bluuebunny/crossref_metadata_2025 huggingface dataset:
Aldosterone-dependent and -independent regulation of the epithelial sodium channel (ENaC) in mouse distal nephron
Authors: Nesterov Viatcheslav , Dahlmann Anke , Krueger Bettina , Bertog Marko , Loffing Johannes , Korbmacher Christoph
Published: August 2012

Aldosterone is thought to be the main hormone to stimulate the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire collecting duct (CD). There is immunohistochemical evidence for an axial gradient of ENaC expression along the ASDN with highest expression in the DCT2 and CNT. However, most of our knowledge about renal ENaC function stems from studies in the cortical collecting duct (CCD). Here we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice maintained on different sodium diets to vary plasma aldosterone levels. Single-channel recordings demonstrated amiloride-sensitive Na+channels in DCT2/CNT with biophysical properties typical for ENaC previously described in CNT/CCD. In animals maintained on a standard salt diet, the average ENaC-mediated whole cell current (Δ Iami) was higher in DCT2/CNT than in CNT/CCD. A low salt diet increased Δ Iamiin CNT/CCD but had little effect on Δ Iamiin DCT2/CNT. To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS−/−) mice that lack aldosterone. In CNT/CCD of AS−/−mice, Δ Iamiwas lower than that in wild-type (WT) animals and was not stimulated by a low salt diet. In contrast, in DCT2/CNT of AS−/−mice, Δ Iamiwas similar to that in DCT2/CNT of WT animals both on a standard and on a low salt diet. We conclude that ENaC function in the DCT2/CNT is largely independent of aldosterone which is in contrast to its known aldosterone sensitivity in CNT/CCD.
Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling
Authors: Lee Min Chul , Okamoto Masahiro , Liu Yu Fan , Inoue Koshiro , Matsui Takashi , Nogami Haruo , Soya Hideaki
Published: August 2012

Although voluntary running has beneficial effects on hippocampal cognitive functions if done abundantly, it is still uncertain whether resistance running would be the same. For this purpose, voluntary resistance wheel running (RWR) with a load is a suitable model, since it allows increased work levels and resultant muscular adaptation in fast-twitch muscle. Here, we examined whether RWR would have potential effects on hippocampal cognitive functions with enhanced hippocampal brain-derived neurotrophic factor (BDNF), as does wheel running without a load (WR). Ten-week-old male Wistar rats were assigned randomly to sedentary (Sed), WR, and RWR (to a maximum load of 30% of body weight) groups for 4 wk. We found that in RWR, work levels increased with load, but running distance decreased by about half, which elicited muscular adaptation for fast-twitch plantaris muscle without causing any negative stress effects. Both RWR and WR led to improved spatial learning and memory as well as gene expressions of hippocampal BDNF signaling-related molecules. RWR increased hippocampal BDNF, tyrosine-related kinase B (TrkB), and cAMP response element-binding (CREB) protein levels, whereas WR increased only BDNF. With both exercise groups, there were correlations between spatial memory and BDNF protein ( r = 0.41), p-CREB protein ( r = 0.44), and work levels ( r = 0.77). These results suggest that RWR plays a beneficial role in hippocampus-related cognitive functions associated with hippocampal BDNF signaling, even with short distances, and that work levels rather than running distance are more determinant of exercise-induced beneficial effects in wheel running with and without a load.
Eye position effects in saccadic adaptation in macaque monkeys
Authors: Wulff Svenja , Bosco Annalisa , Havermann Katharina , Placenti Giacomo , Fattori Patrizia , Lappe Markus
Published: August 2012

The saccadic amplitude of humans and monkeys can be adapted using intrasaccadic target steps in the McLaughlin paradigm. It is generally believed that, as a result of a purely retinal reference frame, after adaptation of a saccade of a certain amplitude and direction, saccades of the same amplitude and direction are all adapted to the same extent, independently from the initial eye position. However, recent studies in humans have put the pure retinal coding in doubt by revealing that the initial eye position has an effect on the transfer of adaptation to saccades of different starting points. Since humans and monkeys show some species differences in adaptation, we tested the eye position dependence in monkeys. Two trained Macaca fascicularis performed reactive rightward saccades from five equally horizontally distributed starting positions. All saccades were made to targets with the same retinotopic motor vector. In each session, the saccades that started at one particular initial eye position, the adaptation position, were adapted to shorter amplitude, and the adaptation of the saccades starting at the other four positions was measured. The results show that saccades that started at the other positions were less adapted than saccades that started at the adaptation position. With increasing distance between the starting position of the test saccade and the adaptation position, the amplitude change of the test saccades decreased with a Gaussian profile. We conclude that gain-decreasing saccadic adaptation in macaques is specific to the initial eye position at which the adaptation has been induced.
Neural mechanisms for predictive head movement strategies during sequential gaze shifts
Authors: Monteon Jachin A. , Avillac Marie , Yan Xiaogang , Wang Hongying , Crawford J. Douglas
Published: August 2012

Humans adopt very different head movement strategies for different gaze behaviors, for example, when playing sports versus watching sports on television. Such strategy switching appears to depend on both context and expectation of future gaze positions. Here, we explored the neural mechanisms for such behaviors by training three monkeys to make head-unrestrained gaze shifts toward eccentric radial targets. A randomized color cue provided predictive information about whether that target would be followed by either a return gaze shift to center or another, more eccentric gaze shift, but otherwise animals were allowed to develop their own eye-head coordination strategy. In the first two animals we then stimulated the frontal eye fields (FEF) in conjunction with the color cue, and in the third animal we recorded from neurons in the superior colliculus (SC). Our results show that 1) monkeys can optimize eye-head coordination strategies from trial to trial, based on learned associations between color cues and future gaze sequences, 2) these cue-dependent coordination strategies were preserved in gaze saccades evoked during electrical stimulation of the FEF, and 3) two types of SC responses (the saccade burst and a more prolonged response related to head movement) modulated with these cue-dependent strategies, although only one (the saccade burst) varied in a predictive fashion. These data show that from one moment to the next, the brain can use contextual sensory cues to set up internal “coordination states” that convert fixed cortical gaze commands into the brain stem signals required for predictive head motion.
Cortical stimulation causes long-term changes in H-reflexes and spinal motoneuron GABA receptors
Authors: Wang Yu , Chen Yi , Chen Lu , Wolpaw Jonathan R. , Chen Xiang Yang
Published: August 2012

The cortex gradually modifies the spinal cord during development, throughout later life, and in response to trauma or disease. The mechanisms of this essential function are not well understood. In this study, weak electrical stimulation of rat sensorimotor cortex increased the soleus H-reflex, increased the numbers and sizes of GABAergic spinal interneurons and GABAergic terminals on soleus motoneurons, and decreased GABAA and GABAB receptor labeling in these motoneurons. Several months after the stimulation ended the interneuron and terminal increases had disappeared, but the H-reflex increase and the receptor decreases remained. The changes in GABAergic terminals and GABAB receptors accurately predicted the changes in H-reflex size. The results reveal a new long-term dimension to cortical-spinal interactions and raise new therapeutic possibilities.
Functional maps within a single neuron
Authors: Narayanan Rishikesh , Johnston Daniel
Published: August 2012

The presence and plasticity of dendritic ion channels are well established. However, the literature is divided on what specific roles these dendritic ion channels play in neuronal information processing, and there is no consensus on why neuronal dendrites should express diverse ion channels with different expression profiles. In this review, we present a case for viewing dendritic information processing through the lens of the sensory map literature, where functional gradients within neurons are considered as maps on the neuronal topograph. Under such a framework, drawing analogies from the sensory map literature, we postulate that the formation of intraneuronal functional maps is driven by the twin objectives of efficiently encoding inputs that impinge along different dendritic locations and of retaining homeostasis in the face of changes that are required in the coding process. In arriving at this postulate, we relate intraneuronal map physiology to the vast literature on sensory maps and argue that such a metaphorical association provides a fresh conceptual framework for analyzing and understanding single-neuron information encoding. We also describe instances where the metaphor presents specific directions for research on intraneuronal maps, derived from analogous pursuits in the sensory map literature. We suggest that this perspective offers a thesis for why neurons should express and alter ion channels in their dendrites and provides a framework under which active dendrites could be related to neural coding, learning theory, and homeostasis.
Neuromodulator-evoked synaptic metaplasticity within a central pattern generator network
Authors: Kvarta Mark D. , Harris-Warrick Ronald M. , Johnson Bruce R.
Published: August 2012

Synapses show short-term activity-dependent dynamics that alter the strength of neuronal interactions. This synaptic plasticity can be tuned by neuromodulation as a form of metaplasticity. We examined neuromodulator-induced metaplasticity at a graded chemical synapse in a model central pattern generator (CPG), the pyloric network of the spiny lobster stomatogastric ganglion. Dopamine, serotonin, and octopamine each produce a unique motor pattern from the pyloric network, partially through their modulation of synaptic strength in the network. We characterized synaptic depression and its amine modulation at the graded synapse from the pyloric dilator neuron to the lateral pyloric neuron (PD→LP synapse), driving the PD neuron with both long square pulses and trains of realistic waveforms over a range of presynaptic voltages. We found that the three amines can differentially affect the amplitude of graded synaptic transmission independently of the synaptic dynamics. Low concentrations of dopamine had weak and variable effects on the strength of the graded inhibitory postsynaptic potentials (gIPSPs) but reliably accelerated the onset of synaptic depression and recovery from depression independently of gIPSP amplitude. Octopamine enhanced gIPSP amplitude but decreased the amount of synaptic depression; it slowed the onset of depression and accelerated its recovery during square pulse stimulation. Serotonin reduced gIPSP amplitude but increased the amount of synaptic depression and accelerated the onset of depression. These results suggest that amine-induced metaplasticity at graded chemical synapses can alter the parameters of synaptic dynamics in multiple and independent ways.
Evaluating Subpixel Target Detection Algorithms in Hyperspectral Imagery
Authors: Cohen Yuval , August Yitzhak , Blumberg Dan G. , Rotman Stanley R.
Published: August 2012

Our goal in this work is to demonstrate that detectors behave differently for different images and targets and to propose a novel approach to proper detector selection. To choose the algorithm, we analyze image statistics, the target signature, and the target′s physical size, but we do not need any type of ground truth. We demonstrate our ability to evaluate detectors and find the best settings for their free parameters by comparing our results using the following stochastic algorithms for target detection: the constrained energy minimization (CEM), generalized likelihood ratio test (GLRT), and adaptive coherence estimator (ACE) algorithms. We test our concepts by using the dataset and scoring methodology of the Rochester Institute of Technology (RIT) Target Detection Blind Test project. The results show that our concept correctly ranks algorithms for the particular images and targets including in the RIT dataset.
Tunable Cu2O Nanocrystals Fabricated by Free Dealloying of Amorphous Ribbons
Authors: Wang Zhifeng , Qin Chunling , Zhao Weimin , Jia Junqing
Published: August 2012

This work discovers that Cu2O nanocrystals with controllable structures can be synthesized on surfaces of nanoporous Cu and amorphous ribbons by free dealloying of Cu‐based amorphous alloys in acidic solutions. Technological parameters, such as the acid, acid concentration, and dealloying time strongly influence the crystal size, structure and morphology of Cu2O. Cu2O nanocubes are fabricated on surfaces of nanoporous Cu in the hydrofluoric acid treated alloy, while various Cu2O particles are tailored on surfaces of amorphous alloys immersed in hydrochloric acid for different time. The increasing dealloying time and adsorbed oxygen improve the growth rates along the 〈1 0 0〉 direction of Cu2O crystals relative to that of the 〈1 1 1〉 direction, which is the key to change the shapes of Cu2O crystals. The understanding of morphology evolution of Cu2O nanocrystals in this work is helpful in tailoring Cu2O particles with designable shapes and controllable properties in application fields.
Gastric Duplication: A Rare Cause of Massive Lower Gastrointestinal Haemorrhage, Chest Wall Mass, and Enterocutaneous Fistula
Authors: Kesieme Emeka B. , Dongo Andrew E. , Osime Clement O. , Olomu Sylvia C. , Awe Oluwafemi O. , Eze Gerald I. , Eluehike Sylvester U.
Published: August 2012

Gastric duplications are uncommon developmental abnormality reported to present with different clinical scenarios. We present a 2-1/2-year-old Nigerian female who started having intermittent massive lower gastrointestinal haemorrhage at 5 months of age. She subsequently developed a lower chest wall mass and enterocutaneous fistula. She was found to have gastric duplication with fistulous communication with the descending colon, spleen, and lower chest wall. To the best of our knowledge, this is the first paper on gastric duplication resulting in intermittent massive lower gastrointestinal bleeding mainly from splenic capsular erosion and fistula and enterocutaneous fistula resulting from erosion of anterior abdominal wall. Gastric duplication is hence an important rare cause of intermittent massive lower gastrointestinal haemorrhage and spontaneous enterocutaneous fistula in the paediatric population.
Third Graders' Perceptions on Moral Behaviour on Bullying If They Had the Infinite Powers of Superhero Defenders
Authors: Johansson Juha , Hannula Markku S.
Published: August 2012

Bullying is a serious moral concern affecting the victim's welfare and achievement in school. Lately, research on bullying phenomenon has led to successful procedures in which passive bystanders are asked to become defenders of the victims of bullying. This case study explores children's perceptions on moral behaviour on bullying and, moreover, what type of moral voice they would express if they had the infinite powers and means of superhero defenders. Children created masks, posters, and flags for ideal superheroes and described their personalities. In addition, they drew comic strips about the skills they wish to teach new hero students in superhero school. The results indicate that children's moral voices can be divided primarily into justice and care. In addition, some expressed also the dark voice of the vigilante. Findings suggest that superheroes offer one tool for educators and children to ponder about the role of defenders for the victims of bullying. The topic focuses on the core of school life, relationships between pupils, and their moral development. Sixteen third grade children (aged 9-10) from a primary school in Finland took part in the study. The results for two of the children are presented in detail as the basis for discussion.
Neuropsychiatric Symptoms in Parkinson's Disease with Mild Cognitive Impairment and Dementia
Authors: Leroi Iracema , Pantula Hiranmayi , McDonald Kathryn , Harbishettar Vijay
Published: August 2012

Neuropsychiatric symptoms commonly complicate Parkinson’s disease (PD), however the presence of such symptoms in mild cognitive impairment (PD-MCI) specifically has not yet been well described. The objective of this study was to examine and compare the prevalence and profile of neuropsychiatric symptoms in patients with PD-MCI (n= 48) to those with PD and no cognitive impairment (PD-NC,n= 54) and to those with dementia in PD (PDD,n= 25). PD-MCI and PDD were defined using specific consensus criteria, and neuropsychiatric symptoms were assessed with the 12-item Neuropsychiatric Inventory (NPI). Self-rated apathy, depression, and anxiety rating scales were also administered. Over 79% of all participants reported at least one neuropsychiatric symptom in the past month. The proportion in each group who had total NPI scores of ≥4 (“clinically significant”) was as follows: PD-NC, 64.8%; PD-MCI, 62%; PDD 76%. Apathy was reported in almost 50% of those with PD-MCI and PDD, and it was an important neuropsychiatric symptom differentiating PD-MCI from PD-NC. Psychosis (hallucinations and delusions) increased from 12.9% in PD-NC group; 16.7% in PD-MCI group; and 48% in PDD group. Identifying neuropsychiatric symptoms in PD-MCI may have implications for ascertaining conversion to dementia in PD.
A Two‐Stage DEA to Analyze the Effect of Entrance Deregulation on Iranian Insurers: A Robust Approach
Authors: Jalali Naini Seyed Gholamreza , Nouralizadeh Hamid Reza
Published: August 2012

We use two‐stage data envelopment analysis (DEA) model to analyze the effects of entrance deregulation on the efficiency in the Iranian insurance market. In the first stage, we propose a robust optimization approach in order to overcome the sensitivity of DEA results to any uncertainty in the output parameters. Hence, the efficiency of each ongoing insurer is estimated using our proposed robust DEA model. The insurers are then ranked based on their relative efficiency scores for an eight‐year period from 2003 to 2010. In the second stage, a comprehensive statistical analysis using generalized estimating equations (GEE) is conducted to analyze some other factors which could possibly affect the efficiency scores. The first results from DEA model indicate a decline in efficiency over the entrance deregulation period while further statistical analysis confirms that the solvency ignorance which is a widespread paradigm among state owned companies is one of the main drivers of efficiency in the Iranian insurance market.
Apple Can Act as Anti-Aging on Yeast Cells
Authors: Palermo Vanessa , Mattivi Fulvio , Silvestri Romano , La Regina Giuseppe , Falcone Claudio , Mazzoni Cristina
Published: August 2012

In recent years, epidemiological and biochemical studies have shown that eating apples is associated with reduction of occurrence of cancer, degenerative, and cardiovascular diseases. This association is often attributed to the presence of antioxidants such as ascorbic acid (vitamin C) and polyphenols. The substances that hinder the presence of free radicals are also able to protect cells from aging. In our laboratory we used yeast, a unicellular eukaryotic organism, to determinein vivoefficacy of entire apples and their components, such as flesh, skin and polyphenolic fraction, to influence aging and oxidative stress. Our results indicate that all the apple components increase lifespan, with the best result given by the whole fruit, indicating a cooperative role of all apple components.
Stability of DREEM in a Sample of Medical Students: A Prospective Study
Authors: Yusoff Muhamad Saiful Bahri
Published: August 2012

Background. Over the last 15 year, DREEM was applied in various educational settings to appraise educational climate. So far, none of article reported its stability in Malaysian medical students.Objective. To determine stability of the DREEM to measure educational climate at different time and occasions using a sample of medical students.Methodology. A prospective cohort study was done on 196 first year medical students. It was administered to the medical students at four different intervals. The Cronbach's alpha and intraclass correlation analysis were applied to measure internal consistency and agreement level across the intervals. The analysis was done using SPSS 18.Result. A total of 186 (94.9%) medical students responded completely to the DREEM inventory. The overall Cronbach's alpha value of the DREEM at the four measurements ranged between 0.91 and 0.94. The average Cronbach's alpha values of the five subscales ranged between 0.45 and 0.83. The ICC coefficient values for the DREEM total score was 0.67 and its subscales ranged between 0.51 and 0.62.Conclusion. This study supported satisfactory levels of stability and internal consistency of the DREEM to measure educational climate over multiple observations in a sample of Malaysian medical students. Continued research is required to optimise its psychometric credential across educational settings.
Scutellaria baicalensisExtracts and Flavonoids Protect Rat L6 Cells from Antimycin A-Induced Mitochondrial Dysfunction
Authors: Im A-Rang , Kim Young-Hwa , Uddin Md. Romij , Lee Hye Won , Chae Seong Wook , Kim Yun Hee , Jung Woo Suk , Kang Bong Ju , Mun Chun Sun , Lee Mi-Young
Published: August 2012

Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts ofScutellaria baicalensisand its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts ofS. baicalensis. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts ofS. baicalensiscompared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts ofS. baicalensis. L6 cells treated with flavonoids and extracts ofS. baicalensisincreased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that theS. baicalensisextracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function.
Electrically Conductive Compounds of Polycarbonate, Liquid Crystalline Polymer, and Multiwalled Carbon Nanotubes
Authors: Pisitsak Penwisa , Magaraphan Rathanawan , Jana Sadhan C.
Published: August 2012

A thermotropic liquid crystalline polymer (LCP) was blended with polycarbonate (PC) and multiwalled carbon nanotube (CNT) with the goal of improving electrical conductivity and mechanical properties over PC. The LCP was anticipated to produce fibrillar domains in PC and help improve the mechanical properties. The study was carried out using two grades of LCP—Vectra A950 (VA950) and Vectra V400P (V400P). The compounds contained 20 wt% LCP and 0.5 to 15 wt% CNT. The compounds were prepared by melt‐blending in a twin‐screw minicompounder and then injection molded using a mini‐injection molder. The fibrillar domains of LCP were found only in the case of PC/VA950 blend. However, these fibrils turned into droplets in the presence of CNT. It was found that CNT preferentially remained inside the LCP domains as predicted from the value of spreading coefficient. The electrical conductivity showed the following order with the numbers in parenthesis representing the electrical percolation threshold of the compounds: PC/CNT (1%) > PC/VA950P/CNT (1%) > PC/V400P/CNT (3%). The storage modulus showed improvements with the addition of CNT and VA950.
Metastatic Renal Cell Carcinoma Change Vascularity
Authors: Azuma Takeshi , Matayoshi Yukihide , Sato Yohsuke , Sato Yujiro , Nagase Yasushi
Published: August 2012

Several molecular targeted agents have been approved for clinical use for metastatic renal cell carcinoma (mRCC). A case of a 32-year-old woman with mRCC is presented. These tumors could change vascularity by administration of molecular agents. We could select a drug timely based on findings of computed tomography. To our knowledge, this is the first report that tumor’s character change induced by molecular targeted agents can be detected and the efficacy of molecular targeted agents can be predicted.
Gender and Side-to-Side Differences of Femoral Condyles
Morphology: Osteometric Data from 360 Caucasian Dried Femori
Authors: Terzidis Ioannis , Totlis Trifon , Papathanasiou Efthymia , Sideridis Aristotelis , Vlasis Konstantinos , Natsis Konstantinos
Published: August 2012

The purpose of the present study was to conduct direct measurements in a large sample of dried femori in order to record certain morphometric parameters of the femoral condyles and determine whether there are gender and side differences. Three hundred sixty (Greek) Caucasian dried femori (180 left and 180 right), from 192 males and 168 females, were measured using a digital caliper. The mean age was 67.52 years. The mean bicondylar width of the femur was 8.86 cm ± 0.42 cm in men and 7.85 cm ± 0.30 cm in women (). The relative values for the medial condylar depth were 6.11 cm ± 0.34 cm and 5.59 cm ± 0.29 cm (); for the lateral condylar depth were 6.11 cm ± 0.33 cm and 5.54 cm ± 0.21 cm (); for the intercondylar width were 2.20 cm ± 0.18 cm and 1.87 cm ± 0.10 cm (); for the intercondylar depth were 2.78 cm ± 0.16 cm and 2.37 cm ± 0.12 cm (). No significant side-to-side difference was observed in any parameter. The femoral condyles differences in anatomy between genders might be useful to the design of total knee prostheses. The contralateral healthy side can be safely used for preoperative templating since there were no significant side differences.
Monthly Rainfall Estimation Using Data-Mining Process
Authors: Terzi Özlem
Published: August 2012

It is important to accurately estimate rainfall for effective use of water resources and optimal planning of water structures. For this purpose, the models were developed to estimate rainfall in Isparta using the data-mining process. The different input combinations having 1-, 2-, 3- and 4-input parameters were tried using the rainfall values of Senirkent, Uluborlu, Eğirdir, and Yalvaç stations in Isparta. The most appropriate algorithm was determined as multilinear regression among the models developed with various data-mining algorithms. The input parameters of Multilinear Regression model were the monthly rainfall values of Senirkent, Uluborlu and Eğirdir stations. The relative error of this model was calculated as 0.7%. It was shown that the data mining process can be used in estimation of missing rainfall values.
Stem Cells as a Tool to Improve Outcomes of Islet Transplantation
Authors: Sims Emily , Evans-Molina Carmella
Published: August 2012

The publication of the promising results of the Edmonton protocol in 2000 generated optimism for islet transplantation as a potential cure for Type 1 Diabetes Mellitus. Unfortunately, follow-up data revealed that less than 10% of patients achieved long-term insulin independence. More recent data from other large trials like the Collaborative Islet Transplant Registry show incremental improvement with 44% of islet transplant recipients maintaining insulin independence at three years of follow-up. Multiple underlying issues have been identified that contribute to islet graft failure, and newer research has attempted to address these problems. Stem cells have been utilized not only as a functional replacement forβcells, but also as companion or supportive cells to address a variety of different obstacles that prevent ideal graft viability and function. In this paper, we outline the manners in which stem cells have been applied to address barriers to the achievement of long-term insulin independence following islet transplantation.
Characterization and Quenching of Autofluorescence in Piglet Testis Tissue and Cells
Authors: Yang Yanfei , Honaramooz Ali
Published: August 2012

Significant intrinsic fluorescence in tissues and in disassociated cells can interfere with fluorescence identification of target cells. The objectives of the present study were (1) to examine an intrinsic fluorescence we observed in both the piglet testis tissue and cells and (2) to test an effective method to block the autofluorescence. We observed that a number of granules within the testis interstitial cells were inherently fluorescent, detectable using epifluorescence microscopy, confocal laser scanning microscopy, and flow cytometry. The emission wavelength of the autofluorescent substance ranged from 425 to 700 nm, a range sufficiently broad that could potentially interfere with fluorescence techniques. When we treated the samples with Sudan Black B for different incubation times, the intrinsic fluorescence was completely masked after treatment for 10–15 min of the testis tissue sections or for 8 min of the testis cells, without compromising specific fluorescence labeling of gonocytes with lectin Dolichos biflorus agglutinin (DBA). We speculate that the lipofuscin or lipofuscin-like pigments within Leydig cell granules were mainly responsible for the observed intrinsic fluorescence in piglet testes. The method described in the present study can facilitate the identification and characterization of piglet gonocytes using fluorescence microscopy.
Pleurotus tuber-regiumPolysaccharides Attenuate Hyperglycemia and Oxidative Stress in Experimental Diabetic Rats
Authors: Huang Hui-Yu , Korivi Mallikarjuna , Chaing Ying-Ying , Chien Ting-Yi , Tsai Ying-Chieh
Published: August 2012

Pleurotus tuber-regiumcontains polysaccharides that are responsible for pharmacological actions, and medicinal effects of these polysaccharides have not yet been studied in diabetic rats. We examined the antidiabetic, antihyperlipidemic, and antioxidant properties ofP. tuber-regiumpolysaccharides in experimental diabetic rats. Forty rats were equally assigned as diabetic high-fat (DHF) diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and DHF+3P, 20 mg/kg bodyweight/8-week). Diabetes was induced by chronic low-dose streptozotocin injections and a high-fat diet to mimic type 2 diabetes. Polysaccharides (1P, 2P, and 3P) were extracted from three different strains ofP. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels substantially decreased, while serum insulin levels were restored by polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol, triglycerides, and low-density lipoprotein levels were significantly(P<0.01)lower in polysaccharide groups. High-density lipoprotein levels were attenuated with polysaccharides against diabetes condition. Polysaccharides inhibited(P<0.01)the lipid peroxidation index (malondialdehyde), and restored superoxide dismutase and glutathione peroxidase activities in the liver of diabetic rats. The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant system that attenuates oxidative stress. We emphasize thatP. tuber-regiumpolysaccharides can be considered as an alternative medicine to treat hyperglycemia and oxidative stress in diabetic rats.
A Second Order Characteristic Method for Approximating Incompressible Miscible Displacement in Porous Media
Authors: Sun Tongjun , Ma Keying
Published: August 2012

An approximation scheme is defined for incompressible miscible displacement in porous media. This scheme is constructed by two methods. Under the regularity assumption for the pressure, cubic Hermite finite element method is used for the pressure equation, which ensures the approximation of the velocity smooth enough. A second order characteristic finite element method is presented to handle the material derivative term of the concentration equation. It is of second order accuracy in time increment, symmetric, and unconditionally stable. The optimalL2-norm error estimates are derived for the scalar concentration.
Normal Families of Zero‐Free Meromorphic Functions
Authors: Li Yuntong
Published: August 2012

Let a(≠0),   b ∈ ℂ, and n and k be two positive integers such that n ≥ 2. Let
ℱ be a family of zero‐free meromorphic functions defined in a domain 𝒟 such
that for each f ∈ ℱ, has at most nk zeros, ignoring multiplicity.
Then ℱ is normal in 𝒟.
Expression of SIRT1 and DBC1 in Developing and Adult Retinas
Authors: Maloney Shawn C. , Antecka Emilia , Odashiro Alexandre N. , Fernandes Bruno F. , Doyle Madeline , Lim Li-Anne , Katib Yousef , Burnier Miguel N.
Published: August 2012

Sirtuin 1 (SIRT1) is a deacetylase that can regulate various biological processes via repression of transcription. Its activity has been linked to the differentiation of neural progenitor cells, although little is known about its function during retinal development. The study described herein was undertaken to evaluate the expression of SIRT1 and its innate inhibitor, DBC1, in retinal tissues and progenitor cells. We found both SIRT1 and DBC1 to be widely expressed in mouse and human retinas, with subtle differences in subcellular distribution of each protein. We further demonstrate that nuclear-localized SIRT1 is only seen in human-derived retinal progenitor cells and not in adult retinas, suggesting that this nuclear localization may be important in retinal development. Moreover, we observed cytoplasmic DBC1 in a subset of progenitor cells as well as in mature ganglion cells, indicating that the progenitor cell subset, which was comprised predominantly of small cells, may represent a population of ganglion cell precursors. Collectively, the data presented in this study provide support for SIRT1 and DBC1 as regulators of retinal development and normal retinal physiology.
Tolerogenic versus Inflammatory Activity of Peripheral Blood Monocytes and Dendritic Cells Subpopulations in Systemic Lupus Erythematosus
Authors: Carvalheiro Tiago , Rodrigues Ana , Lopes Ana , Inês Luís , Velada Isabel , Andreia Ribeiro  , Martinho António , Silva José A. P. , Pais Maria L. , Paiva Artur
Published: August 2012

Abnormalities in monocytes and in peripheral blood dendritic cells (DC) subsets have been reported in systemic lupus erythematosus (SLE). We aim to clarify the tolerogenic or inflammatory role of these cells based on ICOSL or IFN-αand chemokine mRNA expression, respectively, after cell purification. The study included 18 SLE patients with active disease (ASLE), 25 with inactive disease (ISLE), and 30 healthy controls (HG). In purified plasmacytoid DC (pDC) was observed a lower ICOSL mRNA expression in ASLE and an increase in ISLE; similarly, a lower ICOSL mRNA expression in monocytes of ALSE patients was found. However, a higher ICOSL mRNA expression was observed in ASLE compared to HG in myeloid DCs. Interestingly, clinical parameters seem to be related with ICOSL mRNA expression. Regarding the inflammatory activity it was observed in purified monocytes and CD CD16+DCs an increase of CCL2, CXCL9, and CXCL10 mRNA expression in ASLE compared to HG. In myeloid DC no differences were observed regarding chemokines, and IFN-αmRNA expression. In pDC, a higher IFN-αmRNA expression was observed in ASLE. Deviations in ICOSL, chemokine, and IFN-αmRNA expression in peripheral blood monocytes and dendritic cells subpopulations in SLE appear to be related to disease activity.
Micromagnetic Study of Synchronization of Nonlinear Spin-Torque Oscillators to Microwave Current and Field
Authors: Carpentieri M. , Finocchio G. , Giordano A. , Azzerboni B. , Lattarulo F.
Published: August 2012

The nonautonomous dynamics of spin-torque oscillators in presence of both microwave current and field has been numerically studied in nanostructured devices. When both microwave current and field are applied at the same frequency, integer phase locking at different locking ratio is found. In the locking region, a study of the intrinsic phase shift between the locking force (current or field) and the giant magnetoresistive signal as a function of the bias current is also exploited.
CFD Modeling of Solid Suspension in a Stirred Tank: Effect of Drag Models and Turbulent Dispersion on Cloud Height
Authors: Gohel Shitanshu , Joshi Shitalkumar , Azhar Mohammed , Horner Marc , Padron Gustavo
Published: August 2012

Many chemical engineering processes involve the suspension of solid particles in a liquid. In dense systems, agitation leads to the formation of a clear liquid layer above a solid cloud. Cloud height, defined as the location of the clear liquid interface, is a critical measure of process performance. In this study, solid-liquid mixing experiments were conducted and cloud height was measured as a function operating conditions and stirred tank configuration. Computational fluid dynamics simulations were then performed using an Eulerian-Granular multiphase model. The effects of hindered and unhindered drag models and turbulent dispersion force on cloud height were investigated. A comparison of the experimental and computational data showed excellent agreement over the full range of conditions tested.
A Granular Reduction Algorithm Based on Covering Rough Sets
Authors: Yang Tian , Li Zhaowen , Yang Xiaoqing
Published: August 2012

The granular reduction is to delete dispensable elements from a covering.
It is an efficient method to reduce granular structures and get rid of the
redundant information from information systems. In this paper, we develop
an algorithm based on discernability matrixes to compute all the granular
reducts of covering rough sets. Moreover, a discernibility matrix is simplified
to the minimal format. In addition, a heuristic algorithm is proposed as well
such that a granular reduct is generated rapidly.
Oxidative Stress and Its Clinical Applications in Dementia
Authors: Mao Peizhong
Published: August 2012

Dementia is a complex disorder that mostly affects the elderly and represents a significant and growing public health burden in the world. Alzheimer’s disease (AD)- associated dementia and dementia with Lewy bodies (DLB) are the most common forms of dementia, in which oxidative stress is significantly involved. Oxidative stress mechanisms may have clinical applications, that is, providing information for potential biomarkers. Thus brain-rich peptides with an antioxidant property, such as CART (cocaine- and amphetamine-regulated transcript), may be promising new markers. This paper summarizes the progress in research regarding oxidative stress in dementia with a focus on potential biomarkers in the cerebrospinal fluid (CSF) in the main forms of dementia. Other central and peripheral biomarkers, especially those considered oxidative stress related, are also discussed. This paper aims to provide information to improve current understanding of the pathogenesis and progression of dementia. It also offers insight into the differential diagnosis of AD and DLB.
Biomarkers of Response to Akt Inhibitor MK-2206 in Breast Cancer
Authors: Sangai Takafumi , Akcakanat Argun , Chen Huiqin , Tarco Emily , Wu Yun , Do Kim-Anh , Miller Todd W. , Arteaga Carlos L. , Mills Gordon B. , Gonzalez-Angulo Ana Maria , Meric-Bernstam Funda
Published: August 2012

Purpose: We tested the hypothesis that allosteric Akt inhibitor MK-2206 inhibits tumor growth, and that PTEN/PIK3CA mutations confer MK-2206 sensitivity.

Experimental Design: MK-2206 effects on cell signaling were assessed in vitro and in vivo. Its antitumor efficacy was assessed in vitro in a panel of cancer cell lines with differing PIK3CA and PTEN status. Its in vivo efficacy was tested as a single agent and in combination with paclitaxel.

Results: MK-2206 inhibited Akt signaling and cell-cycle progression, and increased apoptosis in a dose-dependent manner in breast cancer cell lines. Cell lines with PTEN or PIK3CA mutations were significantly more sensitive to MK-2206; however, several lines with PTEN/PIK3CA mutations were MK-2206 resistant. siRNA knockdown of PTEN in breast cancer cells increased Akt phosphorylation concordant with increased MK-2206 sensitivity. Stable transfection of PIK3CA E545K or H1047R mutant plasmids into normal-like MCF10A breast cells enhanced MK-2206 sensitivity. Cell lines that were less sensitive to MK-2206 had lower ratios of Akt1/Akt2 and had less growth inhibition with Akt siRNA knockdown. In PTEN-mutant ZR75-1 breast cancer xenografts, MK-2206 treatment inhibited Akt signaling, cell proliferation, and tumor growth. In vitro, MK-2206 showed a synergistic interaction with paclitaxel in MK-2206–sensitive cell lines, and this combination had significantly greater antitumor efficacy than either agent alone in vivo.

Conclusions: MK-2206 has antitumor activity alone and in combination with chemotherapy. This activity may be greater in tumors with PTEN loss or PIK3CA mutation, providing a strategy for patient enrichment in clinical trials. Clin Cancer Res; 18(20); 5816–28. ©2012 AACR.
Novel Tumor Subgroups of Urothelial Carcinoma of the Bladder Defined by Integrated Genomic Analysis
Authors: Hurst Carolyn D. , Platt Fiona M. , Taylor Claire F. , Knowles Margaret A.
Published: August 2012

Purpose: There is a need for improved subclassification of urothelial carcinoma (UC) at diagnosis. A major aim of this study was to search for novel genomic subgroups.

Experimental design: We assessed 160 tumors for genome-wide copy number alterations and mutation in genes implicated in UC. These comprised all tumor grades and stages and included 49 high-grade stage T1 (T1G3) tumors.

Results: Our findings point to the existence of genomic subclasses of the “gold-standard” grade/stage groups. The T1G3 tumors separated into 3 major subgroups that differed with respect to the type and number of copy number events and to FGFR3 and TP53 mutation status. We also identified novel regions of copy number alteration, uncovered relationships between molecular events, and elucidated relationships between molecular events and clinico-pathologic features. FGFR3 mutant tumors were more chromosomally stable than their wild-type counterparts and a mutually exclusive relationship between FGFR3 mutation and overrepresentation of 8q was observed in non-muscle-invasive tumors. In muscle-invasive (MI) tumors, metastasis was positively associated with losses of regions on 10q (including PTEN), 16q and 22q, and gains on 10p, 11q, 12p, 19p, and 19q. Concomitant copy number alterations positively associated with TP53 mutation in MI tumors were losses on 16p, 2q, 4q, 11p, 10q, 13q, 14q, 16q, and 19p, and gains on 1p, 8q, 10q, and 12q. Significant complexity was revealed in events affecting chromosome 9.

Conclusions: These findings may lead to improved biologic understanding and the development of prognostic biomarkers. Novel regions of copy number alteration may reveal potential therapeutic targets. Clin Cancer Res; 18(21); 5865–77. ©2012 AACR.
Selective Targeting of Interferon γ to Stromal Fibroblasts and Pericytes as a Novel Therapeutic Approach to Inhibit Angiogenesis and Tumor Growth
Authors: Bansal Ruchi , Tomar Tushar , Östman Arne , Poelstra Klaas , Prakash Jai
Published: August 2012

New approaches to block the function of tumor stromal cells such as cancer-associated fibroblasts and pericytes is an emerging field in cancer therapeutics as these cells play a crucial role in promoting angiogenesis and tumor growth via paracrine signals. Because of immunomodulatory and other antitumor activities, IFNγ, a pleiotropic cytokine, has been used as an anticancer agent in clinical trials. Unfortunately only modest beneficial effects, but severe side effects, were seen. In this study, we delivered IFNγ to stromal fibroblasts and pericytes, considering its direct antifibrotic activity, using our platelet-derived growth factor-beta receptor (PDGFβR)-binding carrier (pPB-HSA), as these cells abundantly express PDGFβR. We chemically conjugated IFNγ to pPB-HSA using a heterobifunctional PEG linker. In vitro in NIH3T3 fibroblasts, pPB-HSA-IFNγ conjugate activated IFNγ-signaling (pSTAT1α) and inhibited their activation and migration. Furthermore, pPB-HSA-IFNγ inhibited fibroblasts-induced tube formation of H5V endothelial cells. In vivo in B16 tumor-bearing mice, pPB-HSA-IFNγ rapidly accumulated in tumor stroma and pericytes and significantly inhibited the tumor growth while untargeted IFNγ and pPB-HSA carrier were ineffective. These antitumor effects of pPB-HSA-IFNγ were attributed to the inhibition of tumor vascularization, as shown with α-SMA and CD-31 staining. Moreover, pPB-HSA-IFNγ induced MHC-II expression specifically in tumors compared with untargeted IFNγ, indicating the specificity of this approach. This study thus shows the impact of drug targeting to tumor stromal cells in cancer therapy as well as provides new opportunities to use cytokines for therapeutic application. Mol Cancer Ther; 11(11); 2419–28. ©2012 AACR.
Smoking Induces Epithelial-to-Mesenchymal Transition in Non–Small Cell Lung Cancer through HDAC-Mediated Downregulation of E-Cadherin
Authors: Nagathihalli Nagaraj S. , Massion Pierre P. , Gonzalez Adriana L. , Lu Pengcheng , Datta Pran K.
Published: August 2012

Epidemiological studies have shown that most cases of lung cancers (85%–90%) are directly attributable to tobacco smoking. Although association between cigarette smoking and lung cancer is well documented, surprisingly little is known about the molecular mechanisms of how smoking is involved in epithelial-to-mesenchymal transition (EMT) through epigenetic changes. Here, we show that lung cancer patients with a smoking history have low E-cadherin levels and loss of E-cadherin is a poor prognostic factor in smokers. Moreover, the downregulation of E-cadherin correlates with the number of pack years. In an attempt to determine the role of long-term cigarette smoking on EMT, we observed that treatment of lung cell lines with cigarette smoke condensate (CSC) induces EMT through downregulation of epithelial markers, including E-cadherin and upregulation of mesenchymal markers. CSC decreases E-cadherin expression at the transcriptional level through upregulation of LEF1 and Slug, and knockdown of these two proteins increases E-cadherin expression. Importantly, chromatin immunoprecipitation assays suggest that LEF-1 and Slug binding to E-cadherin promoter is important for CSC-mediated downregulation of E-cadherin. The histone deacetylase (HDAC) inhibitor MS-275 reverses CSC-induced EMT, migration, and invasion through the restoration of E-cadherin expression. These results suggest that recruitment of HDACs by transcriptional repressors LEF-1 and Slug is responsible for E-cadherin suppression and EMT in cigarette smokers and provide a potential drug target toward the treatment of lung cancer. Mol Cancer Ther; 11(11); 2362–72. ©2012 AACR.