bluuebunny/crossref_metadata_2025 huggingface dataset:
Foxo3a drives proliferation in anaplastic thyroid carcinoma via transcriptional regulation of cyclin A1: A paradigm shift that impacts current therapeutic strategies
Authors: Marlow Laura A. , von Roemeling Christina A. , Cooper Simon J. , Zhang Yilin , Rohl Stephen D. , Arora Shilpi , Gonzales Irma M. , Azorsa David O. , Reddi Honey V. , Tun Han W. , Döppler Heike R. , Storz Peter , Smallridge Robert C. , Copland John A.
Published: June 2012

The Forkhead transcription factor, FoxO3a, is a known suppressor of primary tumor growth via transcriptional regulation of key genes regulating cell cycle arrest and apoptosis. In many types of cancer, in response to growth factor signaling, FoxO3a is phosphorylated by Akt, resulting in its exclusion from the nucleus. Here we show that FoxO3a remains nuclear in anaplastic thyroid carcinoma (ATC). This correlates with lack of Akt phosphorylation at S473 in ATC cell lines and patient ATC tissues, providing a potential explanation for nuclear FoxO3a. Mechanistically, nuclear FoxO3a promotes cell cycle progression by transcriptional upregulation of cyclin A1, promoting proliferation of human ATC cells. Silencing FoxO3a with a reverse genetics approach leads to down-regulation of CCNA1 mRNA and protein. This combined data implicates an entirely novel function for FoxO3a in ATC promotion by enhancing cell cycle progression and tumor growth via transcriptional upregulation of cyclin A1. This is clinically relevant since we detected highly elevated CCNA1 mRNA and protein levels in ATC patient tumor tissues. Our data indicate therapeutic inactivation of FoxO3a may lead to attenuation of tumor expansion in ATC. This new paradigm also suggests caution related to current dogma focused upon reactivation of FoxO3a as a therapeutic strategy against cancers harboring active PI3-K and Akt signaling pathways.
Nm23-H1 regulates contact inhibition of locomotion which is affected by ephrin-B1
Authors: Tanaka Masamitsu , Kuriyama Sei , Aiba Namiko
Published: June 2012

Contact inhibition of locomotion (CIL) is the process by which cells stop the continual migration in the same direction after collision with another cell. Highly invasive malignant cells exhibit diminished CIL behavior when they contact with stromal cells, which allows stromal invasion of tumors. We show that Nm23-H1 is essential for the suppression of Rac1 through inactivation of Tiam1 at the sites of cell-cell contact, which plays a pivotal role in CIL. U87MG cells show CIL when they contact with normal glia. U87MG did not invade significantly into glias in spheroid confrontation assay, whereas reduction of Nm23-H1 expression in U87MG cells abrogates CIL and they invaded into glias. In U87MG cells, Nm23-H1 is translocated to the sites of contact with glia through association with α-catenin and N-cadherin. In the expression of wild type Nm23-H1, neither Nm23-H1 mutant, which lacks the binding ability with Tiam1, nor α-catenin recovered CIL. Moreover, the expression of ephrin-B1 in tumor cells disrupted CIL and promoted invasion. As one mechanism, ephrin-B1 inhibits the association of Nm23-H1 with Tiam1, which contributes for activation of Rac1. These results indicate a novel function of Nm23-H1 to control CIL, and its negative regulation by ephrin-B1.
SNX9, SNX18 and SNX33 are required for progression through and completion of mitosis
Authors: Ma Maggie P.C. , Chircop Megan
Published: June 2012

Mitosis involves considerable membrane remodelling and vesicular trafficking to generate two independent cells. Consequently, endocytosis and endocytic proteins are required for efficient mitotic progression and completion. Several endocytic proteins also participate in mitosis in an endocytosis-independent manner. Here, we report that the sorting nexin (SNX) 9 subfamily members – SNX9, SNX18 and SNX33 – are required for progression and completion of mitosis. Depletion of any one of these proteins using siRNA induces multinucleation, an indicator of cytokinesis failure, as well as an accumulation of cytokinetic cells. Time-lapse microscopy on siRNA-treated cells reveals a role for SNX9 subfamily members in progression through the ingression and abscission stages of cytokinesis. Depletion of these three proteins disrupted MRLCS19 localization during ingression and recruitment of Rab11-positive recycling endosomes to the intracellular bridge between nascent daughter cells. SNX9 depletion also disrupted the localization of Golgi during cytokinesis. Endocytosis of transferrin (Tfn) was blocked during cytokinesis by depletion of the SNX9 subfamily members, suggesting that these proteins participate in cytokinesis in an endocytosis-dependent manner. In contrast, depletion of SNX9 did not block Tfn uptake during metaphase but did delay chromosome alignment and segregation, suggesting that SNX9 plays an additional non-endocytic role at early mitotic stages. We conclude that SNX9 subfamily members are required for mitosis through both endocytosis-dependent and -independent processes.
Super-resolution imaging of aquaporin-4 orthogonal arrays of particles in cell membranes
Authors: Rossi Andrea , Moritz Tobias J. , Ratelade Julien , Verkman A. S.
Published: June 2012

Aquaporin-4 (AQP4) is a water channel expressed in astrocytes, skeletal muscle and epithelial cells that forms supramolecular aggregates in plasma membranes called orthogonal arrays of particles (OAPs). AQP4 is expressed as a short isoform (M23) that forms large OAPs, and a long isoform (M1) that does not form OAPs by itself but can co-mingle with M23 to form relatively small OAPs. AQP4 OAPs were imaged with ∼20 nm spatial precision by photoactivation localization microscopy (PALM) in cells expressing chimeras of M1- or M23-AQP4 with photoactivatable fluorescent proteins. Native AQP4 was imaged by direct stochastic optical reconstruction microscopy (dSTORM) using primary anti-AQP4 antibody and fluorescent secondary antibodies. We found that OAP area increased from 1878±747 to 3647±958 nm2 with decreasing M1∶M23 ratio from 1∶1 to 1∶3, and became elongated. Two-color dSTORM indicated that M1 and M23 co-assemble in OAPs with a M1-enriched periphery surrounding a M23-enriched core. Native AQP4 in astrocytes formed OAPs of area 2142±829 nm2, which increased to 5137±1119 nm2 with 2-bromopalmitate. PALM of AQP4 OAPs in live cells showed slow diffusion (average D ∼ 10−12 cm2/s) and reorganization. OAP area was not altered by anti-AQP4 IgG autoantibodies (NMO-IgG) that cause the neurological disease neuromyelitis optica. Super-resolution imaging allowed elucidation of novel nanoscale structural and dynamic features of OAPs.
Early developmental gene regulation in Strongylocentrotus purpuratus embryos in response to elevated CO2 seawater conditions
Authors: Hammond LaTisha M. , Hofmann Gretchen E.
Published: June 2012

Ocean acidification, or the increased uptake of CO2 by the ocean due to elevated atmospheric CO2 concentrations, may variably impact marine early life history stages, as they may be especially susceptible to changes in ocean chemistry. Investigating the regulatory mechanisms of early development in an environmental context, or ecological development, will contribute to increased understanding of potential organismal responses to such rapid, large-scale environmental changes. We examined transcript-level responses to elevated seawater CO2 during gastrulation and the initiation of spiculogenesis, two crucial developmental processes in the purple sea urchin, Strongylocentrotus purpuratus. Embryos were reared at the current, accepted oceanic CO2 concentration of 380 microatmospheres (μatm), and at the elevated levels of 1000 and 1350 μatm, simulating predictions for oceans and upwelling regions, respectively. The seven genes of interest comprised a subset of pathways in the primary mesenchyme cell gene regulatory network (PMC GRN) shown to be necessary for the regulation and execution of gastrulation and spiculogenesis. Of the seven genes, qPCR analysis indicated that elevated CO2 concentrations only had a significant but subtle effect on two genes, one important for early embryo patterning, Wnt8, and the other an integral component in spiculogenesis and biomineralization, SM30b. Protein levels of another spicule matrix component, SM50, demonstrated significant variable responses to elevated CO2. These data link the regulation of crucial early developmental processes with the environment that these embryos would be developing within, situating the study of organismal responses to ocean acidification in a developmental context.
Visual attention in a complex search task differs between honeybees and bumblebees
Authors: Morawetz Linde , Spaethe Johannes
Published: June 2012

Mechanisms of spatial attention are used when the amount of gathered information exceeds processing capacity. Such mechanisms have been proposed in bees, but have not yet been experimentally demonstrated. We provide evidence that selective attention influences the foraging performance of two social bee species, the honeybee Apis mellifera and the bumblebee Bombus terrestris. Visual search tasks, originally developed for application in human psychology, were adapted for behavioural experiments on bees. We examined the impact of distracting visual information on search performance, which we measured as error rate and decision time. We found that bumblebees were significantly less affected by distracting objects than honeybees. Based on the results, we conclude that the search mechanism in honeybees is serial like, whereas in bumblebees it shows the characteristics of a restricted parallel-like search. Furthermore, the bees differed in their strategy to solve the speed–accuracy trade-off. Whereas bumblebees displayed slow but correct decision-making, honeybees exhibited fast and inaccurate decision-making. We propose two neuronal mechanisms of visual information processing that account for the different responses between honeybees and bumblebees, and we correlate species-specific features of the search behaviour to differences in habitat and life history.
High speed galloping in the cheetah (Acinonyx jubatus) and the racing greyhound (Canis familiaris): spatio-temporal and kinetic characteristics
Authors: Hudson Penny E. , Corr Sandra A. , Wilson Alan M.
Published: June 2012

The cheetah and racing greyhound are of a similar size and gross morphology and yet the cheetah is able to achieve a far higher top speed. We compared the kinematics and kinetics of galloping in the cheetah and greyhound to investigate how the cheetah can attain such remarkable maximum speeds. This also presented an opportunity to investigate some of the potential limits to maximum running speed in quadrupeds, which remain poorly understood. By combining force plate and high speed video data of galloping cheetahs and greyhounds, we show how the cheetah uses a lower stride frequency/longer stride length than the greyhound at any given speed. In some trials, the cheetahs used swing times as low as those of the greyhounds (0.2 s) so the cheetah has scope to use higher stride frequencies (up to 4.0 Hz), which may contribute to it having a higher top speed that the greyhound. Weight distribution between the animal's limbs varied with increasing speed. At high speed, the hindlimbs support the majority of the animal's body weight, with the cheetah supporting 70% of its body weight on its hindlimbs at 18 m s–1; however, the greyhound hindlimbs support just 62% of its body weight. Supporting a greater proportion of body weight on a particular limb is likely to reduce the risk of slipping during propulsive efforts. Our results demonstrate several features of galloping and highlight differences between the cheetah and greyhound that may account for the cheetah's faster maximum speeds.
Responses of cricket cercal interneurons to realistic naturalistic stimuli in the field
Authors: Dupuy Fabienne , Steinmann Thomas , Pierre Dominique , Christidès Jean-Philippe , Cummins Graham , Lazzari Claudio , Miller John , Casas Jérôme
Published: June 2012

The ability of the insect cercal system to detect approaching predators has been studied extensively in the laboratory and in the field. Some previous studies have assessed the extent to which sensory noise affects the operational characteristics of the cercal system, but these studies have only been carried out in laboratory settings using white noise stimuli of unrealistic nature. Using a piston mimicking the natural airflow of an approaching predator, we recorded the neural activity through the abdominal connectives from the terminal abdominal ganglion of freely moving wood crickets (Nemobius sylvestris) in a semi-field situation. A cluster analysis of spike amplitudes revealed six clusters, or ‘units’, corresponding to six different subsets of cercal interneurons. No spontaneous activity was recorded for the units of larger amplitude, reinforcing the idea they correspond to the largest giant interneurons. Many of the cercal units are already activated by background noise, sometimes only weakly, and the approach of a predator is signaled by an increase in their activity, in particular for the larger-amplitude units. A scaling law predicts that the cumulative number of spikes is a function of the velocity of the flow perceived at the rear of the cricket, including a multiplicative factor that increases linearly with piston velocity. We discuss the implications of this finding in terms of how the cricket might infer the imminence and nature of a predatory attack.
Temperature dependence of locomotor performance in the tropical clawed frog,Xenopus tropicalis
Authors: Herrel Anthony , Bonneaud Camille
Published: June 2012

Amphibians are ideal taxa with which to investigate the effects of climate change on physiology, dispersal capacity and distributional ranges as their physiological performance and fitness is highly dependent on temperature. Moreover, amphibians are among the most endangered vertebrate taxa. Here we use the tropical clawed frog, Xenopus tropicalis, as a model system to explore effects of temperature on locomotor performance. Our analyses show that locomotion is thermally sensitive, as illustrated by significant effects of temperature on terrestrial exertion capacity (time until exhaustion) and aquatic burst speed (maximal burst swimming velocity and maximal burst swimming acceleration capacity). Exertion performance measures had relatively lower temperature optima and narrower performance breadth ranges than measures of burst speed. The narrow 80% performance breadths confirm predictions that animals from stable environments should display high thermal sensitivity and, combined with the divergent temperature optima for exertion capacity and burst speed, underscore the vulnerability of tropical species such as X. tropicalis to even relatively small temperature changes. The temperature sensitivity of locomotor performance traits in X. tropicalis suggests that tropical ectotherms may be impacted by predicted changes in climate.
Isotopic incorporation rates for shark tissues from a long-term captive feeding study
Authors: Kim Sora Lee , del Rio Carlos Martínez , Casper Dave , Koch Paul L.
Published: June 2012

Stable isotope analysis has provided insight into the dietary and habitat patterns of many birds, mammals and teleost fish. A crucial biological parameter to interpret field stable isotope data is tissue incorporation rate, which has not been well studied in large ectotherms. We report the incorporation of carbon and nitrogen into the tissues of leopard sharks (Triakis semifasciata). Because sharks have relatively slow metabolic rates and are difficult to maintain in captivity, no long-term feeding study has been conducted until the point of isotopic steady state with a diet. We kept six leopard sharks in captivity for 1250 days, measured their growth, and serially sampled plasma, red blood cells and muscle for stable carbon and nitrogen isotope analysis. A single-compartment model with first-order kinetics adequately described the incorporation patterns of carbon and nitrogen isotopes for these three tissues. Both carbon and nitrogen were incorporated faster in plasma than in muscle and red blood cells. The rate of incorporation of carbon into muscle was similar to that predicted by an allometric equation relating isotopic incorporation rate to body mass that was developed previously for teleosts. In spite of their large size and unusual physiology, the rates of isotopic incorporation in sharks seem to follow the same patterns found in other aquatic ectotherms.
What Does Human Capital Do? A Review of Goldin and Katz'sThe Race between Education and Technology
Authors: Acemoglu Daron , Autor David
Published: June 2012

Goldin and Katz's The Race between Education and Technology is a monumental achievement that supplies a unified framework for interpreting how the demand and supply of human capital have shaped the distribution of earnings in the U.S. labor market over the twentieth century. This essay reviews the theoretical and conceptual underpinnings of this work and documents the success of Goldin and Katz's framework in accounting for numerous broad labor market trends. The essay also considers areas where the framework falls short in explaining several key labor market puzzles of recent decades and argues that these shortcomings can potentially be overcome by relaxing the implicit equivalence drawn between workers' skills and their job tasks in the conceptual framework on which Goldin and Katz build. The essay argues that allowing for a richer set of interactions between skills and technologies in accomplishing job tasks both augments and refines the predictions of Goldin and Katz's approach and suggests an even more important role for human capital in economic growth than indicated by their analysis. (JEL I20, J24, J31, O30)
Financial Advice
Authors: Inderst Roman , Ottaviani Marco
Published: June 2012

Financial advice could play an essential role in well-functioning markets for retail financial products, given that many consumers find it difficult to evaluate the complex products on offer. However, conflicts of interest, which are pervasive in some parts of the industry, can turn advice into a curse rather than a blessing for consumers, especially when consumers are not sufficiently wary. Through a simple model of financial advice, we overview the pros and cons of various policy interventions, such as imposing mandatory disclosure, banning commissions, and regulating contract cancellation terms. (JEL D14, D18, G21, G28)
The glycated albumin to glycated haemoglobin ratio increases along with the fibrosis stage in non-alcoholic steatohepatitis
Authors: Bando Yukihiro , Kanehara Hideo , Aoki Keiko , Toya Daishy , Notsumata Kazuo , Tanaka Nobuyoshi , Enomoto Hirayuki , Nishiguchi Shu-hei , Nakasho Keiji , Nakamura Hideji , Kasayama Soji , Koga Masafumi
Published: June 2012

Background

We previously reported that the indicator of glycaemic control, glycated albumin (GA) levels, are low in relation to glycaemia in patients with high alanine aminotransferase (ALT) levels in non-alcoholic fatty liver disease because of chronic inflammation, and that the GA/glycated haemoglobin ratio (G/H ratio) is inversely correlated with hepatic function in patients with chronic liver disease. The severity of liver fibrosis is known to be a good indicator for surveillance, and for determining the prognosis and optimal treatment of non-alcoholic steatohepatitis (NASH). In this study, we aimed to investigate the clinical usefulness of measuring the G/H ratio for predicting the severity of liver fibrosis in patients with NASH.

Methods

The study subjects were 36 patients with histologically diagnosed NASH (19 men, 17 women; mean age54.8 ± 12.2 years, body mass index 28.3 ± 5.0 kg/m2). The relationships of the G/H ratio to hepatic function tests and fibrosis stage in the liver were investigated.

Results

The G/H ratio in patients with NASH was inversely correlated with ALT ( P < 0.001) and platelet count ( P < 0.0001). Furthermore, the G/H ratio was positively correlated with the fibrosis stage in liver ( P = 0.003).

Conclusions

These results suggest that the G/H ratio increases along with the fibrosis stage in patients with NASH.
Classification of variant forms of haemoglobin according to the ratio of glycated haemoglobin to glycated albumin
Authors: Miyazaki Ayako , Kohzuma Takuji , Kasayama Soji , Koga Masafumi
Published: June 2012

Background

Asymptomatic variant haemoglobin is increasingly being found in the measurement of glycated haemoglobin (HbA1c) for the management of diabetes mellitus. We compared the HbA1c concentrations measured by high-performance liquid chromatography (HPLC) and immunoassay and glycated albumin (GA) concentrations and calculated the respective ratios in order to classify the variant haemoglobin.

Methods

Twenty different haemoglobin variants from 43 subjects were identified by mass spectrometry and DNA analysis. Since GA accurately reflects glycaemic control in patients with variant haemoglobin, we calculated respective ratios of HbA1c and GA. Haemoglobin variants causing a low ratio of HbA1c measured by HPLC (HPLC-HbA1c) to GA with a normal ratio of HbA1c measured by immunoassay (IA-HbA1c) to GA were classified as C1. A further classification of α and β was used with abnormalities of the α chain or β chain in the haemoglobin gene. Other haemoglobin variants were classified as non-C1. Eight diabetic patients with stable glycaemic control were used as controls.

Results

Twenty forms of variant haemoglobins were classified as C1 α (2 variants; I-Interlaken and Hb J-Meerut), C1 β (15 variants) and non-C1 (3 variants; Hb Himeji, Hb Woolwich, Hb Peterborough). Positive correlations between GA and HPLC-HbA1c or IA-HbA1c were seen in the C1 β patients with diabetes mellitus. The regression line between GA and HPLC-HbA1c, but not that between GA and IA-HbA1c, showed a downward shift in comparison with the data obtained from the diabetic controls.

Conclusions

Variant haemoglobin could be classified by calculating the ratios of HPLC-HbA1c, IA-HbA1c and GA.
PEGylated d-amino acid oxidase restores bactericidal activity of neutrophils in chronic granulomatous disease via hypochlorite
Authors: Nakamura Hideaki , Fang Jun , Mizukami Tomoyuki , Nunoi Hiroyuki , Maeda Hiroshi
Published: June 2012

Chronic granulomatous disease (CGD) causes impaired hydrogen peroxide (H2O2) generation. Consequently, neutrophils in patients with CGD fail to kill infecting pathogens. We expected that supplementation with H2O2 would effectively restore the bactericidal function of neutrophils in CGD. Here, we used polyethylene glycol-conjugated d-amino acid oxidase (PEG-DAO) as an H2O2 source. The enzyme DAO generates H2O2 by using d-amino acid and oxygen as substrates. PEG-DAO plus d-amino acid indeed exerted bacteriostatic activity against Staphylococcus aureus via H2O2 in vitro. Furthermore, use of PEG-DAO plus d-amino acids, which increased the amount of intracellular H2O2, restored bactericidal activity of neutrophils treated with diphenylene iodonium, in which nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was defective. This restoration of bactericidal activity was mediated by myeloperoxidase, with concomitant production of H2O2 by PEG-DAO plus d-Ala. We also confirmed that PEG-DAO treatment restored bactericidal activity of congenitally defective neutrophils from patients with CGD. These results indicate that PEG-DAO can supply additional H2O2 for defective NADPH oxidase of neutrophils from patients with CGD, and thus neutrophils regain bactericidal activity.
Optimal Decision Rules for Product Recalls
Authors: Sezer Ali Devin , Haksöz Çağrı
Published: June 2012

We consider a hypothetical company that is assumed to have just manufactured and sold a number of copies of a product. It is known that, with a small probability, the company has committed a manufacturing fault that will require a recall. The company is able to observe the expiration times of the sold items whose distribution depends on whether the fault is present or absent. At the expiration of each item, a public inspection takes place that may reveal the fault, if it exists. Based on this information, the company can recall the product at any moment and pay back each customer the price of the product. If the company is not able to recall before an inspection reveals the fault, it pays a fine per item sold, which is assumed to be much larger than the price of the product. We compute the optimal recall time that minimizes the expected cost of recall of this company. We then derive and solve a stationary limit recall problem and show that the original problem converges to it as the number of items initially sold increases to ∞. Finally, we propose two extensions of the original model and compute the optimal recall times for these. In the first extension, the expired items are inspected only if they expire earlier than expected; in the second extension, the company is able to conduct internal/private inspections on the expired items. We provide numerical examples and simulation results for all three models.
Soluble urokinase plasminogen activator receptor (suPAR) in the assessment of inflammatory activity of rheumatoid arthritis patients in remission
Authors: Toldi Gergely , Bekő Gabriella , Kádár Gabriella , Mácsai Emília , Kovács László , Vásárhelyi Barna , Balog Attila
Published: June 2012

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker increasingly used for the assessment of systemic inflammation. We aimed to evaluate suPAR for the assessment of inflammatory activity in rheumatoid arthritis (RA) patients in remission.

Methods: In our cross-sectional study we measured plasma suPAR and C-reactive protein (CRP) levels as well as erythrocyte sedimentation rate (ESR) in 120 RA patients at various stages of disease activity and 29 healthy age-matched controls.

Results: suPAR, CRP and ESR values were higher in RA patients compared to healthy individuals. When suPAR levels were analyzed according to DAS28 scores of RA patients, suPAR level in the subgroup with DAS28≤2.6 was lower than in the subgroup with DAS28>2.6, but still higher than in controls [4.45 (3.33–5.56) ng/mL vs. 3.66 (3.10–4.67) ng/mL vs. 2.80 (2.06–3.42) ng/mL, p<0.0001, median (interquartile range)]. In contrast, CRP and ESR values were comparable in the subgroup with DAS28≤2.6 and in healthy individuals. We further analyzed the correlation between the number of tender and/or swollen joints and suPAR levels in RA patients in remission. suPAR values were significantly higher in patients with four tender and/or swollen joints than in patients with 2–3 or 0–1 tender and/or swollen joints.

Conclusions: While CRP and ESR values indicate remission of the chronic inflammatory process in RA, suPAR values are still elevated compared to healthy individuals. suPAR might be particularly valuable in the recognition of inflammatory activity in patients who are in remission according to DAS28 scores but have symptoms of tender and/or swollen joints.
Intensity Reflection Coefficient Based Min-Sum Decoding for Low Density Parity Check Codes
Authors: Islam Mohammad Rakibul , Mahmood Khandaker Sultan , Oshim Md. Farhan Tasnim , Farazi Md. Moshiur Rahman
Published: June 2012

Low Density Parity Check Codes (LDPC) give groundbreaking performance which is known to approach Shannon’s limits for sufficiently large block length. Historically and recently, LDPC have been known to give superior performance than concatenated coding. In the following paper, a proposal to modify the standard Min-Sum (MS) algorithm for decoding LDPC codes is presented. This is done by introduction of a factor, intensity reflection coefficient (IRC),
α-Tocopherol ameliorates nickel induced testicular oxidative and nitrosative stress in albino rats
Authors: Jargar Jameel G. , Yendigeri Saeed M. , Hattiwale Shaheenkousar H. , Dhundasi Salim A. , Das Kusal K.
Published: June 2012

Background: Heavy metals generate free radicals and induce oxidative and nitrosative stress with depletion of antioxidants. In this study, we have evaluated the beneficial effects of α-tocopherol against nickel sulfate exposed testicular dysfunction.

Methods:We studied the effect of supplementation of α-tocopherol (10 mg/100 g body weight, i.m.) on nickel sulfate (2.0 mg/100 g body weight, i.p.) induced testicular oxidative and nitrosative stress in Wister strain male albino rats. Serum and testicular nitric oxide, L-ascorbic acid and serum α-tocopherol concentrations were evaluated. We also evaluated sperm count, motility and histopathology of testes.

Results:Nickel treated rats showed significantly decreased body weight, testicular somatic index, sperm count, sperm motility, serum and testicular L-ascorbic acid concentration and serum α-tocopherol level as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol produced a remarkable improvement of all the above parameters when compared with treatment with nickel alone. Nickel treated rats also had significantly increased serum and testicular nitric oxide concentrations as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol significantly decreased nitric oxide concentrations in both serum and testes, respectively, as compared to nickel treatment alone. Histopathology of the testes revealed tortuous seminiferous tubules, loss of spermatogenesis process (>75%), congestion and necrosis in nickel sulfate treated rats, whereas rats simultaneously treated with nickel sulfate and α-tocopherol had almost normal seminiferous tubules and near normal spermatogenesis as compared to nickel alone treated rats.

Conclusions: Nickel sulfate treatment causes testicular oxidative and nitrosative stress in albino rats, but simultaneous supplementation of α-tocopherol was found to be beneficial in combating against such stresses.
"The Men Were Left Astonished"
Authors: Gray Paul Bryan , Hayes-Bautista David E. , Chamberlin Cynthia L.
Published: June 2012

Following the Mexican victory at Puebla on May 5, 1862, Mexicans in California formed patriotic assemblies, juntas patrióticas, to provide support to Mexico's defense against the French intervention. Between 1863 and 1866, eight women's organizations, juntas patrióticas de señoras, were formed. Their leadership, rhetoric, fund-raising, and extension to other causes indicate that Latinas in California were significantly informed, politicized, and independent.
Holding the Center
Authors: Connor Michan Andrew
Published: June 2012

Early television shows that focused on Los Angeles as subject, such as The City at Night (KTLA) and Jack Linkletter's On the Go (CBS), assured white, middle-class, suburban viewers that they had a place in the larger metropolis by presenting a selective knowledge of its features and issues. On the Go surpassed the entertainment level of The City at Night to address some serious social issues. By the mid-sixties, suburbanization had been fully embraced as the "good life." Shows such as Ralph Story's Los Angeles (KNXT), instead of engaging suburban viewers in metropolitan issues, entertained them with glimpses of the city's "oddities." The change in tone marked the passing of the center of cultural identity from the central city to the suburbs.
Expression of 11β-hydroxysteroid dehydrogenase enzymes in human osteosarcoma: potential role in pathogenesis and as targets for treatments
Authors: Patel Pushpa , Hardy Rowan , Sumathi Vaiyapuri , Bartle Gillian , Kindblom Lars-Gunnar , Grimer Robert , Bujalska Iwona , Stewart Paul M , Rabbitt Elizabeth , Gittoes Neil J L , Cooper Mark S
Published: June 2012

Osteosarcoma (OS) is a primary malignant tumour of bone occurring predominantly in children and young adults. Despite chemotherapy, relapse is common and mortality remains high. Non-transformed osteoblasts are highly sensitive to glucocorticoids, which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme inactivates cortisol (active) to cortisone (inactive) and expression of 11β-HSD2 renders OS cells resistant to glucocorticoids. By contrast, the related enzyme 11β-HSD1 converts cortisone to cortisol and reduces OS cell proliferation in vitro. Some synthetic glucocorticoids (e.g. dehydrodexamethasone (DHD), inactive counterpart of dexamethasone (DEX)) have been reported to be activated by 11β-HSD2. We therefore investigated expression and enzymatic activity of 11β-HSD isozymes in human OS tissue, determined whether 11β-HSD expression has prognostic value in the response to therapy, and evaluated the potential use of synthetic glucocorticoids to selectively target OS cells. OS samples expressed both 11β-HSD1 and 11β-HSD2. 11β-HSD1 expression in pretreatment biopsy specimens positively correlated with primary tumour size. Expression and activity of 11β-HSD1 in post-treatment biopsies were unrelated to the degree of tumour necrosis following chemotherapy. However, high 11β-HSD2 expression in post-treatment biopsies correlated with a poor response to therapy. OS cells that expressed 11β-HSD2 inactivated endogenous glucocorticoids; but these cells were also able to generate DEX from DHD. These results suggest that OS treatment response is related to 11β-HSD2 enzyme expression. Furthermore, OS cells expressing this enzyme could be targeted by treatment with synthetic glucocorticoids that are selectively reactivated by the enzyme.
Biomarkers of hypothalamic–pituitary–adrenal axis activity in mice lacking 11β-HSD1 and H6PDH
Authors: Abrahams Lianne , Semjonous Nina M , Guest Phil , Zielinska Agnieszka , Hughes Beverly , Lavery Gareth G , Stewart Paul M
Published: June 2012

Glucocorticoid concentrations are a balance between production under the negative feedback control and diurnal rhythm of the hypothalamic–pituitary–adrenal (HPA) axis and peripheral metabolism, for example by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyses the reduction of inactive cortisone (11-dehydrocorticosterone (11-DHC) in mice) to cortisol (corticosterone in mice). Reductase activity is conferred upon 11β-HSD1 by hexose-6-phosphate dehydrogenase (H6PDH). 11β-HSD1 is implicated in the development of obesity, and selective 11β-HSD1 inhibitors are currently under development. We sought to address the concern regarding potential up-regulation of the HPA axis associated with inhibition of 11β-HSD1. We assessed biomarkers for allele combinations of 11β-HSD1 and H6PDH derived from double heterozygous mouse crosses. H6PDH knock out (KO) adrenals were 69% larger than WT while 11β-HSD1 KO and double KO (DKO) adrenals were ∼30% larger than WT – indicative of increased HPA axis drive in KO animals. ACTH-stimulated circulating corticosterone concentrations were 2.2-fold higher in H6PDH KO animals and ∼1.5-fold higher in 11β-HSD1 KO and DKO animals compared with WT, proportional to the observed adrenal hypertrophy. KO of H6PDH resulted in a substantial increase in urinary DHC metabolites in males (65%) and females (61%). KO of 11β-HSD1 alone or in combination with H6PDH led to significant increases (36 and 42% respectively) in urinary DHC metabolites in females only. Intermediate 11β-HSD1/H6PDH heterozygotes maintained a normal HPA axis. Urinary steroid metabolite profile by gas chromatography/mass spectrometry as a biomarker assay may be beneficial in assaying HPA axis status clinically in cases of congenital and acquired 11β-HSD1/H6PDH deficiency.
Gene polymorphisms in chronic C virus hepatitis
Authors: Werling Klára , Rácz Károly
Published: June 2012

The hepatitis C virus (HCV) is a major public health problem in the world. Current standard of treatment with pegylated interferonalpha (PegIFN) and ribavirin (RBV) achieves a sustained virological response in 40–50% of those infected with genotype 1. Host genotyping studies have the potential to identify genes and therefore pathogenic processes important in viral clearance, enabling a rational approach to design new drugs, and to identify patients who will most likely respond to current and new treatments. The polymorphisms in IL28B are highly predictive of response to PegIFN and RBV combination therapy for HCV genotype 1 infection. Possibly combined to other baseline features, such as the measurements of IP-10 and HLA-C as well as on-treatment viral kinetics, should allow for improved prediction of response to HCV combination therapy. Host genetics have significant role in spontaneous clearance of HCV. Genotyping of this polymorphism will aid clinical decision making for both current standard of care and potentially for the integration of other agents in the future, providing an opportunity for clinicians to individualize treatment regimens for hepatitis C patients.
Comminution of a prolapsed thrombus after coronary stent implantation using cutting balloon
Authors: Komócsi András , Költô Gyöngyvér , Horváth Iván G. , Kónyi Attila
Published: June 2012

Coronary thrombosis and secondary embolization remain two of the major challenges of intervention in myocardial infarction. Pharmacological dissolution as well as instruments to evacuate the thrombotic mass with or without distal protection have been applied in the acute interventions with variable degrees of success. With time, cross-linking of the fibrin strands results in a resilient, partially organizing coagulate that is more or less attached to the wall of the artery. The currently used devices designed to cope with recently formed thrombus may fail to disrupt these flexible structures, and pharmacological dissolution is also usually ineffective. Here, we report a case with a subacute occlusion; after failure of thrombus extraction, mechanical comminution of a clot with cutting balloons was successfully performed.
Aortobifemoralis graft gennyedés megoldásának kései szövődményeként jelentkező subclavia álaneurysma endovascularis kezelése
Authors: Arató Endre , Kasza Gábor , Sinay László , Benkő László , Fazekas Gábor , Hardi Péter , Füzi Árpád , Nagy Tibor , Masoud Shafei , Jancsó Gábor , Kollár Lajos , Menyhei Gábor
Published: June 2012

Absztrakt

Esetismertetés: Közleményünkben egy relatíve ritka érsebészeti szövődmény nem szokványos műtéti megoldását ismertetjük. Esetünkben Leriche-syndroma miatt aortobifemoralis bypasst végeztünk a betegnél, melyet követően a beültetett Y graft septicussá vált, így az inficiált implantátum eltávolítására kényszerültünk. A hasi aorta elvarrása után az alsó végtagok keringésének biztosítása céljából axillobifemoralis bypassműtétet végeztünk. A későbbiek során a graft el-záródott, de 37 hónappal a műtétet követően a jobb arteria subclavia és az interpositum találkozásánál jelentős méretű anastomosis-aneurysma keletkezett. Ez az embolisatio, ruptura és kompresszió veszélye miatt újabb műtéti megoldást igényelt. A szokványos érsebészeti megoldás helyett (resectio, interpositio) endovascularis megoldást alkalmaztunk. Ennek során a jobb arteria brachialis feltárásából katétertechnikával, borított stent pozicionálásával iktattuk ki az álaneurysmát, megelőzve a vázolt szövődmények kialakulásának lehetőségét. Következtetés: Az újszerű, minimálisan invazív megoldás rendkívül alkalmas rá, hogy magas rizikójú betegeknél elkerüljük az anatómiai régióból fakadó egyéb képletek sérülését, minimalizáljuk a műtéti vérveszteséget, és csökkentsük a hosszú narkózist igénylő feltárásos műtétből fakadó általános szövődményeket.
Description of the Pictorial Assessment of Interpersonal Relationship (PAIR)
Authors: Sándor Mónika , Fülöp Márta , Sebestyén Nóra
Published: June 2012

A tanulmány a Bombi és munkatársai (Bombi, Pinto és Cannoni, 2007) által kifejlesztett PAIR (Pictorial Assessment of Interpersonal Relationship) rajzelemző eljárást ismerteti, mely módszer segítségével a 6–14 éves gyermekek interperszonális kapcsolatokat ábrázoló rajzai elemezhetők és hasonlíthatók össze hat fő szempont mentén (kohézió, távolítás, hasonlóság, érték, érzelmek és konfliktus). Az eljárás olyan kommunikációs eszközként kezeli a rajzokat, mely kiválóan alkalmas a gyermekek szociális világról, társas jelenségekről és társas érzelmekről való tudása tudományosan megbízható megismerésére. Segítségével feltárható hogyan értelmezik a gyermekek az interperszonális jelenségeket (például barátság, versengés, együttműködés stb.), a társadalmi státuszt (szegény, gazdag), milyen módon differenciálnak a különböző társas kapcsolatok között (például baráti és testvérkapcsolat, győztes és vesztes), és hogyan észlelik ugyanazon kapcsolatot különböző feltételek mentén (például harmonikus és konfliktustelített testvéri kapcsolat). A módszer lehetőséget ad arra is, hogy a gyerekek által megjelenített társas interakciókat és az ezeket kísérő érzelmeket egységes rendszerben lehessen értelmezni. Az eljárás előnyei közé tartozik, hogy objektív, kidolgozott komplex rendszerrel rendelkezik a diádikus interperszonális kapcsolatok (két teljes alakban ábrázolt személy) elemzésére, és a klinikai rajzvizsgálatokkal szemben jól alkalmazható olyan fejlődés-szociálpszichológiai kutatásokban is, amelyekben a gyerekek társas kapcsolati tudását kívánják vizsgálni. A jelen tanulmány célja, hogy a részletes ismertetéssel beemelje ezt a rajzos vizsgálatot a hazai fejlődés szociálpszichológiai vizsgálati módszerek sorába.
The role of pharmacotherapeutical audit in the improvement of pharmacotherapy during inpatient rehabilitation care. Experience for the National Institute of Medical Rehabilitation, Hungary
Authors: Boros Erzsébet , Szél István , Dénes Zoltán
Published: June 2012

Pharmacotherapy is one of the most important and dangerous area in hospital health care, that explains why innumerable efforts are made worldwide to improve this process and prevent mistakes. Although clinical audit is a well known and widely used method, it is very rarely used for this purpose and scientific papers dealing with this topic can be scarcely found. In the last 20 years different quality management systems were introduced into the Hungarian hospitals, but most of them are not specific for the medical care. The most important element of quality management systems is the internal, professional audit that serves patient safety. Aims and methods: Authors report their experience on pharmacotherapy audits performed for over a decade in the National Institute for Medical Rehabilitation, Hungary. They review the method of audit meetings in details and discuss the most frequent problems. Results: The results indicate that characteristics of therapeutic mistakes in the rehabilitation practice are similar to those reported in scientific literature. Conclusions: Improving knowledge on pharmacotherapy audits of rehabilitation specialists may be an important part of continuous professional advancement providing facility for dispute on other issues of patient care. Orv. Hetil., 2012, 153, 997–1002.
Robotic surgery in gynecology
Authors: Csorba Roland
Published: June 2012

Minimally invasive surgery has revolutionized gynecological interventions over the past 30 years. The introduction of the da Vinci robotic surgery in 2005 has resulted in large changes in surgical management. The robotic platform allows less experienced laparoscopic surgeons to perform more complex procedures. It can be utilized mainly in general gynecology and reproductive gynecology. The robot is being increasingly used for procedures such as hysterectomy, myomectomy, adnexal surgery, and tubal anastomosis. In urogynecology, the robot is being utilized for sacrocolopexy as well. In the field of gynecologic oncology, the robot is being increasingly used for hysterectomy and lymphadenectomy in oncologic diseases. Despite the rapid and widespread adaption of robotic surgery in gynecology, there are no randomized trials comparing its efficacy and safety to other traditional surgical approaches. This article presents the development, technical aspects and indications of robotic surgery in gynecology, based on the previously published reviews. Robotic surgery can be highly advantageous with the right amount of training, along with appropriate patient selection. Patients will have less blood loss, less post-operative pain, faster recovery, and fewer complications compared to open surgery and laparoscopy. However, until larger randomized control trials are completed which report long-term outcomes, robotic surgery cannot be stated to have priority over other surgical methods. Orv. Hetil., 2012, 153, 967–972.
Action Research with a Family ASL Literacy Program
Authors: Snoddon Kristin
Published: June 2012

This article reports findings from an ethnographic action research study of Deaf and hearing parents and young children participating in a family American Sign Language (ASL) literacy program in Ontario, Canada. The study documents the context for parents’ and children’s learning of ASL in an environment where resources for supporting early ASL literacy have been scarce. Through semi-structured interviews and observations of six individual families or parent-child dyads, the study documents participants’ encounters with professionals who regulate Deaf children and their families’ access to ASL. At the same time, the setting of the ASL Parent-Child Mother Goose Program is presented as a Deaf cultural space and thereby a counter-discourse to medical discourses regarding Deaf identity and bilingualism. This space features the Deaf mother participants’ ASL literacy and numeracy practices and improvisations of ASL rhymes and stories to enhance their suitability for young children. The practices of the ASL Parent-Child Mother Goose Program leader also serve to define and support emergent ASL literacy. In addition, a Deaf cultural space inside a broader context of public services to young Deaf children provides a means for the hearing mother participants to facilitate critical inquiry of issues surrounding bilingualism, ASL, and a Deaf identity.
Identity Texts as Decolonized Writing
Authors: Taylor Shelley K
Published: June 2012

Research indicates that when students’ identities are affirmed in micro-interactions between themselves and teachers, they are more likely to invest themselves academically (Cummins, 2001). Aboriginal students faced with pedagogical materials that negatively represent their culture are loath to invest themselves in their schooling. This reflection on practice describes the implementation of a dual language book project designed to produce positive identity texts to counter damaging representations of marginalized group members. The participant-authors were Aboriginal parents who wrote books intended for their preschool-aged children in their ancestral language and English. These parents created identity texts to reflect their children’s identities back to them in a positive light (Cummins, this volume) and, in so doing, they engaged in a form of “decolonized writing.”