bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasonographic evaluation of the adrenal glands in healthy dogs: repeatability, reproducibility, observer‐dependent variability, and the effect of bodyweight, age and sex
Authors: Mogicato G. , Layssol‐Lamour C. , Conchou F. , Diquelou A. , Raharison F. , Sautet J. , Concordet D.
Published: February 2011

Adrenal length and width were determined from two‐dimensional ultrasound longitudinal images. In study 1, 540 measurements of adrenal glands were attempted from five healthy beagle dogs by three different observers with different levels of expertise in ultrasonography, to determine the variability of adrenal gland measurements. Of these, 484 measurements were included in the statistical analysis, since 16 measurements of the left adrenal gland and 40 for the right could not be visualised by the observer. In study 2, a single measurement of both adrenal glands was taken from each of 146 dogs by the most trained observer from study 1, and the effects of different health status (healthy dogs v dogs with non‐adrenal diseases), bodyweight, age and sex were assessed. A total of 267 measurements were included in the statistical analysis. The lowest intra‐ and inter‐day coefficient of variation values were observed for the left adrenal gland and by the most trained observer. The health status had no statistically significant effect on adrenal gland length or width, whereas age had a significant effect only for the left adrenal gland (the greater the age, the greater the width or length) and sex had a significant effect only for the right adrenal gland (the width was larger in males and the length larger in females). The bodyweight had a significant effect for the length of both adrenal glands (the greater the bodyweight, the greater the length), but not the width. The differences between sd and coefficient of variation values for the width of the left adrenal gland were not statistically significant between the three observers, whereas they were statistically significant for the right adrenal gland.
Sources of variability and comparability between salmonid stomach contents and isotopic analyses: study design lessons and recommendations
Authors: Vinson Mark R. , Budy Phaedra
Published: February 2011

We compared sources of variability and cost in paired stomach content and stable isotope samples from three salmonid species collected in September 2001–2005 and describe the relative information provided by each method in terms of measuring diet overlap and food web study design. Based on diet analyses, diet overlap among brown trout, rainbow trout, and mountain whitefish was high, and we observed little variation in diets among years. In contrast, for sample sizes n ≥ 25, 95% confidence interval (CI) around mean δ15Ν and δ13C for the three target species did not overlap, and species, year, and fish size effects were significantly different, implying that these species likely consumed similar prey but in different proportions. Stable isotope processing costs were US$12 per sample, while stomach content analysis costs averaged US$25.49 ± $2.91 (95% CI) and ranged from US$1.50 for an empty stomach to US$291.50 for a sample with 2330 items. Precision in both δ15Ν and δ13C and mean diet overlap values based on stomach contents increased considerably up to a sample size of n = 10 and plateaued around n = 25, with little further increase in precision.
An experimental examination of temperature interactions in the match–mismatch hypothesis for Pacific cod larvae
Authors: Laurel Benjamin J. , Hurst Thomas P. , Ciannelli Lorenzo
Published: February 2011

The match–mismatch hypothesis (MMH) predicts that marine fish larvae will have their highest rate of growth and survival when they overlap with their prey. However, Pacific cod ( Gadus macrocephalus ) and other gadids continue to thrive in the Bering Sea despite delayed prey production resulting from warming and loss of sea ice. In this study, we examined how temperature mediates growth and survival of Pacific cod larvae under varying match–mismatch conditions. Cod larvae were reared at two temperatures (3 °C and 8 °C) and exposed to one of five different food treatments over a 6-week period: (i) high food (HF) (match); (ii) low food (LF); (iii) HF then LF (HF–LF); and (iv) LF then HF (LF–HF) (2–4 mismatch); and (v) no food (NF) (complete mismatch). Results showed that cold environments allow Pacific cod larvae to bridge gaps in prey availability (i.e., timing and magnitude), but negatively impact survival over longer periods. Under warmer conditions, mismatches in prey significantly impacted growth and survival. However, both yolk reserves and compensatory growth mechanisms reduced the severity of mismatches occurring in the first 3 weeks of development. Our results demonstrate a clear need to incorporate the direct effects of temperature on fish larvae in food limitation models.
A steep genetic cline in yellowtail rockfish,Sebastes flavidus, suggests regional isolation across the Cape Mendocino faunal break
Authors: Hess Jon E. , Vetter Russell D. , Moran Paul
Published: February 2011

As with all Sebastes species, yellowtail rockfish ( S. flavidus ) produce larvae with an extended pelagic juvenile phase that can be advected in coastal currents. While dispersal potential is high, previous research on population genetic characteristics of Sebastes species indicates that apparent realized dispersal can be much lower and can exhibit complex patterns of genetic structure. We assayed 812 bp of the mitochondrial cytochrome b gene and six microsatellite loci in ∼1000 yellowtail rockfish collected from 21 sites that span the species range from southern California to southeastern Alaska. An abrupt genetic cline near Cape Mendocino, California, splits the range into a northern and southern stock, and is highly concordant between our mitochondrial (FCT= 0.32, p ≪ 0.001) and microsatellite (FCT= 0.02, p ≪ 0.001) datasets. We show that this pattern may be due to a combination of physical (oceanographic or other barriers to larval dispersal), biological (habitat differences), and historical events. This study, and both intra- and inter-specific evidence from other marine species suggests Cape Mendocino demarcates two regions experiencing divergent evolutionary trajectories, and should be considered in management strategies.
Genetic analysis reveals two stocks of skipjack tuna (Katsuwonus pelamis) in the northwestern Indian Ocean
Authors: Dammannagoda Sudath T. , Hurwood David A. , Mather Peter B.
Published: February 2011

Skipjack (SJT) ( Katsuwonus pelamis ) is a medium-sized, pelagic, highly dispersive tuna species that occurs widely across tropical and subtropical waters. SJT constitute the largest tuna fishery in the Indian Ocean and are currently managed as a single stock. Patterns of genetic variation in a mtDNA gene and six microsatellite loci were examined to test for stock structure in the northwestern Indian Ocean. 324 individuals were sampled from five major fishing grounds around Sri Lanka and from single sites in the Maldive Islands and the Laccadive Islands. Phylogenetic reconstruction of mtDNA revealed two coexisting divergent clades in the region. Analysis of molecular variance (AMOVA) of mtDNA data revealed significant genetic differentiation among sites (ΦST = 0.2029, P < 0.0001), also supported by spatial AMOVA results. AMOVA of microsatellite data also showed significant differentiation among most sampled sites (FST = 0.0256, P < 0.001), consistent with the mtDNA pattern. STRUCTURE analysis of the microsatellite data revealed two differentiated stocks. While both marker types examined identified two genetic groups, microsatellite analysis indicates that the sampled SJT are likely to represent individuals sourced from discrete breeding grounds that are mixed in feeding grounds in Sri Lankan waters.
Effects of spawning distribution on juvenile Atlantic salmon (Salmo salar) density and growth
Authors: Teichert Maxim A.K. , Foldvik Anders , Forseth Torbjørn , Ugedal Ola , Einum Sigurd , Finstad Anders G. , Hedger Richard D. , Bellier Edwige
Published: February 2011

We test whether the spatial distribution of spawning sites in a natural population is related to the density and individual growth rate of juvenile stream-dwelling salmonids. For this purpose, fine-scale data on the spatial distribution of Atlantic salmon ( Salmo salar ) nest sites, juvenile densities and body size, and habitat characteristics were combined. The area of nests summed over reaches of 25 m in length was positively correlated with local young-of-the-year (YOY) densities and was the strongest predictor of local densities. In turn, increased YOY densities were related to slower growth, and YOY density was the strongest predictor of YOY size. Measured habitat variables had little effect on YOY density over the spatial scale examined, which suggests that redistribution of YOY salmon according to habitat preferences was limited. The distribution of spawning sites was therefore the best predictor of local densities and subsequently YOY growth. Thus, during the YOY stage when dispersal is limited, patchy spawning distributions combined with local density-dependence may be the dominant factor responsible for spatial variation in growth.
Estimation of soil suction from the soil-water characteristic curve
Authors: Fredlund Delwyn G. , Sheng Daichao , Zhao Jidong
Published: February 2011

Soil-water characteristic curves (SWCCs) are routinely used for the estimation of unsaturated soil property functions (e.g., permeability functions, water storage functions, shear strength functions, and thermal property functions). This paper examines the possibility of using the SWCC for the estimation of in situ soil suction. The paper focuses on the limitations of estimating soil suctions from the SWCC and also suggests a context under which soil suction estimations should be used. The potential range of estimated suction values is known to be large because of hysteresis between drying and wetting SWCCs. For this, and other reasons, the estimation of in situ suctions from the SWCC has been discouraged. However, a framework is suggested in this paper for estimating the median value for in situ soil suction along with a likely range of soil suction values (i.e., maximum and minimum values). The percentage error in the estimation of soil suction from the SWCC is shown to be lowest for sand soils and highest for clay soils.
Collapse behavior of soil in a Brazilian region affected by a rising water table
Authors: Vilar Orencio Monje , Rodrigues Roger Augusto
Published: February 2011

Collapsible soils are usually nonsaturated, low density, and metastable-structured soils that are known to exhibit a volume reduction following an episode of moisture increase or suction reduction. This paper describes the collapsible behavior of clayey sand based on controlled soil suction tests carried out on undisturbed samples from the city of Pereira Barreto, in the State of São Paulo, Brazil. Foundation settlements due to soil collapse are common in this region and occurred during the filling of the reservoir of the Três Irmãos Dam, which induced the elevation of the groundwater table in different parts of Pereira Barreto. This paper shows that collapse strains depend on the stress and soil suction acting in the sample and that saturation is not necessary for a collapse to occur. The influence of soil suction, gradual wetting, and the wetting and drying cycle on the collapsible behavior of the soil is also shown and discussed.
Supramolecular encapsulation of benzimidazole-derived drugs by cucurbit[7]uril
Authors: Koner Apurba L. , Ghosh Indrajit , Saleh Na'il , Nau Werner M.
Published: February 2011

UV–vis and NMR spectroscopic techniques were employed to demonstrate the ability of the synthetic macrocyclic host cucurbit[7]uril (CB7) to solubilize and stabilize widely used fungicides and anthelmintic drugs of the benzimidazole family in water, namely, albendazole (ABZ), carbendazim (CBZ), thiabendazole (TBZ), fuberidazole (FBZ), and the parent benzimidazole (BZ). CB7 binds the protonated forms of these guests very strongly (e.g., K = 2.6 × 107 L/mol for ABZ) but their neutral forms significantly more weakly (e.g., K = 6.5 × 104 L/mol for ABZ), which reflects a complexation-induced increase of their pKa values by 2.6 units for ABZ, 2.5 units for CBZ, 4.0 units for TBZ, 3.8 units for FBZ, and 3.5 units for BZ. The absolute drug solubilities increased upon complexation from 0.003 to 0.300 mmol/L for ABZ, from 0.160 to 1.12 mmol/L for CBZ, from 0.110 to 1.11 mmol/L for TBZ, and from 0.25 to 0.75 mmol/L for FBZ (for BZ, the solubility enhancement was found to be insignificant). Complexation by CB7 further improves the photostability of the drugs and alters their photophysical properties.
Synthesis and spectroelectrochemical investigation of two tetraarylporphyrins
Authors: Krüger Robin A. , Terpstra Andrea S. , Sutherland Todd C.
Published: February 2011

A free-base tetraarylporphyrin was synthesized by the [2+2] macrocyclization of a dipyrromethane derivative with 3,4,5-tris(dodecyloxy)benzaldehyde in 61% yield. The free-base porphyrin was metallated with zinc acetate in 94% conversion. The free-base and metallated porphyrins show typical intense Soret bands at 426 and 425 nm, respectively, along with the expected number and intensity of Q-bands. Both porphyrins are also fluorescent and display small Stokes shifts between 13 and 18 nm. Cyclic voltammetry established that each porphyrin underwent two reversible one-electron oxidations at 492 and 725 mV (vs Fc/Fc+(ferrocene reference)) for the free-base porphyrin and at 329 and 589 mV (vs Fc/Fc+) for the Zn-metalloporphyrin. Electron-transfer rates were also determined to fall between 1.2 × 10−3and 2.4 × 10−3cm s–1. In addition, spectroelectrochemistry and density functional theory calculations of the oxidized products were carried out to confirm the macrocyclic ring oxidations.
Photogeneration and reactivity of acyl nitroso compounds
Authors: Evans Anthony S. , Cohen Andrew D. , Gurard-Levin Zachary A. , Kebede Naod , Celius Tevye C. , Miceli Alexander P. , Toscano John P.
Published: February 2011

Acyl nitroso compounds have been generated by photolysis of several different classes of precursors including 9,10-dimethylanthracene adducts, nitrodiazo compounds, and 1,2,4-oxadiazole-4-oxides. Consideration of the nitronate-like resonance structure of nitrodiazo compounds led to an examination of the photochemistry of nitronates with α-leaving groups. Photolysis of such nitronates has been shown to generate an acyl nitroso species along with a carbene intermediate. Nanosecond time-resolved infrared (TRIR) spectroscopy has been used to detect photogenerated acyl nitroso compounds directly and to examine their reaction kinetics with amines and thiols. The mechanism of acyl nitroso aminolysis by primary amines involves general base catalysis, while the mechanism of aminolysis by secondary amines is strictly bimolecular. Thiols do not seem to be reactive with acyl nitroso compounds on the microsecond time scale, but thiolates are quite reactive. The reaction between benzoyl nitroside and an organic-soluble thiolate, tetrabutylammonium dodecanethiolate, proceeds via a proposed tetrahedral intermediate, which is observable by TRIR spectroscopy.
The disruption of central CO2 chemosensitivity in a mouse model of Rett syndrome
Authors: Zhang Xiaoli , Su Junda , Cui Ningren , Gai Hongyu , Wu Zhongying , Jiang Chun
Published: February 2011

People with Rett syndrome (RTT) have breathing instability in addition to other neuropathological manifestations. The breathing disturbances contribute to the high incidence of unexplained death and abnormal brain development. However, the cellular mechanisms underlying the breathing abnormalities remain unclear. To test the hypothesis that the central CO2 chemoreception in these people is disrupted, we studied the CO2 chemosensitivity in a mouse model of RTT. The Mecp2-null mice showed a selective loss of their respiratory response to 1–3% CO2 (mild hypercapnia), whereas they displayed more regular breathing in response to 6–9% CO2 (severe hypercapnia). The defect was alleviated with the NE uptake blocker desipramine (10 mg·kg−1·day−1 ip, for 5–7 days). Consistent with the in vivo observations, in vitro studies in brain slices indicated that CO2 chemosensitivity of locus coeruleus (LC) neurons was impaired in Mecp2-null mice. Two major neuronal pH-sensitive Kir currents that resembled homomeric Kir4.1 and heteromeric Ki4.1/Kir5.1 channels were identified in the LC neurons. The screening of Kir channels with real-time PCR indicated the overexpression of Kir4.1 in the LC region of Mecp2-null mice. In a heterologous expression system, an overexpression of Kir4.1 resulted in a reduction in the pH sensitivity of the heteromeric Kir4.1-Kir5.1 channels. Given that Kir4.1 and Kir5.1 subunits are also expressed in brain stem respiration-related areas, the Kir4.1 overexpression may not allow CO2 to be detected until hypercapnia becomes severe, leading to periodical hyper- and hypoventilation in Mecp2-null mice and, perhaps, in people with RTT as well.
Collagen IV contributes to nitric oxide-induced angiogenesis of lung endothelial cells
Authors: Wang Huafang , Su Yunchao
Published: February 2011

Nitric oxide (NO) mediates endothelial angiogenesis via inducing the expression of integrin αvβ3. During angiogenesis, endothelial cells adhere to and migrate into the extracellular matrix through integrins. Collagen IV binds to integrin αvβ3, leading to integrin activation, which affects a number of signaling processes in endothelial cells. In the present study, we evaluated the role of collagen IV in NO-induced angiogenesis. We found that NO donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (NOC-18) causes increases in collagen IV mRNA and protein in lung endothelial cells and collagen IV release into the medium. Addition of collagen IV into the coating of endothelial culture increases endothelial monolayer wound repair, proliferation, and tube formation. Inhibition of collagen IV synthesis using gene silencing attenuates NOC-18-induced increases in monolayer wound repair, cell proliferation, and tube formation as well as in the phosphorylation of focal adhesion kinase (FAK). Integrin blocking antibody LM609 prevents NOC-18-induced increase in endothelial monolayer wound repair. Inhibition of protein kinase G (PKG) using the specific PKG inhibitor KT5823 or PKG small interfering RNA prevents NOC-18-induced increases in collagen IV protein and mRNA and endothelial angiogenesis. Together, these results indicate that NO promotes collagen IV synthesis via a PKG signaling pathway and that the increase in collagen IV synthesis contributes to NO-induced angiogenesis of lung endothelial cells through integrin-FAK signaling. Manipulation of collagen IV could be a novel approach for the prevention and treatment of diseases such as alveolar capillary dysplasia, severe pulmonary arterial hypertension, and tumor invasion.
Accumulation of CD4+T cells in the colon of CsA-treated mice following myeloablative conditioning and bone marrow transplantation
Authors: Perez Jacqueline , Brandon J. Anthony , Cohen Donald A. , Jennings C. Darrell , Kaplan Alan M. , Bryson J. Scott
Published: February 2011

Syngeneic graft vs. host disease (SGVHD) was first described as a graft vs. host disease-like syndrome that developed in rats following syngeneic bone marrow transplantation (BMT) and cyclosporin A (CsA) treatment. SGVHD can be induced by reconstitution of lethally irradiated mice with syngeneic bone marrow cells followed by 21 days of treatment with the immunosuppressive agent CsA. Clinical symptoms of the disease appear 2–3 wk following cessation of CsA therapy, and disease-associated inflammation occurs primarily in the colon and liver. CD4+T cells have been shown to play an important role in the inflammatory response observed in the gut of SGVHD mice. Time-course studies revealed a significant increase in migration of CD4+T cells into the colon during CsA therapy, as well as significantly elevated mRNA levels of TNF-α, proinflammatory chemokines, and cell adhesion molecules in colonic tissue of CsA-treated animals compared with BMT controls, as early as day 14 post-BMT. Homing studies revealed a greater migration of labeled CD4+T cells into the gut of CsA-treated mice at day 21 post-BMT than control animals via CsA-induced upregulation of mucosal addressin cell adhesion molecule. This study demonstrates that, during the 21 days of immunosuppressive therapy, functional mechanisms are in place that result in increased homing of CD4+T effector cells to colons of CsA-treated mice.
TNF-α potentiates lysophosphatidic acid-induced COX-2 expression via PKD in human colonic myofibroblasts
Authors: Rodriguez Perez Citlali Ekaterina , Nie Wenxian , Sinnett-Smith James , Rozengurt Enrique , Yoo James
Published: February 2011

The myofibroblast (MFB) has recently been identified as an important mediator of tumor necrosis factor-α (TNF-α)-associated colitis and cancer, but the mechanism(s) involved remains incompletely understood. Here, we show that treatment of 18Co cells, a model of human colonic MFBs, with TNF-α and lysophosphatidic acid (LPA) induced striking synergistic cyclooxygenase-2 (COX-2) protein expression and production of PGE2. This effect was prevented by the LPA1receptor antagonist Ki16425, the Giα-specific inhibitor pertussis toxin, and by the preferential protein kinase (PK) C inhibitors GF109203X and Go6983. As a known downstream target of LPA and PKC, we tested whether PKD, recently implicated in the regulation of COX-2 expression in MFB, was involved in this response. TNF-α, while having no detectable effect on the activation of PKD when added alone, augmented PKD activation stimulated by LPA, as measured by PKD autophosphorylation at Ser910. LPA-induced PKD activation was also inhibited by Ki16425, pertussis toxin, GF109203X, and Go6983. Transfection of 18Co cells with short interfering RNA targeting PKD completely inhibited the synergistic increase in COX-2 protein, demonstrating a critical role of PKD in this response. Our results imply that cross talk between TNF-α and LPA results in the amplification of COX-2 protein expression via a conserved PKD-dependent signaling pathway that appears to involve the LPA1receptor and the G protein Giα. PKD plays a critical role in the expression of COX-2 in human colonic MFBs and may contribute to an inflammatory microenvironment that promotes tumor growth.
Iron loading and oxidative stress in theAtm−/−mouse liver
Authors: McDonald Cameron J. , Ostini Lesa , Wallace Daniel F. , John Abraham N. , Watters Dianne J. , Subramaniam V. Nathan
Published: February 2011

Ataxia-Telangiectasia (A-T) is an autosomal recessive disorder resulting in a myriad of abnormalities, including progressive neurodegeneration and cancer predisposition. At the cellular level, A-T is a disease of chronic oxidative stress (OS) causing damage to proteins, lipids, and DNA. OS is contributed to by pro-oxidative transition metals such as iron that catalyze the conversion of weakly reactive oxygen species to highly reactive hydroxyl radicals. Iron-associated OS has been linked to neurodegeneration in Alzheimer's and Parkinson's diseases and development of lymphoid tumors (which afflict ∼30% of A-T patients). To investigate iron regulation in A-T, iron indexes, regulatory genes, and OS markers were studied in livers of wild-type and Ataxia telangiectasia mutated ( Atm) null mice on control or high-iron diets. Atm−/−mice had increased serum iron, hepatic iron, and ferritin and significantly higher Hepcidin compared with wild-type mice. When challenged with the high-iron diet, Bmp6 and Hfe expression was significantly increased. Atm−/−mice had increased protein tyrosine nitration and significantly higher Heme Oxygenase (decycling) 1 levels that were substantially increased by a high-iron diet. Ferroportin gene expression was significantly increased; however, protein levels were unchanged. We demonstrate that Atm−/−mice have a propensity to accumulate iron that is associated with a significant increase in hepatic OS. The iron-induced increase in hepcidin peptide in turn suppresses ferroportin protein levels, thus nullifying the upregulation of mRNA expression in response to increased OS. Our results suggest that increased iron status may contribute to the chronic OS seen in A-T patients and development of disease pathology.
Sry-box (Sox) transcription factors in gastrointestinal physiology and disease
Authors: Gracz A. D. , Magness S. T.
Published: February 2011

The genetic mechanisms underlying tissue maintenance of the gastrointestinal tract are critical for the proper function of the digestive system under normal physiological stress. The identification of transcription factors and related signal transduction pathways that regulate stem cell maintenance and lineage allocation is attractive from a clinical standpoint in that it may provide targets for novel cell- or drug-based therapies. Sox [sex-determining region Y ( Sry) box-containing] factors are a family of transcription factors that are emerging as potent regulators of stem cell maintenance and cell fate decisions in multiple organ systems and might provide valuable insight toward the understanding of these processes in endodermally derived tissues of the gastrointestinal tract. In this review, we focus on the known genetic functions of Sox factors and their roles in epithelial tissues of the esophagus, stomach, intestine, colon, pancreas, and liver. Additionally, we discuss pathological conditions in the gastrointestinal tract that are associated with a dysregulation of Sox factors. Further study of Sox factors and their role in gastrointestinal physiology and pathophysiology may lead to advances that facilitate control of tissue maintenance and development of advanced clinical therapies.
Intrarenal transfer of an intracellular fluorescent fusion of angiotensin II selectively in proximal tubules increases blood pressure in rats and mice
Authors: Li Xiao C. , Cook Julia L. , Rubera Isabelle , Tauc Michel , Zhang Fan , Zhuo Jia L.
Published: February 2011

The present study tested the hypothesis that intrarenal adenoviral transfer of an intracellular cyan fluorescent fusion of angiotensin II (ECFP/ANG II) selectively in proximal tubules of the kidney increases blood pressure by activating AT1 (AT1a) receptors. Intrarenal transfer of ECFP/ANG II was induced in the superficial cortex of rat and mouse kidneys, and the sodium and glucose cotransporter 2 (sglt2) promoter was used to drive ECFP/ANG II expression selectively in proximal tubules. Intrarenal transfer of ECFP/ANG II induced a time-dependent, proximal tubule-selective expression of ECFP/ANG II in the cortex, which peaked at 2 wk and was sustained for 4 wk. ECFP/ANG II expression was low in the glomeruli and the entire medulla and was absent in the contralateral kidney or extrarenal tissues. At its peak of expression in proximal tubules at day 14, ANG II was increased by twofold in the kidney ( P < 0.01) and more than threefold in proximal tubules ( P < 0.01), but remained unchanged in plasma or urine. Systolic blood pressure was increased in ECFP/ANG II-transferred rats by 28 ± 6 mmHg ( P < 0.01), whereas fractional sodium excretion was decreased by 20% ( P < 0.01) and fractional lithium excretion was reduced by 24% ( P < 0.01). These effects were blocked by losartan and prevented in AT1a knockout mice. Transfer of a scrambled ECFP/ANG IIc had no effects on blood pressure, kidney, and proximal tubule ANG II, or sodium excretion. These results provide evidence that proximal tubule-selective transfer of an intracellular ANG II fusion protein increases blood pressure by activating AT1a receptors and increasing sodium reabsorption in proximal tubules.
High salt differentially regulates surface NKCC2 expression in thick ascending limbs of Dahl salt-sensitive and salt-resistant rats
Authors: Haque Mohammed Ziaul , Ares Gustavo Rosier , Caceres Paulo Sebastian , Ortiz Pablo Alfredo
Published: February 2011

NaCl reabsorption by the thick ascending limb of the loop of Henle (THAL) occurs via the apical Na-K-2Cl cotransporter, NKCC2. Overall, NKCC2 activity and NaCl reabsorption are regulated by the amount of NKCC2 at the apical surface, and also by phosphorylation. Dahl salt-sensitive rats (SS) exhibit higher NaCl reabsorption by the THAL compared with Dahl salt-resistant rats (SR), and they become hypertensive during high-salt (HS) intake. However, the effect of HS on THAL transport, surface NKCC2 expression, and NKCC2 NH2-terminus phosphorylation has not been studied. We hypothesized that HS enhances surface NKCC2 and its phosphorylation in THALs from Dahl SS. THAL suspensions were obtained from a group of SS and SR rats on normal-salt (NS) or HS intake. In SR rats THAL NaCl transport measured as furosemide-sensitive oxygen consumption was decreased by HS (−34%, P < 0.05). In contrast, HS did not affect THAL transport in SS rats. As expected, HS increased systolic blood pressure only in SS rats (Δ 23 ± 2 mmHg, P < 0.002) but not in SR rats (Δ 5 ± 3 mmHg). We next tested the effect of HS intake on apical surface NKCC2 and its NH2-terminus threonine phosphorylation (P-NKCC2) in SS and SR rats. HS intake decreased surface NKCC2 by 15 ± 2% ( P < 0.03) in THALs from SR without affecting total NKCC2 or NH2-terminus P-NKCC2. In contrast, in SS rats HS intake increased surface NKCC2 by 54 ± 6% ( P < 0.01) without affecting total NKCC2 expression or P-NKCC2. We conclude that HS intake causes different effects on surface NKCC2 in SS and SR rats. Our data suggest that enhanced surface NKCC2 in SS rats might contribute to enhanced NaCl reabsorption in SS rats during HS intake.
Multi-scale lung modeling
Authors: Tawhai Merryn H. , Bates Jason H. T.
Published: February 2011

Multi-scale modeling of biological systems has recently become fashionable due to the growing power of digital computers as well as to the growing realization that integrative systems behavior is as important to life as is the genome. While it is true that the behavior of a living organism must ultimately be traceable to all its components and their myriad interactions, attempting to codify this in its entirety in a model misses the insights gained from understanding how collections of system components at one level of scale conspire to produce qualitatively different behavior at higher levels. The essence of multi-scale modeling thus lies not in the inclusion of every conceivable biological detail, but rather in the judicious selection of emergent phenomena appropriate to the level of scale being modeled. These principles are exemplified in recent computational models of the lung. Airways responsiveness, for example, is an organ-level manifestation of events that begin at the molecular level within airway smooth muscle cells, yet it is not necessary to invoke all these molecular events to accurately describe the contraction dynamics of a cell, nor is it necessary to invoke all phenomena observable at the level of the cell to account for the changes in overall lung function that occur following methacholine challenge. Similarly, the regulation of pulmonary vascular tone has complex origins within the individual smooth muscle cells that line the blood vessels but, again, many of the fine details of cell behavior average out at the level of the organ to produce an effect on pulmonary vascular pressure that can be described in much simpler terms. The art of multi-scale lung modeling thus reduces not to being limitlessly inclusive, but rather to knowing what biological details to leave out.
AMPA receptor subunit GluR1 (GluA1) serine-845 site is involved in synaptic depression but not in spine shrinkage associated with chemical long-term depression
Authors: He Kaiwen , Lee Angela , Song Lihua , Kanold Patrick O. , Lee Hey-Kyoung
Published: February 2011

The structure of dendritic spines is highly plastic and can be modified by neuronal activity. In addition, there is evidence that spine head size correlates with the synaptic α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor (AMPAR) content, which suggests that they may be coregulated. Although there is evidence that there are overlapping mechanisms for structural and functional plasticity, the extent of the overlap needs further investigation. Specifically, it is unknown whether AMPAR levels determine spine size or whether both are regulated via parallel pathways. We studied the correlation between spine structural plasticity and long-term synaptic plasticity following chemical-induced long-term depression (chemLTD). In particular, we examined whether the regulation of AMPARs, which is implicated in LTD, is critical for spine morphological plasticity. We used mutant mice specifically lacking the serine-845 site on the type 1 glutamate receptor (GluR1, or GluA1) subunit of AMPARs (mutants). These mice specifically lack N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent LTD and NMDAR activation-induced AMPAR endocytosis. We found that chemLTD causes a rapid and persistent shrinkage in spine head volume of hippocampal CA1 pyramidal neurons in wild types similar to that reported in other studies using low-frequency stimulation (LFS)-induced LTD. Surprisingly, we found that although S845A mutant mice display impaired chemLTD, the shrinkage of spine head volume occurred to a similar magnitude to that observed in wild types. Our results suggest that there is dissociation in the molecular mechanisms underlying functional LTD and spine shrinkage and that GluR1-S845 regulation is not necessary for spine morphological plasticity.
Top-Down Proteomic Identification of Furin-Cleavedα-Subunit of Shiga Toxin 2 fromEscherichia coliO157:H7 Using MALDI-TOF-TOF-MS/MS
Authors: Fagerquist Clifton K. , Sultan Omar
Published: February 2011

A method has been developed to identify theα-subunit of Shiga toxin 2 (α-Stx2) fromEscherichia coliO157:H7 using matrix-assisted laser desorption/ionization time-of-flight-time-of-flight tandem mass spectrometry (MALDI-TOF-TOF-MS/MS) and top-down proteomics using web-based software developed in-house. Expression of Stx2 was induced by culturingE. coliO157:H7 on solid agar supplemented with an antibiotic that elicits the bacterial SOS-response. Bacterial cell lysates were incubated in the presence of furin, a human enzyme, that cleavesα-Stx2 into A1 (~28 kDa) and A2 (~5 kDa) protein fragments. A subsequent disulfide reduction step unlinked A1 from A2. MALDI-TOF-MS of the furin-digested/disulfide-reduced sample showed a peak at mass-to-charge () 5286 that corresponded to the A2 fragment. No peak was observed that corresponded to the A1 fragment although its presence was confirmed by bottom-up proteomics. The peak at 5286 was definitively identified by MALDI-TOF-TOF-MS/MS and top-down proteomics as the A2 fragment ofα-Stx2.
Prospects of Back Surface Field Effect in Ultra-Thin High-Efficiency CdS/CdTe Solar Cells from Numerical Modeling
Authors: Amin Nowshad , Matin M. A. , Aliyu M. M. , Alghoul M. A. , Karim M. R. , Sopian K.
Published: February 2011

Polycrystalline CdTe shows greater promises for the development of cost-effective, efficient, and reliable thin film solar cells. Results of numerical analysis using AMPS-1D simulator in exploring the possibility of ultrathin, high efficiency, and stable CdS/CdTe cells are presented. The conventional baseline case structure of CdS/CdTe cell has been explored with reduced CdTe absorber and CdS window layer thickness, where 1 μm thin CdTe and 50 nm CdS layers showed reasonable efficiencies over 15%. The viability of 1 μm CdTe absorber layer together with possible back surface field (BSF) layers to reduce minority carrier recombination loss at the back contact in ultra thin CdS/CdTe cells was investigated. Higher bandgap material like ZnTe and low bandgap materials like Sb2Te3and As2Te3as BSF were inserted to reduce the holes barrier height in the proposed ultra thin CdS/CdTe cells. The proposed structure of SnO2/Zn2SnO4/CdS/CdTe/As2Te3/Cu showed the highest conversion efficiency of 18.6% (Voc= 0.92 V,Jsc= 24.97 mA/cm2, and FF = 0.81). However, other proposed structures such as SnO2/Zn2SnO4/CdS/CdTe/Sb2Te3/Mo and SnO2/Zn2SnO4/CdS/CdTe/ZnTe/Al have also shown better stability at higher operating temperatures with acceptable efficiencies. Moreover, it was found that the cells normalized efficiency linearly decreased with the increased operating temperature with relatively lower gradient, which eventually indicates better stability of the proposed ultra thin CdS/CdTe cells.
Ethanol Extract of the Flower Chrysanthemum morifolium Augments Pentobarbital‐Induced Sleep Behaviors: Involvement of Cl− Channel Activation
Authors: Kim Jae-Wook , Han Jin-Yi , Hong Jin Tae , Li Rihua , Eun Jae Soon , Oh Ki-Wan
Published: February 2011

Dried Chrysanthemum morifolium flowers have traditionally been used in Korea for the treatment
of insomnia. This study was performed to investigate whether the ethanol extract of Chrysanthemum
morifolium flowers (EFC) enhances pentobarbital‐induced sleep behaviors. EFC prolonged sleep time
induced by pentobarbital similar to muscimol, a GABAA receptors agonist. EFC also increased sleep
rate and sleep time when administrated with pentobarbital at a subhypnotic dosage. Both EFC and
pentobarbital increased chloride (Cl−) influx in primary cultured cerebellar granule cells. EFC
increased glutamic acid decarboxylase (GAD) expression levels, but had no effect on the expression
of α1‐, β2‐, and γ2‐subunits of the GABAA receptor in the hippocampus of a mouse brain. This is in
contrast to treatment with pentobarbital, which showed decreased α1‐subunit expression and no
change in GAD expression. In conclusion, EFC augments pentobarbital‐induced sleep behaviors;
these effects may result from Cl− channel activation.
Metastatic Insulinoma in a Patient with Type 2 Diabetes Mellitus: Case Report and Review of the Literature
Authors: Abbasakoor Noormuhammad Oosman , Healy Marie Louise , O'Shea Donal , Maguire Donal , Muldoon Cian , Sheahan Kieran , O'Toole Dermot
Published: February 2011

Pancreatic neuroendocrine tumors (NETs) are extremely rare, and although insulinomas are the commonest, less than 10% of insulinomas are malignant. Most patients with insulinomas present with neuroglycopenic symptoms and weight gain attributable to insulin excess. Here, we report a case where a 67-year-old lady with a background history of type 2 diabetes mellitus and breakthrough hyperinsulinism who presented with coma. The biochemical profile revealed features typical of insulinoma, and CT and endosonography confirmed a pancreatic tumor with large volume right-sided liver metastases (biopsy confirming a neuroendocrine tumor). The patient underwent successful one-step RO surgical resection, distal pancreatectomy, splenectomy, and right hepatectomy, and 9 months postoperatively, she remains free of recurrent disease. She remains a diabetic.
Animal Models for Periodontal Disease
Authors: Oz Helieh S. , Puleo David A.
Published: February 2011

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.
Abrogating TNF-α Expression Prevents Bystander Destruction of Normal Tissues during iNOS-Mediated Elimination of Intraocular Tumors
Authors: Coursey Terry G. , Chen Peter W. , Niederkorn Jerry Y.
Published: February 2011

Although intraocular tumors reside in an immune privileged site, some tumors are rejected nonetheless. For example, intraocular adenovirus-induced (Ad5E1; adenovirus type 5 early region 1) tumors are rejected in syngeneic C57BL/6 mice by one of two pathways. One pathway leads to extensive necrosis of innocent bystander cells and culminates in destruction of the eye, a condition called phthisis. The second pathway is characterized by piecemeal tumor cell death that rids the eye of the tumor while preserving the architecture and function of the eye. To study the mechanisms of phthisical tumor rejection, we isolated a cell clone–designated clone 2.1 that consistently undergoes rejection in a phthisical manner. CD4+ T cells and macrophages were required for phthisical rejection of intraocular clone 2.1 tumors and M1 macrophages were involved in mediating tumor rejection. In vitro and in vivo inhibition of iNOS (inducible nitric oxide synthase) abolished macrophage-mediated killing of tumor cells and rejection of intraocular tumors. A role for M1 macrophages was further supported by investigations showing that intraocular tumors grew progressively in IFN-γ KO (knockout) mice. Studies in mice deficient in TNF-α, TNF receptor-1, or TNF receptor-2 revealed that although TNF-α was not needed for tumor rejection, it was required for the development of necrotizing inflammation and phthisis of tumor-bearing eyes. Together, our findings suggest new strategies to successfully eliminate ocular tumors while preserving the integrity of the eye. Cancer Res; 71(7); 2445–54. ©2011 AACR.
Association between Head Circumference and Body Size
Authors: Geraedts Erica J. , van Dommelen Paula , Caliebe Janina , Visser Remco , Ranke Michael B. , van Buuren Stef , Wit Jan M. , Oostdijk Wilma
Published: February 2011

Background/Aims: Studies on the association between head circumference (HC) and height or weight have shown variable results. Methods: Using data from the Dutch nationwide survey performed in 1997 (n = 14,500), we calculated correlations for different ages, and fitted a regression model for the estimation of HC. HC versus height charts were created for different age groups. Data from children from other ethnic groups and children with various growth disorders were plotted on the charts and compared with reference data. Results: Correlations between HC and height or weight showed similar patterns: highest at birth, followed by a rapid decline to a stable level and a peak in adolescence. On charts containing the regression line ±2 standard deviations for subjects aged 0–2 months and 2 months to 21 years, Turkish and Moroccan children, as well as children with idiopathic short stature and small for gestational age, had a normal HC for height, whereas children with an insulin-like growth factor 1 receptor defect or Sotos syndrome showed trends towards a smaller or larger HC for height, respectively. Conclusion: HC correlates strongly with height and weight. The charts of HC for height may serve as an additional tool to interpret HC in short or tall children.
Experiences in Central Pancreatectomy
Authors: Kang Chang Moo , Lee Jae-Myeong , Kim Myung Wook , Yoon Dong Sub , Park Joon Seong , Lee Woo Jung
Published: February 2011

Background: Non-cancerous pancreatic lesions have been increasing, and function-preserving pancreatectomy may be an adequate approach to them. Recent advanced experience of major pancreatectomy has stimulated interest in central pancreatectomy (CP). Materials and Methods: Nineteen patients who underwent CP for benign and borderline malignant lesions of the pancreas from January 1990 to December 2007 were retrospectively reviewed. We also summarized recent literature reporting more than 10 cases of CP. Result: Nine patients (47.4%) experienced postoperative complications. Pancreatic leak was noted in 7 patients (36.8%). Two patients (10.5%) required reoperation due to intractable pancreatic leak and postoperative bleeding. No mortality was noted. During the follow-up period (median 35 months, range 3–182 months), only 1 patient (5.3%) developed new-onset diabetes after successful CP. In a comparative study, similar perioperative morbidity was noted between CP and extended distal pancreatectomy with splenectomy (extended DP-S); however, the operation time and postoperative hospital stay were significantly longer in the CP group and the incidence of new-onset diabetes was much lower in the CP group as compared with the DP-S group (p < 0.05). Conclusion: CP can be carefully selected as an appropriate surgical option for benign and borderline malignant lesions limited to the pancreatic neck area.
Characterization of Differentially Methylated Regions in 3 Bovine Imprinted Genes: A Model for Studying Human Germ-Cell and Embryo Development
Authors: Hansmann T. , Heinzmann J. , Wrenzycki C. , Zechner U. , Niemann H. , Haaf T.
Published: February 2011

Correct imprinting is crucial for normal fetal and placental development in mammals. Experimental evidence in animal models and epidemiological studies in humans suggest that assisted reproductive technologies (ARTs) can interfere with imprinted gene regulation in gametogenesis and early embryogenesis. Bos taurus is an agriculturally important species in which ARTs are commonly employed. Because this species exhibits a similar preimplantation development and gestation length as humans, it is increasingly being used as a model for human germ-cell and embryo development. However, in contrast to humans and mice, there is relatively little information on bovine imprinted genes. Here, we characterized the bovine intergenic IGF2-H19 imprinting control region (ICR) spanning approximately 3 kb. We identified a 300-bp differentially methylated region (DMR) approximately 6 kb upstream of the H19 promoter, containing a CpG island with CTCF-binding site and high sequence similarity with the human intergenic ICR. Additional differentially methylated CpG islands lie –6 kb to –3 kb upstream of the promoter, however these are less conserved. Both classical bisulfite sequencing and bisulfite pyrosequencing demonstrated complete methylation of the IGF2-H19 ICR in sperm, complete demethylation in parthenogenetic embryos having only the female genome, and differential methylation in placental and somatic tissues. In addition, we established pyrosequencing assays for the previously reported bovine SNRPN and PEG3 DMRs. The observed methylation patterns were consistent with genomic imprinting in all analyzed tissues/cell types. The identified IGF2-H19 ICR and the developed quantitative methylation assays may prove useful for further studies on the relationship between ARTs and imprinting defects in the bovine model.