bluuebunny/crossref_metadata_2025 huggingface dataset:
A SPATIALLY RESOLVED SSC SHOCK-IN-JET MODEL
Authors: RICHTER STEPHAN , SPANIER FELIX
Published: April 2012

In this paper a spatially resolved, fully self-consistent SSC model is presented. The observable spectral energy distribution (SED) evolves entirely from a low energetic delta distribution of injected electrons by means of the implemented microphysics of the jet. These are in particular the properties of the shock and the ambient plasma, which can be varied along the jet axis. Hence a large variety of scenarios can be computed, e.g. the acceleration of particles via multiple shocks. Two acceleration processes, shock acceleration and stochastic acceleration, are taken into account. From the resulting electron distribution the SED is calculated taking into account synchrotron radiation, inverse Compton scattering (full cross section) and synchrotron self absorption. The model can explain SEDs where cooling processes are crucial. It can verify high variability results from acausal simulations and produce variability not only via injection of particles, but due to the presence of multiple shocks. Furthermore a fit of the data, obtained in the 2010 multi-frequency campaign of Mrk501, is presented.
Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism
Authors: Le Blanc Solange , Garrick Michael D. , Arredondo Miguel
Published: April 2012

Heme-Fe is an important source of dietary iron in humans; however, the mechanism for heme-Fe uptake by enterocytes is poorly understood. Heme carrier protein 1 (HCP1) was originally identified as mediating heme-Fe transport although it later emerged that it was a folate transporter. We asked what happened to heme-Fe and folate uptake and the relative abundance of hcp1 and ho1 mRNA in Caco-2 cells after knockdown by transfection with HCP1-directed short hairpin (sh)RNA. Control Caco-2 cells were cultured in bicameral chambers with 0–80 μM heme-Fe for selected times. Intracellular Fe and heme concentration increased in Caco-2 cells reflecting higher external heme-Fe concentrations. Maximum Fe, heme, and heme oxygenase 1 (HO1) expression and activity were observed between 12 and 24 h of incubation. Quantitative RT-PCR for hcp1 revealed that its mRNA decreased at 20 μM heme-Fe while ho1 mRNA and activity increased. When shRNA knocked down hcp1 mRNA, heme-55Fe uptake and [3H]folate transport mirrored the mRNA decrease, ho1 mRNA increased, and flvcr mRNA was unchanged. These data argue that HCP1 is involved in low-affinity heme-Fe uptake not just in folate transport.
Mammalian target of rapamycin and the kidney. II. Pathophysiology and therapeutic implications
Authors: Lieberthal Wilfred , Levine Jerrold S.
Published: April 2012

The mTOR pathway plays an important role in a number of common renal diseases, including acute kidney injury (AKI), diabetic nephropathy (DN), and polycystic kidney diseases (PKD). The activity of mTOR complex 1 (mTORC1) is necessary for renal regeneration and repair after AKI, and inhibition of mTORC1 by rapamycin has been shown to delay recovery from ischemic AKI in animal studies, and to prolong delayed graft function in humans who have received a kidney transplant. For this reason, administration of rapamycin should be delayed or discontinued in patients with AKI until full recovery of renal function has occurred. On the other hand, inappropriately high mTORC1 activity contributes to the progression of the metabolic syndrome, the development of type 2 diabetes, and the pathogenesis of DN. In addition, chronic hyperactivity of mTORC1, and possibly also mTORC2, contributes to cyst formation and enlargement in a number of forms of PKD. Inhibition of mTOR, using either rapamycin (which inhibits predominantly mTORC1) or “catalytic” inhibitors (which effectively inhibit both mTORC1 and mTORC2), provide exciting possibilities for novel forms of treatment of DN and PKD. In this second part of the review, we will examine the role of mTOR in the pathophysiology of DN and PKD, as well as the potential utility of currently available and newly developed inhibitors of mTOR to slow the progression of DN and/or PKD.
ENaC inhibition stimulates Cl−secretion in the mouse cortical collecting duct through an NKCC1-dependent mechanism
Authors: Pech Vladimir , Thumova Monika , Kim Young Hee , Agazatian Diana , Hummler Edith , Rossier Bernard C. , Weinstein Alan M. , Nanami Masayoshi , Wall Susan M.
Published: April 2012

In cortical collecting ducts (CCDs) perfused in vitro, inhibiting the epithelial Na+channel (ENaC) reduces Cl−absorption. Since ENaC does not transport Cl−, the purpose of this study was to determine how ENaC modulates Cl−absorption. Thus, Cl−absorption was measured in CCDs perfused in vitro that were taken from mice given aldosterone for 7 days. In wild-type mice, we observed no effect of luminal hydrochlorothiazide on either Cl−absorption or transepithelial voltage ( VT). However, application of an ENaC inhibitor [benzamil (3 μM)] to the luminal fluid or application of a Na+-K+-ATPase inhibitor to the bath reduced Cl−absorption by ∼66–75% and nearly obliterated lumen-negative VT. In contrast, ENaC inhibition had no effect in CCDs from collecting duct-specific ENaC-null mice (Hoxb7:CRE, Scnn1aloxlox). Whereas benzamil-sensitive Cl−absorption did not depend on CFTR, application of a Na+-K+-2Cl−cotransport inhibitor (bumetanide) to the bath or ablation of the gene encoding Na+-K+-2Cl−cotransporter 1 (NKCC1) blunted benzamil-sensitive Cl−absorption, although the benzamil-sensitive component of VTwas unaffected. In conclusion, first, in CCDs from aldosterone-treated mice, most Cl−absorption is benzamil sensitive, whereas thiazide-sensitive Cl−absorption is undetectable. Second, benzamil-sensitive Cl−absorption occurs by inhibition of ENaC, possibly due to elimination of lumen-negative VT. Finally, benzamil-sensitive Cl−flux occurs, at least in part, through transcellular transport through a pathway that depends on NKCC1.
Effects of K+-deficient diets with and without NaCl supplementation on Na+, K+, and H2O transporters' abundance along the nephron
Authors: Nguyen Mien T. X. , Yang Li E. , Fletcher Nicholas K. , Lee Donna H. , Kocinsky Hetal , Bachmann Sebastian , Delpire Eric , McDonough Alicia A.
Published: April 2012

Dietary potassium (K+) restriction and hypokalemia have been reported to change the abundance of most renal Na+and K+transporters and aquaporin-2 isoform, but results have not been consistent. The aim of this study was to reexamine Na+, K+and H2O transporters' pool size regulation in response to removing K+from a diet containing 0.74% NaCl, as well as from a diet containing 2% NaCl (as found in American diets) to blunt reducing total diet electrolytes. Sprague-Dawley rats ( n = 5–6) were fed for 6 days with one of these diets: 2% KCl, 0.74% NaCl (2K1Na, control chow) compared with 0.03% KCl, 0.74% NaCl (0K1Na); or 2% KCl, 2%NaCl (2K2Na) compared with 0.03% KCl, 2% NaCl (0K2Na, Na+replete). In both 0K1Na and 0K2Na there were significant decreases in: 1) plasma [K+] (<2.5 mM); 2) urinary K+excretion (<5% of control); 3) urine osmolality and plasma [aldosterone], as well as 4) an increase in urine volume and medullary hypertrophy. The 0K2Na group had the lowest [aldosterone] (172.0 ± 17.4 pg/ml) and lower blood pressure (93.2 ± 4.9 vs. 112.0 ± 3.1 mmHg in 2K2Na). Transporter pool size regulation was determined by quantitative immunoblotting of renal cortex and medulla homogenates. The only differences measured in both 0K1Na and 0K2Na groups were a 20–30% decrease in cortical β-ENaC, 30–40% increases in kidney-specific Ste20/SPS1-related proline/alanine-rich kinase, and a 40% increase in medullary sodium pump abundance. The following proteins were not significantly changed in both the 0 K groups: Na+/H+exchanger isoform 3; Na+-K+-Cl−cotransporter; Na+-Cl−cotransporter, oxidative stress response kinase-1; renal outer medullary K+channel; autosomal recessive hypercholesterolemia; c-Src, aquaporin 2 isoform; or renin. Thus, despite profound hypokalemia and renal K+conservation, we did not confirm many of the changes that were previously reported. We predict that changes in transporter distribution and activity are likely more important for conserving K+than changes in total abundance.
BMP-2 induces a profibrotic phenotype in adult renal progenitor cells through Nox4 activation
Authors: Simone Simona , Cosola Carmela , Loverre Antonia , Cariello Marica , Sallustio Fabio , Rascio Federica , Gesualdo Loreto , Schena Francesco Paolo , Grandaliano Giuseppe , Pertosa Giovanni
Published: April 2012

Adult renal progenitor cells (ARPCs) isolated from the human kidney may contribute to repair featuring acute kidney injury (AKI). Bone morphogenetic proteins (BMPs) regulate differentiation, modeling, and regeneration processes in several tissues. The aim of this study was to evaluate the biological actions of BMP-2 in ARPCs in vitro and in vivo. BMP-2 was expressed in ARPCs of normal adult human kidneys, and it was upregulated in vivo after delayed graft function (DGF) of renal transplantation, a condition of AKI. ARPCs expressed BMP receptors, suggesting their potential responsiveness to BMP-2. Incubation of ARPCs with this growth factor enhanced reactive oxygen species (ROS) production, NADPH oxidase activity, and Nox4 protein expression. In vivo, Nox4 was localized in BMP-2-expressing CD133+ cells at the tubular level after DGF. BMP-2 incubation induced α-smooth muscle actin (SMA), collagen I, and fibronectin protein expression in ARPCs. Moreover, α-SMA colocalized with CD133 in vivo after DGF. The oxidative stimulus (H2O2) induced α-SMA expression in ARPCs, while the antioxidant N-acetyl-cysteine inhibited BMP-2-induced α-SMA expression. Nox4 silencing abolished BMP-2-induced NADPH oxidase activation and myofibroblastic induction. We showed that 1) ARPCs express BMP-2, 2) this expression is increased in a model of AKI; 3) BMP-2 may induce the commitment of ARPCs toward a myofibroblastic phenotype in vitro and in vivo; and 4) this profibrotic effect is mediated by Nox4 activation. Our findings suggest a novel mechanism linking AKI with progressive renal damage.
Autoregulation and conduction of vasomotor responses in a mathematical model of the rat afferent arteriole
Authors: Sgouralis Ioannis , Layton Anita T.
Published: April 2012

We have formulated a mathematical model for the rat afferent arteriole (AA). Our model consists of a series of arteriolar smooth muscle cells and endothelial cells, each of which represents ion transport, cell membrane potential, and gap junction coupling. Cellular contraction and wall mechanics are also represented for the smooth muscle cells. Blood flow through the AA lumen is described by Poiseuille flow. The AA model's representation of the myogenic response is based on the hypothesis that changes in hydrostatic pressure induce changes in the activity of nonselective cation channels. The resulting changes in membrane potential then affect calcium influx through changes in the activity of the voltage-gated calcium channels, so that vessel diameter decreases with increasing pressure values. With this configuration, the model AA maintains roughly stable renal blood flow within a physiologic range of blood flow pressure. Model simulation of vasoconstriction initiated from local stimulation also agrees well with findings in the experimental literature, notably those of Steinhausen et al. (Steinhausen M, Endlich K, Nobiling R, Rarekh N, Schütt F. J Physiol 505: 493–501, 1997), which indicated that conduction of vasoconstrictive response decays more rapidly in the upstream flow direction than downstream. The model can be incorporated into models of integrated renal hemodynamic regulation.
Long-term actions of BDNF on inhibitory synaptic transmission in identified neurons of the rat substantia gelatinosa
Authors: Lu Van B. , Colmers William F. , Smith Peter A.
Published: April 2012

Peripheral nerve injury promotes the release of brain-derived neurotrophic factor (BDNF) from spinal microglial cells and primary afferent terminals. This induces an increase in dorsal horn excitability that contributes to “central sensitization” and to the onset of neuropathic pain. Although it is accepted that impairment of GABAergic and/or glycinergic inhibition contributes to this process, certain lines of evidence suggest that GABA release in the dorsal horn may increase after nerve injury. To resolve these contradictory findings, we exposed rat spinal cord neurons in defined-medium organotypic culture to 200 ng/ml BDNF for 6 days to mimic the change in spinal BDNF levels that accompanies peripheral nerve injury. Morphological and electrophysiological criteria and glutamic acid decarboxylase (GAD) immunohistochemistry were used to distinguish putative inhibitory tonic-islet-central neurons from putative excitatory delay-radial neurons. Whole cell recording in the presence of 1 μM tetrodotoxin showed that BDNF increased the amplitude of GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) in both cell types. It also increased the amplitude and frequency of spontaneous, action potential-dependent IPSCs (sIPSCs) in putative excitatory neurons. By contrast, BDNF reduced sIPSC amplitude in inhibitory neurons but frequency was unchanged. This increase in inhibitory drive to excitatory neurons and decreased inhibitory drive to inhibitory neurons seems inconsistent with the observation that BDNF increases overall dorsal horn excitability. One of several explanations for this discrepancy is that the action of BDNF in the substantia gelatinosa is dominated by previously documented increases in excitatory synaptic transmission rather than by impediment of inhibitory transmission.
Intrinsic voltage dynamics govern the diversity of spontaneous firing profiles in basal forebrain noncholinergic neurons
Authors: Ovsepian Saak V. , Dolly J. Oliver , Zaborszky Laszlo
Published: April 2012

Spontaneous firing and behavior-related changes in discharge profiles of basal forebrain (BF) neurons are well documented, albeit the mechanisms underlying the variety of activity modes and intermodal transitions remain elusive. With the use of cell-attached recordings, this study identifies a range of spiking patterns in diagonal band Broca (DBB) noncholinergic cells of rats and tentatively categorizes them into low-rate random, tonic, and cluster firing activities. It demonstrates further that the multiplicity of discharge profiles is sustained intrinsically and persists after blockade of glutamate-, glycine/GABA-, and cholinergic synaptic inputs. Stimulation of muscarinic receptors, blockade of voltage-gated Ca2+-, and small conductance (SK) Ca2+-activated K+ currents as well as chelating of intracellular Ca2+ concentration accelerate low-rate random and tonic firing and favor transition of neurons into cluster firing mode. A similar trend towards higher discharge rates with switch of neurons into cluster firing has been revealed by activation of neuropeptide Y (NPY) receptors with the NPY or NPY1 receptor agonist [Leu31,Pro34]-NPY. Whole cell current-clamp analysis demonstrates that the variety of spiking modes and intermodal transitions could be induced within the same neuronal population by injection of bias depolarizing or hyperpolarizing currents. Taken together, these data demonstrate the intrinsic and highly variable character of regenerative firing in BF noncholinergic cells, subject to powerful modulation by classical neurotransmitters, NPY, and small membrane currents.
Electrophysiological classes of layer 2/3 pyramidal cells in monkey prefrontal cortex
Authors: Zaitsev A. V. , Povysheva N. V. , Gonzalez-Burgos G. , Lewis D. A.
Published: April 2012

The activity of supragranular pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) neurons is hypothesized to be a key contributor to the cellular basis of working memory in primates. Therefore, the intrinsic membrane properties, a crucial determinant of a neuron's functional properties, are important for the role of DLPFC pyramidal neurons in working memory. The present study aimed to investigate the biophysical properties of pyramidal cells in layer 2/3 of monkey DLPFC to create an unbiased electrophysiological classification of these cells. Whole cell voltage recordings in the slice preparation were performed in 77 pyramidal cells, and 24 electrophysiological measures of their passive and active intrinsic membrane properties were analyzed. Based on the results of cluster analysis of 16 independent electrophysiological variables, 4 distinct electrophysiological classes of monkey pyramidal cells were determined. Two classes contain regular-spiking neurons with low and high excitability and constitute 52% of the pyramidal cells sampled. These subclasses of regular-spiking neurons mostly differ in their input resistance, minimum current that evoked firing, and current-to-frequency transduction properties. A third class of pyramidal cells includes low-threshold spiking cells (17%), which fire a burst of three-five spikes followed by regular firing at all suprathreshold current intensities. The last class consists of cells with an intermediate firing pattern (31%). These cells have two modes of firing response, regular spiking and bursting discharge, depending on the strength of stimulation and resting membrane potential. Our results show that diversity in the functional properties of DLPFC pyramidal cells may contribute to heterogeneous modes of information processing during working memory and other cognitive operations that engage the activity of cortical circuits in the superficial layers of the DLPFC.
Intracortical circuits amplify sound-evoked activity in primary auditory cortex following systemic injection of salicylate in the rat
Authors: Stolzberg Daniel , Chrostowski Michael , Salvi Richard J. , Allman Brian L.
Published: April 2012

A high dose of sodium salicylate temporarily induces tinnitus, mild hearing loss, and possibly hyperacusis in humans and other animals. Salicylate has well-established effects on cochlear function, primarily resulting in the moderate reduction of auditory input to the brain. Despite decreased peripheral sensitivity and output, salicylate induces a paradoxical enhancement of the sound-evoked field potential at the level of the primary auditory cortex (A1). Previous electrophysiologic studies have begun to characterize changes in thalamorecipient layers of A1; however, A1 is a complex neural circuit with recurrent intracortical connections. To describe the effects of acute systemic salicylate treatment on both thalamic and intracortical sound-driven activity across layers of A1, we applied current-source density (CSD) analysis to field potentials sampled across cortical layers in the anesthetized rat. CSD maps were normally characterized by a large, short-latency, monosynaptic, thalamically driven sink in granular layers followed by a lower amplitude, longer latency, polysynaptic, intracortically driven sink in supragranular layers. Following systemic administration of salicylate, there was a near doubling of both granular and supragranular sink amplitudes at higher sound levels. The supragranular sink amplitude input/output function changed from becoming asymptotic at approximately 50 dB to sharply nonasymptotic, often dominating the granular sink amplitude at higher sound levels. The supragranular sink also exhibited a significant decrease in peak latency, reflecting an acceleration of intracortical processing of the sound-evoked response. Additionally, multiunit (MU) activity was altered by salicylate; the normally onset/sustained MU response type was transformed into a primarily onset response type in granular and infragranular layers. The results from CSD analysis indicate that salicylate significantly enhances sound-driven response via intracortical circuits.
1H and 13C NMR assignments of dihydropipataline, the main of four long‐chain 1‐(3,4‐methylenedioxyphenyl)‐alkanes from Piper darienence D.C.
Authors: Meléndez-Rodríguez Myriam , Rendón Willy , Chávez Galia , Martínez-Guajardo Gerardo , Joseph-Nathan Pedro
Published: April 2012

Four 1‐(3,4‐methylenedioxyphenyl)‐alkanes having linear ten, eleven, twelve and fourteen carbon atom chains, found in the roots of Piper darienence D.C., were separated by HPLC and their structures determined by mass spectrometry and NMR spectroscopy. Conventional 1D NMR methods were used for 1H chemical shifts assignment of the main compound dihydropipataline (3) [1‐(3,4‐methylenedioxyphenyl)‒dodecane]. The 13C NMR assignment was carried out using conventional considerations and 2D NMR techniques (HETCOR and FLOCK) in combination with spectral 13C NMR simulation and ab initio DFT‐GIAO NMR calculations.
Myelodysplastic Syndrome with t(1;7) Associated with Marked Dysmegakarypoiesis & Severe Thrombocytopenia: A Case Report and Review of the Literature
Authors: Gilbertson Michael , Tuckfield Annabel , Juneja Surender
Published: April 2012

We present the case of a 70-year-old woman who had a bone marrow examination performed to investigate marked thrombocytopenia in the context of a recent history of metastatic glucagonoma. Surprisingly this identified marked dysmegakaryopoiesis and fulfilled diagnostic criteria for refractory cytopenia with multilineage dysplasia, with a relatively uncommon associated cytogenetic lesion t(1;7). We present the case and review the literature of this cytogenetic lesion.
Leaf Area and Structural Changes after Thinning in Even-AgedPicea rubensandAbies balsameaStands in Maine, USA
Authors: DeRose R. Justin , Seymour Robert S.
Published: April 2012

We tested the hypothesis that changes in leaf area index (LAI m2 m−2) and mean stand diameter following thinning are due to thinning type and residual density. The ratios of pre- to postthinning diameter and LAI were used to assess structural changes between replicated crown, dominant, and low thinning treatments to 33% and 50% residual density in even-agedPicea rubensandAbies balsameastands with and without a precommercial thinning history in Maine, USA. Diameter ratios varied predictably by thinning type: low thinnings were <0.7, crown thinnings were >0.7 but <1.0, and dominant thinnings were >1.0 . LAI change was affected by type and intensity of thinning. On average, 33% density reduction removed <50% of LAI, whereas 50% density reduction removed >50% of LAI. Overall reduction of LAI was generally greatest in dominant thinnings (54%), intermediate in crown thinnings (46%), and lowest in low thinnings (35%). Upon closer examination by crown classes, the postthinning distribution of LAI between upper and lower crown classes varied by thinning history, thinning method, and amount of density reduction.
A Decrease in NiO‐MgO Phase Through Its Solid Solution Equilibrium with Tetragonal (La1−zSrz) 2Ni1−yMgyO4−δ: Effect on Catalytic Partial Oxidation of Methane
Authors: Yin Xiong , Hong Liang , Gong Zhengliang
Published: April 2012

Calcination of an oxide mixture consisting of 0.4 La2O3, 0.2 SrCO3, (1 − x)NiO, and xMgO at 800∘C results in an equilibrium between tetragonal phase and NiO‐MgO phase. Forming rock‐salt NiO‐MgO facilitates the NiO to join the tetragonal phase. The size of the NiO‐MgO phase in the resulting composite is reduced with the increase in MgO (the x
value). The composite thus obtained is used to catalyze partial oxidation of methane, and the maximum methane conversion of ca. 93% is achieved when x = 0.2. A further rise in x
value results in a monotonic decrease in the methane conversion. X‐ray diffraction, electron microscopy, and chemosorption all confirm a decrease in both size and amount of the supported Ni0
clusters with the increase in MgO dosage. The reduction in size promotes the dispersion of Ni0
sites and gives rise to both high activity and strong coking resistance.
Paraoxonases-2 and -3 Are Important Defense Enzymes againstPseudomonas aeruginosaVirulence Factors due to Their Anti-Oxidative and Anti-Inflammatory Properties
Authors: Schweikert Eva-Maria , Amort Julianna , Wilgenbus Petra , Förstermann Ulrich , Teiber John F. , Horke Sven
Published: April 2012

The pathogenPseudomonas aeruginosacauses serious damage in immunocompromised patients by secretion of various virulence factors, among them the quorum sensing N-(3-oxododecanoyl)-L-homoserine lactone (3OC12) and the redox-active pyocyanin (PCN). Paraoxonase-2 (PON2) may protect againstP. aeruginosainfections, as it efficiently inactivates 3OC12 and diminishes PCN-induced oxidative stress. This defense could be circumvented because 3OC12 mediates intracellular Ca2+-rise in host cells, which causes rapid inactivation and degradation of PON2. Importantly, we recently found that the PON2 paralogue PON3 prevents mitochondrial radical formation. Here we investigated its role as additional potential defense mechanism againstP. aeruginosainfections. Our studies demonstrate that PON3 diminished PCN-induced oxidative stress. Moreover, it showed clear anti-inflammatory potential by protecting against NF-κB activation and IL-8 release. The latter similarly applied to PON2. Furthermore, we observed a Ca2+-mediated inactivation and degradation of PON3, again in accordance with previous findings for PON2. Our results suggest that the anti-oxidative and anti-inflammatory functions of PON2 and PON3 are an important part of our innate defense system againstP. aeruginosainfections. Furthermore, we conclude thatP. aeruginosacircumvents PON3 protection by the same pathway as for PON2. This may help identifying underlying mechanisms in order to sustain the protection afforded by these enzymes.
Photothermal Deflection Spectroscopy Study of Nanocrystalline Si (nc-Si) Thin Films Deposited on Porous Aluminum with PECVD
Authors: Ktifa S. , Ghrib M. , Saadallah F. , Ezzaouia H. , Yacoubi N.
Published: April 2012

We have studied the optical properties of nanocrystalline silicon (nc-Si) film deposited by plasma enhancement chemical vapor deposition (PECVD) on porous aluminum structure using, respectively, the Photothermal Deflection Spectroscopy (PDS) and Photoluminescence (PL). The aim of this work is to investigate the influence of anodisation current on the optical properties of the porous aluminum silicon layers (PASL). The morphology characterization studied by atomic force microscopy (AFM) technique has shown that the grain size of (nc-Si) increases with the anodisation current. However, a band gap shift of the energy gap was observed.
Etiopathogenesis of Insulin Autoimmunity
Authors: Kanatsuna Norio , Papadopoulos George K. , Moustakas Antonis K. , Lenmark Åke
Published: April 2012

Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.
Cardiovascular Events in Cancer Patients Treated with Highly or Moderately Emetogenic Chemotherapy: Results from a Population-Based Study
Authors: Vo Thao T. , Nelson Jeanenne J.
Published: April 2012

Studies on cardiovascular safety in cancer patients treated with highly or moderately emetogenic chemotherapy (HEC or MEC), who may have taken the antiemetic, aprepitant, have been limited to clinical trials and postmarketing spontaneous reports. Our study explored background rates of cardiovascular disease (CVD) events among HEC- or MEC-treated cancer patients in a population-based setting to contextualize events seen in a new drug development program and to determine at a high level whether rates differed by aprepitant usage. Medical and pharmacy claims data from the 2005–2007 IMPACT National Benchmark Database were classified into emetogenic chemotherapy categories and CVD outcomes. Among 5827 HEC/MEC-treated patients, frequencies were highest for hypertension (16–21%) and composites of venous (7–12%) and arterial thromboembolic events (4–7%). Aprepitant users generally did not experience higher frequencies of events compared to nonusers. Our study serves as a useful benchmark of background CVD event rates in a population-based setting of cancer patients.
Fluoride Adsorption by Pumice from Aqueous Solutions
Authors: Mahvi Amir Hossein , Heibati Behzad , Mesdaghinia Alireza , Yari Ahmad Reza
Published: April 2012

Drinking water provides many vital elements for the human body, but the presence of some dissolved elements more than permissible concentration can endanger human health. Among the dissolved elements in drinking water, fluoride is noticeable, because both the very low or very high concentrations have adverse health impacts such as dental caries. Therefore, fluoride concentration should be kept in acceptable levels. In this study Pumice was used for fluoride removal. It was found that Fluoride sorption kinetic was fitted by pseudo‐second‐order model. The maximum sorption capacity of Pumice was found to be 13.51 mg/g at laboratory temperature (24°C). Maximum sorption study occurred at pH= 3. Results of Isotherm showed the fluoride sorption has been well fitted with Freundlich isotherm model. This study has demonstrated that Pumice can be used as effective adsorbents for fluoride removal from aqueous solutions. The adsorbent prepared in this study was cheap and efficient in removal of fluoride than other adsorbents.
Nanospheres Prepared by Self-Assembly of Random Copolymers in Supercritical Carbon Dioxide
Authors: Yoshida Eri
Published: April 2012

The synthesis of spherical particles was attained by the direct self-assembly of poly[2-(perfluorooctyl)ethyl acrylate-random-acrylic acid], P(POA-r-AA), and by the indirect self-assembly poly[POA-random-2-(dimethylamino)ethyl acrylate], P(POA-r-DAA), with dicarboxylic acids in supercritical carbon dioxide (scCO2). The copolymers formed spherical particles with hundreds of nanometer diameters in a heterogeneous state at pressures lower than the cloud point pressure. The formation of spherical particles was also dependent on the temperature. The formation of spherical particles could be optimized through varying the solvent quality by the manipulation of the CO2pressure and temperature for the different copolymer compositions. The dynamic light scattering and1H NMR studies demonstrated that the nanospheres had the micellar structures consisting of the CO2-philic POA shells and the CO2-phobic AA or DAA cores including the main chain cores. The nanospheres produced the superhydrophobic surfaces based on the water-proof shells of the POA units.
Bismuth Basic Nitrate as a Novel Adsorbent for Azo Dye Removal
Authors: Abdullah E. A. , Abdullah A. H. , Zainal Z. , Hussein M. Z. , Ban T. K.
Published: April 2012

Bismuth basic nitrate (BBN) and its TiO2‐Ag modified sorbent, PTBA were successfully synthesized via a precipitation method. The structural characteristics of prepared sorbents were determined through different analytical techniques. The potential use of prepared sorbents for organic compounds′ removal was evaluated using Methyl Orange and Sunset Yellow dyes as model pollutants in aqueous solutions. The experimental results showed that the presence of TiO2 and Ag particles during the crystal growth of bismuth basic nitrate has an effect on the crystal structure, point of zero charge (pHpzc), pore volume and diameter. The lower binding energy of Ti 2p core level peak indicates the octahedral coordination of TiO2 particles on the PTBA surface. The alteration of hydrophilic‐hydrophobic characteristics of sorbent′s surface improves the adsorptive performance of the modified sorbent and provides an efficient route for organic contaminants′ removal from aqueous solutions.
Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer
Authors: Worsham Maria J. , Lu Mei , Chen Kang Mei , Stephen Josena K. , Havard Shaleta , Schweitzer Vanessa P.
Published: April 2012

Genetic events specific to the pathogenesis of malignancy can offer clues to the tumorigenesis process. The objective of this study was to identify gene alterations that differentiate tumor and nontumor lesions in squamous head and neck cancer (HNSCC). DNA from 220 primary HNSCC with concurrently present tumor and nontumor lesions from the same patient was interrogated for genomic alterations of loss or gain of copy. Conditional logistic regression dealt with tumor and non-tumor records within a patient. Of 113 genes, 53 had univariate effects (P<0.01), of which 16 genes remained in the multivariable model withP<0.01. The model had a C-index (ROC) of 0.93. Loss ofCDKN2Band gain ofBCL6, FGF3, andPTP4A3predicted tumor. Loss ofBAK1andCCND1and gain ofSTCHpredicted nontumor. This highly powered model assigned alterations in 16 genes specific for malignant versus nonmalignant lesions, supporting their contribution to the pathogenesis of HNSCC as well as their potential utility as relevant targets for further evaluation as markers of early detection and progression.
Local‐ and Global‐Statistics‐Based Active Contour Model for Image Segmentation
Authors: Wu Boying , Yang Yunyun
Published: April 2012

This paper presents a local‐ and global‐statistics‐based active contour model for image segmentation by applying the globally convex segmentation method. We first propose a convex energy functional with a local‐Gaussian‐distribution‐fitting term with spatially varying means and variances and an auxiliary global‐intensity‐fitting term. A weight function that varies dynamically with the location of the image is applied to adjust the weight of the global‐intensity‐fitting term dynamically. The weighted total variation norm is incorporated into the energy functional to detect boundaries easily. The split Bregman method is then applied to minimize the proposed energy functional more efficiently. Our model has been applied to synthetic and real images with promising results. With the local‐Gaussian‐distribution‐fitting term, our model can also handle some texture images. Comparisons with other models show the advantages of our model.
Adipose-Derived Mesenchymal Stromal/Stem Cells: Tissue Localization, Characterization, and Heterogeneity
Authors: Baer Patrick C. , Geiger Helmut
Published: April 2012

Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources. It is easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose-derived mesenchymal stromal/stem cells (ASCs) yields a high amount of stem cells, which is essential for stem-cell-based therapies and tissue engineering. Several studies have provided evidence that ASCs in situ reside in a perivascular niche, whereas the exact localization of ASCs in native adipose tissue is still under debate. ASCs are isolated by their capacity to adhere to plastic. Nevertheless, recent isolation and culture techniques lack standardization. Cultured cells are characterized by their expression of characteristic markers and their capacity to differentiate into cells from meso-, ecto-, and entodermal lineages. ASCs possess a high plasticity and differentiate into various cell types, including adipocytes, osteoblasts, chondrocytes, myocytes, hepatocytes, neural cells, and endothelial and epithelial cells. Nevertheless, recent studies suggest that ASCs are a heterogeneous mixture of cells containing subpopulations of stem and more committed progenitor cells. This paper summarizes and discusses the current knowledge of the tissue localization of ASCs in situ, their characterization and heterogeneityin vitro, and the lack of standardization in isolation and culture methods.
Mass Spectra Analyses of Amides and Amide Dimers of Steviol, Isosteviol, and Steviolbioside
Authors: Lee Lin-Wen , Lee Tzong-Huei , Lin Ching-Tung , Chen Tiffany , Lin Pen-Yuan
Published: April 2012

The mass spectra of a series of stevioside analogues including the amide and dimer compounds of steviol, isosteviol, and steviolbioside were examined. Positive ion mass spectral fragmentation of new steviol, isosteviol, and steviolbioside amides and the amide dimers are reported and discussed. The techniques included their synthesis procedures, fast-atom bombardment (FAB), and LC/MS/MS mass spectra. Intense [M+H]+ and [M+Na]+ ion peaks were observed on the FAB and ESI spectra. LC/MS/MS also yielded ES+ and ES− ion peaks that fairly agreed with the results of the FAB and ESI studies. Mass spectral analysis of compounds 4p-q, 5a-g, 6, and 7 revealed the different cleavage pathway patterns that can help in identifying the structures of steviolbioside and its amide derivatives.
Distinct Signal Transduction Abnormalities and Erythropoietin Response in Bone Marrow Hematopoietic Cell Subpopulations of Myelodysplastic Syndrome Patients
Authors: Spinelli Elena , Caporale Roberto , Buchi Francesca , Masala Erico , Gozzini Antonella , Sanna Alessandro , Sassolini Francesca , Valencia Ana , Bosi Alberto , Santini Valeria
Published: April 2012

Purpose: Myelodysplastic syndromes (MDS) are heterogeneous clonal diseases characterized by cytopenias as a result of ineffective hematopoiesis. Little is known about alterations in signal transduction pathways in MDS.

Experimental Design: Multiparameter flow cytometry was used to evaluate the proteolytic activation of caspase-3 and the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and STAT5 specifically in defined CD34+, CD45+, or CD71+CD45− bone marrow (BM) cells from 60 MDS cases and normal controls, both at baseline and following stimulation with granulocyte colony-stimulating factor (G-CSF) and erythropoietin.

Results: In CD71+CD45− cells from a subpopulation of 36 MDS cases who were predicted to be responsive by clinical parameters (endogenous erythropoietin levels, transfusion dependency, percentage of blasts in the BM), erythropoietin failed to activate ERK1/2 or STAT5 in 23 of 36 cases, but it was effective in 13 of 36 cases, although to a significantly lower degree than in CD71+CD45− cells from healthy donor BM. The erythropoietin response in vivo correlated with in vitro erythropoietin-dependent STAT5 activation in 20 of 22 cases. STAT5 was significantly activated at baseline in MDS cells compared with normal controls, whereas caspase-3 was activated in CD34+ and CD45+ MDS cells, and was activated more often in the RA and RAEB-1 MDS subtypes. G-CSF stimulation activated ERK1/2 and STAT5 equally in MDS and normal CD34+ cells.

Conclusions: Abnormalities in the response to growth factors are restricted to erythropoietin stimulation in CD71+CD45− cells and correlate with the clinical response to erythropoietin. Activation of baseline signal transduction for proliferative and apoptotic signals is altered in MDS but with different patterns among the various BM subpopulations. Clin Cancer Res; 18(11); 3079–89. ©2012 AACR.
SAP155-Mediated Splicing of FUSE-Binding Protein-Interacting Repressor Serves as a Molecular Switch for c-myc Gene Expression
Authors: Matsushita Kazuyuki , Kajiwara Toshiko , Tamura Mai , Satoh Mamoru , Tanaka Nobuko , Tomonaga Takeshi , Matsubara Hisahiro , Shimada Hideaki , Yoshimoto Rei , Ito Akihiro , Kubo Shuji , Natsume Tohru , Levens David , Yoshida Minoru , Nomura Fumio
Published: April 2012

The Far UpStream Element (FUSE)-binding protein-interacting repressor (FIR), a c-myc transcriptional suppressor, is alternatively spliced removing the transcriptional repression domain within exon 2 (FIRΔexon2) in colorectal cancers. SAP155 is a subunit of the essential splicing factor 3b (SF3b) subcomplex in the spliceosome. This study aims to study the significance of the FIR–SAP155 interaction for the coordination of c-myc transcription, pre-mRNA splicing, and c-Myc protein modification, as well as to interrogate FIRΔexon2 for other functions relating to altered FIR pre-mRNA splicing. Knockdown of SAP155 or FIR was used to investigate their reciprocal influence on each other and on c-myc transcription, pre-mRNA splicing, and protein expression. Pull down from HeLa cell nuclear extracts revealed the association of FIR, FIRΔexon2, and SF3b subunits. FIR and FIRΔexon2 were coimmunoprecipitated with SAP155. FIR and FIRΔexon2 adenovirus vector (Ad–FIR and Ad–FIRΔexon2, respectively) were prepared to test for their influence on c-myc expression. FIR, SAP155, SAP130, and c-myc were coordinately upregulated in human colorectal cancer. These results reveal that SAP155 and FIR/FIRΔexon2 form a complex and are mutually upregulating. Ad–FIRΔexon2 antagonized Ad–FIR transcriptional repression of c-myc in HeLa cells. Because FIRΔexon2 still carries RRM1 and RRM2 and binding activity to FUSE, it is able to displace repression competent FIR from FUSE in electrophoretic mobility shift assays, thus thwarting FIR-mediated transcriptional repression by FUSE. Thus aberrant FIRΔexon2 production in turn sustained c-Myc expression. In conclusion, altered FIR and c-myc pre-mRNA splicing, in addition to c-Myc expression by augmented FIR/FIRΔexon2–SAP155 complex, potentially contribute to colorectal cancer development. Mol Cancer Res; 10(6); 787–99. ©2012 AACR.
Carotid Magnetization-Prepared Rapid Acquisition With Gradient-Echo Signal Is Associated With Acute Territorial Cerebral Ischemic Events Detected by Diffusion-Weighted MRI
Authors: McNally J. Scott , Kim Seong-Eun , Yoon Hyo-Chun , Findeiss Laura K. , Roberts John A. , Nightingale Daniel R. , Narra Krishna K. , Parker Dennis L. , Treiman Gerald S.
Published: April 2012

Background—

Carotid intraplaque hemorrhage has been associated with symptomatic stroke and can be accurately detected with magnetization-prepared rapid acquisition with gradient-echo (MPRAGE). Currently, there are no studies analyzing carotid MPRAGE signal and territorial ischemic events defined by diffusion restriction in the acute setting. Our aim was to determine the association of carotid MPRAGE signal with acute territorial ischemic events using carotid MPRAGE and brain diffusion tensor imaging.

Methods and Results—

After the addition of the MPRAGE sequence to the neck MR angiographic protocol, 159 patients with suspected acute stroke were evaluated with both brain diffusion tensor imaging and carotid MPRAGE sequences over 2 years, providing 318 carotid artery and paired brain images for analysis. Forty-eight arteries were excluded due to extracarotid sources of brain ischemia and 4 were excluded due to carotid occlusion. Two hundred sixty-six arteries were eligible for data analysis. Carotid MPRAGE-positive signal was associated with an acute cerebral territorial ischemic event with a relative risk of 6.4 (
P
<0.001). The relative risk of a diffusion tensor imaging-positive territorial ischemic event with carotid MPRAGE-positive signal was increased in mild, moderate, and severe stenosis categories (10.3,
P
<0.001; 2.9,
P
=0.01; and 2.2,
P
=0.01, respectively).

Conclusions—

In the workup of acute stroke, carotid MPRAGE-positive signal was associated with an increased risk of territorial cerebral ischemic events as detected objectively by brain diffusion tensor imaging. The relative risk of stroke was increased in all carotid stenosis categories but was most elevated in the mild stenosis category.
Energy Transfer from High-Shear, Low-Frequency Internal Waves to High-Frequency Waves near Kaena Ridge, Hawaii
Authors: Sun Oliver M. , Pinkel Robert
Published: April 2012

Evidence is presented for the transfer of energy from low-frequency inertial–diurnal internal waves to high-frequency waves in the band between 6 cpd and the buoyancy frequency. This transfer links the most energetic waves in the spectrum, those receiving energy directly from the winds, barotropic tides, and parametric subharmonic instability, with those most directly involved in the breaking process. Transfer estimates are based on month-long records of ocean velocity and temperature obtained continuously over 80–800 m from the research platform (R/P) Floating Instrument Platform (FLIP) in the Hawaii Ocean Mixing Experiment (HOME) Nearfield (2002) and Farfield (2001) experiments, in Hawaiian waters. Triple correlations between low-frequency vertical shears and high-frequency Reynolds stresses, 〈uiw∂Ui/∂z〉, are used to estimate energy transfers. These are supported by bispectral analysis, which show significant energy transfers to pairs of waves with nearly identical frequency. Wavenumber bispectra indicate that the vertical scales of the high-frequency waves are unequal, with one wave of comparable scale to that of the low-frequency parent and the other of much longer scale. The scales of the high-frequency waves contrast with the classical pictures of induced diffusion and elastic scattering interactions and violates the scale-separation assumption of eikonal models of interaction. The possibility that the observed waves are Doppler shifted from intrinsic frequencies near f or N is explored. Peak transfer rates in the Nearfield, an energetic tidal conversion site, are on the order of 2 × 10−7 W kg−1 and are of similar magnitude to estimates of turbulent dissipation that were made near the ridge during HOME. Transfer rates in the Farfield are found to be about half the Nearfield values.
Sensible Heat Flux in Near-Neutral Conditions over the Sea
Authors: Mahrt L. , Vickers Dean , Andreas Edgar L , Khelif Djamal
Published: April 2012

The variation of the sea surface sensible heat flux is investigated using data from the Gulf of Tehuantepec Experiment (GOTEX) and from eight additional aircraft datasets representing a variety of surface conditions. This analysis focuses on near-neutral conditions because these conditions are common over the sea and are normally neglected, partly because of uncertain reliability of measurements of the small air–sea temperature difference. For all of the datasets, upward heat flux is observed for slightly stable conditions. The frequency of this “countergradient” heat flux increases with increasing wind speed and is possibly related to sea spray or microscale variations of surface temperature on the wave scale. Upward area-averaged sensible heat flux for slightly stable conditions can also be generated by mesoscale heterogeneity of the sea surface temperature (SST). Significant measurement errors cannot be ruled out.

The countergradient heat flux for weakly stable conditions is least systematic for weaker winds, even though it occurs with weak winds in all of the datasets. In an effort to reduce offset errors and different SST processing and calibration procedures among field programs, the authors adjusted the SST in each field program to minimize the countergradient flux for weak winds. With or without this adjustment for the combined dataset, the extent of the upward heat flux for weakly stable conditions increases with increasing wind speed.