bluuebunny/crossref_metadata_2025 huggingface dataset:
Reciprocal regulation of the primary sodium absorptive pathways in rat intestinal epithelial cells
Authors: Coon Steven , Kekuda Ramesh , Saha Prosenjit , Sundaram Uma
Published: December 2010

Sodium absorption in the mammalian small intestine occurs predominantly by two primary pathways that include Na/H exchange (NHE3) and Na-glucose cotransport (SGLT1) on the brush border membrane (BBM) of villus cells. However, whether NHE3 and SGLT1 function together to regulate intestinal sodium absorption is unknown. Nontransformed small intestinal epithelial cells (IEC-18) were transfected with either NHE3 or SGLT1 small interfering RNAs (siRNAs) and were grown in confluent monolayers on transwell plates to measure the effects on Na absorption. Uptake studies were performed as well as molecular studies to determine the effects on NHE3 and SGLT1 activity. When IEC-18 monolayers were transfected with silencing NHE3 RNA, the cells demonstrated decreased NHE3 activity as well as decreased NHE3 mRNA and protein. However, in NHE3 siRNA-transected cells, SGLT1 activity, mRNA, and protein in the BBM were significantly increased. Thus, inhibition of NHE3 expression regulates the expression and function of SGLT1 in the BBM of intestinal epithelial cells. In addition, IEC-18 cells transected with silencing SGLT1 RNA demonstrated an inhibition of Na-dependent glucose uptake and a decrease in SGLT1 activity, mRNA, and protein levels. However, in these cells, Na/H exchange activity was significantly increased. Furthermore, NHE3 mRNA and protein levels were also increased. Therefore, the inhibition of SGLT1 expression stimulates the transcription and function of NHE3 and vice versa in the BBM of intestinal epithelial cells. Thus this study demonstrates that the major sodium absorptive pathways together function to regulate sodium absorption in epithelial cells.
Gap junction permeability: selectivity for anionic and cationic probes
Authors: Kanaporis G. , Brink P. R. , Valiunas V.
Published: December 2010

Gap junction channels formed by different connexins exhibit specific permeability to a variety of larger solutes including second messengers, polypeptides, and small interfering RNAs. Here, we report the permeability of homotypic connexin26 (Cx26), Cx40, Cx43, and Cx45 gap junction channels stably expressed in HeLa cells to solutes with different size and net charge. Channel permeability was determined using simultaneous measurements of junctional conductance and the cell-cell flux of a fluorescent probe. All four connexins allowed passage of both cationic and anionic probes, but the transfer rates were connexin dependent. The negatively charged probes [Lucifer yellow (LY; median axial diameter 9.9 Å, charge −2), carboxyfluorescein (CF; 8.2 Å; −2), and Alexa Fluor350 (AF350, 5.4 Å; −1)] exhibited the following permeability order: Cx43 > Cx45 > Cx26 > Cx40. In contrast, for the positively charged species permeability, the orders were as follows: Cx26 ≈ Cx43 ≈ Cx40 ≈ Cx45 for N, N, N-trimethyl-2-[methyl-(7-nitro-2,1,3-benzoxadiol-4-yl) amino] ethanaminium (NBD-m-TMA; 5.5 Å, +1) and Cx26 ≥ Cx43 ≈ Cx40 > Cx45 for ethidium bromide (10.3 Å, +1). Comparison of probe permeability relative to K+ revealed that Cx43 and Cx45 exhibited similar permeability for NBD-m-TMA and AF350, indicating weak charge selectivity. However, lesser transfer of CF and LY through Cx45 relative to Cx43 channels suggests stronger size-dependent discrimination of solute. The permeability of NBD-m-TMA for Cx40 and Cx26 channels was approximately three times higher than to anionic AF350 despite the fact that both have similar minor diameters, suggesting charge selectivity. In conclusion, these results confirm that channels formed from individual connexins can discriminate for solutes based on size and charge, suggesting that channel selectivity may be a key factor in cell signaling.
Regulation of AQP2 localization by S256 and S261 phosphorylation and ubiquitination
Authors: Tamma Grazia , Robben Joris H. , Trimpert Christiane , Boone Michelle , Deen Peter M. T.
Published: December 2010

Vasopressin-induced water reabsorption coincides with phosphorylation of aquaporin-2 (AQP2) at S256 (pS256), dephosphorylation at S261, and its translocation to the apical membrane, whereas treatment with the phorbol ester 12-tetradecanoylphorbol-13-acetate (TPA) induces AQP2 ubiquitination at K270, its internalization, and lysosomal degradation. In this study we investigated the relationship between S256 and S261 phosphorylation in AQP2 and its ubiquitination and trafficking in MDCK cells. Forskolin stimulation associated with increased pS256 and decreased pS261 AQP2, indicating that MDCK cells are a good model. After forskolin stimulation, TPA-induced ubiquitination of AQP2 preceded phosphorylation of AQP2 at S261, which in the first instance occurred predominantly on ubiquitinated AQP2. Forskolin-induced changes in pS261 were also observed for AQP2-S256A and AQP2-S256D, which constitutively localize in vesicles and the apical membrane, respectively. Although pS261 varies with forskolin as with wild-type AQP2, AQP2-S256A is not increased in its ubiquitination. Our data reveal that pS261 occurred independently of AQP2 localization and suggest that pS261 follows ubiquitination and endocytosis and may stabilize AQP2 ubiquitination and intracellular localization. The absence of increased ubiquitination of AQP2-S256A indicates that its intracellular location is due to the lack of pS256. Furthermore, AQP2-S261A and AQP2-S261D localized to vesicles, which was due to their increased ubiquitination, because changing K270 into Arg in both mutants resulted in their localization in the apical membrane. Although still increased in its ubiquitination, AQP2-S256D-S261D localized in the apical membrane. AQP2-S256D-K270R-Ub, however, localized to intracellular vesicles. Although our localization of AQP2-S261A/D is different from that of others, these data indicate that constitutive S256 phosphorylation counterbalances S261D-induced ubiquitination and internalization or changes its structure to allow distribution to the apical membrane. The vesicular localization of AQP2-S256D-K270R-Ub, however, indicates that the dominant apical sorting of S256D can again be overruled by constitutive ubiquitination. These data indicate that the membrane localization of AQP2 is determined by the balance of the extents of phosphorylation and ubiquitination.
Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes
Authors: Lu Lei , Li Tiantian , Williams Graham , Petit Elizabeth , Borowsky Mark , Walker W. Allan
Published: December 2010

It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC), including an increased expression of digestive hydrolases. However, the molecular mechanisms are not well understood, particularly in the human gut. Here we report a microarray analysis of HC-induced changes in gene expression in H4 cells (a well-characterized human fetal small intestinal epithelial cell line). This study identified a large number of HC-regulated genes, some involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication. HC also regulates the expression of genes important for cell maturation such as development of cell polarity, tight junction formation, and interactions with extracellular matrices. Using human small intestinal xenografts, we also show that HC can regulate the expression of genes important for intestinal epithelial cell maturation. Our dataset may serve as a useful resource for understanding and dissecting the molecular mechanisms of intestinal epithelial cell maturation.
Cancer-related inflammation and Barrett's carcinogenesis: interleukin-6 and STAT3 mediate apoptotic resistance in transformed Barrett's cells
Authors: Zhang Hui Ying , Zhang Qiuyang , Zhang Xi , Yu Chunhua , Huo Xiaofang , Cheng Edaire , Wang David H. , Spechler Stuart J. , Souza Rhonda F.
Published: December 2010

Cancer-related inflammation recently has been proposed as a major physiological hallmark of malignancy. Some genetic alterations known to promote cellular proliferation and induce malignant transformation also may participate in an intrinsic inflammatory pathway that produces a cancer-promoting inflammatory microenvironment. Little is known about this intrinsic inflammatory pathway in Barrett's esophagus. We have used a series of nontransformed and transformed human Barrett's epithelial cell lines developed in our laboratory to explore the potential contribution of interleukin (IL)-6 and signal transducer and activator of transcription (STAT3) (key molecules in the intrinsic inflammatory pathway) to Barrett's carcinogenesis. We determined IL-6 mRNA expression and protein secretion and protein expression of activated phospho-STAT3 and its downstream target myeloid cell leukemia (mcl)-1 (Mcl-1). We used an IL-6 blocking antibody and two JAK kinase inhibitors (AG490 and JAK inhibitor I) to assess whether STAT3 activation is IL-6 dependent. We also used small interfering RNAs (siRNAs) to STAT3 and Mcl-1 to assess effects of STAT3 pathway inhibition on apoptosis. Phospho-STAT3 was expressed only by transformed Barrett's cells, which also exhibited higher levels of IL-6 mRNA and of IL-6 and Mcl-1 proteins than nontransformed Barrett's cells. STAT3 phosphorylation could be blocked by IL-6 blocking antibody and by AG490 and JAK inhibitor I. In transformed Barrett's cells, rates of apoptosis following exposure to deoxycholic acid were significantly increased by transfection with siRNAs for STAT3 and Mcl-1. We conclude that activation of the IL-6/STAT3 pathway in transformed Barrett's epithelial cells enables them to resist apoptosis. These findings demonstrate a possible contribution of the intrinsic inflammatory pathway to carcinogenesis in Barrett's esophagus.
Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart
Authors: Harada Masahide , Tsuji Yukiomi , Ishiguro Yuko S. , Takanari Hiroki , Okuno Yusuke , Inden Yasuya , Honjo Haruo , Lee Jong-Kook , Murohara Toyoaki , Sakuma Ichiro , Kamiya Kaichiro , Kodama Itsuo
Published: December 2010

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.
Three-dimensional reconstruction of the human capillary network and the intramyocardial micronecrosis
Authors: Kaneko Noboru , Matsuda Ryuko , Toda Masashi , Shimamoto Ken
Published: December 2010

Three-dimensional reconstruction of the human heart was performed to define the structure of the intramyocardial microvasculature. A total of 200 consecutive serial sections of 6 μm each were prepared from the left ventricular tissue of an autopsied human heart with normal coronary arteries. The corresponding arteriole, venule, and all capillaries were reconstructed using three-dimensional software. The capillary network extended right and left along the cardiomyocyte with major and minor axes of about 130 and 120 μm, respectively. The capillary length from an arteriole to an adjacent venule was about 350 μm. Two types of sack-like structures, the precapillary sinus and the capillary sinus, were present in the capillary network, and many capillaries diverged from these sinuses. The cardiomyocytes were covered with reticular capillaries. In contrast, the precapillary and capillary sinuses were surrounded by many cardiomyocytes. The arterial and venous capillaries were positioned alternately, forming a lattice pattern. Intramyocardial microcirculatory units forming a capillary network from an arteriole to adjacent venules on both sides were present. The sizes of myocardial micronecroses corresponded to that of the intramyocardial microcirculatory unit. These results show that the capillary network is an ordered and anatomically regulated structure and that the microcirculatory unit and the precapillary and capillary sinuses may play an important role in maintaining the intramyocardial microcirculation during contraction and relaxation.
Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis
Authors: Gelosa Paolo , Sevin Gulnur , Pignieri Alice , Budelli Silvia , Castiglioni Laura , Blanc-Guillemaud Vanessa , Lerond Laurence , Tremoli Elena , Sironi Luigi
Published: December 2010

Thromboxane A2 and other eicosanoids such as isoprostanes contribute to vascular proliferation and atherosclerosis by binding to the thromboxane/prostaglandin endoperoxide receptors. The effects of terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, on aorta remodeling were evaluated in spontaneously hypertensive stroke-prone rats (SHRSPs), a model of severe hypertension, endothelial dysfunction, vascular inflammation, and cerebrovascular diseases. Male SHRSPs were allocated to three groups receiving a standard diet ( n = 5) or a high-sodium permissive diet plus vehicle ( n = 6) or plus terutroban (30 mg·kg−1·day−1; n = 6). After 6 wk of dietary treatment, all of the animals were injected with bromodeoxyuridine and simultaneously euthanized for aorta collection. The aortic media thickness-to-lumen ratio significantly ( P < 0.0001) increased in the salt-loaded rats compared with the rats fed a standard diet, whereas terutroban treatment completely prevented media thickening ( P < 0.001). When compared with vehicle, terutroban was also effective in preventing cell proliferation in the media, as indicated by the reduced number of bromodeoxyuridine-positive ( P < 0.0001) and proliferating cell nuclear antigen-positive cells ( P < 0.0001). Severe fibrosis characterized by a significant accumulation of collagen and fibronectin in the vascular wall was observed in the vehicle-treated rats ( P < 0.01) but was completely prevented by terutroban ( P < 0.001). The latter also inhibited heat shock protein-47 ( P < 0.01) and TGF-1β expression ( P < 0.001), which were significantly increased by the high-salt diet. In conclusion, terutroban prevents the development of aorta hyperplasia and has beneficial effects on fibrotic processes by affecting TGF-β and heat shock protein-47 expression in SHRSPs. These findings provide mechanistic data supporting the beneficial effects of terutroban in preventing or retarding atherogenesis.
Lower oxidative DNA damage despite greater ROS production in muscles from rats selectively bred for high running capacity
Authors: Tweedie Constance , Romestaing Caroline , Burelle Yan , Safdar Adeel , Tarnopolsky Mark A. , Seadon Scott , Britton Steven L. , Koch Lauren G. , Hepple Russell T.
Published: December 2010

Artificial selection in rat has yielded high-capacity runners (HCR) and low-capacity runners (LCR) that differ in intrinsic (untrained) aerobic exercise ability and metabolic disease risk. To gain insight into how oxygen metabolism may have been affected by selection, we compared mitochondrial function, oxidative DNA damage (8-dihydroxy-guanosine; 8dOHG), and antioxidant enzyme activities in soleus muscle (Sol) and gastrocnemius muscle (Gas) of adult and aged LCR vs. HCR rats. In Sol of adult HCR rats, maximal ADP-stimulated respiration was 37% greater, whereas in Gas of adult HCR rats, there was a 23% greater complex IV-driven respiratory capacity and 54% greater leak as a fraction of electron transport capacity (suggesting looser mitochondrial coupling) vs. LCR rats. H2O2 emission per gram of muscle was 24–26% greater for both muscles in adult HCR rats vs. LCR, although H2O2 emission in Gas was 17% lower in HCR, after normalizing for citrate synthase activity (marker of mitochondrial content). Despite greater H2O2 emission, 8dOHG levels were 62–78% lower in HCR rats due to 62–96% higher superoxide dismutase activity in both muscles and 47% higher catalase activity in Sol muscle in adult HCR rats, with no evidence for higher 8 oxoguanine glycosylase (OGG1; DNA repair enzyme) protein expression. We conclude that genetic segregation for high running capacity has generated a molecular network of cellular adaptations, facilitating a superior response to oxidative stress.
Muscle oxidative capacity during IL-6-dependent cancer cachexia
Authors: White James P. , Baltgalvis Kristen A. , Puppa Melissa J. , Sato Shuichi , Baynes John W. , Carson James A.
Published: December 2010

Many diseases are associated with catabolic conditions that induce skeletal muscle wasting. These various catabolic states may have similar and distinct mechanisms for inducing muscle protein loss. Mechanisms related to muscle wasting may also be related to muscle metabolism since glycolytic muscle fibers have greater wasting susceptibility with several diseases. The purpose of this study was to determine the relationship between muscle oxidative capacity and muscle mass loss in red and white hindlimb muscles during cancer cachexia development in the Apc Min/+ mouse. Gastrocnemius and soleus muscles were excised from Apc Min/+ mice at 20 wk of age. The gastrocnemius muscle was partitioned into red and white portions. Body mass (−20%), gastrocnemius muscle mass (−41%), soleus muscle mass (−34%), and epididymal fat pad (−100%) were significantly reduced in severely cachectic mice ( n = 8) compared with mildly cachectic mice ( n = 6). Circulating IL-6 was fivefold higher in severely cachectic mice. Cachexia significantly reduced the mitochondrial DNA-to-nuclear DNA ratio in both red and white portions of the gastrocnemius. Cytochrome c and cytochrome- c oxidase complex subunit IV (Cox IV) protein were reduced in all three muscles with severe cachexia. Changes in muscle oxidative capacity were not associated with altered myosin heavy chain expression. PGC-1α expression was suppressed by cachexia in the red and white gastrocnemius and soleus muscles. Cachexia reduced Mfn1 and Mfn2 mRNA expression and markers of oxidative stress, while Fis1 mRNA was increased by cachexia in all muscle types. Muscle oxidative capacity, mitochondria dynamics, and markers of oxidative stress are reduced in both oxidative and glycolytic muscle with severe wasting that is associated with increased circulating IL-6 levels.
Tyrosine hydroxylase immunoreactivity as indicator of sympathetic activity: simultaneous evaluation in different tissues of hypertensive rats
Authors: Burgi Katia , Cavalleri Marina T. , Alves Adilson S. , Britto Luiz R. G. , Antunes Vagner R. , Michelini Lisete C.
Published: December 2010

Vasomotor control by the sympathetic nervous system presents substantial heterogeneity within different tissues, providing appropriate homeostatic responses to maintain basal/stimulated cardiovascular function both at normal and pathological conditions. The availability of a reproducible technique for simultaneous measurement of sympathetic drive to different tissues is of great interest to uncover regional patterns of sympathetic nerve activity (SNA). We propose the association of tyrosine hydroxylase immunoreactivity (THir) with image analysis to quantify norepinephrine (NE) content within nerve terminals in arteries/arterioles as a good index for regional sympathetic outflow. THir was measured in fixed arterioles of kidney, heart, and skeletal muscle of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (123 ± 2 and 181 ± 4 mmHg, 300 ± 8 and 352 ± 8 beats/min, respectively). There was a differential THir distribution in both groups: higher THir was observed in the kidney and skeletal muscle (∼3–4-fold vs. heart arterioles) of WKY; in SHR, THir was increased in the kidney and heart (2.4- and 5.3-fold vs. WKY, respectively) with no change in the skeletal muscle arterioles. Observed THir changes were confirmed by either: 1) determination of NE content (high-performance liquid chromatography) in fresh tissues (SHR vs. WKY): +34% and +17% in kidney and heart, respectively, with no change in the skeletal muscle; 2) direct recording of renal (RSNA) and lumbar SNA (LSNA) in anesthetized rats, showing increased RSNA but unchanged LSNA in SHR vs. WKY. THir in skeletal muscle arterioles, NE content in femoral artery, and LSNA were simultaneously reduced by exercise training in the WKY group. Results indicate that THir is a valuable technique to simultaneously evaluate regional patterns of sympathetic activity.
Acute heat treatment improves insulin-stimulated glucose uptake in aged skeletal muscle
Authors: Gupte Anisha A. , Bomhoff Gregory L. , Touchberry Chad D. , Geiger Paige C.
Published: December 2010

Aging is associated with insulin resistance and decreased insulin-stimulated glucose uptake into skeletal muscle. Although the mechanisms underlying age-related insulin resistance are not clearly defined, impaired defense against inflammation and tissue oxidative stress are likely causes. Heat shock proteins (HSPs) have been shown to protect tissue from oxidative stress and inhibit the activation of stress kinases such as JNK, known to interfere with the insulin signaling pathway. While the induction of HSPs via chronic heat treatment has been shown to protect skeletal muscle from obesity-related insulin resistance, the ability of heat treatment to improve insulin action in aged skeletal muscle is not known. In the present study, one bout of in vivo heat treatment applied to 24-mo-old Fischer 344 rats improved insulin-stimulated glucose uptake after 24 h in slow-twitch soleus muscles. In vitro heat treatment applied to young (3-mo-old) and aged (24-mo-old) soleus muscles increased expression of HSP72 and inhibited anisomycin-induced activation of JNK. In contrast, heat treatment had no effect on p38 MAPK, a MAPK strongly activated with anisomycin. Prior inhibition of HSP72 transcription with the pharmacological inhibitor KNK437 eliminated the ability of heat treatment to blunt JNK activation. This suggests that the ability of heat treatment to inhibit JNK activation in skeletal muscle is dependent on increased HSP72 expression. In conclusion, an acute bout of heat treatment can increase insulin-stimulated glucose uptake in aged skeletal muscle, with the underlying mechanism likely to be HSP72-mediated JNK inhibition.
Cyclic Nucleotide Phosphodiesterase 1 Regulates Lysosome-Dependent Type I Collagen Protein Degradation in Vascular Smooth Muscle Cells
Authors: Cai Yujun , Miller Clint L. , Nagel David J. , Jeon Kye-Im , Lim Soyeon , Gao Pingjin , Knight Peter A. , Yan Chen
Published: December 2010

Objective—

The phenotypic modulation of vascular smooth muscle cells (VSMCs) to a synthetic phenotype is vital during pathological vascular remodeling and the development of various vascular diseases. An increase in type I collagen (collagen I) has been implicated in synthetic VSMCs, and cyclic nucleotide signaling is critical in collagen I regulation. Herein, we investigate the role and underlying mechanism of cyclic nucleotide phosphodiesterase 1 (PDE1) in regulating collagen I in synthetic VSMCs.

Methods and Results—

The PDE1 inhibitor IC86340 significantly reduced collagen I in human saphenous vein explants undergoing spontaneous remodeling via ex vivo culture. In synthetic VSMCs, high basal levels of intracellular and extracellular collagen I protein were markedly decreased by IC86340. This attenuation was due to diminished protein but not mRNA. Inhibition of lysosome function abolished the effect of IC86340 on collagen I protein expression. PDE1C but not PDE1A is the major isoform responsible for mediating the effects of IC86340. Bicarbonate-sensitive soluble adenylyl cyclase/cAMP signaling was modulated by PDE1C, which is critical in collagen I degradation in VSMCs.

Conclusion—

These data demonstrate that PDE1C regulates soluble adenylyl cyclase/cAMP signaling and lysosome-mediated collagen I protein degradation, and they suggest that PDE1C plays a critical role in regulating collagen homeostasis during pathological vascular remodeling.
Quarky Calcium Release in the Heart
Authors: Brochet Didier X.P. , Xie Wenjun , Yang Dongmei , Cheng Heping , Lederer W. Jonathan
Published: December 2010

Rationale:

In cardiac myocytes, “Ca
2+
sparks” represent the stereotyped elemental unit of Ca
2+
release arising from activation of large arrays of ryanodine receptors (RyRs), whereas “Ca
2+
blinks” represent the reciprocal Ca
2+
depletion signal produced in the terminal cisterns of the junctional sarcoplasmic reticulum. Emerging evidence, however, suggests possible substructures in local Ca
2+
release events.

Objective:

With improved detection ability and sensitivity provided by simultaneous spark–blink pair measurements, we investigated possible release events that are smaller than sparks and their interplay with regular sparks.

Methods and Results:

We directly visualized small solitary release events amid noise: spontaneous Ca
2+
quark-like or “quarky” Ca
2+
release (QCR) events in rabbit ventricular myocytes. Because the frequency of QCR events in paced myocytes is much higher than the frequency of Ca
2+
sparks, the total Ca
2+
leak attributable to the small QCR events is approximately equal to that of the spontaneous Ca
2+
sparks. Furthermore, the Ca
2+
release underlying a spark consists of an initial high-flux stereotypical release component and a low-flux highly variable QCR component. The QCR part of the spark, but not the initial release, is sensitive to cytosolic Ca
2+
buffering by EGTA, suggesting that the QCR component is attributable to a Ca
2+
-induced Ca
2+
release mechanism. Experimental evidence, together with modeling, suggests that QCR events may depend on the opening of rogue RyR2s (or small cluster of RyR2s).

Conclusions:

QCR events play an important role in shaping elemental Ca
2+
release characteristics and the nonspark QCR events contribute to “invisible” Ca
2+
leak in health and disease.
MARF and Opa1 Control Mitochondrial and Cardiac Function in Drosophila
Authors: Dorn Gerald W. , Clark Charles F. , Eschenbacher William H. , Kang Min-Young , Engelhard John T. , Warner Stephen J. , Matkovich Scot J. , Jowdy Casey C.
Published: December 2010

Rationale:

Mitochondria interact via actions of outer and inner membrane fusion proteins. The role of mitochondrial fusion in functioning of the heart, where mitochondria comprise ≈30% of cardiomyocyte volume and their intermyofilament spatial arrangement with other mitochondria is highly ordered, is unknown.

Objective:

Model and analyze mitochondrial fusion defects in
Drosophila melanogaster
heart tubes with tincΔ4Gal4-directed expression of RNA interference (RNAi) for mitochondrial assembly regulatory factor (MARF) and optic atrophy (Opa)1.

Methods and Results:

Live imaging analysis revealed that heart tube–specific knockdown of MARF or Opa1 increases mitochondrial morphometric heterogeneity and induces heart tube dilation with profound contractile impairment. Sarcoplasmic reticular structure was unaffected. Cardiomyocyte expression of human mitofusin (mfn)1 or -2 rescued MARF RNAi cardiomyopathy, demonstrating functional homology between
Drosophila
MARF and human mitofusins. Suppressing mitochondrial fusion increased compensatory expression of nuclear-encoded mitochondrial genes, indicating mitochondrial biogenesis. The MARF RNAi cardiomyopathy was prevented by transgenic expression of superoxide dismutase 1.

Conclusions:

Mitochondrial fusion is essential to cardiomyocyte mitochondrial function and regeneration. Reactive oxygen species are key mediators of cardiomyopathy in mitochondrial fusion-defective cardiomyocytes. Postulated mitochondrial–endoplasmic reticulum interactions mediated uniquely by mfn2 appear dispensable to functioning of the fly heart.
Early Changes of Tissue Perfusion After Tissue Plasminogen Activator in Hyperacute Ischemic Stroke
Authors: An Hongyu , Ford Andria L. , Vo Katie , Eldeniz Cihat , Ponisio Rosana , Zhu Hongtu , Li Yimei , Chen Yasheng , Powers William J. , Lee Jin-Moo , Lin Weili
Published: December 2010

Background and Purpose—

It is hypothesized that tissue plasminogen activator rescues brain tissue by improving perfusion. In this study, we aimed to examine acute regional perfusion changes and how they influence infarction and clinical outcome.

Methods—

Three sequential MR scans were performed in 15 tissue plasminogen activator-treated patients within 3.5 (tp1), at 6 hours (tp2), and at 1 month (tp3) after stroke onset. “Hypoperfusion” was defined if mean transit time prolongation was more than a threshold (4 thresholds: 3, 4, 5, and 6 seconds). Four regions of interest were classified: (1) “reperfusion”—hypoperfused at tp1, normal at tp2; (2) “nonreperfusion”—hypoperfused at tp1 and tp2; (3) “normal perfusion”—normal at tp1 and tp2; and (4) “new hypoperfusion”—normal at tp1 and hypoperfused at tp2. Risk of infarction was calculated within each region of interest. Associations between tissue perfusion changes and clinical variables were evaluated using stepwise multiple linear regressions. Moreover, the association between National Institutes of Health Stroke Scale changes and perfusion alterations was assessed using linear mixed effect models.

Results—

Regardless of the mean transit time threshold chosen, the risk of infarction in nonreperfused regions (40% to 68%, thresholds 3 to 6 seconds) was higher than reperfused regions (9% to 30%,
P
<0.05), and it was higher in new hypoperfusion regions (9% to 33%) than normal perfusion regions (3% to 4%,
P
<0.05). Volume of new hypoperfusion was significantly associated with onset-to-treatment time and initial hypoperfused volume. Overall relative reperfusion was significantly associated with National Institutes of Health Stroke Scale improvement.

Conclusion—

Early tissue perfusion changes influenced final tissue fate. The development of new hypoperfusion may result from delay in tissue plasminogen activator and a large initial lesion.
Early Activation of Intracranial Collateral Vessels Influences the Outcome of Spontaneous Internal Carotid Artery Dissection
Authors: Silvestrini Mauro , Altamura Claudia , Cerqua Raffaella , Pedone Claudio , Balucani Clotilde , Luzzi Simona , Bartolini Marco , Provinciali Leandro , Vernieri Fabrizio
Published: December 2010

Background and Purpose—

The effectiveness of different treatments for internal carotid artery (ICA) dissection has not been well defined. Lack of early prognostic indicators may represent a major problem in adequately identifying the most appropriate option for treatment. This study aimed at evaluating the influence of patients' vascular risk profiles and of early cerebral hemodynamic changes in determining the clinical evolution after ICA dissection.

Methods—

Sixty-six stroke patients with ICA occlusion due to spontaneous artery dissection were included. Transcranial Doppler was performed within 24 hours from symptom onset to examine cerebral arteries and the patency of the 3 major intracranial collateral vessels (ophthalmic artery and anterior and posterior communicating arteries). Possible recanalization of the occluded ICA within the first month was evaluated. Stroke severity at onset was assessed with the National Institutes of Health Stroke Scale, whereas outcome was defined according to the modified Rankin Scale score at 90 days after stroke onset.

Results—

Forty patients had at least 2 activated intracranial collateral vessels. The remaining 26 patients, with none or only 1 collateral vessel, showed a significant increased risk of poor recovery (modified Rankin Scale score ≥2; adjusted relative risk=14.9; 95% CI, 3.24 to 68.46). Poor recovery was not associated with the occurrence of recanalization, with stroke severity at onset, or with vascular risk profile.

Conclusions—

Early assessment of cerebral hemodynamic status and, in particular, the activation of intracranial collateral vessels, may help in predicting the outcome of stroke patients with ICA lumen occlusion as a result of spontaneous dissection.
Processes of Care and Medical Complications in Patients With Stroke
Authors: Ingeman Annette , Andersen Grethe , Hundborg Heidi H. , Svendsen Marie L. , Johnsen Søren P.
Published: December 2010

Background and Purpose—

The relationship between processes of care and the risk of medical complications in patients with stroke remains unclear. We therefore examined the association in a population-based follow-up study.

Methods—

We identified 11 757 patients admitted for stroke to stroke units in 2 Danish counties in 2003 to 2008. The examined processes of care included early admission to a stroke unit, early initiation of antiplatelet or oral anticoagulant therapy, early CT/MRI scan, and early assessment by a physiotherapist and an occupational therapist of nutritional risk and of swallowing function and early mobilization.

Results—

Overall, 25.3% (n=2969) of the patients experienced ≥1 medical complications during hospitalization. The most common medical complications were urinary tract infection (15.5%), pneumonia (8.8%), and constipation (7.0%). We found indications of an inverse dose–response relationship between the number of processes of care that the patients received and the risk of medical complications. The lowest risk of complications was found among patients who received all relevant processes of care compared with patients who failed to receive any of the processes (ie, adjusted ORs ranged from 0.42 [95% CI, 0.24 to 0.74] for pressure ulcer to 0.64 [95% CI, 0.44 to 0.93] for pneumonia). Of the individual processes of care, early mobilization was associated with the lowest risk of complications.

Conclusions—

Higher quality of acute stroke care was associated with a lower risk of medical complications.
Good-death Beliefs and Cognition in Himalayan Pilgrimage
Authors: Nordin Andreas
Published: December 2010

This article discusses the notions of a good death associated with Hindu pilgrimages in the Nepalese and Tibetan Himalayas. Using theories and concepts from the cognitive anthropology of religion and from the cognitive science of religion—particularly the cultural epidemiological method—my objective is to explain why certain systems of thought and behaviour are favoured over others in cultural transmission. My thesis is that the apprehension of contagion and/or contamination, combined with prevailing cultural representations, exerts selective pressure on the formation of beliefs about good death. Pilgrimage sites are associated with intuitions about contagious and contaminating contact, avert the pollution of death, and provide links to supernatural agents.
What is Esotericism? Cultural Studies Approaches and the Problems of Definition in Religious Studies
Authors: Bergunder Michael
Published: December 2010

There is an ongoing debate whether esotericism could be a meaningful subject for Religious Studies. The recent history of the academic research into esotericism will be presented and critically discussed, how it has tried to define its subject and how this discussions have reached an impasse. It is proposed that certain theoretical perspectives from cultural studies offer alternative ways in determining a research subject, especially one based on Ernesto Laclau’s concept of “empty signifiers.” This argument will be followed by a methodological application that translates the theoretical considerations into a concrete and specific research design of discursive networks.
Turning a Critical Eye on Science and Religion: Theological Assumptions and Soteriological Rhetoric
Authors: Gironi Fabio
Published: December 2010

The aim of this paper is to offer a critical evaluation of the field of “science and religion” through a brief description of its academic evolution, of the kind of scholars involved in it, and the publications belonging to it. Some elements of this discourse will be highlighted and criticized, namely a number of eurocentric theological assumptions, and what I will define as a “soteriological rhetoric” which serves as a legitimating device for the field, both ubiquitously employed in the work of the scholars involved in the field. I will argue, moreover, that such a rhetoric is the direct product of confessional interests, which disguise the field’s theological apologetical aims with appeals to the universal welfare of an ethnocentrically limited conception of “humanity.”
Molecular and morphometric characterisation of Xiphinema globosum Sturhan, 1978 (Nematoda: Longidoridae) from Spain
Authors: Landa Blanca , Cantalapiedra-Navarrete Carolina , Palomares-Rius Juan , Castillo Pablo , Gutiérrez-Gutiérrez Carlos
Published: December 2010

During a recent nematode survey in natural environments of the Los Alcornocales Regional Park narrow valleys, viz., the renowned 'canutos' excavated in the mountains that maintain a humid microclimate, in southern Spain, an amphimictic population of Xiphinema globosum was identified. Morphological and morphometric studies on this population fit the original and previous descriptions and represent the first report from Spain and southern Europe. Molecular characterisation of X. globosum from Spain using D2-D3 expansion regions of 28S rRNA, 18S rRNA and ITS1-rRNA is provided and maximum likelihood and Bayesian inference analysis were used to reconstruct phylogenetic relationships within X. globosum and other Xiphinema species. A supertree solution of the different phylogenetic trees obtained in this study and in other published studies using rDNA genes are presented using the matrix representation parsimony method (MRP) and the most similar supertree method (MSSA). The results revealed a closer phylogenetic relationship of X. globosum with X. diversicaudatum, X. bakeri and with some sequences of unidentified Xiphinema spp. deposited in GenBank.
Is Xinjiang an Internal Colony?
Authors: Sautman Barry
Published: December 2010

Scholars and journalists use the phrase ‘internal colonialism’ to sum up the relationship between the PRC central government and Xinjiang, and the region does have ethnic conflict and a low degree of autonomy. Its relationship with the PRC centre and the political economy of Han/minority interaction indicate, however, that none of the elements of the internal colonialist concept are sufficiently present to warrant characterising Xinjiang as an internal colony of China.
The Population Landscape of Xinjiang/East Turkestan
Authors: Toops Stanley
Published: December 2010

The demographic structure of East Turkestan (Xinjiang) has undergone enormous change since the 1980s. This article profiles several factors affecting demographic change including migration, social and economic issues as well as policy implementation. The regional distinctiveness of East Turkestan (North, South, and Central) is examined through the use of maps from 1991 and 1995 that tabulate data for each county in the region. The resultant population landscape of East Turkestan is the local response to Ürümqi’s regional implementation of China’s national policies in the face of international forces.
Urgunge Onon: An Appreciation
Authors: Humphrey Caroline
Published: December 2010

It is particularly important for us to celebrate Urgunge Onon’s 80th birthday. Urgunge was the inspiration for the founding of the Mongolia and Inner Asia Studies Unit in 1986. I remember well how one day Urgunge travelled from Leeds to give me an important message. He said, ‘This country of Britain where I have made my home has a very distinguished tradition of Mongolian Studies, but now it looks as though it will die out.’ ‘What do you mean?’ I asked. Urgunge replied, ‘Without a proper institution, everything will be dissipated, there will be no centre, and no-one will see to it that there is a new generation of Mongolists to follow us. You owe it to your teachers, Owen Lattimore and myself, to see that this does not happen. Together, we can do something.’ This conversation was how the idea of founding a Unit was born, and the Unit has now produced several ‘generations’ of young scholars and many publications, including this journal Inner Asia.
An Introduction to the History and Religion of the Buryat Mongols of Shinehen in China
Authors: HÜrelbaatar A.
Published: December 2010

There are over 6,000 Buryat Mongols (Buryats hereafter) in Hülün Buir League of Inner Mongolian Autonomous Region, China. Most of the Shinehen Buryats came originally from among the Aga Buryats in Russia after 1918. Although the history of Shinehen Buryats is relatively short, their experiences, as this paper aims to show, are special in many ways. Not much is written about them. The aim of this paper is simple, briefly to introduce the Shinehen Buryats by examining their migrations and the last eighty years of their historical experience in different political power contexts. I discuss their hardships, the continuity of their traditions, the decline and re-emergence of their religious practices, and their current relation to the Buryats in Russia.
Neo-Shamanism in the Context of the Contemporary Ethno-Cultural Situation in the Republic of Buryatia
Authors: Zhukovskaya N. L.
Published: December 2010

It is often said that there is a ‘revival’ of shamanism in Siberia today. The article argues, however, that in Buryatia alongside this resurgence there are new phenomena, which we would more accurately call ‘Neo-shamanic’. Amongst these phenomena are: the combining of shamanic with secular careers; the creation of an Association of shamans; the participation of shamans in popular media events; the desire of shamans to express their point of view in the academic environment; and the contemporary shamans’ elevation of shamanism to world religion status. The Association has promoted some mass rituals, which have been integrated (often problematically) into local mythic worldviews, and the combination of shamanic with academic pursuits has also turned out to be an uncomfortable one. Such new activities show that shamanism evolves historically, though it also retains a fundament based on locality and ancestors.
Resisting Colonialism in the Uzbek Historical Novel Kecha va Kunduz (Night and Day), 1936
Authors: Lyons Shawn T.
Published: December 2010

In this essay on the Uzbek author and poet Abdulhamid Sulayman Cholpon (1897–1938), his novel Kecha va Kunduz (Night and Day) is examined as a bold critique of both Russian and Soviet colonialism in early twentieth century Central Asia. Despite increasing censorship and previous arrests by Soviet authorities, Cholpon subtly employs a variety of techniques including satire and farce to undermine the legitimacy of the Soviet government that was being established around him. Bitterly portraying the hypocrisy and collusion of jadid reformists, Muslim clerics and local Russian officials, this unfinished novel, which was halted by the author’s execution in 1938, remains as one of the darkest comments on Soviet Central Asian history in the Uzbek language.
Educating Mongols and Making ‘Citizens’ of Manchukuo
Authors: Narangoa Li
Published: December 2010

To control its new possessions Japan needed a mobilisation strategy of its own. In developing this strategy Japan placed great emphasis on education. The Japanese authorities saw education as tool for shaping society to serve their purposes and as part of their broader efforts to establish their dominance. This essay focuses on Japanese education policies towards the Mongols in Manchukuo. The Mongols of Manchukuo had a special place in Japanese policies in the new state. A clear Mongol political presence was essential to the Japanese construction of Manchukuo as a multi-ethnic state. The central problem for the Japanese was whether to make the Mongols of Manchukuo good and useful citizens of Manchukuo or whether to make them the spearhead of a larger Japanese orientated Mongol state north of China. Japan's education policies amongst the Mongols reflected these contradictory aspirations and therefore highlight Japan's general educational dilemmas in its Asian colonies.
The Politics of Writing History in China: A Comparison of Official and Private Histories
Authors: Yang Haiying
Published: December 2010

This paper examines the ways in which ‘history’ is recorded, written or narrated, thereby exploring the interface between history and anthropology. The discussion focuses on the Hui Muslim Rebellion in the Qing period, which broke out at the end of the 19th century, spreading over a vast area in the northwest of the empire and Central Asia. State-sponsored publications of history such as Tong shi (General History) or others describe the Hui Rebellion as a ‘revolt by an ethnic minority against the Qing dynasty’. They do not describe the pillage, atrocities and massacres perpetrated by the insurgent Hui troops. However, regional history books compiled in various localities describe the serious destruction caused by the Hui rebel army. The paper also explores the diverse representations of the rebellion by Mongol and Hui historians. While recognising the courage of the Hui insurgents whom the Mongolian army fought, the privately written Mongolian chronicles describe the rise and fall of the Rebellion in a relatively neutral and objective manner. Hui historical sources provide an entirely different perspective, revealing the religious motivation of the rebellion, and providing the basis for the sort of ethnohistorical project that Zhang calls a ‘history of people's way of life’. Given these widely differing perspectives in the historical records, the paper urges the exploration of the commonality between the anthropological approach to history and Zhang's ‘history of a way of life’ approach so as to better elucidate historical incidents that have had a major impact on history.
Chinese Communities in Western Siberia in the 1920s–1930s
Authors: Boyko Vladimir
Published: December 2010

This paper aims to outline the origins and main dimensions of the Chinese immigrant communities which were established in the Russian heartland (Western Siberia) during the interwar period (1920s—1930s). It argues that Chinese – primarily male groups – had managed to adapt peacefully, though temporarily, into the local environment due their particular mentality and social features: they were often occupying free labour and demographic lacunae, caused by the losses of men in WWI/Russian civil war and devastation of economy/infrastructure. The growth of authoritarian tendencies under the Stalinist regime in Soviet Union, economic shortcomings and the ethnic purges of 1930s closed the agenda of Chinese presence in theWestern Siberian, aswell as in thewhole Soviet scene. Actually all persons of Chinese origin were accused of being ‘outside’ (Japan's) collaborators, and they were assassinated or, at best, forwarded to concentration camps. Just a few survived. The Chinese in Western Siberia represented a very particular socio-demographic and ethnical phenomenon, remarkably distinctive fromother similar, Russian Far East or worldwide, immigrant communities.