamide-incubated muscles was observed. Naloxone caused a concentration-related increase of cAMP in the absence of IBMX, but caused no change in its presence.</P><P>Conclusions</P><P>The enhancement of myocardial contractility by naloxone in the presence of stimulation of adenylyl cyclase activity appears to be mediated by inhibition of PDE, specifically PDE III.</P>

Cytokeratin-positive interstitial reticulum cell sarcoma: a case report with cytological, immunohistochemical, and ultrastructural findings

Kwon, J. E.,Yang, W-I.,Kim, H. K.,Kwon, K. W.,Kwon, T. J.,Choi, E. C.,Lee, K. G. Blackwell Publishing Ltd 2009 Cytopathology Vol.20 No.3

Effect of plastic anisotropy of weld on limit load of undermatched middle cracked tension specimens

ALEXANDROV, S.,CHUNG, K.-H.,CHUNG, K. Blackwell Publishing Ltd 2007 Fatigue & Fracture of Engineering Materials and St Vol.30 No.4

<P>ABSTRACT</P><P>Plastic anisotropy may have a significant effect on the limit load of structures. The present paper shows its effect on the limit load of well-undermatched middle cracked tension specimens assuming that the base material is elastic and the weld material obeys Hill's quadratic orthotropic yield criterion in rigid-perfect plasticity. The solution is based on a kinematically admissible velocity field, which is compatible with a stress field satisfying the equilibrium equations and the yield criterion in the plastic zone. The velocity field is singular in the vicinity of the bi-material interface, which is typical for isotropic materials.</P>