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>

Applying an activity system to online collaborative group work analysis

Choi, Hyungshin,Kang, Myunghee Blackwell Publishing Ltd 2010 BRITISH JOURNAL OF EDUCATIONAL TECHNOLOGY - Vol.41 No.5

<P>Abstract</P><P>This study determines whether an activity system provides a systematic framework to analyse collaborative group work. Using an activity system as a unit of analysis, the research examined learner behaviours, conflicting factors and facilitating factors while students engaged in collaborative work via asynchronous computer-mediated communication. The online postings from the two highest and lowest performing groups of students during one semester were analysed, coded and reorganised. The coded postings of these four groups were then compared using an activity system to identify the difference in patterns of learner behaviours. The conflicting and facilitating factors that students encountered were identified as well. The findings provide implications for online collaborative learning environment design and mediating strategies. The study also addresses some of the challenges in using an activity system to analyse collaborative learning activities and provides suggestions for future research.</P>

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>

Positive and negative feedback regulatory loops of thiol-oxidative stress response mediated by an unstable isoform of &sgr;^R in actinomycetes

Kim, Min-Sik,Hahn, Mi-Young,Cho, Yoobok,Cho, Sang-Nae,Roe, Jung-Hye Blackwell Publishing Ltd 2009 Molecular microbiology Vol.73 No.5

<P>Summary</P><P>Alternate sigma factors provide an effective way of diversifying bacterial gene expression in response to environmental changes. In <I>Streptomyces coelicolor</I> where more than 65 sigma factors are predicted, &sgr;<SUP>R</SUP> is the major regulator for response to thiol-oxidative stresses. &sgr;<SUP>R</SUP> becomes available when its bound anti-sigma factor RsrA is oxidized at sensitive cysteine thiols to form disulphide bonds. &sgr;<SUP>R</SUP> regulon includes genes for itself and multiple thiol-reducing systems, which constitute positive and negative feedback loops respectively. We found that the positive amplification loop involves an isoform of &sgr;<SUP>R</SUP> (&sgr;<SUP>R′</SUP>) with an N-terminal extension of 55 amino acids, produced from an upstream start codon. A major difference between constitutive &sgr;<SUP>R</SUP> and inducible &sgr;<SUP>R′</SUP> is that the latter is markedly unstable (<I>t</I><SUB>1/2</SUB> ∼ 10 min) compared with the former (> 70 min). The rapid turnover of &sgr;<SUP>R′</SUP> is partly due to induced ClpP1/P2 proteases from the &sgr;<SUP>R</SUP> regulon. This represents a novel way of elaborating positive and negative feedback loops in a control circuit. Similar phenomenon may occur in other actinomycetes that harbour multiple start codons in the <I>sigR</I> homologous gene. We observed that <I>sigH</I> gene, the <I>sigR</I> orthologue in <I>Mycobacterium smegmatis</I>, produces an unstable larger isoform of &sgr;<SUP>H</SUP> upon induction by thiol-oxidative stress.</P>

Non-classical exocytosis of &agr;-synuclein is sensitive to folding states and promoted under stress conditions

Jang, Ara,Lee, He-Jin,Suk, Ji-Eun,Jung, Jin-Woo,Kim, Kwang-Pyo,Lee, Seung-Jae Blackwell Publishing Ltd 2010 Journal of Neurochemistry Vol.113 No.5

<P><I>J. Neurochem.</I> (2010) <B>113</B>, 1263–1274.</P><P>Abstract</P><P>Parkinson’s disease is characterized by deposition of misfolded/aggregated &agr;-synuclein proteins in multiple regions of the brain. Neurons can release &agr;-synuclein; through this release, pathological forms of &agr;-synuclein are propagated between neurons, and also cause neuroinflammation. In this study, we demonstrate that release of &agr;-synuclein is consistently increased under various protein misfolding stress conditions in both neuroblastoma and primary neuron models. This release is mediated by a non-classical, endoplasmic reticulum (ER)/Golgi-independent exocytosis, and stress-induced release coincides with increased translocation of &agr;-synuclein into vesicles. Both vesicle translocation and secretion were blocked by attachment of a highly stable, globular protein to &agr;-synuclein, whereas forced protein misfolding resulted in an increase in both of these activities. Mass spectrometry analysis showed a higher degree of oxidative modification in secreted &agr;-synuclein than in the cellular protein. Together, these results suggest that structurally abnormal, damaged &agr;-synuclein proteins translocate preferentially into vesicles and are released from neuronal cells via exocytosis.</P>

Expression and clinicopathological significance of human growth and transformation-dependent protein (HGTD-P) in uterine cervical cancer

Cho, Young-Eun,Kim, Jee-Youn,Kim, Yong-Jun,Kim, Youn-Wha,Lee, Sun,Park, Jae-Hoon Blackwell Publishing Ltd 2010 Histopathology Vol.57 No.3

Recurrence detection in differentiated thyroid cancer patients with elevated serum level of antithyroglobulin antibody: special emphasis on using ¹⁸F-FDG PET/CT

Seo, Ji Hyoung,Lee, Sang Woo,Ahn, Byeong-Cheol,Lee, Jaetae Blackwell Publishing Ltd 2010 Clinical endocrinology Vol.72 No.4

<P>Summary</P><P>Objective </P><P>A clinical challenge is presented by differentiated thyroid cancer (DTC) patients who show increased serum antithyroglobulin antibody (TgAb) level with undetectable thyroglobulin (Tg) and negative radioiodine whole body scan (I-WBS). The aim of this study is to investigate the recurrence in DTC patients with elevated TgAb by using <SUP>18</SUP>F-FDG PET/CT (PET/CT) in addition to I-WBS and neck ultrasonography (USG).</P><P>Subjects and design </P><P>A total of 276 TgAb+ patients were enrolled. Recurrence was assessed and compared between TgAb+ and TgAb- patients. TgAb+ patients were further categorized into two groups of 35–140 U/ml (Group A) and 140 U/ml or greater (Group B), according to receiver operating characteristic (ROC) curve analysis. Tumoural status was evaluated regarding the TgAb positivity and the degree of increase of TgAb.</P><P>Results </P><P>Thirty-seven (13·4%) of 276 TgAb+ patients were finally diagnosed with recurrence, compared with 21 (13·5%) of 156 TgAb- patients (<I>P</I> = 0·987). There was a correlation between TgAb level and recurrence (<I>P</I> = 0·032). Recurrence was more common in Group B than Group A (27·8% and 9·9%, respectively, <I>P</I> = 0·001). Recurrence was found in 37·5% of 24 TgAb+/Tg- patients who showed a gradually increasing tendency in serial measurements of TgAb. Sixteen cervical foci (21·1%) missed on neck USG and 17 lesions (22·4%) located outside the neck were additionally detected with PET/CT in TgAb+ patients.</P><P>Conclusions </P><P>TgAb plays a complementary role to Tg in the detection of recurrence of DTC. Tumour recurrence was more frequent in patients with elevated TgAb level over 140 U/ml or a trend toward increasing levels. PET/CT could provide additional information to I-WBS and neck USG in detecting tumour recurrence in patients with elevated TgAb.</P>

The <i>UV</i>–optical colour dependence of galaxy clustering in the local universe

Loh, Yeong-Shang,Rich, R. Michael,Heinis, Sé,bastien,Scranton, Ryan,Mallery, Ryan P.,Salim, Samir,Martin, D. Christopher,Wyder, Ted,Arnouts, Sté,phane,Barlow, Tom A.,Forster, Karl,Friedman Blackwell Publishing Ltd 2010 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.407 No.1

<P>ABSTRACT</P><P>We measure the UV-optical colour dependence of galaxy clustering in the local Universe. Using the clean separation of the red and blue sequences made possible by the <I>NUV</I>−<I>r</I> colour–magnitude diagram, we segregate the galaxies into red, blue and intermediate ‘green’ classes. We explore the clustering as a function of this segregation by removing the dependence on luminosity and by excluding edge-on galaxies as a means of a non-model dependent veto of highly extincted galaxies. We find that ξ(<I>r</I><SUB>p</SUB>, π) for both red and green galaxies shows strong redshift-space distortion on small scales – the ‘finger-of-God’ effect, with green galaxies having a lower amplitude than is seen for the red sequence, and the blue sequence showing almost no distortion. On large scales, ξ(<I>r</I><SUB>p</SUB>, π) for all three samples show the effect of large-scale streaming from coherent infall. On scales of 1 <I>h</I><SUP>−1</SUP> Mpc < <I>r</I><SUB>p</SUB> < 10 <I>h</I><SUP>−1</SUP> Mpc, the projected auto-correlation function <I>w</I><SUB>p</SUB>(<I>r</I><SUB>p</SUB>) for red and green galaxies fits a power law with slope γ∼ 1.93 and amplitude <I>r</I><SUB>0</SUB>∼ 7.5 and 5.3, compared with γ∼ 1.75 and <I>r</I><SUB>0</SUB>∼ 3.9 <I>h</I><SUP>−1</SUP> Mpc for blue sequence galaxies. Compared to the clustering of a fiducial <I>L</I>* galaxy, the red, green and blue have a relative bias of 1.5, 1.1 and 0.9, respectively. The <I>w</I><SUB>p</SUB>(<I>r</I><SUB>p</SUB>) for blue galaxies display an increase in convexity at ∼ 1 <I>h</I><SUP>−1</SUP> Mpc, with an excess of large-scale clustering. Our results suggest that the majority of blue galaxies are likely central galaxies in less massive haloes, while red and green galaxies have larger satellite fractions, and preferentially reside in virialized structures. If blue sequence galaxies migrate to the red sequence via processes like mergers or quenching that take them through the green valley, such a transformation may be accompanied by a change in environment in addition to any change in luminosity and colour.</P>