bluuebunny/crossref_metadata_2025 huggingface dataset:
The Palaeozoic palaeogeography of central Gondwana
Authors: Torsvik Trond H. , Cocks L. Robin M.
Published: October 2011

Nine new palaeogeographical maps of central Gondwana are presented at intervals within the Palaeozoic from the Middle Cambrian at 510 Ma to the end of the Permian at 250 Ma. The area covered includes all of Africa, Madagascar, India and Arabia as well as adjacent regions, including parts of southern Europe, much of South America (including the Falkland Isles) and Antarctica. After final assembly in the Late Neoproterozoic the southern margin was largely passive throughout the Palaeozoic, apart from some local orogeny in the Cambrian in the final stages of the largely Neoproterozoic Pan-African Orogeny and during the Late Palaeozoic Gondwanide Orogeny. The northern peri-Gondwana margin was active during the Early Palaeozoic but the NW part became passive by the earliest Ordovician when the Rheic Ocean opened between Gondwana and Avalonia. This was eventually followed by the latest Silurian or Early Devonian opening of the Palaeotethys Ocean between Gondwana and Iberia, Armorica and associated terranes and, much later, the rifting and opening of the Neotethys Ocean near the close of the Permian. In the Late Carboniferous, Gondwana merged with Laurussia to form Pangea. That accretion took place outside the area to the NW, although the consequent orogenic activity extended to Morocco and Algeria. Most of the centre of Gondwana was land throughout the Palaeozoic but with extensive shelf seas over the craton margins, particularly the northern margin from the Cambrian to the Devonian on which the important north African and Arabian hydrocarbon source rocks were deposited in the Lower Silurian (with the chief reservoirs in the adjacent Upper Ordovician) and Upper Devonian. There were also substantial Upper Carboniferous and later non-marine lake basins in central and southern Africa in which the Karroo Supergroup was deposited. The South Pole was located within the area from the Early Palaeozoic to the Mid-Permian and central Gondwana was therefore greatly affected by two ice ages: the short but sharp Hirnantian glaciation at the end of the Ordovician and another lasting sporadically for more than 25 Ma during the later Carboniferous and Early Permian.
Rhcg1 and NHE3b are involved in ammonium-dependent sodium uptake by zebrafish larvae acclimated to low-sodium water
Authors: Shih Tin-Han , Horng Jiun-Lin , Liu Sian-Tai , Hwang Pung-Pung , Lin Li-Yih
Published: October 2011

To investigate whether Na+uptake by zebrafish is dependent on NH4+excretion, a scanning ion-selective electrode technique was applied to measure Na+and NH4+gradients at the yolk-sac surface of zebrafish larvae. Low-Na+acclimation induced an inward Na+gradient (uptake), and a combination of low Na+and high NH4+induced a larger inward Na+gradient. When measuring the ionic gradients, raising the external NH4+level (5 mM) blocked NH4+excretion and Na+uptake; in contrast, raising the external Na+level (10 mM) simultaneously enhanced Na+uptake and NH4+excretion. The addition of MOPS buffer (5 mM), which is known to block NH4+excretion, also suppressed Na+uptake. These results showed that Na+uptake and NH4+excretion by larval skin are associated when ambient Na+level is low. Knockdown of Rhcg1 translation with morpholino-oligonucleotides decreased both NH4+excretion and Na+uptake by the skin and Na+content of whole larvae. Knockdown of nhe3b translation or inhibitor (5-ethylisopropyl amiloride) treatment also decreased both the NH4+excretion and Na+uptake. This study provides loss-of-function evidence for the involvement of Rhcg1 and NHE3b in the ammonium-dependent Na+uptake mechanism in zebrafish larvae subjected to low-Na+water.
Enhanced central and conduit pulmonary arterial reservoir function offsets reduced ductal systolic outflow during constriction of the fetal ductus arteriosus
Authors: Smolich Joseph J. , Penny Daniel J. , Mynard Jonathan P.
Published: October 2011

Constriction of the fetal ductus arteriosus (DA) has disparate effects on mean and phasic hemodynamics, as mean DA blood flow is preserved until constriction is severe, but DA systolic and diastolic blood velocities change with only mild constriction. To determine the basis of this disparity and its physiological significance, seven anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and during mild, moderate, and severe DA constriction (defined as pulmonary-aortic mean pressure differences of 4, 8, and 14 mmHg, respectively), produced with an adjustable snare. With DA constriction, mean DA flow was initially maintained but decreased with severe constriction ( P < 0.05) in conjunction with a reduction ( P < 0.05) in PT flow (i.e., right ventricular output). By contrast, DA systolic flow fell progressively during DA constriction ( P < 0.001), due to decreased transmission of both early and midsystolic proximal flow-enhancing forward-running compression waves into the DA. However, DA constriction was also accompanied by greater systolic storage of blood in the PT and main PA ( P < 0.025), and increased retrograde diastolic flow from compliant major branch PA ( P < 0.001). Transductal discharge of these central and conduit PA blood reservoirs in diastole offset systolic DA flow reductions. These data suggest that, during DA constriction in the fetus, enhanced central and conduit PA reservoir function constitutes an important compensatory mechanism that contributes to preservation of mean DA flow via a systolic-to-diastolic redistribution of phasic DA flow.
Two microRNAs, miR-330 and miR-125b-5p, mark the juxtaglomerular cell and balance its smooth muscle phenotype
Authors: Medrano Silvia , Monteagudo Maria C. , Sequeira-Lopez Maria Luisa S. , Pentz Ellen S. , Gomez R. Ariel
Published: October 2011

We have shown that microRNAs (miRNAs) are necessary for renin cell specification and kidney vascular development. Here, we used a screening strategy involving microarray and in silico analyses, along with in situ hybridization and in vitro functional assays to identify miRNAs important for renin cell identity. Microarray studies using vascular smooth muscle cells (SMCs) of the renin lineage and kidney cortex under normal conditions and after reacquisition of the renin phenotype revealed that of 599 miRNAs, 192 were expressed in SMCs and 234 in kidney cortex. In silico analysis showed that the highly conserved miR-330 and miR-125b-5p have potential binding sites in smoothelin ( Smtn), calbindin 1, smooth muscle myosin heavy chain, α-smooth muscle actin, and renin genes important for the myoepithelioid phenotype of the renin cell. RT-PCR studies confirmed miR-330 and miR-125b-5p expression in kidney and SMCs. In situ hybridization revealed that under normal conditions, miR-125b-5p was expressed in arteriolar SMCs and in juxtaglomerular (JG) cells. Under conditions that induce reacquisition of the renin phenotype, miR-125b-5p was downregulated in arteriolar SMCs but remained expressed in JG cells. miR-330, normally absent, was expressed exclusively in JG cells of treated mice. In vitro functional studies showed that overexpression of miR-330 inhibited Smtn expression in SMCs. On the other hand, miR-125b-5p increased Smtn expression, whereas its inhibition reduced Smtn expression. Our results demonstrate that miR-330 and miR-125b-5p are markers of JG cells and have opposite effects on renin lineage cells: one inhibiting and the other favoring their smooth muscle phenotype.
Cholinergic modulation of response gain in the primary visual cortex of the macaque
Authors: Soma Shogo , Shimegi Satoshi , Osaki Hironobu , Sato Hiromichi
Published: October 2011

ACh modulates neuronal activity throughout the cerebral cortex, including the primary visual cortex (V1). However, a number of issues regarding this modulation remain unknown, such as the effect and its function and the receptor subtypes involved. To address these issues, we combined extracellular single-unit recordings and microiontophoretic administration of ACh and measured V1 neuronal responses to drifting sinusoidal grating stimuli in anesthetized macaque monkeys. ACh was found to have mostly facilitatory effects on the visual responses, although some cases of suppressive effects were also seen. To assess the functional role of ACh, we further examined how ACh modulates the stimulus contrast-response function, finding that the response gain increased with the facilitatory effect. The response facilitation was completely or strongly blocked by atropine (At), a muscarinic ACh receptor (mAChR) antagonist, in almost all neurons (96% of cells), whereas any residual effect after At administration was fully removed by mecamylamine, a nicotinic AChR (nAChR) antagonist, suggesting a predominant role for mAChRs in this mechanism. Furthermore, we found no laminar distribution bias for the facilitatory modulation, although the relative contribution of mAChRs was smaller in layer 4C than in other layers. The suppressive effect was blocked completely by At. These results demonstrate that ACh plays an important role in visual information processing in V1 by controlling the response gain via mAChRs across all cortical layers and via nAChRs, mainly in layer 4C.
Low-threshold calcium currents contribute to locomotor-like activity in neonatal mice
Authors: Anderson Tatiana M. , Abbinanti Matthew D. , Peck Jack H. , Gilmour Megan , Brownstone Robert M. , Masino Mark A.
Published: October 2011

In this study, we examined the contribution of a low-threshold calcium current [ICa(T)] to locomotor-related activity in the neonatal mouse. Specifically, the role of ICa(T)was studied during chemically induced, locomotor-like activity in the isolated whole cord and in a genetically distinct population of ventromedial spinal interneurons marked by the homeobox gene Hb9. In isolated whole spinal cords, cycle frequency was decreased in the presence of low-threshold calcium channel blockers, which suggests a role for ICa(T)in the network that produces rhythmic, locomotor-like activity. Additionally, we used Hb9 interneurons as a model to study the cellular responses to application of low-threshold calcium channel blockers. In transverse slice preparations from transgenic Hb9::enhanced green fluorescent protein neonatal mice, N-methyl-d-aspartate-induced membrane potential oscillations in identified Hb9 interneurons also slowed in frequency with application of nickel when fast, spike-mediated, synaptic transmission was blocked with TTX. Voltage-clamp and immunolabeling experiments confirmed expression of ICa(T)and channels, respectively, in Hb9 interneurons located in the ventromedial spinal cord. Taken together, these results provide support that T-type calcium currents play an important role in network-wide rhythm generation during chemically evoked, fictive locomotor activity.
Vibrissae motor cortex unit activity during whisking
Authors: Friedman Wendy A. , Zeigler H. Philip , Keller Asaf
Published: October 2011

Rats generate stereotyped exploratory (5–12 Hz) vibrissa movements when navigating through their environment. Like other rhythmic behaviors, the production of whisking relies on a subcortical pattern generator. However, the relatively large vibrissae representation in motor cortex (vMCx) suggests that cortex also contributes to the control of whisker movements. The goal of this study was to examine the relationship between neuronal activity in vMCx and the kinematics of vibrissae movements. We recorded multiunit activity (MUA) and single units in the rhythmic region of vMCx while measuring vibrissa position in awake, head-restrained rats. The rats were engaged in one of two behavioral tasks where they were rewarded for either 1) producing noncontact whisking epochs that met specified criteria (epochs ≥4 Hz, whisks >5 mm) or 2) whisking to contact an object. There was significant coherence between the frequency of MUA and vibrissae movements during free-air whisking but not when animals were using their vibrissae to contact an object. Spike rate in vMCx was most frequently correlated with the amplitude of vibrissa movements; correlations with movement frequency did not exceed chance levels. These findings suggest that the specific parameter under cortical control may be the amplitude of whisker movements.
Transmitting Intrinsic Value Priorities from Mothers to Adolescents: The Moderating Role of a Supportive Family Environment
Authors: Lekes Natasha , Joussemet Mireille , Koestner Richard , Taylor Geneviève , Hope Nora H. , Gingras Isabelle
Published: October 2011

This study tested the degree to which a need-supportive family environment influences adolescents' endorsement of the value priorities that their mothers wish for them. Mothers and their adolescents (N=280) rated the importance of three intrinsic values (personal growth, close relationships, and community contribution) and three extrinsic values (wealth, fame, and attractiveness). Results revealed that mothers placed greater emphasis on intrinsic over extrinsic values than did adolescents. Furthermore, the congruence of mothers' and adolescents' emphasis on intrinsic values was moderated by the extent to which adolescents experienced satisfaction of their basic needs for autonomy, relatedness, and competence at home. Finally, the well-being of both adolescents and mothers was associated with the degree to which they prioritized intrinsic over extrinsic values. Implications for research on the transmission of values and goals are discussed.
New Criteria of Indication and Selection of Patients to Cochlear Implant
Authors: Sampaio André L. L. , Araújo Mercêdes F. S. , Oliveira Carlos A. C. P.
Published: October 2011

Numerous changes continue to occur in cochlear implant candidacy. In general, these have been accompanied by concomitant and satisfactory changes in surgical techniques. Together, this has advanced the utility and safety of cochlear implantation. Most devices are now approved for use in patients with severe to profound unilateral hearing loss rather then the prior requirement of a bilateral profound loss. Furthermore, studies have begun utilizing short electrode arrays for shallow insertion in patients with considerable low-frequency residual hearing. This technique will allow the recipient to continue to use acoustically amplified hearing for the low frequencies simultaneously with a cochlear implant for the high frequencies. The advances in design of, and indications for, cochlear implants have been matched by improvements in surgical techniques and decrease in complications. The resulting improvements in safety and efficacy have further encouraged the use of these devices. This paper will review the new concepts in the candidacy of cochlear implant. Medline data base was used to search articles dealing with the following topics: cochlear implant in younger children, cochlear implant and hearing preservation, cochlear implant for unilateral deafness and tinnitus, genetic hearing loss and cochlear implant, bilateral cochlear implant, neuropathy and cochlear implant and neural plasticity, and the selection of patients for cochlear implant.
IL-17F Induces CCL20 in Bronchial Epithelial Cells
Authors: Nozato Kyoko , Fujita Junichi , Kawaguchi Mio , Ohara Gen , Morishima Yuko , Ishii Yukio , Huang Shau-Ku , Kokubu Fumio , Satoh Hiroaki , Hizawa Nobuyuki
Published: October 2011

IL-17F plays a crucial role in airway inflammatory diseases including asthma, but its function has not been fully elucidated. CCL20 is also involved in allergic airway inflammation, while its regulatory mechanisms remain to be defined. To further identify a novel role of IL-17F, the expression of CCL20 by IL-17F in bronchial epithelial cells and the signaling mechanisms involved were investigated. Bronchial epithelial cells were stimulated with IL-17F, and the levels of CCL20 gene and protein measured, with the effects of the addition of various kinase inhibitors and siRNAs also investigated. IL-17F significantly induced the expression of CCL20 gene and protein. Pretreatment with inhibitors for MEK1/2, Raf1 and MSK1, and overexpression of a Raf1 dominant-negative mutant significantly diminished IL-17F-induced CCL20 production. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked CCL20 expression. These findings suggest that IL-17F is able to induce CCL20 via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. The IL-17F/CCL20 axis may be a novel pharmacological target for asthma.
Direct Quantitative Detection and Identification of Lactococcal Bacteriophages from Milk and Whey by Real-Time PCR: Application for the Detection of Lactococcal Bacteriophages in Goat's Raw Milk Whey in France
Authors: Ly-Chatain Mai Huong , Durand Loïc , Rigobello Véronique , Vera Annabelle , Demarigny Yann
Published: October 2011

The presence ofLactococcusbacteriophages in milk can partly or completely inhibit milk fermentation. To prevent the problems associated with the bacteriophages, the real-time PCR was developed in this study for direct detection from whey and milk of three main groups ofLactococcusbacteriophages, c2, 936, and P335. The optimization of DNA extraction protocol from complex matrices such as whey and milk was optimized allowed the amplification of PCR without any matrix and nontarget contaminant interference. The real-time PCR program was specific and with the detection limit of 102PFU/mL. The curve slopes were −3.49, −3.69, and −3.45 with the amplification efficiency estimated at 94%, 94%, and 98% and the correlation coefficient () of 0.999, 0.999, and 0.998 for c2, 936 and P335 group, respectively. This method was then used to detect the bacteriophages in whey and goat's raw milk coming from three farms located in the Rhône-Alpes region (France).
Impact of Vehicular Array Position on Urban MIMO Channel Characteristics
Authors: Squires Christopher C. , Willink Tricia J.
Published: October 2011

MIMO channel measurements have been performed in urban environments with antenna arrays positioned on the roof and sides of the measurement vehicle. Analysis of the data shows that the array's position on the vehicle, along with the location and orientation of the vehicle with respect to the transmitter, can have a considerable impact on the channel characteristics observed. Array elements on the vehicle's roof receive the same multipath components, and, therefore, have identically distributed channel responses. However, the characteristics of the multipath components observed at each side of the vehicle can differ significantly. Specifically, shadowing from the vehicle combined with the directionality of the side-mounted array elements affects the angular distribution and powers of the received multipath components, affecting the achievable diversity and channel capacity. This can have significant impact on system performance and should be considered when designing and analyzing vehicular-based signalling techniques.
Practical Stability in terms of Two Measures for Impulsive Differential Equations with “Supremum”
Authors: Hristova S. G. , Georgieva A.
Published: October 2011

The object of investigations is a system of impulsive differential equations with “supremum.” These equations are not widely studied yet, and at the same time they are adequate mathematical model of many real world processes in which the present state depends significantly on its maximal value on a past time interval. Practical stability for a nonlinear system of impulsive differential equations with “supremum” is defined and studied. It is applied Razumikhin method with piecewise continuous scalar Lyapunov functions and comparison results for scalar impulsive differential equations. To unify a variety of stability concepts and to offer a general framework for the investigation of the stability theory, the notion of stability in terms of two measures has been applied to both the given system and the comparison scalar equation. An example illustrates the usefulness of the obtained sufficient conditions.
Characterization of Series Resistance and Mobility Degradation Parameter and Optimizing Choice of Oxide Thickness in Thin OxideN-Channel MOSFET
Authors: Maouhoub Noureddine , Rais Khalid
Published: October 2011

We present two methods to extract the series resistance and the mobility degradation parameter in short-channel MOSFETs. The principle of the first method is based on the comparison between the exponential model and the classical model of effective mobility and for the second method is based on directly calculating the two parameters by solving a system of two equations obtained by using two different points in strong inversion at small drain bias from the characteristic (). The results obtained by these techniques have shown a better agreement with data measurements and allowed in the same time to determine the surface roughness amplitude and its influence on the maximum drain current and give the optimal oxide thickness.
Atg14: A Key Player in Orchestrating Autophagy
Authors: Obara Keisuke , Ohsumi Yoshinori
Published: October 2011

Phosphorylation of phosphatidylinositol (PtdIns) by a PtdIns 3-kinase is an essential process in autophagy. Atg14, a specific subunit of one of the PtdIns 3-kinase complexes, targets the complex to the probable site of autophagosome formation, thereby, sorting the complex to function specifically in autophagy. The N-terminal half of Atg14, containing coiled-coil domains, is required to form the PtdIns 3-kinase complex and target it to the proper site. The C-terminal half of yeast Atg14 is suggested to be involved in the formation of a normal-sized autophagosome. The C-terminal half of mammalian Atg14 contains the Barkor/Atg14(L) autophagosome-targeting sequence (BATS) domain that preferentially binds to the highly curved membranes containing PtdIns(3)Pand is proposed to target the PtdIns 3-kinase complex efficiently to the isolation membrane. Thus, the N- and C-terminal halves of Atg14 are likely to have an essential core function and a regulatory role, respectively.
Cloning and Characterization of the ζ‐Carotene Desaturase Gene from Chlorella protothecoides CS‐41
Authors: Li Meiya , Gan Zhibing , Cui Yan , Shi Chunlei , Shi Xianming
Published: October 2011

To elucidate the lutein biosynthesis pathway in the lutein‐producing alga, Chlorella protothecoides CS‐41, the ζ‐carotene desaturase gene (zds) was isolated from Chlorella protothecoides using the approach of rapid amplification of cDNA ends. The full‐length cDNA sequence was 2031 bp and contained 1755 bp putative open reading frame which encodes a 584 amino acid deduced polypeptide whose computed molecular weight was 63.7 kDa. Sequence homology research indicated that the nucleotide and putative protein had sequence identities of 72.5% and 69.5% with those of the green alga Chlamydomonas reinhardtii, respectively. Phylogenetic analysis demonstrated that the ZDS from C. protothecoides CS‐41 had a closer relationship with those of chlorophyta and higher plants than with those of other species. In addition, we also found that the zds gene expression was upregulated in response to light.
Acoustic Phonons in Nanowires with Embedded Heterostructures
Authors: Ayedh Hussein M. , Wacker Andreas
Published: October 2011

Acoustic phonons are studied in finite nanowires based on the elastic continuum model. The phonon dispersion relations are compared for different types of approximations both for pure nanowires and nanowire heterostructures including cubic and wurtzite materials. We find that the isotropic approximation highly underestimates the frequency of torsional modes. The impact of heterostructures on the lowest modes is rather weak and can be described by an average of the different structure parameters.
Retinal Image Matching Using Hierarchical Vascular Features
Authors: Bhuiyan Alauddin , Lamoureux Ecosse , Nath Baikunth , Ramamohanarao Kotagiri , Wong Tien Y.
Published: October 2011

We propose a method for retinal image matching that can be used in image matching for person identification or patient longitudinal study. Vascular invariant features are extracted from the retinal image, and a feature vector is constructed for each of the vessel segments in the retinal blood vessels. The feature vectors are represented in a tree structure with maintaining the vessel segments actual hierarchical positions. Using these feature vectors, corresponding images are matched. The method identifies the same vessel in the corresponding images for comparing the desired feature(s). Initial results are encouraging and demonstrate that the proposed method is suitable for image matching and patient longitudinal study.
Multiple-Scale Interactions Affecting Tropical Cyclone Track Changes
Authors: Luo Zhexian , Davidson Noel E. , Ping Fan , Zhou Weican
Published: October 2011

Tropical Cyclone (TC) track changes associated with Rossby wave energy dispersion are simulated in a shallow water primitive equation model with an initial field where a TC is located south of a subtropical high. An anticyclone east of the TC appears because of Rossby wave energy dispersion. The connection of the anticyclone with the subtropical high leads to a poleward TC track deflection. The TC eventually moves across the axis of the subtropical ridge. The formation of the track may be attributed to the nonlinear interaction between the subtropical high and the TC. This work validates the conceptual model proposed by previous observational research. The scenario of the nonlinear interaction between the TC and the subtropical high may also be modified through the influence of mesoscale vortices. The main modifications are (1) the anticyclone induced by energy dispersion of the TC weakens, (2) the connection between the anticyclone and the subtropical high is delayed, and (3) the TC shifts more westward and does not move across the ridge axis. We propose that some of the mesoscale vortices are axisymmetrized by the TC and results in an increase in TC size which modifies the properties of the energy dispersion. The phase and group speeds decrease and produce a simulated track deflection to the left compared to the simulation without mesoscale vortices. Our numerical results demonstrate that multiple scale nonlinear interactions have an essential role in influencing TC track changes.
Fast Determination of Manganese in Milk and Similar Infant Food Samples Using Multivariate Optimization and GF AAS
Authors: de Amorim Flávia Regina , Nascentes Clésia Cristina , Franco Milton Batista , da Silva José Bento Borba
Published: October 2011

Manganese is an essential element, but high levels in foods can be toxic mainly for children. A fast and efficient method to determine Mn in milk and other infant foods using slurries and liquid samples is presented. Slurries were prepared in ultrapure water with 10 minutes of sonication. Liquid samples were diluted in ultrapure water when necessary. Multivariate optimization was used to establish some optimal analytical parameters through a fractional factorial design and a central composite design. Slurred and diluted samples were analyzed directly by GF AAS. The method presented limit of detection of (0.98 ± 0.04) μg L−1, characteristic mass of (2.9 ± 0.3) pg (recommended value 2 pg), RSD of 2.3% (n = 5), and linear range from 0.98 to 20.0 μg L−1 using iridium as permanent modifier. The accuracy was evaluated analyzing two certified reference materials: nonfat milk powder (SRM1549) and whole milk powder (SRM8435). The powdered samples concentrations were between 0.210 and 26.3 μg g−1.
The Evolution of the Mitochondria‐to‐Calcium Release Units Relationship in Vertebrate Skeletal Muscles
Authors: Franzini-Armstrong Clara , Boncompagni Simona
Published: October 2011

The spatial relationship between mitochondria and the membrane systems, more specifically the calcium release units (CRUs) of skeletal muscle, is of profound functional significance. CRUs are the sites at which Ca2+ is released from the sarcoplasmic reticulum during muscle activation. Close mitochondrion‐CRU proximity allows the organelles to take up Ca2+ and thus stimulate aerobic metabolism. Skeletal muscles of most mammals display an extensive, developmentally regulated, close mitochondrion‐CRU association, fostered by tethering links between the organelles. A comparative look at the vertebrate subphylum however shows that this specific association is only present in the higher vertebrates (mammals). Muscles in all other vertebrates, even if capable of fast activity, rely on a less precise and more limited mitochondrion‐CRU proximity, despite some tethering connections. This is most evident in fish muscles. Clustering of free subsarcolemmal mitochondria in proximity of capillaries is also more frequently achieved in mammalian than in other vertebrates.
Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: The Difficulty in Interpreting Proof-of-Concept Studies
Authors: Gordon Jessica , Spiera Robert
Published: October 2011

Tyrosine kinase inhibitors (TKIs) have emerged as a targeted therapy of interest for the treatment of systemic sclerosis (SSc). Recently, several groups have performed pilot or “proof-of-concept” studies to determine the feasibility of this approach for the treatment of the cutaneous and pulmonary manifestations of this multisystem disease. The conclusions drawn by these different studies have been conflicting, and some controversy has arisen as to whether tyrosine kinase inhibition is a treatment approach worthy of continued study. This paper summarizes this research to date with emphasis on the challenges in interpreting proof-of-concept studies in this patient group.
A Novel Sandwich Electrochemical Immunosensor Based on the DNA-Derived Magnetic Nanochain Probes for Alpha-Fetoprotein
Authors: Gan Ning , Jia Liyong , Zheng Lei
Published: October 2011

One novel electrochemical immunosensor was constructed by immobilizing capture antibody of alpha-fetoprotein (AFP Ab1) on a nafion/nanogold-particle modified glassy carbon electrode. With a sandwich immunoassay, one DNA-derived magnetic nanoprobe, simplified as DNA/(ZMPs—HRP-AFP Ab2)n, was employed for the detection of AFP. The fabricated procedure of the proposed biosensor was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. The performance and factors influencing the performance of the biosensor were also evaluated. Under optimal conditions, the developed biosensor exhibited a well-defined electrochemical behavior toward the reduction of AFP ranging from 0.01 to 200 ng/mL with a detection limit of 4 pg/mL (S/N=3). The biosensor was applied to the determination of AFP in serum with satisfactory results. It is important to note that the sandwich nanochainmodified electro-immunosensor provided an alternative substrate for the immobilization of other tumor markers.
Glucan Particles for Macrophage Targeted Delivery of Nanoparticles
Authors: Soto Ernesto R. , Caras Abaigeal C. , Kut Lindsey C. , Castle Melissa K. , Ostroff Gary R.
Published: October 2011

Glucan particles (GPs) are hollow, porous 2–4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of soluble payloads (DNA, siRNA, protein, and small molecules) encapsulated inside the hollow GPs via core polyplex and layer-by-layer (LbL) synthetic strategies. In this communication, we report the incorporation of nanoparticles as cores inside GPs (GP-NP) or electrostatically bound to the surface of chemically derivatized GPs (NP-GP). GP nanoparticle formulations benefit from the drug encapsulation properties of NPs and the macrophage-targeting properties of GPs. GP nanoparticle formulations were synthesized using fluorescent anionic polystyrene nanoparticles allowing visualization and quantitation of NP binding and encapsulation. Mesoporous silica nanoparticles (MSNs) containing the chemotherapeutic doxorubicin (Dox) were bound to cationic GPs. Dox-MSN-GPs efficiently delivered Dox into GP phagocytic cells resulting in enhanced Dox-mediated growth arrest.
Revisiting the Role of Neighbourhood Change in Social Exclusion and Inclusion of Older People
Authors: Burns Victoria F. , Lavoie Jean-Pierre , Rose Damaris
Published: October 2011

Objective. To explore how older people who are “aging in place” are affected when the urban neighbourhoods in which they are aging are themselves undergoing socioeconomic and demographic change.Methods. A qualitative case study was conducted in two contrasting neighbourhoods in Montréal (Québec, Canada), the analysis drawing on concepts of social exclusion and attachment.Results. Participants express variable levels of attachment to neighbourhood. Gentrification triggered processes of social exclusion among older adults: loss of social spaces dedicated to older people led to social disconnectedness, invisibility, and loss of political influence on neighbourhood planning. Conversely, certain changes in a disadvantaged neighbourhood fostered their social inclusion.Conclusion. This study thus highlights the importance of examining the impacts of neighbourhood change when exploring the dynamics of aging in place and when considering interventions to maintain quality of life of those concerned.
VEGF Spliced Variants: Possible Role of Anti-Angiogenesis Therapy
Authors: Hilmi Caroline , Guyot Mélanie , Pagès Gilles
Published: October 2011

Angiogenesis has been targeted in retinopathies, psoriasis, and a variety of cancers (colon, breast, lung, and kidney). Among these tumour types, clear cell renal cell carcinomas (RCCs) are the most vascularized tumours due to mutations of the von Hippel Lindau gene resulting in HIF-1 alpha stabilisation and overexpression of Vascular Endothelial Growth Factor (VEGF). Surgical nephrectomy remains the most efficient curative treatment for patients with noninvasive disease, while VEGF targeting has resulted in varying degrees of success for treating metastatic disease. VEGF pre-mRNA undergoes alternative splicing generating pro-angiogenic isoforms. However, the recent identification of novel splice variants of VEGF with anti-angiogenic properties has provided some insight for the lack of current treatment efficacy. Here we discuss an explanation for the relapse to anti-angiogenesis treatment as being due to either an initial or acquired resistance to the therapy. We also discuss targeting angiogenesis via SR (serine/arginine-rich) proteins implicated in VEGF splicing.
Mood and Balance are Associated with Free-Living Physical Activity of People after Stroke Residing in the community
Authors: Alzahrani Matar A. , Dean Catherine M. , Ada Louise , Dorsch Simone , Canning Colleen G.
Published: October 2011

Purpose. To determine which characteristics are most associated with free-living physical activity in community-dwelling ambulatory people after stroke.Method. Factors (age, gender, side of stroke, time since stroke, BMI, and spouse), sensory-motor impairments (weakness, contracture, spasticity, coordination, proprioception, and balance), and non-sensory-motor impairments (cognition, language, perception, mood, and confidence) were collected on 42 people with chronic stroke. Free-living physical activity was measured using an activity monitor and reported as time on feet and activity counts.Results. Univariate analysis showed that balance and mood were correlated with time on feet (r=0.42, 0.43,P<0.01) and also with activity counts (r=0.52, 0.54,P<0.01). Stepwise multiple regression showed that mood and balance accounted for 25% of the variance in time on feet and 40% of the variance in activity counts.Conclusions. Mood and balance are associated with free-living physical activity in ambulatory people after stroke residing in the community.
Sellar and Parasellar Metastatic Tumors
Authors: Altay Tamer , Krisht Khaled M. , Couldwell William T.
Published: October 2011

The sellar and parasellar (SPS) region is a complex area rich in vital neurovascular structures and as such may be the location of first manifestation of a systemic malignancy. Metastases to this region are rare; breast cancer is the most common source among those that metastasize to the SPS region. Ophthalmoplegia, headache, retroorbital or facial pain, diabetes insipidus, and visual field defects are the most commonly reported symptoms. Lack of specific clinical and radiological features renders SPS metastases difficult to differentiate from the other frequently encountered lesions in this area, especially when there is no known history of a primary disease. Currently accepted management is multimodality therapy that includes biopsy and/or palliative surgical resection, radiation, and chemotherapy. Although no significant survival benefits have been shown by the surgical series, surgical resection may improve quality of life. Here we review the relevant literature and present six illustrative cases from our own institution.
High -Factor Wideband Resonators for Millimeter and Submillimeter Applications
Authors: Gaevskaya Tatiana , Karpovich Victor , Rodionova Valentina
Published: October 2011

Physical principles for designing a multipurpose set of high -factor quasioptical and corrugated resonators with automatic frequency tuning (, ) that can operate in the frequency band from 37.5 to 400 GHz are presented. The electrodynamical calculation methods of resonators, the constructive particularities of resonators, the methods and results of the experimental researches are considered. This set of resonators can be used as a universal measuring resonator for measuring radio-signal fluctuations and parameters of different media, in particular, nanotube composites and high-temperature superconductors.
MicroRNA-148a Suppresses Tumor Cell Invasion and Metastasis by Downregulating ROCK1 in Gastric Cancer
Authors: Zheng Biqiang , Liang Linhui , Wang Chunmeng , Huang Shenglin , Cao Xi , Zha Ruopeng , Liu Li , Jia Deshui , Tian Qi , Wu Jianghong , Ye Yanwei , Wang Qifeng , Long Ziwen , Zhou Ye , Du Chunyan , He Xianghuo , Shi Yingqiang
Published: October 2011

Purpose: MicroRNAs (miRNA) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer metastasis.

Experimental Design: We examined miR-148a levels in 90 gastric cancer samples by qRT-PCR and analyzed the clinicopathologic significance of miR-148a expression. The gastric cancer cells stably expressing miRNA-148a were analyzed for migration and invasion assays in vitro and metastasis assays in vivo; the target genes of miR-148a were further explored.

Results: We found that miR-148a expression was suppressed by more than 4-fold in gastric cancer compared with their corresponding nontumorous tissues, and the downregulated miR-148a was significantly associated with tumor-node-metastasis (TNM) stage and lymph node-metastasis. Functional assays showed that overexpression of miR-148a suppressed gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the 2 sites of 3′ untranslated region of ROCK1. Moreover, in gastric cancer tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited gastric cancer cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a–induced suppression of gastric cancer cell migration and invasion.

Conclusions: miR-148a functions as a tumor metastasis suppressor in gastric cancer, and downregulation of miR-148a contributes to gastric cancer lymph node-metastasis and progression. miR-148a may have a therapeutic potential to suppress gastric cancer metastasis. Clin Cancer Res; 17(24); 7574–83. ©2011 AACR.
Targeting Radiation-Induced G2 Checkpoint Activation with the Wee-1 Inhibitor MK-1775 in Glioblastoma Cell Lines
Authors: Sarcar Bhaswati , Kahali Soumen , Prabhu Antony H. , Shumway Stuart D. , Xu Yang , Demuth Tim , Chinnaiyan Prakash
Published: October 2011

The purpose of this study was to determine the capacity of MK-1775, a potent Wee-1 inhibitor, to abrogate the radiation-induced G2 checkpoint arrest and modulate radiosensitivity in glioblastoma cell models and normal human astrocytes. The radiation-induced checkpoint response of established glioblastoma cell lines, glioblastoma neural stem (GNS) cells, and astrocytes were determined in vitro by flow cytometry and in vivo by mitosis-specific staining using immunohistochemistry. Mechanisms underlying MK-1775 radiosensitization were determined by mitotic catastrophe and γH2AX expression. Radiosensitivity was determined in vitro by the clonogenic assay and in vivo by tumor growth delay. MK-1775 abrogated the radiation-induced G2 checkpoint and enhanced radiosensitivity in established glioblastoma cell lines in vitro and in vivo, without modulating radiation response in normal human astrocytes. MK-1775 appeared to attenuate the early-phase of the G2 checkpoint arrest in GNS cell lines, although the arrest was not sustained and did not lead to increased radiosensitivity. These results show that MK-1775 can selectively enhance radiosensitivity in established glioblastoma cell lines. Further work is required to determine the role Wee-1 plays in checkpoint activation of GNS cells. Mol Cancer Ther; 10(12); 2405–14. ©2011 AACR.
Dual Inhibition of Tumor Energy Pathway by 2-Deoxyglucose and Metformin Is Effective against a Broad Spectrum of Preclinical Cancer Models
Authors: Cheong Jae-Ho , Park Eun Sung , Liang Jiyong , Dennison Jennifer B. , Tsavachidou Dimitra , Nguyen-Charles Catherine , Wa Cheng Kwai , Hall Hassan , Zhang Dong , Lu Yiling , Ravoori Murali , Kundra Vikas , Ajani Jaffer , Lee Ju-Seog , Ki Hong Waun , Mills Gordon B.
Published: October 2011

Tumor cell proliferation requires both growth signals and sufficient cellular bioenergetics. The AMP-activated protein kinase (AMPK) pathway seems dominant over the oncogenic signaling pathway suppressing cell proliferation. This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxyglucose (2DG) and AMPK agonists, AICAR and metformin. We evaluated the in vitro antitumor activity of 2DG, metformin or AICAR alone, and 2DG in combination either with metformin or AICAR. We examined in vivo efficacy using xenograft mouse models. 2DG alone was not sufficient to promote tumor cell death, reflecting the limited efficacy showed in clinical trials. A combined use of 2DG and AICAR also failed to induce cell death. However, 2DG and metformin led to significant cell death associated with decrease in cellular ATP, prolonged activation of AMPK, and sustained autophagy. Gene expression analysis and functional assays revealed that the selective AMPK agonist AICAR augments mitochondrial energy transduction (OXPHOS) whereas metformin compromises OXPHOS. Importantly, forced energy restoration with methyl pyruvate reversed the cell death induced by 2DG and metformin, suggesting a critical role of energetic deprivation in the underlying mechanism of cell death. The combination of 2DG and metformin inhibited tumor growth in mouse xenograft models. Deprivation of tumor bioenergetics by dual inhibition of energy pathways might be an effective novel therapeutic approach for a broad spectrum of human tumors. Mol Cancer Ther; 10(12); 2350–62. ©2011 AACR.
Cytokine Induction of Tumor Necrosis Factor Receptor 2 Is Mediated by STAT3 in Colon Cancer Cells
Authors: Hamilton Kathryn E. , Simmons James G. , Ding Shengli , Van Landeghem Laurianne , Lund P. Kay
Published: October 2011

The IL-6/STAT3 and TNFα/NFκB pathways are emerging as critical mediators of inflammation-associated colon cancer. TNF receptor (TNFR) 2 expression is increased in inflammatory bowel diseases, the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated cancer, and by combined interleukin (IL) 6 and TNFα. The molecular mechanisms that regulate TNFR2 remain undefined. This study used colon cancer cell lines to test the hypothesis that IL-6 and TNFα induce TNFR2 via STAT3 and/or NFκB. Basal and IL-6 + TNFα–induced TNFR2 were decreased by pharmacologic STAT3 inhibition. NFκB inhibition had little effect on IL-6 + TNFα–induced TNFR2, but did inhibit induction of endogenous IL-6 and TNFR2 in cells treated with TNFα alone. Chromatin immunoprecipitation (ChIP) revealed cooperative effects of IL-6 + TNFα to induce STAT3 binding to a −1,578 STAT response element in the TNFR2 promoter but no effect on NFκB binding to consensus sites. Constitutively active STAT3 was sufficient to induce TNFR2 expression. Overexpression of SOCS3, a cytokine-inducible STAT3 inhibitor, which reduces tumorigenesis in preclinical models of colitis-associated cancer, decreased cytokine-induced TNFR2 expression and STAT3 binding to the −1,578 STAT response element. SOCS3 overexpression also decreased proliferation of colon cancer cells and dramatically decreased anchorage-independent growth of colon cancer cells, even cells overexpressing TNFR2. Collectively, these studies show that IL-6- and TNFα-induced TNFR2 expression in colon cancer cells is mediated primarily by STAT3 and provide evidence that TNFR2 may contribute to the tumor-promoting roles of STAT3. Mol Cancer Res; 9(12); 1718–31. ©2011 AACR.
Titrated Sedation with Propofol for Medical Thoracoscopy: A Feasibility and Safety Study
Authors: Tschopp Jean-Marie , Purek Lesek , Frey Jean-Georges , Schnyder Jean-Marie , Diaper John , Cartier Vanessa , Licker Marc
Published: October 2011

Background: Bispectral index (BIS) is a valuable tool for assessing the depth of sedation and guiding the administration of sedative drugs. We previously demonstrated the benefits of BIS-guided propofol sedation in patients undergoing flexible bronchoscopy. Objective: To examine the feasibility and safety profile of propofol sedation in patients undergoing medical thoracoscopy (MT). Methods: Patients undergoing MT for diagnostic evaluation or treatment of pleuropulmonary diseases were enrolled over a 2-year period. Nurses and chest physicians were trained by anesthetists to provide analgosedation, to detect and correct cardiopulmonary disturbances. The level of sedation was optimized individually by titrating the propofol infusion according to the BIS and clinical evaluation. Patients’ clinical data, procedure time, medications and any adverse events were recorded. Results: Fifty-three patients (60% male) with a median age of 62 years (range 19–84 years) underwent MT. The operative procedure lasted a median time of 28 min (range 9–112 min). The median doses of anesthetic drugs were 145 mg of propofol (range 20–410 mg) and 84 µg of fentanyl (range 0–225 µg). Hemodynamic disturbances occurred in 39 patients (bradycardia n = 4, tachycardia n = 12, hypotension n = 34) and required drug administration in only 4 cases. Hypoxemic events (n = 4) resolved upon gentle patient stimulation (verbal command, chin lift, oral cannula). All patients could be discharged from the recovery unit within 105 min after the procedure. Conclusions: BIS-guided propofol sedation is a safe method that might replace midazolam sedation in MT and can be managed by well-trained nonanesthesiologist personnel.