bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnographic Approaches to Digital Media
Authors: Coleman E. Gabriella
Published: September 2010

This review surveys and divides the ethnographic corpus on digital media into three broad but overlapping categories: the cultural politics of digital media, the vernacular cultures of digital media, and the prosaics of digital media. Engaging these three categories of scholarship on digital media, I consider how ethnographers are exploring the complex relationships between the local practices and global implications of digital media, their materiality and politics, and their banal, as well as profound, presence in cultural life and modes of communication. I consider the way these media have become central to the articulation of cherished beliefs, ritual practices, and modes of being in the world; the fact that digital media culturally matters is undeniable but showing how, where, and why it matters is necessary to push against peculiarly narrow presumptions about the universality of digital experience.
Sense and the Senses: Anthropology and the Study of Autism
Authors: Solomon Olga
Published: September 2010

As a clinical category and a sociocultural phenomenon, autism occupies a prominent albeit ambiguous place in ongoing social science and humanities debates about empathy, intersubjectivity, intentionality, epistemological certainty, and moral agency. Autism is used as a counterexample to feeling empathy and understanding other people's beliefs and intentions. Alternatively, it is given as evidence of the limitless potential and neurodiversity of the human mind. This review examines the field of autism research relevant to anthropology of the senses. It considers the production of knowledge about autism as a clinically relevant category at the intersection of sense as culturally organized competence in meaning making and the senses as a culturally normative and institutionally ratified sensory and perceptual endowment. In such a distinction, both sense and the senses are paths toward and objects of the empirical understanding of autism.
The Anthropology of Secularism
Authors: Cannell Fenella
Published: September 2010

Recent debates on this topic have been heavily shaped by two paradigms: Asad's deconstructivism and Taylor's Catholic/Hegelian revisionism. This article outlines the arguments of each but frames them within the longer history of arguments that make claims for the reality of secularization and alternate sources for claims that “the secular” is a historically constructed category, including arguments from radical theology and (differently) in the anthropology of India. It is argued that implicit claims for the hierarchical ordering of reality in modernity, in which the political is seen as more real than the religious, continue to create disjunctures in the range of debate that new ethnography has the opportunity to address.
Cooperative Breeding and its Significance to the Demographic Success of Humans
Authors: Kramer Karen L.
Published: September 2010

The demographic success of humans compared with other closely related species can be attributed to the relatively rapid pace of reproduction and improved chances of survival. The assistance that mothers receive from others to help raise children is a common theme in explaining this gain in surviving fertility. Cooperative breeding in its broad definition describes such a social system in which nonmaternal helpers support offspring who are not their own. In traditional societies, kin and nonkin of different ages and sex contribute both to child care and to provisioning older children. This review discusses empirical evidence for human cooperative breeding and its demographic significance and highlights the ways in which humans are similar to and different from other cooperative breeders. An emphasis is placed on cross-cultural comparison and variability in allocare strategies. Because helping in humans occurs within a subsistence pattern of food sharing and labor cooperation, both kin selection and mutualism may explain why children are often raised with nonmaternal help. Cooperative breeding is relevant to debates in anthropology concerning the evolution of human life history, sociality, and psychology and has implications for demographic patterns in today's world as well as in the past.
Exhibiting Archaeology: Archaeology and Museums
Authors: Barker Alex W.
Published: September 2010

From their beginnings, archaeology museums have reflected a complex and dynamic balance between the demands of developing, documenting, and preserving objects on the one hand and sharing knowledge, access, and control on the other. This balance has informed and inflected the ways that museums present the past, including both practical aspects of pedagogy and exhibition design as well as more critical and contested issues of authority, authenticity, and reflexivity in interpretation. Meeting the complex requirements of curation, deliberate collections growth, management, and conservation, as well as the need to respond to continuing challenges to the museum's right and title to hold various forms of cultural property, archaeological museums play an active role in both preserving and shaping the public's view of the past and reflect the prospects and perils of being at once a temple to the muses and a forum for sometimes contentious public discourse.
Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat
Authors: Chen Angela Y. , DeLano Frank A. , Valdez Shakti R. , Ha Jessica N. , Shin Hainsworth Y. , Schmid-Schönbein Geert W.
Published: September 2010

Physiological fluid shear stress evokes pseudopod retraction in normal leukocytes by a mechanism that involves the formyl peptide receptor (FPR) as mechanosensor. In hypertensives, such as the spontaneously hypertensive rat (SHR), leukocytes lack the normal fluid shear response. The increased activity of matrix metalloproteinases (MMPs, including MMP-9) in SHR plasma is associated with cleavage of several cell membrane receptors. We hypothesize that the attenuated fluid shear response in leukocytes (neutrophils) of the SHR is due to extracellular proteolytic cleavage of the FPR. We show that suspended SHR neutrophils in whole blood sheared in a cone-and-plate device or individual neutrophils adherent to a glass surface and subject to fluid shear exhibited reduced pseudopod retractions compared with neutrophils of control Wistar-Kyoto (WKY) rats. SHR neutrophils and naïve Wistar rat neutrophils exposed to SHR plasma also exhibited impaired fluid shear responses as shown by their inability to project pseudopods with fluid shear. Labeling of extracellular FPR revealed that the FPR density in SHR neutrophils is on average 27% reduced compared with those of the WKY rats. Exposure of Wistar rat neutrophils to the gelatinase MMP-9 (final concentration 5 nM) led to attenuation of fluid shear response and decrease in extracellular FPR density. Chronic treatment of the SHR with a broad-acting MMP inhibitor, doxycycline, significantly improved the fluid shear response and increased the FPR extracellular density of SHR neutrophils. These results suggest that proteolytic cleavage of the FPR may interfere with normal fluid shear-induced pseudopod retractions in SHR neutrophils.
Skeletal muscle-endothelial cell cross talk through angiotensin II
Authors: Bellamy Leeann M. , Johnston Adam P. W. , De Lisio Michael , Parise Gianni
Published: September 2010

The role of angiotensin II (ANG II) in postnatal vasculogenesis and angiogenesis during skeletal muscle (SKM) regeneration is unknown. We examined the capacity of ANG II to stimulate capillary formation and growth during cardiotoxin-induced muscle regeneration in ACE inhibitor-treated ANG II type 1a receptor knockout (AT1a−/−) and C57Bl/6 control mice. Analysis of tibialis anterior (TA) cross-sections revealed 17% and 23% reductions in capillarization in AT1a−/− and captopril treated mice, respectively, when compared with controls, 21 days postinjury. Conversely, no differences in capillarization were detected at early time points (7 and 10 days). These results identify ANG II as a regulator of angiogenesis but not vasculogenesis in vivo. In vitro angiogenesis assays of human umbilical vein endothelial cells (HUVECs) further confirmed ANG II as proangiogeneic as 71% and 124% increases in tube length and branch point number were observed following ANG II treatment. Importantly, treatment of HUVECs with conditioned media from differentiated muscle cells resulted in an 84% and 203% increase in tube length and branch point number compared with controls, which was abolished following pretreatment of the cells with an angiotensin-converting enzyme inhibitor. The pro-angiogenic effect of ANG II can be attributed to an enhanced endothelial cell migration because both transwell and under agarose migration assays revealed a 37% and 101% increase in cell motility, respectively. Collectively, these data highlight ANG II as a proangiogenic regulator during SKM regeneration in vivo and more importantly demonstrates that ANG II released from SKM can signal endothelial cells and regulate angiogenesis through the induction of endothelial cell migration.
Endothelin-1-induced activation of rat renal pelvic contractions depends on cyclooxygenase-1 and Rho kinase
Authors: Grisk Olaf , Packebusch Martin , Steinbach Antje C. , Schlüter Torsten , Kopp Ulla C. , Rettig Rainer
Published: September 2010

Upper urinary tract peristalsis is generated in the proximal renal pelvis that connects to the renal parenchyma at the pelvis-kidney junction. It may be exposed to the high renal endothelin-1 (ET-1) concentrations. Dietary NaCl restriction increases renal pelvic ETA receptor expression. We investigated the contribution of ETA and ETB receptors to ET-1-stimulated rat renal pelvic contractions and whether the sensitivity of renal pelvic contractile activity to ET-1 stimulation increases with dietary NaCl restriction. We tested whether ET-1-induced contractile activity depends on cyclooxygenase (COX)-1 or -2 and to what extent spontaneous as well as agonist-induced peristalsis depends on Rho kinases (ROCK). Contractions of isolated renal pelvises were investigated by myography. ET-1 concentration-dependently increased pelvic contractile activity up to 400% of basal activity. ETA but not ETB receptor blockade inhibited ET-1-induced pelvic contractions. Basal and ET-1-stimulated contractions were similar in renal pelvises from rats on a high-NaCl diet or on a NaCl-deficient diet. COX-1 inhibition reduced spontaneous and almost completely blocked the ET-1-induced pelvic contractions. ROCK inhibition reduced spontaneous and ET-1 stimulated pelvic contractile activity by 90%. RT-PCR revealed that both ROCK isoenzymes are present in the renal pelvic wall. Western blot analyses did not show increased phosphorylation of ROCK substrates myosin phosphatase target subunit 1, ezrin, radixin, and moesin in ET-1-treated isolated renal pelvises. ET-1 is a powerful ETA receptor-dependent activator of renal pelvic contractions. COX-1 and ROCK activity are required for the ET-1 effects on pelvic contractions, which are not significantly affected by dietary NaCl intake.
Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats
Authors: Jackson Janna R. , Ryan Michael J. , Hao Yanlei , Alway Stephen E.
Published: September 2010

Hindlimb suspension (HLS) elicits muscle atrophy, oxidative stress, and apoptosis in skeletal muscle. Increases in oxidative stress can have detrimental effects on muscle mass and function, and it can potentially lead to myonuclear apoptosis. Resveratrol is a naturally occurring polyphenol possessing both antioxidant and antiaging properties. To analyze the capacity of resveratrol to attenuate oxidative stress, apoptosis and muscle force loss were measured following 14 days of HLS. Young (6 mo) and old (34 mo) rats were administered either 12.5 mg·kg−1·day−1 of trans-resveratrol, or 0.1% carboxymethylcellulose for 21 days, including 14 days of HLS. HLS induced a significant decrease in plantarflexor isometric force, but resveratrol blunted this loss in old animals. Resveratrol increased gastrocnemius catalase activity, MnSOD activity, and MnSOD protein content following HLS. Resveratrol reduced hydrogen peroxide and lipid peroxidation levels in muscles from old animals after HLS. Caspase 9 abundance was reduced and Bcl-2 was increased, but other apoptotic markers were not affected by resveratrol in the gastrocnemius muscle after HLS. The data indicate that resveratrol has a protective effect against oxidative stress and muscle force loss in old HLS animals; however, resveratrol was unable to attenuate apoptosis following HLS. These results suggest that resveratrol has the potential to be an effective therapeutic agent to treat muscle functional decrements via improving the redox status associated with disuse.
Rho-associated kinase plays a role in rabbit urethral smooth muscle contraction, but not via enhanced myosin light chain phosphorylation
Authors: Walsh Michael P. , Thornbury Keith , Cole William C. , Sergeant Gerard , Hollywood Mark , McHale Noel
Published: September 2010

The involvement of Rho-associated kinase (ROK) in activation of rabbit urethral smooth muscle contraction was investigated by examining the effects of two structurally distinct inhibitors of ROK, Y27632 and H1152, on the contractile response to electric field stimulation, membrane depolarization with KCl, and α1-adrenoceptor stimulation with phenylephrine. Both compounds inhibited contractions elicited by all three stimuli. The protein kinase C inhibitor GF109203X, on the other hand, had no effect. Urethral smooth muscle strips were analyzed for phosphorylation of three potential direct or indirect substrates of ROK: 1) myosin regulatory light chains (LC20) at S19, 2) the myosin-targeting subunit of myosin light chain phosphatase (MYPT1) at T697 and T855, and 3) cofilin at S3. The following results were obtained: 1) under resting tension, LC20was phosphorylated to 0.65 ± 0.02 mol Pi/mol LC20( n = 21) at S19; 2) LC20phosphorylation did not change in response to KCl or phenylephrine; 3) ROK inhibition had no effect on LC20phosphorylation in the absence or presence of contractile stimuli; 4) under resting conditions, MYPT1 was partially phosphorylated at T697 and T855 and cofilin at S3; 5) phosphorylation of MYPT1 and cofilin was unaffected by KCl or phenylephrine; and 6) KCl- and phenylephrine-induced contraction-relaxation cycles did not correlate with actin polymerization-depolymerization. We conclude that ROK plays an important role in urethral smooth muscle contraction, but not via inhibition of MLCP or polymerization of actin.
Fucosylated chondroitin sulfate attenuates renal fibrosis in animals submitted to unilateral ureteral obstruction: a P-selectin-mediated event?
Authors: Melo-Filho Nelson M. , Belmiro Celso L. , Gonçalves Rômulo G. , Takiya Christina M. , Leite Maurilo , Pavão Mauro S. G. , Mourão Paulo A. S.
Published: September 2010

Fibrosis is the end point of most renal diseases, and several glycosaminoglycans have been shown to attenuate this process. Marine invertebrate glycosaminoglycans with unique structures have opened the possibility to test these new compounds on renal fibrosis. The effect of a fucosylated chondroitin sulfate from an echinoderm marine species is reported with the use of a model of renal fibrosis in rats, termed unilateral ureteral obstruction. Animals were given 4 mg/kg body wt of fucosylated chondroitin sulfate intraperitoneally, once a day. After 14 days, their kidneys were examined by histological, immunohistochemical, and biochemical methods. Compared with control mice, collagen deposition decreased in the course of renal fibrosis in the animals receiving fucosylated chondroitin sulfate, as revealed by Sirius red staining and hydroxyproline content. The cellularity related to myofibroblasts and macrophages was also reduced, as was the production of transforming growth factor (TGF)-β. The glycosaminoglycan content increased in the renal interstitium of animals submitted to unilateral ureteral obstruction compared with the control contralateral kidney, mostly due to an increase of chondroitin sulfate content. Interestingly, no change in the pattern of glycosaminoglycan deposition was observed after administration of fucosylated chondroitin sulfate. Fibrosis induced by unilateral ureteral obstruction is attenuated in P-selectin-deficient mice, which also do not respond to the invertebrate glycosaminoglycan. In conclusion, fucosylated chondroitin sulfate attenuates renal fibrosis on a ureteral obstruction model in mice preponderantly through a P-selectin-mediated mechanism.
Protein kinase C regulates urea permeability in the rat inner medullary collecting duct
Authors: Wang Yanhua , Klein Janet D. , Liedtke Carole M. , Sands Jeff M.
Published: September 2010

Hypertonicity increases urea transport independently of, as well as synergistically with, vasopressin in the inner medullary collect duct (IMCD). We previously showed that hypertonicity does not increase the level of cAMP in the IMCD, but it does increase the level of intracellular calcium. Since we also showed that hypertonicity increases both the phosphorylation and biotinylation of the urea transporters UT-A1 and UT-A3, this would suggest involvement of a calcium-dependent protein kinase in the regulation of urea transport in the inner medulla. In this study, we investigated whether protein kinase C (PKC), which is present in the IMCD, is a regulator of urea permeability. We tested the effect of PKC inhibitors and activators on urea permeability in the isolated, perfused rat terminal IMCD. Increasing osmolality from 290 to 690 mosmol/kgH2O significantly stimulated (doubled) urea permeability; it returned to control levels on inhibition of PKC with either 10 μM chelerythrine or 50 μM rottlerin. To determine the potential synergy between vasopressin and PKC, phorbol dibutyrate (PDBu) was used to stimulate PKC. Vasopressin stimulated urea permeability 247%. Although PDBu alone did not change basal urea permeability, in the presence of vasopressin, it significantly increased urea permeability an additional 92%. The vasopressin and PDBu-stimulated urea permeability was reduced to AVP alone levels by inhibition of PKC. We conclude that hypertonicity stimulates urea transport through a PKC-mediated phosphorylation. Whether PKC directly phosphorylates UT-A1 and/or UT-A3 or phosphorylates it as a consequence of a cascade of activations remains to be determined.
AMP-activated protein kinase inhibits KCNQ1 channels through regulation of the ubiquitin ligase Nedd4-2 in renal epithelial cells
Authors: Alzamora Rodrigo , Gong Fan , Rondanino Christine , Lee Jeffrey K. , Smolak Christy , Pastor-Soler Núria M. , Hallows Kenneth R.
Published: September 2010

The KCNQ1 K+channel plays a key role in the regulation of several physiological functions, including cardiac excitability, cardiovascular tone, and body electrolyte homeostasis. The metabolic sensor AMP-activated protein kinase (AMPK) has been shown to regulate a growing number of ion transport proteins. To determine whether AMPK regulates KCNQ1, we studied the effects of AMPK activation on KCNQ1 currents in Xenopus laevis oocytes and collecting duct epithelial cells. AMPK activation decreased KCNQ1 currents and channel surface expression in X. laevis oocytes, but AMPK did not phosphorylate KCNQ1 in vitro, suggesting an indirect regulatory mechanism. As it has been recently shown that the ubiquitin-protein ligase Nedd4-2 inhibits KCNQ1 plasma membrane expression and that AMPK regulates epithelial Na+channels via Nedd4-2, we examined the role of Nedd4-2 in the AMPK-dependent regulation of KCNQ1. Channel inhibition by AMPK was blocked in oocytes coexpressing either a dominant-negative or constitutively active Nedd4-2 mutant, or a Nedd4-2 interaction-deficient KCNQ1 mutant, suggesting that Nedd4-2 participates in the regulation of KCNQ1 by AMPK. KCNQ1 is expressed at the basolateral membrane in mouse polarized kidney cortical collecting duct (mpkCCDc14) cells and in rat kidney. Treatment with the AMPK activators AICAR (2 mM) or metformin (1 mM) reduced basolateral KCNQ1 currents in apically permeabilized polarized mpkCCDc14cells. Moreover, AICAR treatment of rat kidney slices ex vivo induced AMPK activation and intracellular redistribution of KCNQ1 from the basolateral membrane in collecting duct principal cells. AICAR treatment also induced increased ubiquitination of KCNQ1 immunoprecipitated from kidney slice homogenates. These results indicate that AMPK inhibits KCNQ1 activity by promoting Nedd4-2-dependent channel ubiquitination and retrieval from the plasma membrane.
In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule
Authors: Ackermann Daniel , Gresko Nikolay , Carrel Monique , Loffing-Cueni Dominique , Habermehl Daniel , Gomez-Sanchez Celso , Rossier Bernard C. , Loffing Johannes
Published: September 2010

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the aldosterone-sensitive distal nephron (ASDN), which comprises the segment-specific cells of late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). We used MR- and GR-specific antibodies to study localization and regulation of MR and GR in kidneys of rats with altered plasma aldosterone and corticosterone levels. In control rats, MR and GR were found in cell nuclei of thick ascending limb (TAL), DCT, CNT, CD cells, and intercalated cells (IC). GR was also abundant in cell nuclei and the subapical compartment of proximal tubule (PT) cells. Dietary NaCl loading, which lowers plasma aldosterone, caused a selective removal of GR from cell nuclei of 11β-HSD2-positive ASDN. The nuclear localization of MR was unaffected. Adrenalectomy (ADX) resulted in removal of MR and GR from the cell nuclei of all epithelial cells. Aldosterone replacement rapidly relocated the receptors in the cell nuclei. In ASDN cells, low-dose corticosterone replacement caused nuclear localization of MR, but not of GR. The GR was redistributed to the nucleus only in PT, TAL, early DCT, and IC that express no or very little 11β-HSD2. In ASDN cells, nuclear GR localization was only achieved when corticosterone was replaced at high doses. Thus ligand-induced nuclear translocation of MR and GR are part of MR and GR regulation in the kidney and show remarkable segment- and cell type-specific characteristics. Differential regulation of MR and GR may alter the level of heterodimerization of the receptors and hence may contribute to the complexity of corticosteroid effects on ASDN function.
Vortex formation time-to-left ventricular early rapid filling relation: model-based prediction with echocardiographic validation
Authors: Ghosh Erina , Shmuylovich Leonid , Kovács Sándor J.
Published: September 2010

During early rapid filling, blood aspirated by the left ventricle (LV) generates an asymmetric toroidal vortex whose development has been quantified using vortex formation time (VFT), a dimensionless index defined by the length-to-diameter ratio of the aspirated (equivalent cylindrical) fluid column. Since LV wall motion generates the atrioventricular pressure gradient resulting in the early transmitral flow (Doppler E-wave) and associated vortex formation, we hypothesized that the causal relation between VFT and diastolic function (DF), parametrized by stiffness, relaxation, and load, can be elucidated via kinematic modeling. Gharib et al. (Gharib M, Rambod E, Kheradvar A, Sahn DJ, Dabiri JO. Proc Natl Acad Sci USA 103: 6305–6308, 2006) approximated E-wave shape as a triangle and calculated VFTGharib as triangle (E-wave) area (cm) divided by peak (Doppler M-mode derived) mitral orifice diameter (cm). We used a validated kinematic model of filling for the E-wave as a function of time, parametrized by stiffness, viscoelasticity, and load. To calculate VFTkinematic, we computed the curvilinear E-wave area (using the kinematic model) and divided it by peak effective orifice diameter. The derived VFT-to-LV early rapid filling relation predicts VFT to be a function of peak E-wave-to-peak mitral annular tissue velocity (Doppler E′-wave) ratio as (E/E′)3/2. Validation utilized 262 cardiac cycles of simultaneous echocardiographic high-fidelity hemodynamic data from 12 subjects. VFTGharib and VFTkinematic were calculated for each subject and were well-correlated ( R2 = 0.66). In accordance with prediction, VFTkinematic to (E/E′)3/2 relationship was validated ( R 2 = 0.63). We conclude that VFTkinematic is a DF index computable in terms of global kinematic filling parameters of stiffness, viscoelasticity, and load. Validation of the fluid mechanics-to-chamber kinematics relation unites previously unassociated DF assessment methods and elucidates the mechanistic basis of the strong correlation between VFT and (E/E′)3/2.
Dipole Source Analyses of Early Median Nerve SEP Components Obtained From Subdural Grid Recordings
Authors: Baumgärtner Ulf , Vogel Hagen , Ohara Shinji , Treede Rolf-Detlef , Lenz Fred A.
Published: September 2010

The median nerve N20 and P22 SEP components constitute the initial response of the primary somatosensory cortex to somatosensory stimulation of the upper extremity. Knowledge of the underlying generators is important both for basic understanding of the initial sequence of cortical activation and to identify landmarks for eloquent areas to spare in resection planning of cortex in epilepsy surgery. We now set out to localize the N20 and P22 using subdural grid recording with special emphasis on the question of the origin of P22: Brodmann area 4 versus area 1. Electroencephalographic dipole source analysis of the N20 and P22 responses obtained from subdural grids over the primary somatosensory cortex after median nerve stimulation was performed in four patients undergoing epilepsy surgery. Based on anatomical landmarks, equivalent current dipoles of N20 and P22 were localized posterior to ( n = 2) or on the central sulcus ( n = 2). In three patients, the P22 dipole was located posterior to the N20 dipole, whereas in one patient, the P22 dipole was located on the same coordinate in anterior-posterior direction. On average, P22 sources were found to be 6.6 mm posterior [and 1 mm more superficial] compared with the N20 sources. These data strongly suggest a postcentral origin of the P22 SEP component in Brodmann area 1 and render a major precentral contribution to the earliest stages of processing from the primary motor cortex less likely.
Microstimulation of Posterior Parietal Cortex Biases the Selection of Eye Movement Goals During Search
Authors: Mirpour Koorosh , Ong Wei Song , Bisley James W.
Published: September 2010

People can find objects in a visual scene fast and effortlessly. It is thought that this may be accomplished by creating a map of the outside world that incorporates bottom-up sensory and top-down cognitive inputs—a priority map. Eye movements are made toward the location represented by the highest activity on the priority map. We hypothesized that the lateral intraparietal area (LIP) of posterior parietal cortex acts as such a map. To test this, we performed low current microstimulation on animals trained to perform a foraging task and asked whether we could bias the animals to make a saccade to a particular stimulus, by creating an artificial peak of activity at the location representing that stimulus on the map. We found that microstimulation slightly biased the animals to make saccades to visual stimuli at the stimulated location, without actively generating saccades. The magnitude of this effect was small, but it appeared to be similar for all visual stimuli. We interpret these results to mean that microstimulation slightly biased saccade goal selection to the object represented at the stimulated location in LIP.
Cholinergic Modulation of Neuronal Excitability in the Accessory Olfactory Bulb
Authors: Smith Richard S. , Araneda Ricardo C.
Published: September 2010

The accessory olfactory bulb (AOB), the first relay of chemosensory information in the Vomeronasal system, receives extensive cholinergic innervation from the basal forebrain. Cholinergic modulation of neuronal activity in the olfactory bulb has been hypothesized to play an important role in olfactory processing; however, little is known about the cellular actions of acetylcholine (ACh) within the AOB. Here using in vitro slice preparation, we show that muscarinic acetylcholine receptor (mAChR) activation increases neuronal excitability of granule and mitral/tufted cells (GCs and MCs) in the AOB. Activation of mAChRs increased excitability of GCs by three distinct mechanisms: induction of a long-lasting depolarization, activation of a slow afterdepolarization (sADP), and an increase in excitatory glutamatergic input due to MC depolarization. The depolarization and sADP were elicited by the selective agonist 4-[[[(3-chlorophenyl)amino]carbonyl]oxy]- N,N,N-trimethyl-2-butyn-1-aminium chloride (100 μM) and blocked by low concentrations of pirenzepine (300 nM), indicating that they result from activation of M1-like mAChRs. In contrast, cholinergic stimulation increased the excitability of MCs via recruitment of nicotinic AChRs (nAChRs) and M1-like mAChRs. Submaximal activation of these receptors, however, decreased the excitability of MCs. Surprisingly, we found that unlike GCs in the main olfactory bulb, GCs in the AOB are excited by mAChR activation in young postnatal neurons, suggesting marked differences in cholinergic regulation of development between these two regions of the olfactory bulb.
Visual Stimulation Decorrelates Neuronal Activity
Authors: Oram Mike W.
Published: September 2010

The accuracy of neuronal encoding depends on the response statistics of individual neurons and the correlation of the activity between different neurons. Here, the dynamics of the neuronal response statistics in the anterior superior temporal sulcus of the macaque monkey is described. A transient reduction in the normalized trial-by-trial variability and decorrelation of the responses with both the activity of other neurons and previous activity of the same neuron are found at response onset. The variability of neuronal activity and its correlation structure return to the levels observed in the resting state 50–100 ms after response onset, except for marked increases in the signal correlation between neurons. The transient changes in the response statistics are seen even if there is little or no stimulus-elicited activity, indicating the effect is due to network properties rather than to activity changes per se. Modeling also indicates that the observed variations in response variability and correlation structure of the neuronal activity over time cannot be attributed to changes in firing rate. However, a reset of the underlying spike-generating process, possibly due to the driving input changing from recurrent to feedforward inputs, captures most of the observed changes. The nonstationarity indicated by the changes in correlation structure around response onset increases coding efficiency: compared with the mutual information calculated without regard to the transitory changes, the decorrelation increases the information conveyed by the initial response of modeled neuronal pairs by ≤24% and suggests that an integration time of as little as 50 ms is sufficient to extract 95% the available information during the initial response period.
Nanocrack Formation in Hematite through the Dehydration of Goethite and the Carbon Infiltration from Biotar
Authors: Kashiwaya Yoshiaki , Akiyama Tomohiro
Published: September 2010

The cracks in nano‐order are generated and propagated when the combined water is released during the dehydration. If the nanopore can be utilized for a reaction site, the overall reaction can be extremely accelerated. On the other hand, it is well known that woody biomass is an attractive alternative fuel for the reduction of CO2 emission. However, the process of biomass pyrolysis is disturbed by the tar which causes a clogging in gas tubing system. Hata et al. found that the tar was consumed almost 100% in the iron ore layer having nanocrack or nanopore. The nanocracks formed in hematite crystals after dehydration of goethite were about 4 nm in width, which is in excellent agreement with the result of BET measurement. When the carbon deposited from tar into the nanocracks, reduction reactions were occurred simultaneously. The deposited carbons completely infilled into the nanocracks and the void in the sample.
On the Critical Case in Oscillation for Differential Equations with a Single Delay and with Several Delays
Authors: Baštinec Jaromír , Berezansky Leonid , Diblík Josef , Šmarda Zdeněk
Published: September 2010

New nonoscillation and oscillation criteria are derived for scalar delay differential equations and
and t ≥ t0, in the critical case including equations with several unbounded delays,
without the usual assumption that the parameters
a, h, ak, and hk of the equations are continuous functions. These conditions improve and extend some known oscillation results in the critical case for delay differential equations.
Evaluation of Traditional Indian Antidiabetic Medicinal Plants for Human Pancreatic Amylase Inhibitory Effect In Vitro
Authors: Ponnusamy Sudha , Ravindran Remya , Zinjarde Smita , Bhargava Shobha , Ravi Kumar Ameeta
Published: September 2010

Pancreatic α‐amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia via control of starch breakdown. Eleven Ayurvedic Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α‐amylase inhibition, in order to assess and evaluate their inhibitory potential on pancreatic α‐amylase. Analysis of 91 extracts, showed that 10 exhibited strong Human Pancreatic Amylase (HPA) inhibitory potential. Of these, 6 extracts showed concentration dependent inhibition with IC50 values, namely, cold and hot water extracts from Ficus bengalensis bark (4.4 and 125 μgmL−1), Syzygium cumini seeds (42.1 and 4.1 μgmL−1), isopropanol extracts of Cinnamomum verum leaves (1.0 μgmL−1) and Curcuma longa rhizome (0.16 μgmL−1). The other 4 extracts exhibited concentration independent inhibition, namely, methanol extract of Bixa orellana leaves (49 μgmL−1), isopropanol extract from Murraya koenigii leaves (127 μgmL−1), acetone extracts from C. longa rhizome (7.4 μgmL−1) and Tribulus terrestris seeds (511 μgmL−1). Thus, the probable mechanism of action of the above fractions is due to their inhibitory action on HPA, thereby reducing the rate of starch hydrolysis leading to lowered glucose levels. Phytochemical analysis revealed the presence of alkaloids, proteins, tannins, cardiac glycosides, flavonoids, saponins and steroids as probable inhibitory compounds.
Brick1 Is an Essential Regulator of Actin Cytoskeleton Required for Embryonic Development and Cell Transformation
Authors: Escobar Beatriz , de Cárcer Guillermo , Fernández-Miranda Gonzalo , Cascón Alberto , Bravo-Cordero José J. , Montoya María C. , Robledo Mercedes , Cañamero Marta , Malumbres Marcos
Published: September 2010

Brick1 (Brk1) is the less-studied component of the Wave/Scar pathway involved in the branched nucleation of actin fibers. The clinical relevance of Brk1 is emphasized by correlative data showing that Von Hippel-Lindau (VHL) patients that also lose the BRK1 gene are protected against the development of tumors. This contrasts with recent evidence suggesting that the Wave complex may function as an invasion suppressor in epithelial cancers. Here, we show that the downregulation of Brk1 results in abnormal actin stress fiber formation and vinculin distribution and loss of Arp2/3 and Wave proteins at the cellular protrusions. Brk1 is required for cell proliferation and cell transformation by oncogenes. In addition, Brk1 downregulation results in defective directional migration and invasive growth in renal cell carcinoma cells as well as in other tumor cell types. Finally, genetic ablation of Brk1 results in dramatic defects in embryo compaction and development, suggesting an essential role for this protein in actin dynamics. Thus, genetic loss or inhibition of BRK1 is likely to be protective against tumor development due to proliferation and motility defects in affected cells. Cancer Res; 70(22); 9349–59. ©2010 AACR.
A New Paradigm for Aptamer Therapeutic AS1411 Action: Uptake by Macropinocytosis and Its Stimulation by a Nucleolin-Dependent Mechanism
Authors: Reyes-Reyes E. Merit , Teng Yun , Bates Paula J.
Published: September 2010

AS1411 is a first-in-class anticancer agent, currently in phase II clinical trials. It is a quadruplex-forming oligodeoxynucleotide that binds to nucleolin as an aptamer, but its mechanism of action is not completely understood. Mechanistic insights could lead to clinically useful markers for AS1411 response and to novel targeted therapies. Previously, we proposed a model where cell surface nucleolin serves as the receptor for AS1411, leading to selective uptake in cancer cells. Here, we compare uptake of fluorophore-labeled AS1411 (FL-AS1411) in DU145 prostate cancer cells (sensitive to AS1411) and Hs27 nonmalignant skin fibroblasts (resistant to AS1411). Uptake of FL-AS1411 occurred by endocytosis in both cell types and was much more efficient than an inactive, nonquadruplex oligonucleotide. Unexpectedly, uptake of FL-AS1411 was lower in cancer cells compared with Hs27 cells. However, the mechanism of uptake was different, occurring by macropinocytosis in cancer cells, but by a nonmacropinocytic pathway in Hs27 cells. Additionally, treatment of various cancer cells with AS1411 caused hyperstimulation of macropinocytosis, provoking an increase in its own uptake, whereas no stimulation was observed for nonmalignant cells. Nucleolin was not required for initial FL-AS1411 uptake in DU145 cells but was necessary for induced macropinocytosis and FL-AS1411 uptake at later times. Our results are inconsistent with the previous mechanistic model but confirm that nucleolin plays a role in mediating AS1411 effects. The data suggest a new model for AS1411 action as well as a new role for nucleolin in stimulating macropinocytosis, a process with potential applications in drug delivery. Cancer Res; 70(21); 8617–29. ©2010 AACR.
An Introduction to Instrumental Variables Analysis: Part 1
Authors: Bennett Derrick A.
Published: September 2010

There are several examples in the medical literature where the associations of treatment effects predicted by observational studies have been refuted by evidence from subsequent large-scale randomised trials. This is because of the fact that non-experimental studies are subject to confounding – and confounding cannot be entirely eliminated even if all known confounders have been measured in the study as there may be unknown confounders. The aim of this 2-part methodological primer is to introduce an emerging methodology for estimating treatment effects using observational data in the absence of good randomised evidence known as the method of instrumental variables.
Gender Imbalances Induced by Age Limits in Stroke Trials
Authors: Foerch Christian , Czapowski Dirk , Misselwitz Bjoern , Steinmetz Helmuth , Neumann-Haefelin Tobias ,   for the Arbeitsgruppe Schlaganfall Hessen (ASH)
Published: September 2010

Background: Gender differences in life expectancy result in a higher proportion of women in the older population. This causes a female preponderance among elderly patients with ischaemic stroke. On the other hand, upper age limits are frequently used in clinical trials, in part due to safety reasons and logistical concerns. In this study, we model how applying upper age limits will lead to a gender disparity in stroke trials, favouring the inclusion of men rather than women. Methods: We analyzed a prospective hospital-based stroke registry covering the entire Federal State of Hesse, Germany. All cases with admission between 2003 and 2005 and a final diagnosis of ischaemic stroke (ICD10:I63) were selected. For various upper age limits (70, 75, 80, 85 and 90 years), we calculated the proportion of men and women excluded based on their age when applying the respective age span to the study population. Results: A total of 34,754 patients were analyzed, and 17,748 (51%) hereof were women. Their mean age was 73.6 ± 12.1 years. The women were older than the men (76.8 ± 11.7 years vs. 70.2 ± 11.7 years; p < 0.001). All upper age limits provoked a significant gender disparity by leaving a higher proportion of female than male patients outside the admissible range. In particular, selecting 80 years as the upper age cut-off excluded 19% of all male patients but 44% of all female patients (p < 0.001). Conclusions: Setting an upper age limit for ischaemic stroke trials is likely not to be gender neutral but withholds a higher proportion of female than male patients from study participation. Investigators should be aware of such gender imbalances, which may involuntarily be transferred into routine clinical practice.
Association between Non-Diminutive Hyperplastic Polyps and Synchronous Advanced Colorectal Neoplasms
Authors: Lim Hyun Min , Kim Eun Ran , Kim Jin Yong , Chang Dong Kyung , Son Hee Jung , Rhee Poong-Lyul , Kim Jae J. , Rhee Jong Chul , Kim Young-Ho
Published: September 2010

Background/Aims: Many studies have suggested that hyperplastic polyps (HPs) are associated with adenomas and even malignancy. We investigated whether or not HPs are associated with the presence of synchronous advanced colorectal neoplasms as a function of their size and location. Methods: A total of 2,482 asymptomatic patients who underwent screening colonoscopies were classified into the following two groups: cases with advanced neoplasms and controls without advanced neoplasms. The proximal colon was defined as all segments proximal to the splenic flexure. We defined diminutive HPs as <6 mm in diameter and non-diminutive HPs as ≧6 mm in diameter. Results: The median age of the patients was 51 years. 76.8% (n = 1,909) of the patients were males. 82 patients (3.3%) had at least one advanced neoplasm. Based on multivariate analysis, the independent risk factors for advanced neoplasms were old age (OR = 2.81), male gender (OR = 2.92), non-advanced adenomas (OR = 3.57), and non-diminutive HPs (OR = 4.75, p = 0.000). Having at least one non-diminutive HP in either the proximal or distal colon was associated with an increased risk of advanced neoplasm, with no statistically significant difference (proximal vs. distal colon, OR = 5.95 vs. 5.36). Conclusions: These results suggest that non-diminutive HPs are important markers of advanced colorectal neoplasms regardless of location.
Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion
Authors: Farnebo S. , Winbladh A. , Zettersten E.K. , Sandström P. , Gullstrand P. , Samuelsson A. , Theodorson E. , Sjöberg F.
Published: September 2010

Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.
In vivo Acid Etching Effect on Bacteria within Caries-Affected Dentin
Authors: Gu F. , Bresciani E. , Barata T.J. , Fagundes T.C. , Navarro M.F. , Dickens S.H. , Fenno J.C. , Peters M.C.
Published: September 2010

Acid etching procedures may disrupt residual bacteria and contribute to the success of incomplete caries removal followed by adhesive restoration. This study evaluated the in vivo effect of acid etching on cariogenic bacterial activity within affected dentin after minimally invasive treatment of caries lesions. Twenty-eight carious permanent teeth received standardized selective caries removal and random acid etch treatment (E) or not (NE) prior to adhesive restoration. Baseline and 3-month dentin biopsies were collected. The number of bacteria and activity of total bacterial cells and Streptococcus mutans were determined by quantitative PCR and RT-PCR. No statistically significant differences were observed in total bacterial number and activity between E and NE treatments (p > 0.3008). For NE, however, the residual S. mutans bacterial cells were reduced (p = 0.0027), while the activity per cell was significantly increased (p = 0.0010) after reentry at 3 months after restoration. This effect was not observed in group E. Although no significant differences were found between groups, this study suggests that acid etching of affected dentin prior to adhesive restoration may directly or indirectly have an inhibitive effect on the activity of residual cariogenic bacteria. Further research is required to investigate this potential effect.
Overestimation of Lumbar Spine Calcium with Dual Energy X-Ray Absorptiometry Scanning due to the Prescription of Lanthanum Carbonate in Patients with Chronic Kidney Disease
Authors: Fürstenberg Antje , Buscombe John , Davenport Andrew
Published: September 2010

Background/Aims: Dual energy X-ray absorptiometry (DEXA) scanning is used to assess bone mineral content and diagnose osteoporosis. We had noted anecdotal cases of patients attending for DEXA scanning following recent ingestion of barium-containing radiocontrast media, resulting in spuriously increased bone mineral content. Lanthanum carbonate is prescribed to chronic kidney disease patients as a non-calcium-containing phosphate binder, and as lanthanum is denser than barium, we wondered whether this could affect DEXA scan bone mineral estimations. Methods: DEXA scan records were reviewed from a cohort of 169 chronic dialysis patients, 24 (14%) of whom were prescribed lanthanum carbonate. Results: Estimation of segmental bone mineral content by DEXA was similar between the groups for the arms, legs, ribs, thoracic spine, hips and pelvis, apart from the lumbar spine for which it was greater for the lanthanum group (1.05 ± 0.05 vs. 0.98 ± 0.01 gm/cm2, p < 0.05). Similarly, T and Z scores were higher in the lanthanum group for the lumbar spine (T score: –0.2 ± 0.4 vs. –0.92 ± 0.1; Z score: 0.68 ± 0.4 vs. –0.01 ± 0.1; p < 0.05), but not different for the hip (T score: –1.108 ± 0.28 vs. –0.966 ± 0.09; Z: score –0.49 ± 0.25 vs. –0.3 ± 0.01). Conclusion: DEXA scanning in patients prescribed lanthanum can lead to an erroneously high estimation of bone mineral content in areas of the skeleton adjacent to the bowel when the electron beam meets lanthanum.